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<title>
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Entry
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- *142410 - HNF1 HOMEOBOX A; HNF1A
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*142410</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cytogenetics">Cytogenetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#nomenclature">Nomenclature</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/142410">Table View</a>
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</li>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
|
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
|
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</a>
|
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</h4>
|
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</div>
|
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
|
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000135100;t=ENST00000257555" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=6927" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=142410" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000135100;t=ENST00000257555" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000545,NM_001306179,NM_001406915,XM_024449168" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000545" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=142410" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
|
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</div>
|
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</div>
|
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
|
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<span class="panel-title">
|
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=00800&isoform_id=00800_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/HNF1A" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/184265,1708747,4262739,6102835,85396996,85397794,119618632,119618633,119618634,148733228,194391056,219526038,219526040,219526042,219526044,219526046,219526048,219526050,219526052,219526054,219526056,219526058,219526060,219526062,219526064,219526066,219526068,219526070,301072494,301072496,304560899,304560901,304560903,304560905,304560907,304560909,304560911,304560913,304560918,304560928,304560930,304560932,304560935,304560938,1370462750,1370766223,1370766225,1370766227,1370766229,1677538666,1779541913,2244986564,2462534144,2813266253" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P20823" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="http://biogps.org/#goto=genereport&id=6927" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000135100;t=ENST00000257555" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=HNF1A" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=HNF1A" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+6927" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/HNF1A" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:6927" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/6927" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr12&hgg_gene=ENST00000257555.11&hgg_start=120978543&hgg_end=121002512&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11621" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:11621" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/hnf1a" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=142410[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=142410[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/HNF1A/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000135100" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=HNF1A" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=HNF1A" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HNF1A" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/HNF1A" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HNF1A&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA36380" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:11621" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:98504" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/HNF1A#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:98504" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/6927/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002878/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=6927" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-021206-12" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:6927" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HNF1A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1187306007, 128667008, 254915003, 41607009, 609570008, 733471003<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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142410
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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HNF1 HOMEOBOX A; HNF1A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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TRANSCRIPTION FACTOR 1; TCF1<br />
|
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HEPATOCYTE NUCLEAR FACTOR-1-ALPHA<br />
|
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HEPATOCYTE NUCLEAR FACTOR 1; HNF1<br />
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HEPATIC NUCLEAR FACTOR-1-ALPHA<br />
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ALBUMIN PROXIMAL FACTOR
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HNF1A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HNF1A</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
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Cytogenetic location: <a href="/geneMap/12/887?start=-3&limit=10&highlight=887">12q24.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:120978543-121002512&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">12:120,978,543-121,002,512</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
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<a href="/clinicalSynopsis/table?mimNumber=222100,125853,612520,142330,600496,144700" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
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View Clinical Synopses
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</a>
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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<a href="/geneMap/12/887?start=-3&limit=10&highlight=887">
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12q24.31
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</a>
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<span class="mim-font">
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{Diabetes mellitus, insulin-dependent}
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<span class="mim-font">
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<a href="/entry/222100"> 222100 </a>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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{Diabetes mellitus, noninsulin-dependent, 2}
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/125853"> 125853 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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Diabetes mellitus, insulin-dependent, 20
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<td>
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<span class="mim-font">
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<a href="/entry/612520"> 612520 </a>
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</td>
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<span class="mim-font">
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<span class="mim-font">
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Hepatic adenoma, somatic
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/142330"> 142330 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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<span class="mim-font">
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MODY, type III
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/600496"> 600496 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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<span class="mim-font">
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Renal cell carcinoma
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</span>
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</td>
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<span class="mim-font">
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<a href="/entry/144700"> 144700 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/142410" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/142410" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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<div id="mimCloningFold" class="collapse in mimTextToggleFold">
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<p>Using a rat Hnf1 cDNA-derived probe, <a href="#2" class="mim-tip-reference" title="Bach, I., Galcheva-Gargova, Z., Mattei, M.-G., Simon-Chazottes, D., Guenet, J.-L., Cereghini, S., Yaniv, M. <strong>Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse.</strong> Genomics 8: 155-164, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1707031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1707031</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90238-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1707031">Bach et al. (1990)</a> isolated HNF1 clones from a human liver cDNA library. The deduced 631-amino acid human HNF1 protein contains a homeodomain in its N-terminal half and shares close similarity with the 628-amino acid rat protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1707031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The amino acid sequence of HNF1 displays distant sequence homology to the homeodomains of homeotic genes (see <a href="/entry/142950">142950</a>) (<a href="#11" class="mim-tip-reference" title="Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., Crabtree, G. R. <strong>Interaction of a liver-specific nuclear factor with the fibrinogen and alpha-1-antitrypsin promoters.</strong> Science 238: 688-692, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3499668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3499668</a>] [<a href="https://doi.org/10.1126/science.3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3499668">Courtois et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<br />
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<div>
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<a id="geneFunction" class="mim-anchor"></a>
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<h4 href="#mimGeneFunctionFold" id="mimGeneFunctionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimGeneFunctionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<div id="mimGeneFunctionFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>The orderly and sequential activation of genes during development is thought to be related to the selective expression of groups of regulatory proteins acting primarily at the level of transcription. <a href="#11" class="mim-tip-reference" title="Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., Crabtree, G. R. <strong>Interaction of a liver-specific nuclear factor with the fibrinogen and alpha-1-antitrypsin promoters.</strong> Science 238: 688-692, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3499668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3499668</a>] [<a href="https://doi.org/10.1126/science.3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3499668">Courtois et al. (1987)</a> found a nuclear protein in hepatocytes, but not in other cell types, that binds to a sequence required for hepatocyte-specific transcription of the genes for the alpha and beta chains of fibrinogen (<a href="/entry/134820">134820</a>, <a href="/entry/134830">134830</a>) and alpha-1-antitrypsin (<a href="/entry/107400">107400</a>). This protein, called hepatocyte nuclear factor-1 (HNF1) by them, interacts with sequences required for optimal promoter function of the genes mentioned. The promoter or enhancer regions for several viral and cellular genes not expressed in the liver did not compete for binding to these sequences. HNF1 is predominantly expressed in liver and kidney. The restricted expression of HNF1 and its selective interaction with the control regions of several liver-specific genes suggested to <a href="#11" class="mim-tip-reference" title="Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., Crabtree, G. R. <strong>Interaction of a liver-specific nuclear factor with the fibrinogen and alpha-1-antitrypsin promoters.</strong> Science 238: 688-692, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3499668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3499668</a>] [<a href="https://doi.org/10.1126/science.3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3499668">Courtois et al. (1987)</a> that it is involved in developmentally regulated gene expression in the liver. HNF1 binds to the promoters of a variety of genes that are expressed exclusively in the liver, e.g., fibrinogen-alpha and -beta, albumin (<a href="/entry/103600">103600</a>), alpha-fetoprotein (<a href="/entry/104150">104150</a>), alpha-1-antitrypsin, liver-type pyruvate kinase (<a href="/entry/609712">609712</a>), transthyretin (<a href="/entry/176300">176300</a>), aldolase B (<a href="/entry/612724">612724</a>), and hepatitis B virus large surface protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Dimerization among transcription factors is a frequent finding in the regulation of eukaryotic gene expression. HNF1-alpha functions as a dimer. <a href="#31" class="mim-tip-reference" title="Mendel, D. B., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., Crabtree, G. R. <strong>Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.</strong> Science 254: 1762-1767, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1763325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1763325</a>] [<a href="https://doi.org/10.1126/science.1763325" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1763325">Mendel et al. (1991)</a> identified DCOH (<a href="/entry/126090">126090</a>), a dimerization cofactor of HNF1-alpha, which displayed a restricted tissue distribution and did not bind to DNA but, rather, selectively stabilized HNF1-alpha dimers. <a href="#25" class="mim-tip-reference" title="Hua, Q.-X., Zhao, M., Narayana, N., Nakagawa, S. H., Jia, W., Weiss, M. A. <strong>Diabetes-associated mutations in a beta-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface.</strong> Proc. Nat. Acad. Sci. 97: 1999-2004, 2000. Note: Erratum: Proc. Nat. Acad. Sci. 98: 13472 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10696112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10696112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10696112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.5.1999" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10696112">Hua et al. (2000)</a> showed that the dimerization motif of HNF1-alpha forms an intermolecular 4-helix bundle. The bundle is destabilized by a subset of mutations associated with maturity-onset diabetes of the young (MODY; <a href="/entry/606391">606391</a>). Impaired dimerization of the beta-cell transcription factor thus provides a molecular mechanism of metabolic deregulation in diabetes mellitus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10696112+1763325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="van Wering, H. M., Huibregtse, I. L., van der Zwan, S. M., de Bie, M. S., Dowling, L. N., Boudreau, F., Rings, E. H. H. M., Grand, R. J., Krasinski, S. D. <strong>Physical interaction between GATA-5 and hepatocyte nuclear factor-1-alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter.</strong> J. Biol. Chem. 277: 27659-27667, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12011060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12011060</a>] [<a href="https://doi.org/10.1074/jbc.M203645200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12011060">Van Wering et al. (2002)</a> showed that mouse Gata5 (<a href="/entry/611496">611496</a>) and Hnf1-alpha interacted in vitro and in transfected COS-7 cells. The interaction required the C-terminal zinc finger and basic region of Gata5 and the homeodomain of Hnf1-alpha. Physical association of GATA5 and HNF1-alpha was required for synergistic activation of the human lactase-phlorizin hydrolase (LCT; <a href="/entry/603202">603202</a>) promoter. Deletion of the HNF1-alpha activation domains or interruption of the HNF1-binding sites in the LCT promoter resulted in complete loss of transcriptional activity, whereas deletion of the GATA5 activation domains or interruption of the GATA-binding sites reduced, but did not eliminate, transcriptional activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12011060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To gain insight into the transcriptional regulatory networks that specify and maintain human tissue diversity, <a href="#35" class="mim-tip-reference" title="Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A. <strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong> Science 303: 1378-1381, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14988562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14988562</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14988562[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1089769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14988562">Odom et al. (2004)</a> used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1-alpha, HNF4-alpha (<a href="/entry/600281">600281</a>), and HNF6 (<a href="/entry/604164">604164</a>), together with RNA polymerase II (see <a href="/entry/180660">180660</a>), in human liver and pancreatic islets. <a href="#35" class="mim-tip-reference" title="Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A. <strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong> Science 303: 1378-1381, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14988562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14988562</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14988562[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1089769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14988562">Odom et al. (2004)</a> identified tissue-specific regulatory circuits formed by HNF1-alpha, HNF4-alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. <a href="#35" class="mim-tip-reference" title="Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A. <strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong> Science 303: 1378-1381, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14988562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14988562</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14988562[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1089769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14988562">Odom et al. (2004)</a> concluded that their results suggested how misregulation of HNF4-alpha can contribute to type 2 diabetes (<a href="/entry/125853">125853</a>). They found that HNF1-alpha is bound to at least 222 target genes in hepatocytes. HNF1-alpha occupied the promoter regions of 106 genes within pancreatic islets, 30% of which were also bound by HNF1-alpha in hepatocytes. In islets, fewer chaperones and enzymes were bound by HNF1-alpha than in hepatocytes, and the receptors and signal transduction machinery regulated by HNF1-alpha varied between the 2 tissues. <a href="#35" class="mim-tip-reference" title="Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A. <strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong> Science 303: 1378-1381, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14988562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14988562</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14988562[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1126/science.1089769" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14988562">Odom et al. (2004)</a> found that HNF4-alpha bound to the promoters of about 12% of hepatocyte islet genes represented on the microarray. HNF4-alpha acted in a much larger number of hepatocyte and beta-cell genes than did HNF1-alpha, suggesting that HNF4-alpha has broad activities in these 2 tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14988562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., Fraenkel, E. <strong>Tissue-specific transcriptional regulation has diverged significantly between human and mouse.</strong> Nature Genet. 39: 730-732, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17529977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17529977</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17529977[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng2047" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17529977">Odom et al. (2007)</a> analyzed the binding of FOXA2 (<a href="/entry/600288">600288</a>), HNF1A, HNF4A, and HNF6 to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, 41 to 89% of the binding events seemed to be species-specific. Importantly, the binding sites varied widely between species in ways that could not be predicted from human-mouse sequence alignments alone. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17529977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Bach, I., Galcheva-Gargova, Z., Mattei, M.-G., Simon-Chazottes, D., Guenet, J.-L., Cereghini, S., Yaniv, M. <strong>Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse.</strong> Genomics 8: 155-164, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1707031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1707031</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90238-p" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1707031">Bach et al. (1990)</a> assigned the human HNF1 gene to chromosome 12q24.3 by in situ hybridization, and the mouse gene to 5F by RFLP analysis of interspecific mouse backcrosses. One other gene, that for short chain acyl-CoA-dehydrogenase (<a href="/entry/606885">606885</a>), had also been assigned to chromosomes 12 and 5 in man and mouse, respectively. <a href="#29" class="mim-tip-reference" title="Kuo, C. J., Conley, P. B., Hsieh, C.-L., Francke, U., Crabtree, G. R. <strong>Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1.</strong> Proc. Nat. Acad. Sci. 87: 9838-9842, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2263635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2263635</a>] [<a href="https://doi.org/10.1073/pnas.87.24.9838" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2263635">Kuo et al. (1990)</a> also assigned the HNF1 gene to 12q22-qter in the human and to chromosome 5 in the mouse. By means of somatic cell hybrids segregating either human or rat chromosomes, <a href="#42" class="mim-tip-reference" title="Szpirer, C., Riviere, M., Cortese, R., Nakamura, T., Islam, M. Q., Levan, G., Szpirer, J. <strong>Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF).</strong> Genomics 13: 293-300, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1535333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1535333</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90245-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1535333">Szpirer et al. (1992)</a> independently assigned the TCF1 gene to human chromosome 12 and found that it was located also on rat chromosome 12, thereby defining a new segment of homology between the 2 species (and a segment of mouse chromosome 5). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1535333+2263635+1707031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>MODY, a single-gene disorder responsible for 2 to 5% of noninsulin-dependent (type II) diabetes mellitus (NIDDM; <a href="/entry/125853">125853</a>), is characterized by autosomal dominant inheritance and an age of onset of 25 years or younger. <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al. (1996)</a> narrowed the localization of a form of MODY (MODY3; <a href="/entry/600496">600496</a>) to chromosome 12q24.2 by a combination of genetic linkage and fluorescence in situ hybridization. To identify the nature of the MODY3 gene, <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al. (1996)</a> used a combination of approaches, including testing genes known to be on 12q to see if they mapped into the contig to which MODY3 mapped, exon trapping, and cDNA selection, for which human pancreatic islet cDNA was used (insulin secretion is abnormal in MODY3 patients, making islets a likely site of expression of MODY3 mRNA and protein). They identified 14 genes encoding known proteins, 12 known expressed sequence tags (ESTs), and 9 new ESTs. They found mutations in the gene encoding hepatocyte nuclear factor-1-alpha, a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene. In all, <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al. (1996)</a> identified 6 different mutations which were associated with MODY3 (e.g., <a href="#0001">142410.0001</a>). In several pedigrees individuals were found who inherited the mutant allele and the at-risk chromosome 12 haplotype but were nondiabetic or only showed evidence of impaired glucose tolerance or diabetes during pregnancy. These individuals were expected eventually to develop diabetes mellitus. In one member of a family NIDDM was diagnosed at the age of 65 years, at which time he was mildly obese, suggesting that he had late-onset NIDDM rather than MODY. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8945470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#48" class="mim-tip-reference" title="Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P. J., Boriraj, V. V., Chevre, J.-C., Boccio, V., Cox, R. D., Lathrop, G. M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G. I., Froguel, P. <strong>Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).</strong> Hum. Molec. Genet. 6: 583-586, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097962</a>] [<a href="https://doi.org/10.1093/hmg/6.4.583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9097962">Vaxillaire et al. (1997)</a> examined 10 unrelated Caucasian families in whom MODY/NIDDM cosegregated with markers for MODY3 and found 10 different mutations in the TCF1 gene, all of which cosegregated with diabetes (see <a href="#0003">142410.0003</a> and <a href="#0004">142410.0004</a>). In these families, they found no obvious relationships between the nature of the mutations observed (i.e., frameshift, nonsense, or missense), or their location in the gene, with clinical features of diabetes (e.g., age at onset, severity). The authors stated that the mechanisms by which mutations in the TCF1 gene caused diabetes mellitus were unclear, but might include abnormal pancreatic islet development during fetal life, as well as impaired transcriptional regulation of genes that play a key role in normal pancreatic beta-cell function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Urhammer, S. A., Rasmussen, S. K., Kaisaki, P. J., Oda, N., Yamagata, K., Moller, A. M., Fridberg, M., Hansen, L., Hansen, T., Bell, G. I., Pedersen, O. <strong>Genetic variation in the hepatocyte nuclear factor-1-alpha gene in Danish Caucasians with late-onset NIDDM.</strong> Diabetologia 40: 473-475, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9112026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9112026</a>] [<a href="https://doi.org/10.1007/s001250050703" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9112026">Urhammer et al. (1997)</a> found a variety of variations in the TCF1 gene in 245 Danish NIDDM patients and 242 age-matched controls. The frequencies of the variants were similar in the 2 groups except that an arg583-to-gln mutation was found in 2 of the 245 NIDDM patients and in none of the control subjects. The authors concluded that genetic variation in the TCF1 gene is not a common factor contributing to NIDDM susceptibility in white subjects of Danish ancestry. <a href="#45" class="mim-tip-reference" title="Urhammer, S. A., Moller, A. M., Nyholm, B., Ekstrom, C. T., Eiberg, H., Clausen, J. O., Hansen, T., Pedersen, O., Schmitz, O. <strong>The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1-alpha gene on estimates of the pancreatic beta-cell function in Caucasian glucose-tolerant first-degree relatives of type 2 diabetic patients.</strong> J. Clin. Endocr. Metab. 83: 3992-3995, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9814481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9814481</a>] [<a href="https://doi.org/10.1210/jcem.83.11.5228" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9814481">Urhammer et al. (1998)</a> studied the frequent amino acid polymorphisms ile27 to leu and ser487 to asn of the TCF1 gene to determine whether they were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among Caucasian glucose-tolerant first-degree relatives of NIDDM patients. The authors concluded that these polymorphisms had no major impact on the pancreatic beta-cell function, as estimated during an oral and intravenous glucose challenge. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9112026+9814481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#44" class="mim-tip-reference" title="Urhammer, S. A., Hansen, T., Ekstrom, C. T., Eiberg, H., Pederson, O. <strong>The Ala/Val98 polymorphism of the hepatocyte nuclear factor-1-alpha gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test: evidence from studies of 231 glucose-tolerant first degree relatives of type 2 diabetic probands.</strong> J. Clin. Endocr. Metab. 83: 4506-4509, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9851800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9851800</a>] [<a href="https://doi.org/10.1210/jcem.83.12.5359" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9851800">Urhammer et al. (1998)</a> studied the TCF1 ala98-to-val polymorphism in glucose-tolerant first-degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an oral glucose tolerance test (OGTT) with measurements of plasma glucose, serum insulin, and serum C-peptide during the test. Thirty-three heterozygous carriers of the ala98-to-val variant were identified, whereas no subjects had the variant in its homozygous form. Carriers of ala98 to val had a 20% reduction in serum C-peptide at 30 minutes during the OGTT compared to wildtype carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and ala98 homozygotes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9851800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a study of 15 UK MODY families for mutations in the TCF1 gene, <a href="#17" class="mim-tip-reference" title="Frayling, T. M., Bulman, M. P., Ellard, S., Appleton, M., Dronsfield, M. J., Mackie, A. D. R., Baird, J. D., Kaisaki, P. J., Yamagata, K., Bell, G. I., Bain, S. C., Hattersley, A. T. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.</strong> Diabetes 46: 720-725, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075818</a>] [<a href="https://doi.org/10.2337/diab.46.4.720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9075818">Frayling et al. (1997)</a> found 8 different mutations in 11 families (73%). A previously reported mutation, the insertion of a C in the C tract encoding the sequence 289-pro-pro-pro-291 (<a href="#0001">142410.0001</a>), was present in 4 of the families. A screen of a further 32 probands with early-onset (less than 40 years of age) NIDDM showed the mutation in 2 additional families. This common mutation was present on at least 3 different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than founder effect. Thus, <a href="#17" class="mim-tip-reference" title="Frayling, T. M., Bulman, M. P., Ellard, S., Appleton, M., Dronsfield, M. J., Mackie, A. D. R., Baird, J. D., Kaisaki, P. J., Yamagata, K., Bell, G. I., Bain, S. C., Hattersley, A. T. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.</strong> Diabetes 46: 720-725, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075818</a>] [<a href="https://doi.org/10.2337/diab.46.4.720" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9075818">Frayling et al. (1997)</a> concluded that TSF1 mutations are a common cause of MODY in UK families and result in early-onset NIDDM with a progressive clinical course. <a href="#21" class="mim-tip-reference" title="Hansen, T., Eiberg, H., Rouard, M., Vaxillaire, M., Moller, A. M., Rasmussen, S. K., Fridberg, M., Urhammer, S. A., Holst, J. J., Almind, K., Echwald, S. M., Hansen, L., Bell, G. I., Pedersen, O. <strong>Novel MODY3 mutations in the hepatocyte nuclear factor-1-alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.</strong> Diabetes 46: 726-730, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075819</a>] [<a href="https://doi.org/10.2337/diab.46.4.726" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9075819">Hansen et al. (1997)</a> sequenced the coding region and intron-exon boundaries of the TCF1 gene in 9 unrelated Danish Caucasian subjects with MODY and found mutations in 5. These 5 mutations were found in neither 84 NIDDM patients nor in 84 control subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9075818+9075819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>MODY3 is characterized by a severe insulin secretory defect, compared with MODY2 (<a href="/entry/125851">125851</a>), a glucokinase-deficient diabetes. Because of the rapid progress to overt diabetes and the high prevalence of the requirement for insulin treatment in patients with MODY3, <a href="#50" class="mim-tip-reference" title="Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J. <strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong> Diabetes 46: 1643-1647, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313763">Yamada et al. (1997)</a> screened the HNF1A gene for mutations in Japanese subjects with insulin-dependent diabetes mellitus (IDDM; <a href="/entry/222100">222100</a>). Mutations were identified in 3 (5.5%) of the 55 unrelated subjects with IDDM (e.g., <a href="#0001">142410.0001</a>, <a href="#0005">142410.0005</a>, and <a href="#0006">142410.0006</a>). None of these mutations was found in 200 normal chromosomes from nondiabetic subjects. The results indicated that mutation in the HNF1A gene can lead to development not only of early-onset NIDDM but also of IDDM. In a subclassification of IDDM, the HNF1A-deficient type should be distinguished from the classic type of autoimmune-based IDDM in Japanese. All of these mutations were heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Ellard, S. <strong>Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young.</strong> Hum. Mutat. 16: 377-385, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11058894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11058894</a>] [<a href="https://doi.org/10.1002/1098-1004(200011)16:5<377::AID-HUMU1>3.0.CO;2-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11058894">Ellard (2000)</a> stated that 65 different mutations in the TCF1 gene had been found to cause MODY3 in a total of 116 families worldwide. They noted that diagnostic and predictive genetic testing is possible for the majority of patients with MODY, opening new avenues for the classification, prediction, and perhaps eventually the prevention of diabetes in these families. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11058894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Fajans, S. S., Bell, G. I., Polonsky, K. S. <strong>Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.</strong> New Eng. J. Med. 345: 971-980, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11575290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11575290</a>] [<a href="https://doi.org/10.1056/NEJMra002168" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11575290">Fajans et al. (2001)</a> reported that mutations in the HNF1A gene have been identified in all racial and ethnic backgrounds, including European, Chinese, Japanese, African, and American Indian. Mutations in the HNF1A gene appear to be the most common cause of MODY among adults seen in diabetic clinics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11575290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> found germline TCF1 mutations in 2 individuals who had previously had a liver-tumor resection and had familial diabetes. One of these individuals had a hepatocellular carcinoma that had developed in an adenoma and had a gly574-to-ser mutation (<a href="#0013">142410.0013</a>). This mutation was described by <a href="#10" class="mim-tip-reference" title="Collet, C., Ducorps, M, Mayaudon, H., Dupuy, O., Ceppa, F., Boutin, P., Froguel, P., Bauduceau, B. <strong>Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1-alpha in Africans with diabetes.</strong> Diabetes Metab. 28: 39-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938027</a>]" pmid="11938027">Collet et al. (2002)</a> as frequent in Africans with diabetes. These results suggested that germline mutations of TCF1 may predispose to benign liver tumor development, and may explain the previously described cosegregation of liver adenoma with diabetes mellitus in a large family (<a href="#15" class="mim-tip-reference" title="Foster, J. H., Donohue, T. A., Berman, M. M. <strong>Familial liver-cell adenomas and diabetes mellitus.</strong> New Eng. J. Med. 299: 239-241, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/207987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">207987</a>] [<a href="https://doi.org/10.1056/NEJM197808032990508" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="207987">Foster et al., 1978</a>). <a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> suggested the results of their studies indicated that individuals with MODY could benefit from liver monitoring to detect early tumor occurrence, and individuals with liver adenomas, especially those with a family history of the same condition, should be tested for diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11938027+207987+12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To elucidate the function of a molecular hotspot, <a href="#8" class="mim-tip-reference" title="Chi, Y.-I., Frantz, J. D., Oh, B.-C., Hansen, L., Dhe-Paganon, S., Shoelson, S. E. <strong>Diabetes mutations delineate an atypical POU domain in HNF-1-alpha.</strong> Molec. Cell 10: 1129-1137, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12453420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12453420</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00704-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12453420">Chi et al. (2002)</a> cocrystallized human HNF1A amino acids 83 to 279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules were bound to the promoter. Each contained a homeodomain (POU-H) and a second domain structurally similar to POU-specific (POU-S) domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains created a stable interface that further distinguished HNF1A from other flexible POU-homeodomain proteins. <a href="#8" class="mim-tip-reference" title="Chi, Y.-I., Frantz, J. D., Oh, B.-C., Hansen, L., Dhe-Paganon, S., Shoelson, S. E. <strong>Diabetes mutations delineate an atypical POU domain in HNF-1-alpha.</strong> Molec. Cell 10: 1129-1137, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12453420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12453420</a>] [<a href="https://doi.org/10.1016/s1097-2765(02)00704-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12453420">Chi et al. (2002)</a> determined that 76% of MODY3-associated missense mutations in HNF1A occur in the region encompassing amino acids 98 to 272, which includes the POU-H and POU-S domains and a nuclear localization signal. They subdivided these mutations according to functional classes predicted to affect DNA binding, POU-S/POU-H domain interactions, protein stability, and nuclear localization. The largest class affected DNA binding, either through direct interactions or indirectly by perturbing local environment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12453420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>To estimate the prevalence of MODY3 in Norwegian diabetic pedigrees, <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> screened a total of 130 families for HNF1A mutations; 42 families with clinical MODY, 75 with suspected MODY, and 13 pedigrees with multiplex type 1 diabetes (IDDM). Twenty-two families with clinical MODY, 15 families with suspected MODY, and 1 family with type 1 diabetes multiplex harbored HNF1A mutations. Thus, in about half of Norwegian families with clinical MODY, mutations in the HNF1A gene could be detected. Eight of the 18 different mutations identified were novel. Haplotypes were determined for recurrent mutations, indicating a founder effect in Norway for the hotspot mutation P291fsinsC (<a href="#0001">142410.0001</a>) and possibly also for P112L (<a href="#0015">142410.0015</a>) and R131W (<a href="#0016">142410.0016</a>). Two mutant HNF1A proteins were unable to bind DNA and at least 5 mutants showed defective nuclear translocation. Transcriptional activation was reduced for most of the MODY3-associated mutants. Accordingly, the functional studies of HNF1A mutants indicated that beta-cell dysfunction in MODY3 is caused by loss-of-function mechanisms like reduced DNA binding, impaired transcriptional activation, and defects in subcellular localization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#27" class="mim-tip-reference" title="Johansen, A., Ek, J., Mortensen, H. B., Pedersen, O., Hansen, T. <strong>Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.</strong> J. Clin. Endocr. Metab. 90: 4607-4614, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15928245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15928245</a>] [<a href="https://doi.org/10.1210/jc.2005-0196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15928245">Johansen et al. (2005)</a> examined the prevalence and nature of mutations in the 3 common MODY genes HNF4A (<a href="/entry/600281">600281</a>), GCK (<a href="/entry/138079">138079</a>), and TCF1 in Danish patients with a clinical diagnosis of MODY and determined metabolic differences in probands with and without mutations in HNF4A, GCK, and TCF1. They identified 29 different mutations in 38 MODY families. Fifteen of the mutations were novel. The variants segregated with diabetes within the families, and none of the variants were found in 100 normal Danish chromosomes. Their findings suggested a relative prevalence of 3% of MODY1 (<a href="/entry/125850">125850</a>) (2 different mutations in 2 families), 10% of MODY2 (7 in 8), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY. No significant differences in biochemical and anthropometric measurements were observed at baseline examinations. Forty-nine percent of the families carried mutations in the 3 examined MODY genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15928245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#37" class="mim-tip-reference" title="Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J. <strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong> Hum. Molec. Genet. 14: 603-614, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15649945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15649945</a>] [<a href="https://doi.org/10.1093/hmg/ddi057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15649945">Rebouissou et al. (2005)</a> screened 35 renal neoplasms for HNF1A and HNF1B (<a href="/entry/189907">189907</a>) inactivation. In 2 of 13 clear cell renal carcinomas, the authors found a monoallelic germline mutation (<a href="#0001">142410.0001</a> and <a href="#0022">142410.0022</a>) of HNF1A with no associated suppression of target mRNA expression. In normal and tumor renal tissues, there was a network of transcription factors differentially regulated in tumor subtypes. There was a related cluster of coregulated genes associating HNF1A, HNF4A, FABP1 (<a href="/entry/134650">134650</a>), and UGT2B7 (<a href="/entry/600068">600068</a>). <a href="#37" class="mim-tip-reference" title="Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J. <strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong> Hum. Molec. Genet. 14: 603-614, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15649945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15649945</a>] [<a href="https://doi.org/10.1093/hmg/ddi057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15649945">Rebouissou et al. (2005)</a> suggested that germline mutation of HNF1A may predispose to renal tumors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15649945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#40" class="mim-tip-reference" title="Ridker, P. M., Pare, G., Parker, A., Zee, R. Y. L., Danik, J. S., Buring, J. E., Kwiatkowski, D., Cook, N. R., Miletich, J. P., Chasman, D. I. <strong>Loci related to metabolic syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.</strong> Am. J. Hum. Genet. 82: 1185-1192, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18439548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18439548</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18439548[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2008.03.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18439548">Ridker et al. (2008)</a> performed a multistage genomewide association study of CRP (<a href="/entry/123260">123260</a>) levels and found significant association with 7 loci, 1 of which was HNF1A. <a href="#38" class="mim-tip-reference" title="Reiner, A. P., Barber, M. J., Guan, Y., Ridker, P. M., Lange, L. A., Chasman, D. I., Walston, J. D., Cooper, G. M., Jenny, N. S., Rieder, M. J., Durda, J. P., Smith, J. D., Novembre, J., Tracy, R. P., Rotter, J. I., Stephens, M., Nickerson, D. A., Krauss, R. M. <strong>Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1-alpha are associated with C-reactive protein.</strong> Am. J. Hum. Genet. 82: 1193-1201, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18439552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18439552</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18439552[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2008.03.017" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18439552">Reiner et al. (2008)</a> reported an association between common variants of the HNF1A gene and plasma CRP concentrations in 2 independent populations of older adults. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18439552+18439548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Penetrance of HNF1A Mutations in Diabetes</em></strong></p><p>
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<a href="#33" class="mim-tip-reference" title="Mirshahi, U. L., Colclough, K., Wright, C. F., Wood, A. R., Beaumont, R. N., Tyrrell, J., Laver, T. W., Stahl, R., Golden, A., Goehringer, J. M, Geisinger-Regeneron DiscovEHR Collaboration, Frayling, T. F., Hattersley, A. T., Carey, D. J., Weedon, M. N., Patel, K. A. <strong>Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.</strong> Am. J. Hum. Genet. 109: 2018-2028, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36257325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36257325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36257325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2022.09.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36257325">Mirshahi et al. (2022)</a> comprehensively assessed the penetrance and prevalence of pathogenic variants in HNF1A, HNF4A, and GCK that account for more than 80% of monogenic diabetes. <a href="#33" class="mim-tip-reference" title="Mirshahi, U. L., Colclough, K., Wright, C. F., Wood, A. R., Beaumont, R. N., Tyrrell, J., Laver, T. W., Stahl, R., Golden, A., Goehringer, J. M, Geisinger-Regeneron DiscovEHR Collaboration, Frayling, T. F., Hattersley, A. T., Carey, D. J., Weedon, M. N., Patel, K. A. <strong>Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.</strong> Am. J. Hum. Genet. 109: 2018-2028, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36257325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36257325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36257325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2022.09.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36257325">Mirshahi et al. (2022)</a> analyzed clinical and genetic data from 1,742 clinically referred probands, 2,194 family members, clinically unselected individuals from a US health system-based cohort of 132,194 individuals, and a UK population-based cohort of 198,748 individuals, and found that 1 in 1,500 individuals harbor a pathogenic variant in one of these genes. The penetrance of pathogenic GCK variants was similar (89 to 97%) across all cohorts. The penetrance of diabetes for HNF1A and HNF4A pathogenic variants was substantially lower in the clinically unselected individuals compared to clinically referred probands and was dependent on the setting (32% in the population, 49% in the health system cohort, 86% in a family member, and 98% in probands for HNF1A). The relative risk of diabetes was similar across the clinically unselected cohorts, highlighting the role of environment/ other genetic factors. The authors suggested that for HNF1A and HNF4A, genetic interpretation and counseling should be tailored to the setting in which a pathogenic monogenic variant was identified. GCK is an exception with near-complete penetrance in all settings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36257325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Liver adenomas are benign tumors at risk of malignant transformation. In a genomewide search for loss of heterozygosity (LOH) associated with liver adenomas, <a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> found a deletion in 12q in 5 of 10 adenomas. In most cases, LOH at 12q was the only recurrent genetic alteration observed, suggesting the presence of a tumor-suppressor gene in that region. A minimal common region of deletion was defined in 12q24 that included the TCF1 gene. <a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> found biallelic inactivation of TCF1 in 10 of 16 screened adenomas, and heterozygous germline mutations were present in 3 affected individuals. Furthermore, 2 well-differentiated hepatocellular carcinomas occurring in normal liver, out of 30 HCCs screened, contained somatic biallelic mutations. These results indicated that inactivation of TCF1, whether sporadic or associated with MODY3, is an important genetic event in the occurrence of human liver adenomas, and may be an early step in the development of some hepatocellular carcinomas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#19" class="mim-tip-reference" title="Gonzalez, F. J., Liu, S.-Y., Kozak, C. A., Nebert, D. W. <strong>Decreased Hnf-1 gene expression in mice homozygous for a 1.2-centimorgan deletion on chromosome 7.</strong> DNA Cell Biol. 9: 771-776, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2264930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2264930</a>] [<a href="https://doi.org/10.1089/dna.1990.9.771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2264930">Gonzalez et al. (1990)</a> found that newborn mice homozygous for a 1.2-cM deletion of chromosome 7 do not show the increased activity of CYP2E (<a href="/entry/124040">124040</a>), which is regulated by the transcription factor Hnf1. They suggested that the deleted region of chromosome 7 contains a gene encoding a transacting factor that is epistatic in a regulatory cascade that includes Hnf1 gene expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2264930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#36" class="mim-tip-reference" title="Pontoglio, M., Barra, J., Hadchouel, M., Doyen, A., Kress, C., Bach, J. P., Babinet, C., Yaniv, M. <strong>Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome.</strong> Cell 84: 575-585, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598044</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81033-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8598044">Pontoglio et al. (1996)</a> found that mice with inactivation of the Hnf1 gene through homologous recombination failed to thrive and died around weaning after a progressive wasting syndrome with marked liver enlargement. The transcription rate of genes such as albumin and alpha-1-antitrypsin was reduced, while the gene coding the phenylalanine hydroxylase (<a href="/entry/612349">612349</a>) was totally silent, giving rise to phenylketonuria. Mutant mice also suffered from severe Fanconi syndrome (see <a href="/entry/227650">227650</a>) caused by renal proximal tubular dysfunction. The resulting massive urinary glucose lost led to energy and water wasting. <a href="#36" class="mim-tip-reference" title="Pontoglio, M., Barra, J., Hadchouel, M., Doyen, A., Kress, C., Bach, J. P., Babinet, C., Yaniv, M. <strong>Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome.</strong> Cell 84: 575-585, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598044</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)81033-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8598044">Pontoglio et al. (1996)</a> commented that Hnf1-deficient mice may provide a model for human renal Fanconi syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8598044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., Stoffel, M. <strong>Hepatocyte nuclear factor-1-alpha is an essential regulator of bile acid and plasma cholesterol metabolism.</strong> Nature Genet. 27: 375-382, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279518</a>] [<a href="https://doi.org/10.1038/86871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279518">Shih et al. (2001)</a> explored the molecular basis for the hypercholesterolemia of Tcf1 -/- mice using oligonucleotide microchip expression analysis. <a href="#41" class="mim-tip-reference" title="Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., Stoffel, M. <strong>Hepatocyte nuclear factor-1-alpha is an essential regulator of bile acid and plasma cholesterol metabolism.</strong> Nature Genet. 27: 375-382, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279518</a>] [<a href="https://doi.org/10.1038/86871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279518">Shih et al. (2001)</a> demonstrated that Tcf1 -/- mice have a defect in bile acid transport, increased bile acid and liver cholesterol synthesis, and impaired high-density lipoprotein (HDL) metabolism. Tcf1 -/- liver has decreased expression of the basolateral membrane bile acid transporters Slc10a1 (<a href="/entry/182396">182396</a>), Slc21a3 (<a href="/entry/602883">602883</a>), and Slc21a5, leading to impaired portal bile acid uptake and elevated plasma bile acid concentrations. In intestine and kidneys, Tcf1 -/- mice lack expression of the ileal bile acid transporter (Slc10a2; <a href="/entry/601295">601295</a>), resulting in increased fecal and urinary bile acid excretion. Tcf1 protein also regulates transcription of Nr1h4 (<a href="/entry/603826">603826</a>), encoding the farnesoid X receptor-1 (Fxr1), thereby leading to reduced expression of small heterodimer partner-1 (Shp1; <a href="/entry/604630">604630</a>) and repression of Cyp7a1 (<a href="/entry/118455">118455</a>), the rate-limiting enzyme in the classic bile acid biosynthesis pathway. In addition, hepatocyte bile acid storage protein is absent from Tcf1 -/- mice. Increased plasma cholesterol of Tcf1 -/- mice resides predominantly in large buoyant HDL particles. This is most likely due to reduced activity of the HDL-catabolic enzyme hepatic lipase (<a href="/entry/151670">151670</a>) and increased expression of HDL-cholesterol esterifying enzyme lecithin:cholesterol acyltransferase (LCAT; <a href="/entry/606967">606967</a>). <a href="#41" class="mim-tip-reference" title="Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., Stoffel, M. <strong>Hepatocyte nuclear factor-1-alpha is an essential regulator of bile acid and plasma cholesterol metabolism.</strong> Nature Genet. 27: 375-382, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279518</a>] [<a href="https://doi.org/10.1038/86871" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11279518">Shih et al. (2001)</a> concluded that TCF1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid in HDL-cholesterol metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Hiraiwa, H., Pan, C.-J., Lin, B., Akiyama, T. E., Gonzalez, F. J., Chou, J. Y. <strong>A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1-alpha-null mice.</strong> J. Biol. Chem. 276: 7963-7967, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11121425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11121425</a>] [<a href="https://doi.org/10.1074/jbc.M010523200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11121425">Hiraiwa et al. (2001)</a> investigated whether there is a molecular link between HNF1A deficiency and function of the G6Pase (<a href="/entry/602671">602671</a>) system. Transactivation studies revealed that HNF1A is required for transcription of the G6PT gene. Hepatic G6PT mRNA levels and microsomal G6P transport activity are also markedly reduced in Hnf1a -/- mice as compared with Hnf1a +/+ and Hnf1a +/- littermates. On the other hand, hepatic G6Pase mRNA expression and activity are upregulated in Hnf1a -/- mice, consistent with observations that G6Pase expression is increased in diabetic animals. Taken together, these results strongly suggest that metabolic abnormalities in Hnf1a-null mice are caused in part by G6PT deficiency and by perturbations of the G6Pase system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11121425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., Hui, L. <strong>Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors.</strong> Nature 475: 386-389, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21562492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21562492</a>] [<a href="https://doi.org/10.1038/nature10116" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21562492">Huang et al. (2011)</a> demonstrated the direct induction of functional hepatocyte-like (induced hepatocyte, iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4 (<a href="/entry/600576">600576</a>), Hnf1-alpha, and Foxa3 (<a href="/entry/602295">602295</a>) and inactivation of p19(Arf) (<a href="/entry/600160">600160</a>). iHep cells showed typical epithelial morphology, expressed hepatic genes, and acquired hepatocyte functions. Notably, transplanted iHep cells repopulated the livers of fumarylacetoacetate hydrolase-deficient (Fah-null; see <a href="/entry/613871">613871</a>) mice and rescued almost half of recipients from death by restoring liver functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21562492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Although the symbol TCF1 (transcription factor-1) is used in the literature for this gene, its official designation is HNF1A. It should not be confused with the TCF7 gene (<a href="/entry/189908">189908</a>), which has also been referred to as TCF1 (T cell-specific transcription factor-1) in the literature.</p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>22 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=142410[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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HEPATIC ADENOMA, SOMATIC, INCLUDED<br />
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TYPE 1 DIABETES MELLITUS 20, INCLUDED
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HNF1A, 1-BP INS, 872C
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs587776825 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587776825;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs587776825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs587776825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016062 OR RCV000016063 OR RCV000022617 OR RCV000117225 OR RCV000490055 OR RCV001255183 OR RCV001506982 OR RCV002221997 OR RCV003445070" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016062, RCV000016063, RCV000022617, RCV000117225, RCV000490055, RCV001255183, RCV001506982, RCV002221997, RCV003445070" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016062...</a>
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<p><strong><em>Maturity-Onset Diabetes of the Young, Type 3</em></strong></p><p>
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In a patient from an Edinburgh pedigree with MODY3 (<a href="/entry/600496">600496</a>), <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al. (1996)</a> found in exon 4 of the TCF1 gene an insertion of a cytosine at codon 291 (pro), resulting in a frameshift and synthesis of a truncated mutant protein of 315 amino acids. This mutation was present in all affected members and no unaffected members of this family. It was not found on screening 55 healthy nondiabetic white subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8945470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using a rapid screening PCR method for frameshift mutations in the HNF1A gene in the screening of 60 MODY probands defined according to strict diagnostic criteria, <a href="#16" class="mim-tip-reference" title="Frayling, T. M., Bulman, M. P., Appleton, M., Hattersley, A. T., Ellard, S. <strong>A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes.</strong> Hum. Genet. 101: 351-354, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9439666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9439666</a>] [<a href="https://doi.org/10.1007/s004390050640" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9439666">Frayling et al. (1997)</a> detected mutations in 11 (18%); the insertion mutation accounted for 13% of the MODY cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9439666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Ellard, S. <strong>Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young.</strong> Hum. Mutat. 16: 377-385, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11058894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11058894</a>] [<a href="https://doi.org/10.1002/1098-1004(200011)16:5<377::AID-HUMU1>3.0.CO;2-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11058894">Ellard (2000)</a> stated that the C insertion in the poly(C) tract of exon 4 had been reported in 22 of the 116 families with MODY3 worldwide who were identified by the finding of a mutation in the TCF1 gene. The total number of different mutations described was 65. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11058894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> found the P291fsinsC mutation in 9 families, 8 of Norwegian origin. Microsatellite analysis data suggested that in 7 of these families the mutant allele had a common origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Hepatic Adenoma</em></strong></p><p>
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In studies of hepatic adenomas (<a href="/entry/142330">142330</a>) demonstrating biallelic inactivation of TCF1, <a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> observed the pro291fsX316 frameshift mutation (<a href="#0001">142410.0001</a>) in heterozygous state in the tumor tissue of 2 individuals, one with multiple adenoma and the other with hepatocellular carcinoma (<a href="/entry/114550">114550</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Renal Cell Carcinoma</em></strong></p><p>
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In a 78-year-old man with clear cell renal carcinoma (see <a href="/entry/144700">144700</a>), <a href="#37" class="mim-tip-reference" title="Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J. <strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong> Hum. Molec. Genet. 14: 603-614, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15649945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15649945</a>] [<a href="https://doi.org/10.1093/hmg/ddi057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15649945">Rebouissou et al. (2005)</a> identified heterozygosity for the 872insC mutation. Mutation screening of a tumor sample detected the germline mutation without mutation/deletion of the second allele. The man was diagnosed with diabetes mellitus in his sixth decade that was controlled by diet and oral hypoglycemic agents. No relatives had a diagnosis of renal carcinoma or diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15649945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Type 1 Diabetes Mellitus 20</em></strong></p><p>
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In a Japanese subject with type 1 diabetes mellitus (T1D20; <a href="/entry/612520">612520</a>) in whom insulin treatment was begun when hyperglycemia and ketonuria were noticed at 15 years of age, <a href="#50" class="mim-tip-reference" title="Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J. <strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong> Diabetes 46: 1643-1647, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313763">Yamada et al. (1997)</a> identified a heterozygous frameshift mutation of codon pro291 resulting from insertion of a C in a poly(C) tract. (They designated this mutation P291fsinsC.) The mutation was predicted to result in a mutant truncated protein of 340 amino acids. The same mutation had been observed in British, German, and Finnish MODY families (<a href="#6" class="mim-tip-reference" title="Byrne, M. M., Sturis, J., Menzel, S., Yamagata, K., Fajans, S. S., Dronsfield, M. J., Bain, S. C., Hattersley, A. T., Velho, G., Froguel, P., Bell, G. I., Polonsky, K. S. <strong>Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12.</strong> Diabetes 45: 1503-1510, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8866553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8866553</a>] [<a href="https://doi.org/10.2337/diab.45.11.1503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8866553">Byrne et al., 1996</a>; <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al., 1996</a>; <a href="#28" class="mim-tip-reference" title="Kaisaki, P. J., Menzel, S., Lindner, T., Oda, N., Rjasanowski, I., Sahm, J., Meincke, G., Schulze, J., Schmechel, H., Petzold, C., Ledermann, H. M., Sachse, G., Boriraj, V. V., Menzel, R., Kerner, W., Turner, R. C., Yamagata, K., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.</strong> Diabetes 46: 528-535, 1997. Note: Erratum: Diabetes 46: 1239 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9032114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9032114</a>] [<a href="https://doi.org/10.2337/diab.46.3.528" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9032114">Kaisaki et al., 1997</a>). Thus, <a href="#50" class="mim-tip-reference" title="Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J. <strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong> Diabetes 46: 1643-1647, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313763">Yamada et al. (1997)</a> concluded that this site in exon 4 of the HNF1A gene appears to be a mutation hotspot. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9313763+9032114+8866553+8945470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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HNF1A, PRO447LEU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853236 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853236;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853236?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853236" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016065 OR RCV000713784 OR RCV000762891 OR RCV001526899 OR RCV001810399" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016065, RCV000713784, RCV000762891, RCV001526899, RCV001810399" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016065...</a>
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<p>In their family A, <a href="#51" class="mim-tip-reference" title="Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong> Nature 384: 455-457, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>] [<a href="https://doi.org/10.1038/384455a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8945470">Yamagata et al. (1996)</a> found that MODY3 (<a href="/entry/600496">600496</a>) was associated with a single amino acid substitution in exon 7 of the TCF1 gene: codon 447 was changed from CCG (pro) to CTG (leu). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8945470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#21" class="mim-tip-reference" title="Hansen, T., Eiberg, H., Rouard, M., Vaxillaire, M., Moller, A. M., Rasmussen, S. K., Fridberg, M., Urhammer, S. A., Holst, J. J., Almind, K., Echwald, S. M., Hansen, L., Bell, G. I., Pedersen, O. <strong>Novel MODY3 mutations in the hepatocyte nuclear factor-1-alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.</strong> Diabetes 46: 726-730, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075819</a>] [<a href="https://doi.org/10.2337/diab.46.4.726" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9075819">Hansen et al. (1997)</a> found this mutation in a glucose-tolerant lean male who had relatives with MODY. He showed a low insulin secretion rate during oral glucose tolerance test (OGTT), but a 2-fold increase in pancreatic beta-cell response after intravenous glucose and a 2.5- to 4-fold increase in beta-cell response after either intravenous tolbutamide or intravenous glucagon loads. <a href="#21" class="mim-tip-reference" title="Hansen, T., Eiberg, H., Rouard, M., Vaxillaire, M., Moller, A. M., Rasmussen, S. K., Fridberg, M., Urhammer, S. A., Holst, J. J., Almind, K., Echwald, S. M., Hansen, L., Bell, G. I., Pedersen, O. <strong>Novel MODY3 mutations in the hepatocyte nuclear factor-1-alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.</strong> Diabetes 46: 726-730, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075819</a>] [<a href="https://doi.org/10.2337/diab.46.4.726" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9075819">Hansen et al. (1997)</a> concluded that early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by hyperexcitability of beta-cells to intravenous secretagogues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9075819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2135842335 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2135842335;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2135842335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2135842335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016066</a>
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<p>In a family in which 4 members of 3 generations had MODY3 (<a href="/entry/600496">600496</a>), <a href="#48" class="mim-tip-reference" title="Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P. J., Boriraj, V. V., Chevre, J.-C., Boccio, V., Cox, R. D., Lathrop, G. M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G. I., Froguel, P. <strong>Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).</strong> Hum. Molec. Genet. 6: 583-586, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097962</a>] [<a href="https://doi.org/10.1093/hmg/6.4.583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9097962">Vaxillaire et al. (1997)</a> found deletion of a guanine from codon glycine-292 (G292fsdelG) resulting in frameshift in the TCF1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853237 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853237;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853237" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853237" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016067 OR RCV001384610 OR RCV001794449 OR RCV002464065" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016067, RCV001384610, RCV001794449, RCV002464065" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016067...</a>
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<p>In a family with multiple members with MODY3 (<a href="/entry/600496">600496</a>) in 3 generations, <a href="#48" class="mim-tip-reference" title="Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P. J., Boriraj, V. V., Chevre, J.-C., Boccio, V., Cox, R. D., Lathrop, G. M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G. I., Froguel, P. <strong>Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).</strong> Hum. Molec. Genet. 6: 583-586, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097962</a>] [<a href="https://doi.org/10.1093/hmg/6.4.583" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9097962">Vaxillaire et al. (1997)</a> found a TAC-to-TGC transition in codon 122 of the TCF1 gene, predicted to cause an amino acid change from tyrosine to cysteine (Y122C). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853238 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853238;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853238" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016068 OR RCV000255916 OR RCV000445525 OR RCV002051786 OR RCV002288493 OR RCV004752708" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016068, RCV000255916, RCV000445525, RCV002051786, RCV002288493, RCV004752708" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016068...</a>
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<p>In a Japanese subject who developed type 1 diabetes mellitus (T1D20; <a href="/entry/612520">612520</a>) 1 year after the diagnosis of T2D at 8 years of age, <a href="#50" class="mim-tip-reference" title="Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J. <strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong> Diabetes 46: 1643-1647, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313763">Yamada et al. (1997)</a> identified heterozygosity for an arg272-to-his (R272H) mutation in the DNA binding domain of the HNF1A gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 TYPE 1 DIABETES MELLITUS 20</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853239 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853239;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853239?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016069 OR RCV000030492 OR RCV002514104 OR RCV004699116" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016069, RCV000030492, RCV002514104, RCV004699116" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016069...</a>
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<p>In a Japanese patient with sudden-onset type 1 diabetes (T1D20; <a href="/entry/612520">612520</a>) at 20 years of age, <a href="#50" class="mim-tip-reference" title="Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J. <strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong> Diabetes 46: 1643-1647, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313763">Yamada et al. (1997)</a> identified heterozygosity for an arg583-to-gly (R583G) mutation in the transactivation domain of HNF1A. When first diagnosed there was marked hyperglycemia and 'absolute' insulin deficiency, prompting the initiation of insulin therapy. Control of blood glucose levels by exogenous insulin was poor, and complications of diabetes (proliferative retinopathy, cataracts, and sensorimotor neuropathy) developed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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HNF1A, A-C, -58, PROMOTER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2135818776 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2135818776;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2135818776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2135818776" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016070 OR RCV001794450 OR RCV002225265" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016070, RCV001794450, RCV002225265" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016070...</a>
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<p><a href="#20" class="mim-tip-reference" title="Gragnoli, C., Lindner, T., Cockburn, B. N., Kaisaki, P. J., Gragnoli, F., Marozzi, G., Bell, G. I. <strong>Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4-alpha binding site in the promoter of the hepatocyte nuclear factor-1-alpha gene.</strong> Diabetes 46: 1648-1651, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313764</a>] [<a href="https://doi.org/10.2337/diacare.46.10.1648" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9313764">Gragnoli et al. (1997)</a> found an A-to-C substitution at nucleotide -58 of the promoter region of the HNF1A gene that cosegregated with MODY3 (<a href="/entry/600496">600496</a>). This mutation is located in a highly conserved region of the promoter and disrupted the binding site for the transcription factor HNF-4-alpha (<a href="/entry/600281">600281</a>), mutations in the gene encoding HNF-4-alpha being another cause of MODY (MODY1; <a href="/entry/125850">125850</a>). This result demonstrated that decreased levels of HNF1-alpha per se can cause MODY. Moreover, it indicated that both the promoter and the coding regions of the HNF1A gene should be screened for mutations in subjects thought to have MODY. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853240 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853240;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853240?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016071 OR RCV003230366" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016071, RCV003230366" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016071...</a>
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<p><a href="#22" class="mim-tip-reference" title="Hegele, R. A., Cao, H., Harris, S. B., Hanley, A. J. G., Zinman, B. <strong>The hepatic nuclear factor-1-alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.</strong> J. Clin. Endocr. Metab. 84: 1077-1082, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084598</a>] [<a href="https://doi.org/10.1210/jcem.84.3.5528" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10084598">Hegele et al. (1999)</a> identified a gly319-to-ser (G319S) variant in the HNF1A gene in Ontario Oji-Cree with early-onset type 2 diabetes (<a href="/entry/125853">125853</a>). G319S is in the proline II-rich domain of the trans-activation site of HNF1A and alters a glycine residue that is conserved throughout evolution. S319 was absent from 990 alleles from 6 other ethnic groups, suggesting that it is private for Oji-Cree. The S319 allele was more prevalent in diabetic than in nondiabetic Oji-Cree (0.209 vs 0.087; P = 0.000001). S319/S319 homozygotes and S319/G319 heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95% CI, 2.65-6.03) and 1.97 (95% CI, 1.44-2.70) compared with G319/G319 homozygotes. There was a significant difference in the mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319 subjects being affected in the fifth, fourth, and third decades of life, respectively. Among nondiabetic subjects, S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319 homozygotes. The authors concluded that the G319S variant is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>That the majority of Oji-Cree subjects with diabetes did not have the HNF1A S319 variant suggested to <a href="#23" class="mim-tip-reference" title="Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J. G., Anderson, C. M. <strong>Peroxisome proliferator-activated receptor-gamma-2 P12A and type 2 diabetes in Canadian Oji-Cree.</strong> J. Clin. Endocr. Metab. 85: 2014-2019, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10843190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10843190</a>] [<a href="https://doi.org/10.1210/jcem.85.5.6610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10843190">Hegele et al. (2000)</a> that there might be other genetic determinants of diabetes susceptibility. In the course of sequencing candidate genes in diabetic subjects who were homozygous for HNF1A G319/G319, they found that some subjects had the PPARG A12 variant (<a href="/entry/601487#0002">601487.0002</a>). PPARG A12 was strongly associated with type 2 diabetes in women, but not in men. The authors concluded that, when taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least 2 genes are involved in determining susceptibility to the disease in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10843190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Triggs-Raine, B. L., Kirkpatrick, R. D., Kelly, S. L., Norquay, L. D., Cattini, P. A., Yamagata, K., Hanley, A. J. G., Zinman, B., Harris, S. B., Barrett, P. H., Hegele, R. A. <strong>HNF1-alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community.</strong> Proc. Nat. Acad. Sci. 99: 4614-4619, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11904371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11904371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11904371[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.062059799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11904371">Triggs-Raine et al. (2002)</a> stated that Oji-Cree type 2 diabetes does not resemble MODY, because affected Oji-Cree subjects are obese and insulin-resistant with elevated plasma insulin concentrations, which clearly were insufficient to prevent diabetes onset. They evaluated the in vitro function of HNF1A G319S both to confirm that the mutation had a functional effect and to determine whether this effect was distinct from those of the complete loss-of-function or dominant-negative mutations seen in the MODY3 phenotype. They also evaluated the impact of the HNF1A G319S mutation on the dynamics of type 2 diabetes onset in the whole Sandy Lake Oji-Cree community. They found that the G319S mutation reduced the in vitro ability of HNF1-alpha to activate transcription by approximately 50%, with no effect on DNA binding or protein stability. There was no evidence of a dominant-negative effect of the mutant protein. Disease onset showed significant differences according to G319S genotype when gauged by the age at which half the subjects had become diabetic. Each dose of G319S accelerated median disease onset by approximately 7 years. Thus, the transactivation-deficient HNF1A G319S mutation affects the dynamics of disease onset. The demonstration of a functional consequence for the G319S mutation provided a mechanistic basis for its strong association with Oji-Cree type 2 diabetes and its unparalleled specificity for diabetes prediction in these people, in whom diabetes presents a significant public health problem. The finding also showed that HNF1A mutations can be associated with typical adult-onset insulin-resistant obesity-related diabetes in addition to maturity-onset diabetes of the young. <a href="#43" class="mim-tip-reference" title="Triggs-Raine, B. L., Kirkpatrick, R. D., Kelly, S. L., Norquay, L. D., Cattini, P. A., Yamagata, K., Hanley, A. J. G., Zinman, B., Harris, S. B., Barrett, P. H., Hegele, R. A. <strong>HNF1-alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community.</strong> Proc. Nat. Acad. Sci. 99: 4614-4619, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11904371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11904371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11904371[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.062059799" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11904371">Triggs-Raine et al. (2002)</a> stated that in the Oji-Cree, HNF1A G319S behaves as a susceptibility allele for type 2 diabetes. Among nondiabetic Oji-Cree, fasting plasma insulin concentration was reduced significantly in HNF1A G319S carriers, suggesting that the partial impairment of function is tolerated when there is no insulin resistance. However, among Oji-Cree with type 2 diabetes, both carriers and noncarriers of the mutation had elevated plasma insulin concentration compared with nondiabetic Oji-Cree. The stress of obesity-induced insulin resistance seemed to expose the partial defect in HNF1A G319S carriers, causing expression of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11904371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853241 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853241;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853241" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016072 OR RCV002250352 OR RCV002298445" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016072, RCV002250352, RCV002298445" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016072...</a>
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<p><a href="#32" class="mim-tip-reference" title="Miedzybrodzka, Z., Hattersley, A. T., Ellard, S., Pearson, D., de Silva, D., Harvey, R., Haites, N. <strong>Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1a gene: implications for predictive testing.</strong> Europ. J. Hum. Genet. 7: 729-732, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482964</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482964">Miedzybrodzka et al. (1999)</a> described a family in which a thr620-to-ile substitution in transcription factor-1 was found in all members affected by MODY (<a href="/entry/600496">600496</a>). The mutation was not fully penetrant, as 2 family members aged 87 and 46 had the mutation but did not have diabetes. The severity and age at diagnosis of diabetes varied widely within the family, and most presented over the age of 25. <a href="#32" class="mim-tip-reference" title="Miedzybrodzka, Z., Hattersley, A. T., Ellard, S., Pearson, D., de Silva, D., Harvey, R., Haites, N. <strong>Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1a gene: implications for predictive testing.</strong> Europ. J. Hum. Genet. 7: 729-732, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482964</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5200358" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10482964">Miedzybrodzka et al. (1999)</a> suggested that TCF1 mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs754470733 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs754470733;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs754470733?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs754470733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs754470733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#18" class="mim-tip-reference" title="Godart, F., Bellanne-Chantelot, C., Clauin, S., Gragnoli, C., Abderrahmani, A., Blanche, H., Boutin, P., Chevre, J. C., Froguel, P., Bailleul, B. <strong>Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1-alpha (TCF1) promoter region in MODY patients.</strong> Hum. Mutat. 15: 173-180, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10649494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10649494</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<173::AID-HUMU6>3.0.CO;2-W" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10649494">Godart et al. (2000)</a> observed a promoter mutation, -119delG, of the TCF1 gene that segregated with MODY3 (<a href="/entry/600496">600496</a>) in a diabetic family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10649494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1169288 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1169288;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1169288?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1169288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1169288" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016074 OR RCV000016075 OR RCV000117233 OR RCV000710268 OR RCV000988920 OR RCV002226650 OR RCV002415417 OR RCV003315502" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016074, RCV000016075, RCV000117233, RCV000710268, RCV000988920, RCV002226650, RCV002415417, RCV003315502" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016074...</a>
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<p><a href="#9" class="mim-tip-reference" title="Chiu, K. C., Chuang, L.-M., Ryu, J. M., Tsai, G. P., Saad, M. F. <strong>The I27L amino acid polymorphism of hepatic nuclear factor-1-alpha is associated with insulin resistance.</strong> J. Clin. Endocr. Metab. 85: 2178-2183, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10852449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10852449</a>] [<a href="https://doi.org/10.1210/jcem.85.6.6618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10852449">Chiu et al. (2000)</a> examined the relationship between the ile27-to-leu (I27L) polymorphism of HNF1-alpha and insulin sensitivity (see <a href="/entry/125853">125853</a>) and beta-cell function assessed by a hyperglycemic clamp. This study included 52 healthy glucose-tolerant and normotensive subjects (age, 19 to 40 years; body mass index, 17.58-35.61 kg/m2; waist/hip ratio, 0.65-1.03). <a href="#9" class="mim-tip-reference" title="Chiu, K. C., Chuang, L.-M., Ryu, J. M., Tsai, G. P., Saad, M. F. <strong>The I27L amino acid polymorphism of hepatic nuclear factor-1-alpha is associated with insulin resistance.</strong> J. Clin. Endocr. Metab. 85: 2178-2183, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10852449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10852449</a>] [<a href="https://doi.org/10.1210/jcem.85.6.6618" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10852449">Chiu et al. (2000)</a> identified 19 LL subjects, 24 IL subjects, and 9 II subjects. The LL group had the highest postchallenge insulin levels at 30 and 90 min (P = 0.038 and P = 0.015, respectively) and also the highest insulin area under curve (P = 0.009) among the 3 genotypes. The LL group was more insulin resistant than the IL and II groups (P = 0.042 for insulin sensitivity index). After adjusting for age, gender, obesity, and ethnicity, the I27L polymorphism was an independent determinant of the insulin sensitivity index (P = 0.001). However, it had no impact on either the first or second phase insulin response. The authors concluded that the I27L polymorphism is associated with insulin resistance, but not beta-cell function. The mechanism of this association is unclear, but HNF1-alpha may play a role in regulating hepatic glucose metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10852449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Babaya, N., Ikegami, H., Fujisawa, T., Nojima, K., Itoi-Babaya, M., Inoue, K., Nakura, J., Abe, M., Yamamoto, M., Jin, J. J., Wu, Z., Miki, T., Fukuda, M., Ogihara, T. <strong>Association of I27L polymorphism of hepatocyte nuclear factor-1-alpha gene with high-density lipoprotein cholesterol level.</strong> J. Clin. Endocr. Metab. 88: 2548-2551, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788852</a>] [<a href="https://doi.org/10.1210/jc.2002-021891" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12788852">Babaya et al. (2003)</a> studied the relationship of the HNF1A gene polymorphism I27L with lipid parameters, in particular with serum HDL cholesterol level, in 356 unrelated Japanese men. Though no significant difference was observed in total cholesterol and triglyceride levels among the 3 genotypes, the serum HDL cholesterol level was significantly associated with the genotype (P less than 0.01). Subjects with the II genotype had low serum HDL cholesterol levels, and those with the LL genotype had high serum HDL cholesterol levels. The authors concluded that the HNF1A gene locus is associated with serum HDL cholesterol level and suggested that the I27 allele is a risk marker for atherosclerosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1566092470 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1566092470;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1566092470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1566092470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016076 OR RCV002221998 OR RCV002326678" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016076, RCV002221998, RCV002326678" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016076...</a>
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<p><a href="#52" class="mim-tip-reference" title="Yoshiuchi, I., Yamagata, K., Yoshimoto, M., Zhu, Q., Yang, Q., Nammo, T., Uenaka, R., Kinoshita, E., Hanafusa, T., Miyagawa, J., Matsuzawa, Y. <strong>Analysis of a non-functional HNF-1-alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.</strong> Hum. Mutat. 18: 345-351, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668618</a>] [<a href="https://doi.org/10.1002/humu.1196" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668618">Yoshiuchi et al. (2001)</a> identified a 142delG frameshift mutation in the TCF1 gene in a family with a strong history of type 1 diabetes (T1D20; <a href="/entry/612520">612520</a>). The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. According to the authors, this was the first case of an unstable mutant HNF1-alpha protein. Reporter gene analysis indicated that the mutant protein had no transactivation activity in HeLa and other cells. Haploinsufficiency for the TCF1 gene may lead to severe forms of diabetes resembling type I diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1169305 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1169305;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1169305?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1169305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1169305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016077 OR RCV000438436 OR RCV000861653 OR RCV003894808" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016077, RCV000438436, RCV000861653, RCV003894808" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016077...</a>
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<p>This mutation was found by <a href="#10" class="mim-tip-reference" title="Collet, C., Ducorps, M, Mayaudon, H., Dupuy, O., Ceppa, F., Boutin, P., Froguel, P., Bauduceau, B. <strong>Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1-alpha in Africans with diabetes.</strong> Diabetes Metab. 28: 39-44, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938027</a>]" pmid="11938027">Collet et al. (2002)</a> to be prevalent in African individuals with diabetes (<a href="/entry/600496">600496</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11938027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an individual who had had a liver-tumor resection and had familial diabetes, <a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> found a gly574-to-ser (G574S) mutation in the TCF1 gene. The hepatocellular carcinoma in this case had developed in an adenoma (<a href="/entry/142330">142330</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853242 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853242;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853242?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#5" class="mim-tip-reference" title="Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J. <strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong> Nature Genet. 32: 312-315, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>] [<a href="https://doi.org/10.1038/ng1001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12355088">Bluteau et al. (2002)</a> found a heterozygous germline mutation, arg583 to gln (R583Q), in an individual with a hyperplastic liver tumor (<a href="/entry/142330">142330</a>) who had had liver-tumor resection and had familial diabetes (<a href="/entry/600496">600496</a>). The substitution involved a highly conserved amino acid. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0015 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853243;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853243?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016080 OR RCV000517471 OR RCV002221999" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016080, RCV000517471, RCV002221999" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016080...</a>
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<p>In a 3-generation Norwegian family with MODY3 (<a href="/entry/600496">600496</a>), <a href="#4" class="mim-tip-reference" title="Bjorkhaug, L., Ye, H., Horikawa, Y., Sovik, O., Molven, A., Njolstad, P. R. <strong>MODY associated with two novel hepatocyte nuclear factor-1-alpha loss-of-function mutations (P112L and Q466X).</strong> Biochem. Biophys. Res. Commun. 279: 792-798, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11162430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11162430</a>] [<a href="https://doi.org/10.1006/bbrc.2000.4024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11162430">Bjorkhaug et al. (2000)</a> found a C-to-T transition at nucleotide 358 in exon 2 of the HNF1A gene, leading to a pro112-to-leu (P112L) amino acid substitution, in all 3 affected members. The phenotype in this family was mild with mild fasting and postprandial hyperglycemia easily controlled by diet only. Diabetes-associated late complications were not observed. P112L mutant protein demonstrated a significantly reduced ability to bind a high affinity HNF1 binding site and to activate transcription. Immunolocalization studies in HeLa cells showed that P112L mutant protein was correctly targeted to the nucleus. <a href="#4" class="mim-tip-reference" title="Bjorkhaug, L., Ye, H., Horikawa, Y., Sovik, O., Molven, A., Njolstad, P. R. <strong>MODY associated with two novel hepatocyte nuclear factor-1-alpha loss-of-function mutations (P112L and Q466X).</strong> Biochem. Biophys. Res. Commun. 279: 792-798, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11162430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11162430</a>] [<a href="https://doi.org/10.1006/bbrc.2000.4024" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11162430">Bjorkhaug et al. (2000)</a> concluded that the P112L mutation seems to impair pancreatic beta-cell function by loss-of-function mechanisms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11162430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#49" class="mim-tip-reference" title="Xu, J. Y., Chan, V., Zhang, W. Y., Wat, N. M. S., Lam, K. S. L. <strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in Chinese MODY families: prevalence and functional analysis.</strong> Diabetologia 45: 744-746, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107757</a>] [<a href="https://doi.org/10.1007/s00125-002-0814-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12107757">Xu et al. (2002)</a> found the HNF1A P112L mutation in a southern Chinese MODY family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> found evidence for possible founder effect of the P112L mutation in the Norwegian population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137853244 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853244;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853244" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016081 OR RCV000441594 OR RCV001794451 OR RCV002464066" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016081, RCV000441594, RCV001794451, RCV002464066" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016081...</a>
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<p><a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> found a C-to-T transition in exon 2 of the HNF1A gene, resulting in an arg131-to-trp (R131W) amino acid substitution, in 5 Norwegian families with MODY3 (<a href="/entry/600496">600496</a>). This mutation had been reported in families from North America and Great Britain. Haplotype analysis indicated possible founder effect for the Norwegian families. Immunofluorescence studies demonstrated incorrect localization and accumulation of protein in both cytoplasm and nucleus. The R131W mutant protein displayed 10 to 15% of binding activity of wildtype and levels of transcription activation close to 50% of wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2135839114 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2135839114;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2135839114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2135839114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016082" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016082" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016082</a>
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<p>In a Norwegian family with MODY3 (<a href="/entry/600496">600496</a>), <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> detected a novel 4-bp deletion in exon 3 of the HNF1A gene (T196fsdelCCAA). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1463923467 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1463923467;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs1463923467?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1463923467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1463923467" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016079 OR RCV002463589" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016079, RCV002463589" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016079...</a>
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<p>In a Norwegian proband with MODY3 (<a href="/entry/600496">600496</a>), <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> found a novel splice site mutation in intron 3 of the HNF1A gene, IVS3-1G-A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0019 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853245 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853245;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853245?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016083 OR RCV000521190 OR RCV001248962 OR RCV002254266" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016083, RCV000521190, RCV001248962, RCV002254266" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016083...</a>
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<p>In a Norwegian proband with MODY3 (<a href="/entry/600496">600496</a>), <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> detected a novel C-to-A transversion in exon 4 of the HNF1A gene resulting in an arg276-to-asp (A276D) amino acid substitution. Mutant protein was targeted to both nucleus and cytoplasm of transfected cells in immunofluorescence assays. DNA binding ability of 30 to 40% of wildtype could be detected; no significant reduction in transcription activation could be demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0020 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2135847417 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2135847417;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs2135847417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs2135847417" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016084" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016084" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016084</a>
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<p>In 3 members of a Norwegian family with MODY3 (<a href="/entry/600496">600496</a>), <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> found a novel 2-bp deletion in exon 7 of the HNF1A gene (S445fsdelAG). Mutant protein was targeted to both nucleus and cytoplasm of transfected cells in immunofluorescence assays. DNA binding ability of 30 to 40% of wildtype could be detected; no significant reduction in transcription activation could be demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0021 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853246 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853246;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853246?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853246" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016085 OR RCV001810400" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016085, RCV001810400" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016085...</a>
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<p>In a Norwegian proband with MODY3 (<a href="/entry/600496">600496</a>), <a href="#3" class="mim-tip-reference" title="Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R. <strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong> J. Clin. Endocr. Metab. 88: 920-931, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>] [<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12574234">Bjorkhaug et al. (2003)</a> detected a novel G-to-C transversion in exon 8 of the HNF1A gene, leading to a ser531-to-thr (S531T) amino acid substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0022 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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RENAL CELL CARCINOMA, CLEAR CELL, INCLUDED<br />
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RENAL CELL CARCINOMA, CHROMOPHOBE, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137853247 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137853247;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137853247?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137853247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137853247" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000016086 OR RCV000016087 OR RCV000016088 OR RCV000503110 OR RCV000763797 OR RCV000835061 OR RCV001810401 OR RCV002371772 OR RCV004752709" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000016086, RCV000016087, RCV000016088, RCV000503110, RCV000763797, RCV000835061, RCV001810401, RCV002371772, RCV004752709" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000016086...</a>
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<p><strong><em>Maturity-Onset Diabetes of the Young, Type 3</em></strong></p><p>
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In a French family with MODY3 (<a href="/entry/600496">600496</a>), <a href="#7" class="mim-tip-reference" title="Chevre, J. C., Hani, E. H., Boutin, P., Vaxillaire, M., Blanche, H., Vionnet, N., Pardini, V. C., Timsit, J., Larger, E., Charpentier, G., Beckers, D., Maes, M., Bellanne-Chantelot, C., Velho, C., Froguel, P. <strong>Mutation screening in 18 Caucasian families suggest the existence of other MODY genes.</strong> Diabetologia 41: 1017-1023, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9754819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9754819</a>] [<a href="https://doi.org/10.1007/s001250051025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9754819">Chevre et al. (1998)</a> identified heterozygosity for a 92G-A transition in exon 1 of the HNF1A gene, resulting in a gly31-to-asp (G31D) substitution in the dimerization domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9754819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Renal Cell Carcinoma</em></strong></p><p>
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In a 76-year-old woman with both clear cell and chromophobe renal carcinomas (see <a href="/entry/144700">144700</a>), <a href="#37" class="mim-tip-reference" title="Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J. <strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong> Hum. Molec. Genet. 14: 603-614, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15649945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15649945</a>] [<a href="https://doi.org/10.1093/hmg/ddi057" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15649945">Rebouissou et al. (2005)</a> identified heterozygosity for the G31D mutation. Mutation screening of the tumor samples detected only the germline G31D mutation. The renal carcinomas manifested in the same kidney with a single renal cyst in the other kidney. None of her relatives had a history of diabetes or renal carcinoma. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15649945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>See Also:</strong>
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<a href="#De1991" class="mim-tip-reference" title="De Simone, V., De Magistris, L., Lazzaro, D., Gerstner, J., Monaci, P., Nicosia, A., Cortese, R. <strong>LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.</strong> EMBO J. 10: 1435-1443, 1991.">De Simone et al. (1991)</a>; <a href="#Mendel1991" class="mim-tip-reference" title="Mendel, D. B., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., Crabtree, G. R. <strong>Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.</strong> Science 254: 1762-1767, 1991.">Mendel et al. (1991)</a>; <a href="#Rey-Campos1991" class="mim-tip-reference" title="Rey-Campos, J., Chouard, T., Yaniv, M., Cereghini, S. <strong>vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.</strong> EMBO J. 10: 1445-1457, 1991.">Rey-Campos et al.
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(1991)</a>
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Babaya, N., Ikegami, H., Fujisawa, T., Nojima, K., Itoi-Babaya, M., Inoue, K., Nakura, J., Abe, M., Yamamoto, M., Jin, J. J., Wu, Z., Miki, T., Fukuda, M., Ogihara, T.
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<strong>Association of I27L polymorphism of hepatocyte nuclear factor-1-alpha gene with high-density lipoprotein cholesterol level.</strong>
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J. Clin. Endocr. Metab. 88: 2548-2551, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12788852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12788852</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12788852" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1210/jc.2002-021891" target="_blank">Full Text</a>]
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<p class="mim-text-font">
|
|
Bach, I., Galcheva-Gargova, Z., Mattei, M.-G., Simon-Chazottes, D., Guenet, J.-L., Cereghini, S., Yaniv, M.
|
|
<strong>Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse.</strong>
|
|
Genomics 8: 155-164, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1707031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1707031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1707031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(90)90238-p" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="3" class="mim-anchor"></a>
|
|
<a id="Bjorkhaug2003" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R.
|
|
<strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong>
|
|
J. Clin. Endocr. Metab. 88: 920-931, 2003.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12574234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12574234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12574234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2002-020945" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="4" class="mim-anchor"></a>
|
|
<a id="Bjorkhaug2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bjorkhaug, L., Ye, H., Horikawa, Y., Sovik, O., Molven, A., Njolstad, P. R.
|
|
<strong>MODY associated with two novel hepatocyte nuclear factor-1-alpha loss-of-function mutations (P112L and Q466X).</strong>
|
|
Biochem. Biophys. Res. Commun. 279: 792-798, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11162430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11162430</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11162430" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1006/bbrc.2000.4024" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="5" class="mim-anchor"></a>
|
|
<a id="Bluteau2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J.
|
|
<strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong>
|
|
Nature Genet. 32: 312-315, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12355088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12355088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12355088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng1001" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="6" class="mim-anchor"></a>
|
|
<a id="Byrne1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Byrne, M. M., Sturis, J., Menzel, S., Yamagata, K., Fajans, S. S., Dronsfield, M. J., Bain, S. C., Hattersley, A. T., Velho, G., Froguel, P., Bell, G. I., Polonsky, K. S.
|
|
<strong>Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12.</strong>
|
|
Diabetes 45: 1503-1510, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8866553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8866553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8866553" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diab.45.11.1503" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="7" class="mim-anchor"></a>
|
|
<a id="Chevre1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chevre, J. C., Hani, E. H., Boutin, P., Vaxillaire, M., Blanche, H., Vionnet, N., Pardini, V. C., Timsit, J., Larger, E., Charpentier, G., Beckers, D., Maes, M., Bellanne-Chantelot, C., Velho, C., Froguel, P.
|
|
<strong>Mutation screening in 18 Caucasian families suggest the existence of other MODY genes.</strong>
|
|
Diabetologia 41: 1017-1023, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9754819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9754819</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9754819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s001250051025" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="8" class="mim-anchor"></a>
|
|
<a id="Chi2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chi, Y.-I., Frantz, J. D., Oh, B.-C., Hansen, L., Dhe-Paganon, S., Shoelson, S. E.
|
|
<strong>Diabetes mutations delineate an atypical POU domain in HNF-1-alpha.</strong>
|
|
Molec. Cell 10: 1129-1137, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12453420/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12453420</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12453420" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s1097-2765(02)00704-9" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="9" class="mim-anchor"></a>
|
|
<a id="Chiu2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Chiu, K. C., Chuang, L.-M., Ryu, J. M., Tsai, G. P., Saad, M. F.
|
|
<strong>The I27L amino acid polymorphism of hepatic nuclear factor-1-alpha is associated with insulin resistance.</strong>
|
|
J. Clin. Endocr. Metab. 85: 2178-2183, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10852449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10852449</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10852449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.6.6618" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="10" class="mim-anchor"></a>
|
|
<a id="Collet2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Collet, C., Ducorps, M, Mayaudon, H., Dupuy, O., Ceppa, F., Boutin, P., Froguel, P., Bauduceau, B.
|
|
<strong>Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1-alpha in Africans with diabetes.</strong>
|
|
Diabetes Metab. 28: 39-44, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11938027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11938027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11938027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="11" class="mim-anchor"></a>
|
|
<a id="Courtois1987" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., Crabtree, G. R.
|
|
<strong>Interaction of a liver-specific nuclear factor with the fibrinogen and alpha-1-antitrypsin promoters.</strong>
|
|
Science 238: 688-692, 1987.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3499668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3499668</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3499668" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.3499668" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="12" class="mim-anchor"></a>
|
|
<a id="De Simone1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
De Simone, V., De Magistris, L., Lazzaro, D., Gerstner, J., Monaci, P., Nicosia, A., Cortese, R.
|
|
<strong>LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.</strong>
|
|
EMBO J. 10: 1435-1443, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673925</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1991.tb07664.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="13" class="mim-anchor"></a>
|
|
<a id="Ellard2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ellard, S.
|
|
<strong>Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young.</strong>
|
|
Hum. Mutat. 16: 377-385, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11058894/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11058894</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11058894" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/1098-1004(200011)16:5<377::AID-HUMU1>3.0.CO;2-2" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="14" class="mim-anchor"></a>
|
|
<a id="Fajans2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Fajans, S. S., Bell, G. I., Polonsky, K. S.
|
|
<strong>Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.</strong>
|
|
New Eng. J. Med. 345: 971-980, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11575290/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11575290</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11575290" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJMra002168" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="15" class="mim-anchor"></a>
|
|
<a id="Foster1978" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Foster, J. H., Donohue, T. A., Berman, M. M.
|
|
<strong>Familial liver-cell adenomas and diabetes mellitus.</strong>
|
|
New Eng. J. Med. 299: 239-241, 1978.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/207987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">207987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=207987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1056/NEJM197808032990508" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="16" class="mim-anchor"></a>
|
|
<a id="Frayling1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frayling, T. M., Bulman, M. P., Appleton, M., Hattersley, A. T., Ellard, S.
|
|
<strong>A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes.</strong>
|
|
Hum. Genet. 101: 351-354, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9439666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9439666</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9439666" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s004390050640" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="17" class="mim-anchor"></a>
|
|
<a id="Frayling1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Frayling, T. M., Bulman, M. P., Ellard, S., Appleton, M., Dronsfield, M. J., Mackie, A. D. R., Baird, J. D., Kaisaki, P. J., Yamagata, K., Bell, G. I., Bain, S. C., Hattersley, A. T.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.</strong>
|
|
Diabetes 46: 720-725, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9075818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diab.46.4.720" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="18" class="mim-anchor"></a>
|
|
<a id="Godart2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Godart, F., Bellanne-Chantelot, C., Clauin, S., Gragnoli, C., Abderrahmani, A., Blanche, H., Boutin, P., Chevre, J. C., Froguel, P., Bailleul, B.
|
|
<strong>Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1-alpha (TCF1) promoter region in MODY patients.</strong>
|
|
Hum. Mutat. 15: 173-180, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10649494/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10649494</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10649494" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<173::AID-HUMU6>3.0.CO;2-W" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="19" class="mim-anchor"></a>
|
|
<a id="Gonzalez1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gonzalez, F. J., Liu, S.-Y., Kozak, C. A., Nebert, D. W.
|
|
<strong>Decreased Hnf-1 gene expression in mice homozygous for a 1.2-centimorgan deletion on chromosome 7.</strong>
|
|
DNA Cell Biol. 9: 771-776, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2264930/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2264930</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2264930" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1089/dna.1990.9.771" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="20" class="mim-anchor"></a>
|
|
<a id="Gragnoli1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Gragnoli, C., Lindner, T., Cockburn, B. N., Kaisaki, P. J., Gragnoli, F., Marozzi, G., Bell, G. I.
|
|
<strong>Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4-alpha binding site in the promoter of the hepatocyte nuclear factor-1-alpha gene.</strong>
|
|
Diabetes 46: 1648-1651, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313764</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diacare.46.10.1648" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="21" class="mim-anchor"></a>
|
|
<a id="Hansen1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hansen, T., Eiberg, H., Rouard, M., Vaxillaire, M., Moller, A. M., Rasmussen, S. K., Fridberg, M., Urhammer, S. A., Holst, J. J., Almind, K., Echwald, S. M., Hansen, L., Bell, G. I., Pedersen, O.
|
|
<strong>Novel MODY3 mutations in the hepatocyte nuclear factor-1-alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.</strong>
|
|
Diabetes 46: 726-730, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9075819/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9075819</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9075819" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diab.46.4.726" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="22" class="mim-anchor"></a>
|
|
<a id="Hegele1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Hanley, A. J. G., Zinman, B.
|
|
<strong>The hepatic nuclear factor-1-alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.</strong>
|
|
J. Clin. Endocr. Metab. 84: 1077-1082, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10084598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10084598</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10084598" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.84.3.5528" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="23" class="mim-anchor"></a>
|
|
<a id="Hegele2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J. G., Anderson, C. M.
|
|
<strong>Peroxisome proliferator-activated receptor-gamma-2 P12A and type 2 diabetes in Canadian Oji-Cree.</strong>
|
|
J. Clin. Endocr. Metab. 85: 2014-2019, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10843190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10843190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10843190" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.85.5.6610" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="24" class="mim-anchor"></a>
|
|
<a id="Hiraiwa2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hiraiwa, H., Pan, C.-J., Lin, B., Akiyama, T. E., Gonzalez, F. J., Chou, J. Y.
|
|
<strong>A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1-alpha-null mice.</strong>
|
|
J. Biol. Chem. 276: 7963-7967, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11121425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11121425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11121425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M010523200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="25" class="mim-anchor"></a>
|
|
<a id="Hua2000" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Hua, Q.-X., Zhao, M., Narayana, N., Nakagawa, S. H., Jia, W., Weiss, M. A.
|
|
<strong>Diabetes-associated mutations in a beta-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 1999-2004, 2000. Note: Erratum: Proc. Nat. Acad. Sci. 98: 13472 only, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10696112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10696112</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10696112[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10696112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.97.5.1999" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="26" class="mim-anchor"></a>
|
|
<a id="Huang2011" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., Hui, L.
|
|
<strong>Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors.</strong>
|
|
Nature 475: 386-389, 2011.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21562492/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21562492</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21562492" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/nature10116" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="27" class="mim-anchor"></a>
|
|
<a id="Johansen2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Johansen, A., Ek, J., Mortensen, H. B., Pedersen, O., Hansen, T.
|
|
<strong>Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.</strong>
|
|
J. Clin. Endocr. Metab. 90: 4607-4614, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15928245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15928245</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15928245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jc.2005-0196" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="28" class="mim-anchor"></a>
|
|
<a id="Kaisaki1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kaisaki, P. J., Menzel, S., Lindner, T., Oda, N., Rjasanowski, I., Sahm, J., Meincke, G., Schulze, J., Schmechel, H., Petzold, C., Ledermann, H. M., Sachse, G., Boriraj, V. V., Menzel, R., Kerner, W., Turner, R. C., Yamagata, K., Bell, G. I.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.</strong>
|
|
Diabetes 46: 528-535, 1997. Note: Erratum: Diabetes 46: 1239 only, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9032114/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9032114</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9032114" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.2337/diab.46.3.528" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="29" class="mim-anchor"></a>
|
|
<a id="Kuo1990" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Kuo, C. J., Conley, P. B., Hsieh, C.-L., Francke, U., Crabtree, G. R.
|
|
<strong>Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 9838-9842, 1990.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2263635/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2263635</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2263635" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.87.24.9838" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="30" class="mim-anchor"></a>
|
|
<a id="Mendel1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mendel, D. B., Hansen, L. P., Graves, M. K., Conley, P. B., Crabtree, G. R.
|
|
<strong>HNF-1-alpha and HNF-1-beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.</strong>
|
|
Genes Dev. 5: 1042-1056, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2044952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2044952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2044952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1101/gad.5.6.1042" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="31" class="mim-anchor"></a>
|
|
<a id="Mendel1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mendel, D. B., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., Crabtree, G. R.
|
|
<strong>Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.</strong>
|
|
Science 254: 1762-1767, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1763325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1763325</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1763325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1763325" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="32" class="mim-anchor"></a>
|
|
<a id="Miedzybrodzka1999" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Miedzybrodzka, Z., Hattersley, A. T., Ellard, S., Pearson, D., de Silva, D., Harvey, R., Haites, N.
|
|
<strong>Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1a gene: implications for predictive testing.</strong>
|
|
Europ. J. Hum. Genet. 7: 729-732, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10482964/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10482964</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10482964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/sj.ejhg.5200358" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="33" class="mim-anchor"></a>
|
|
<a id="Mirshahi2022" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Mirshahi, U. L., Colclough, K., Wright, C. F., Wood, A. R., Beaumont, R. N., Tyrrell, J., Laver, T. W., Stahl, R., Golden, A., Goehringer, J. M, Geisinger-Regeneron DiscovEHR Collaboration, Frayling, T. F., Hattersley, A. T., Carey, D. J., Weedon, M. N., Patel, K. A.
|
|
<strong>Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.</strong>
|
|
Am. J. Hum. Genet. 109: 2018-2028, 2022.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36257325/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36257325</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=36257325[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36257325" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2022.09.014" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="34" class="mim-anchor"></a>
|
|
<a id="Odom2007" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., Fraenkel, E.
|
|
<strong>Tissue-specific transcriptional regulation has diverged significantly between human and mouse.</strong>
|
|
Nature Genet. 39: 730-732, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17529977/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17529977</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17529977[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17529977" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/ng2047" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="35" class="mim-anchor"></a>
|
|
<a id="Odom2004" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A.
|
|
<strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong>
|
|
Science 303: 1378-1381, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14988562/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14988562</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14988562[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14988562" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1126/science.1089769" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="36" class="mim-anchor"></a>
|
|
<a id="Pontoglio1996" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Pontoglio, M., Barra, J., Hadchouel, M., Doyen, A., Kress, C., Bach, J. P., Babinet, C., Yaniv, M.
|
|
<strong>Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome.</strong>
|
|
Cell 84: 575-585, 1996.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8598044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8598044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8598044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/s0092-8674(00)81033-8" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="37" class="mim-anchor"></a>
|
|
<a id="Rebouissou2005" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J.
|
|
<strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong>
|
|
Hum. Molec. Genet. 14: 603-614, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15649945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15649945</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15649945" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/ddi057" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="38" class="mim-anchor"></a>
|
|
<a id="Reiner2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Reiner, A. P., Barber, M. J., Guan, Y., Ridker, P. M., Lange, L. A., Chasman, D. I., Walston, J. D., Cooper, G. M., Jenny, N. S., Rieder, M. J., Durda, J. P., Smith, J. D., Novembre, J., Tracy, R. P., Rotter, J. I., Stephens, M., Nickerson, D. A., Krauss, R. M.
|
|
<strong>Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1-alpha are associated with C-reactive protein.</strong>
|
|
Am. J. Hum. Genet. 82: 1193-1201, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18439552/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18439552</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18439552[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18439552" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2008.03.017" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="39" class="mim-anchor"></a>
|
|
<a id="Rey-Campos1991" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Rey-Campos, J., Chouard, T., Yaniv, M., Cereghini, S.
|
|
<strong>vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.</strong>
|
|
EMBO J. 10: 1445-1457, 1991.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1673926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1673926</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1673926" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1002/j.1460-2075.1991.tb07665.x" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="40" class="mim-anchor"></a>
|
|
<a id="Ridker2008" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Ridker, P. M., Pare, G., Parker, A., Zee, R. Y. L., Danik, J. S., Buring, J. E., Kwiatkowski, D., Cook, N. R., Miletich, J. P., Chasman, D. I.
|
|
<strong>Loci related to metabolic syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.</strong>
|
|
Am. J. Hum. Genet. 82: 1185-1192, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18439548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18439548</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18439548[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18439548" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/j.ajhg.2008.03.015" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="41" class="mim-anchor"></a>
|
|
<a id="Shih2001" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., Stoffel, M.
|
|
<strong>Hepatocyte nuclear factor-1-alpha is an essential regulator of bile acid and plasma cholesterol metabolism.</strong>
|
|
Nature Genet. 27: 375-382, 2001.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11279518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11279518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11279518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/86871" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="42" class="mim-anchor"></a>
|
|
<a id="Szpirer1992" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Szpirer, C., Riviere, M., Cortese, R., Nakamura, T., Islam, M. Q., Levan, G., Szpirer, J.
|
|
<strong>Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF).</strong>
|
|
Genomics 13: 293-300, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1535333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1535333</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1535333" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1016/0888-7543(92)90245-n" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="43" class="mim-anchor"></a>
|
|
<a id="Triggs-Raine2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Triggs-Raine, B. L., Kirkpatrick, R. D., Kelly, S. L., Norquay, L. D., Cattini, P. A., Yamagata, K., Hanley, A. J. G., Zinman, B., Harris, S. B., Barrett, P. H., Hegele, R. A.
|
|
<strong>HNF1-alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 4614-4619, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11904371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11904371</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11904371[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11904371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1073/pnas.062059799" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="44" class="mim-anchor"></a>
|
|
<a id="Urhammer1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Hansen, T., Ekstrom, C. T., Eiberg, H., Pederson, O.
|
|
<strong>The Ala/Val98 polymorphism of the hepatocyte nuclear factor-1-alpha gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test: evidence from studies of 231 glucose-tolerant first degree relatives of type 2 diabetic probands.</strong>
|
|
J. Clin. Endocr. Metab. 83: 4506-4509, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9851800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9851800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9851800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.12.5359" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="45" class="mim-anchor"></a>
|
|
<a id="Urhammer1998" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Moller, A. M., Nyholm, B., Ekstrom, C. T., Eiberg, H., Clausen, J. O., Hansen, T., Pedersen, O., Schmitz, O.
|
|
<strong>The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1-alpha gene on estimates of the pancreatic beta-cell function in Caucasian glucose-tolerant first-degree relatives of type 2 diabetic patients.</strong>
|
|
J. Clin. Endocr. Metab. 83: 3992-3995, 1998.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9814481/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9814481</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9814481" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1210/jcem.83.11.5228" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="46" class="mim-anchor"></a>
|
|
<a id="Urhammer1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Rasmussen, S. K., Kaisaki, P. J., Oda, N., Yamagata, K., Moller, A. M., Fridberg, M., Hansen, L., Hansen, T., Bell, G. I., Pedersen, O.
|
|
<strong>Genetic variation in the hepatocyte nuclear factor-1-alpha gene in Danish Caucasians with late-onset NIDDM.</strong>
|
|
Diabetologia 40: 473-475, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9112026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9112026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9112026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1007/s001250050703" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="47" class="mim-anchor"></a>
|
|
<a id="van Wering2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
van Wering, H. M., Huibregtse, I. L., van der Zwan, S. M., de Bie, M. S., Dowling, L. N., Boudreau, F., Rings, E. H. H. M., Grand, R. J., Krasinski, S. D.
|
|
<strong>Physical interaction between GATA-5 and hepatocyte nuclear factor-1-alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter.</strong>
|
|
J. Biol. Chem. 277: 27659-27667, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12011060/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12011060</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12011060" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1074/jbc.M203645200" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="48" class="mim-anchor"></a>
|
|
<a id="Vaxillaire1997" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P. J., Boriraj, V. V., Chevre, J.-C., Boccio, V., Cox, R. D., Lathrop, G. M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G. I., Froguel, P.
|
|
<strong>Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).</strong>
|
|
Hum. Molec. Genet. 6: 583-586, 1997.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1093/hmg/6.4.583" target="_blank">Full Text</a>]
|
|
|
|
|
|
</p>
|
|
</div>
|
|
</li>
|
|
|
|
<li>
|
|
<a id="49" class="mim-anchor"></a>
|
|
<a id="Xu2002" class="mim-anchor"></a>
|
|
<div class="">
|
|
<p class="mim-text-font">
|
|
Xu, J. Y., Chan, V., Zhang, W. Y., Wat, N. M. S., Lam, K. S. L.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in Chinese MODY families: prevalence and functional analysis.</strong>
|
|
Diabetologia 45: 744-746, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12107757/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12107757</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12107757" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00125-002-0814-9" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="50" class="mim-anchor"></a>
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<a id="Yamada1997" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
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Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J.
|
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<strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong>
|
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Diabetes 46: 1643-1647, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9313763/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9313763</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9313763" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.2337/diacare.46.10.1643" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="51" class="mim-anchor"></a>
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<a id="Yamagata1996" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong>
|
|
Nature 384: 455-457, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8945470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8945470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8945470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/384455a0" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="52" class="mim-anchor"></a>
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<a id="Yoshiuchi2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yoshiuchi, I., Yamagata, K., Yoshimoto, M., Zhu, Q., Yang, Q., Nammo, T., Uenaka, R., Kinoshita, E., Hanafusa, T., Miyagawa, J., Matsuzawa, Y.
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<strong>Analysis of a non-functional HNF-1-alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.</strong>
|
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Hum. Mutat. 18: 345-351, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668618/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668618</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668618" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.1196" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 01/17/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 8/4/2011<br>Marla J. F. O'Neill - updated : 4/19/2010<br>Marla J. F. O'Neill - updated : 6/10/2008<br>George E. Tiller - updated : 2/5/2008<br>Patricia A. Hartz - updated : 10/3/2007<br>Patricia A. Hartz - updated : 8/3/2007<br>John A. Phillips, III - updated : 10/19/2006<br>Ada Hamosh - updated : 6/10/2004<br>John A. Phillips, III - updated : 2/10/2004<br>John A. Phillips, III - updated : 8/21/2003<br>Stylianos E. Antonarakis - updated : 5/5/2003<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 2/15/2002<br>Ada Hamosh - updated : 10/18/2001<br>John A. Phillips, III - updated : 9/25/2001<br>Ada Hamosh - updated : 4/23/2001<br>Ada Hamosh - updated : 3/28/2001<br>John A. Phillips, III - updated : 2/12/2001<br>Victor A. McKusick - updated : 11/29/2000<br>John A. Phillips, III - updated : 8/9/2000<br>Victor A. McKusick - updated : 2/22/2000<br>Victor A. McKusick - updated : 11/8/1999<br>John A. Phillips, III - updated : 9/29/1999<br>John A. Phillips, III - updated : 3/24/1999<br>Victor A. McKusick - updated : 2/13/1998<br>Victor A. McKusick - updated : 2/11/1998<br>Victor A. McKusick - updated : 8/12/1997<br>Victor A. McKusick - updated : 8/7/1997<br>Victor A. McKusick - updated : 4/24/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 11/13/1987
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</span>
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</div>
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</div>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 01/17/2023
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/16/2021<br>carol : 09/04/2020<br>carol : 09/03/2020<br>carol : 09/03/2020<br>alopez : 12/11/2017<br>carol : 10/03/2017<br>carol : 08/04/2016<br>carol : 05/17/2016<br>terry : 11/9/2012<br>alopez : 8/3/2012<br>carol : 3/29/2012<br>carol : 3/29/2012<br>mgross : 10/4/2011<br>terry : 10/4/2011<br>alopez : 8/15/2011<br>terry : 8/4/2011<br>alopez : 4/21/2010<br>terry : 4/19/2010<br>alopez : 4/16/2010<br>alopez : 4/16/2010<br>carol : 4/14/2009<br>terry : 2/19/2009<br>mgross : 10/21/2008<br>carol : 6/11/2008<br>terry : 6/10/2008<br>wwang : 2/7/2008<br>terry : 2/5/2008<br>wwang : 10/25/2007<br>mgross : 10/3/2007<br>mgross : 10/3/2007<br>alopez : 8/3/2007<br>alopez : 10/19/2006<br>carol : 11/18/2005<br>alopez : 3/30/2005<br>alopez : 6/15/2004<br>alopez : 6/15/2004<br>terry : 6/10/2004<br>alopez : 2/10/2004<br>alopez : 8/21/2003<br>mgross : 5/5/2003<br>mgross : 5/5/2003<br>tkritzer : 11/19/2002<br>alopez : 9/25/2002<br>alopez : 9/25/2002<br>tkritzer : 9/23/2002<br>ckniffin : 5/29/2002<br>carol : 4/30/2002<br>cwells : 2/25/2002<br>cwells : 2/20/2002<br>terry : 2/15/2002<br>carol : 1/4/2002<br>carol : 10/18/2001<br>cwells : 9/28/2001<br>cwells : 9/25/2001<br>alopez : 4/30/2001<br>terry : 4/23/2001<br>alopez : 3/29/2001<br>terry : 3/28/2001<br>terry : 2/12/2001<br>carol : 12/18/2000<br>mcapotos : 12/14/2000<br>terry : 11/29/2000<br>mgross : 8/9/2000<br>mcapotos : 4/12/2000<br>alopez : 3/23/2000<br>mcapotos : 3/22/2000<br>mcapotos : 3/14/2000<br>terry : 2/22/2000<br>alopez : 11/12/1999<br>psherman : 11/9/1999<br>terry : 11/8/1999<br>alopez : 11/5/1999<br>alopez : 9/29/1999<br>mgross : 4/7/1999<br>mgross : 3/24/1999<br>dkim : 12/9/1998<br>dkim : 7/21/1998<br>alopez : 5/14/1998<br>mark : 2/22/1998<br>terry : 2/13/1998<br>alopez : 2/11/1998<br>dholmes : 2/4/1998<br>jenny : 8/20/1997<br>terry : 8/12/1997<br>terry : 8/11/1997<br>terry : 8/7/1997<br>terry : 8/7/1997<br>alopez : 4/30/1997<br>alopez : 4/24/1997<br>terry : 4/24/1997<br>mark : 3/7/1997<br>mark : 12/11/1996<br>mark : 12/4/1996<br>terry : 12/3/1996<br>mark : 3/25/1996<br>terry : 3/18/1996<br>carol : 1/5/1995<br>mimadm : 4/14/1994<br>carol : 10/22/1992<br>carol : 6/26/1992<br>carol : 6/24/1992<br>supermim : 3/16/1992
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
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<strong>*</strong> 142410
|
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</span>
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</h3>
|
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
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|
|
HNF1 HOMEOBOX A; HNF1A
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</span>
|
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</h3>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
|
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
TRANSCRIPTION FACTOR 1; TCF1<br />
|
|
HEPATOCYTE NUCLEAR FACTOR-1-ALPHA<br />
|
|
HEPATOCYTE NUCLEAR FACTOR 1; HNF1<br />
|
|
HEPATIC NUCLEAR FACTOR-1-ALPHA<br />
|
|
ALBUMIN PROXIMAL FACTOR
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: HNF1A</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
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|
|
<strong>SNOMEDCT:</strong> 1187306007, 128667008, 254915003, 41607009, 609570008, 733471003;
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: 12q24.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 12:120,978,543-121,002,512 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
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</div>
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<div>
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<br />
|
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="6">
|
|
<span class="mim-font">
|
|
12q24.31
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Diabetes mellitus, insulin-dependent}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
222100
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
{Diabetes mellitus, noninsulin-dependent, 2}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
125853
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Diabetes mellitus, insulin-dependent, 20
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
612520
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hepatic adenoma, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
142330
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
MODY, type III
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
600496
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Renal cell carcinoma
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</span>
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</td>
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<td>
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<span class="mim-font">
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144700
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</span>
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</td>
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<td>
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<span class="mim-font">
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using a rat Hnf1 cDNA-derived probe, Bach et al. (1990) isolated HNF1 clones from a human liver cDNA library. The deduced 631-amino acid human HNF1 protein contains a homeodomain in its N-terminal half and shares close similarity with the 628-amino acid rat protein. </p><p>The amino acid sequence of HNF1 displays distant sequence homology to the homeodomains of homeotic genes (see 142950) (Courtois et al., 1987). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The orderly and sequential activation of genes during development is thought to be related to the selective expression of groups of regulatory proteins acting primarily at the level of transcription. Courtois et al. (1987) found a nuclear protein in hepatocytes, but not in other cell types, that binds to a sequence required for hepatocyte-specific transcription of the genes for the alpha and beta chains of fibrinogen (134820, 134830) and alpha-1-antitrypsin (107400). This protein, called hepatocyte nuclear factor-1 (HNF1) by them, interacts with sequences required for optimal promoter function of the genes mentioned. The promoter or enhancer regions for several viral and cellular genes not expressed in the liver did not compete for binding to these sequences. HNF1 is predominantly expressed in liver and kidney. The restricted expression of HNF1 and its selective interaction with the control regions of several liver-specific genes suggested to Courtois et al. (1987) that it is involved in developmentally regulated gene expression in the liver. HNF1 binds to the promoters of a variety of genes that are expressed exclusively in the liver, e.g., fibrinogen-alpha and -beta, albumin (103600), alpha-fetoprotein (104150), alpha-1-antitrypsin, liver-type pyruvate kinase (609712), transthyretin (176300), aldolase B (612724), and hepatitis B virus large surface protein. </p><p>Dimerization among transcription factors is a frequent finding in the regulation of eukaryotic gene expression. HNF1-alpha functions as a dimer. Mendel et al. (1991) identified DCOH (126090), a dimerization cofactor of HNF1-alpha, which displayed a restricted tissue distribution and did not bind to DNA but, rather, selectively stabilized HNF1-alpha dimers. Hua et al. (2000) showed that the dimerization motif of HNF1-alpha forms an intermolecular 4-helix bundle. The bundle is destabilized by a subset of mutations associated with maturity-onset diabetes of the young (MODY; 606391). Impaired dimerization of the beta-cell transcription factor thus provides a molecular mechanism of metabolic deregulation in diabetes mellitus. </p><p>Van Wering et al. (2002) showed that mouse Gata5 (611496) and Hnf1-alpha interacted in vitro and in transfected COS-7 cells. The interaction required the C-terminal zinc finger and basic region of Gata5 and the homeodomain of Hnf1-alpha. Physical association of GATA5 and HNF1-alpha was required for synergistic activation of the human lactase-phlorizin hydrolase (LCT; 603202) promoter. Deletion of the HNF1-alpha activation domains or interruption of the HNF1-binding sites in the LCT promoter resulted in complete loss of transcriptional activity, whereas deletion of the GATA5 activation domains or interruption of the GATA-binding sites reduced, but did not eliminate, transcriptional activity. </p><p>To gain insight into the transcriptional regulatory networks that specify and maintain human tissue diversity, Odom et al. (2004) used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1-alpha, HNF4-alpha (600281), and HNF6 (604164), together with RNA polymerase II (see 180660), in human liver and pancreatic islets. Odom et al. (2004) identified tissue-specific regulatory circuits formed by HNF1-alpha, HNF4-alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Odom et al. (2004) concluded that their results suggested how misregulation of HNF4-alpha can contribute to type 2 diabetes (125853). They found that HNF1-alpha is bound to at least 222 target genes in hepatocytes. HNF1-alpha occupied the promoter regions of 106 genes within pancreatic islets, 30% of which were also bound by HNF1-alpha in hepatocytes. In islets, fewer chaperones and enzymes were bound by HNF1-alpha than in hepatocytes, and the receptors and signal transduction machinery regulated by HNF1-alpha varied between the 2 tissues. Odom et al. (2004) found that HNF4-alpha bound to the promoters of about 12% of hepatocyte islet genes represented on the microarray. HNF4-alpha acted in a much larger number of hepatocyte and beta-cell genes than did HNF1-alpha, suggesting that HNF4-alpha has broad activities in these 2 tissues. </p><p>Odom et al. (2007) analyzed the binding of FOXA2 (600288), HNF1A, HNF4A, and HNF6 to 4,000 orthologous gene pairs in hepatocytes purified from human and mouse livers. Despite the conserved function of these factors, 41 to 89% of the binding events seemed to be species-specific. Importantly, the binding sites varied widely between species in ways that could not be predicted from human-mouse sequence alignments alone. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Bach et al. (1990) assigned the human HNF1 gene to chromosome 12q24.3 by in situ hybridization, and the mouse gene to 5F by RFLP analysis of interspecific mouse backcrosses. One other gene, that for short chain acyl-CoA-dehydrogenase (606885), had also been assigned to chromosomes 12 and 5 in man and mouse, respectively. Kuo et al. (1990) also assigned the HNF1 gene to 12q22-qter in the human and to chromosome 5 in the mouse. By means of somatic cell hybrids segregating either human or rat chromosomes, Szpirer et al. (1992) independently assigned the TCF1 gene to human chromosome 12 and found that it was located also on rat chromosome 12, thereby defining a new segment of homology between the 2 species (and a segment of mouse chromosome 5). </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>MODY, a single-gene disorder responsible for 2 to 5% of noninsulin-dependent (type II) diabetes mellitus (NIDDM; 125853), is characterized by autosomal dominant inheritance and an age of onset of 25 years or younger. Yamagata et al. (1996) narrowed the localization of a form of MODY (MODY3; 600496) to chromosome 12q24.2 by a combination of genetic linkage and fluorescence in situ hybridization. To identify the nature of the MODY3 gene, Yamagata et al. (1996) used a combination of approaches, including testing genes known to be on 12q to see if they mapped into the contig to which MODY3 mapped, exon trapping, and cDNA selection, for which human pancreatic islet cDNA was used (insulin secretion is abnormal in MODY3 patients, making islets a likely site of expression of MODY3 mRNA and protein). They identified 14 genes encoding known proteins, 12 known expressed sequence tags (ESTs), and 9 new ESTs. They found mutations in the gene encoding hepatocyte nuclear factor-1-alpha, a transcription factor that helps in the tissue-specific regulation of the expression of several liver genes and also functions as a weak transactivator of the rat insulin-I gene. In all, Yamagata et al. (1996) identified 6 different mutations which were associated with MODY3 (e.g., 142410.0001). In several pedigrees individuals were found who inherited the mutant allele and the at-risk chromosome 12 haplotype but were nondiabetic or only showed evidence of impaired glucose tolerance or diabetes during pregnancy. These individuals were expected eventually to develop diabetes mellitus. In one member of a family NIDDM was diagnosed at the age of 65 years, at which time he was mildly obese, suggesting that he had late-onset NIDDM rather than MODY. </p><p>Vaxillaire et al. (1997) examined 10 unrelated Caucasian families in whom MODY/NIDDM cosegregated with markers for MODY3 and found 10 different mutations in the TCF1 gene, all of which cosegregated with diabetes (see 142410.0003 and 142410.0004). In these families, they found no obvious relationships between the nature of the mutations observed (i.e., frameshift, nonsense, or missense), or their location in the gene, with clinical features of diabetes (e.g., age at onset, severity). The authors stated that the mechanisms by which mutations in the TCF1 gene caused diabetes mellitus were unclear, but might include abnormal pancreatic islet development during fetal life, as well as impaired transcriptional regulation of genes that play a key role in normal pancreatic beta-cell function. </p><p>Urhammer et al. (1997) found a variety of variations in the TCF1 gene in 245 Danish NIDDM patients and 242 age-matched controls. The frequencies of the variants were similar in the 2 groups except that an arg583-to-gln mutation was found in 2 of the 245 NIDDM patients and in none of the control subjects. The authors concluded that genetic variation in the TCF1 gene is not a common factor contributing to NIDDM susceptibility in white subjects of Danish ancestry. Urhammer et al. (1998) studied the frequent amino acid polymorphisms ile27 to leu and ser487 to asn of the TCF1 gene to determine whether they were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among Caucasian glucose-tolerant first-degree relatives of NIDDM patients. The authors concluded that these polymorphisms had no major impact on the pancreatic beta-cell function, as estimated during an oral and intravenous glucose challenge. </p><p>Urhammer et al. (1998) studied the TCF1 ala98-to-val polymorphism in glucose-tolerant first-degree relatives of type 2 diabetic patients of the same ethnic origin. All participants, 231 glucose-tolerant offspring of 62 type 2 diabetic probands, underwent an oral glucose tolerance test (OGTT) with measurements of plasma glucose, serum insulin, and serum C-peptide during the test. Thirty-three heterozygous carriers of the ala98-to-val variant were identified, whereas no subjects had the variant in its homozygous form. Carriers of ala98 to val had a 20% reduction in serum C-peptide at 30 minutes during the OGTT compared to wildtype carriers. No significant differences in serum insulin levels during the OGTT were observed between carriers of the variant and ala98 homozygotes. </p><p>In a study of 15 UK MODY families for mutations in the TCF1 gene, Frayling et al. (1997) found 8 different mutations in 11 families (73%). A previously reported mutation, the insertion of a C in the C tract encoding the sequence 289-pro-pro-pro-291 (142410.0001), was present in 4 of the families. A screen of a further 32 probands with early-onset (less than 40 years of age) NIDDM showed the mutation in 2 additional families. This common mutation was present on at least 3 different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than founder effect. Thus, Frayling et al. (1997) concluded that TSF1 mutations are a common cause of MODY in UK families and result in early-onset NIDDM with a progressive clinical course. Hansen et al. (1997) sequenced the coding region and intron-exon boundaries of the TCF1 gene in 9 unrelated Danish Caucasian subjects with MODY and found mutations in 5. These 5 mutations were found in neither 84 NIDDM patients nor in 84 control subjects. </p><p>MODY3 is characterized by a severe insulin secretory defect, compared with MODY2 (125851), a glucokinase-deficient diabetes. Because of the rapid progress to overt diabetes and the high prevalence of the requirement for insulin treatment in patients with MODY3, Yamada et al. (1997) screened the HNF1A gene for mutations in Japanese subjects with insulin-dependent diabetes mellitus (IDDM; 222100). Mutations were identified in 3 (5.5%) of the 55 unrelated subjects with IDDM (e.g., 142410.0001, 142410.0005, and 142410.0006). None of these mutations was found in 200 normal chromosomes from nondiabetic subjects. The results indicated that mutation in the HNF1A gene can lead to development not only of early-onset NIDDM but also of IDDM. In a subclassification of IDDM, the HNF1A-deficient type should be distinguished from the classic type of autoimmune-based IDDM in Japanese. All of these mutations were heterozygous. </p><p>Ellard (2000) stated that 65 different mutations in the TCF1 gene had been found to cause MODY3 in a total of 116 families worldwide. They noted that diagnostic and predictive genetic testing is possible for the majority of patients with MODY, opening new avenues for the classification, prediction, and perhaps eventually the prevention of diabetes in these families. </p><p>Fajans et al. (2001) reported that mutations in the HNF1A gene have been identified in all racial and ethnic backgrounds, including European, Chinese, Japanese, African, and American Indian. Mutations in the HNF1A gene appear to be the most common cause of MODY among adults seen in diabetic clinics. </p><p>Bluteau et al. (2002) found germline TCF1 mutations in 2 individuals who had previously had a liver-tumor resection and had familial diabetes. One of these individuals had a hepatocellular carcinoma that had developed in an adenoma and had a gly574-to-ser mutation (142410.0013). This mutation was described by Collet et al. (2002) as frequent in Africans with diabetes. These results suggested that germline mutations of TCF1 may predispose to benign liver tumor development, and may explain the previously described cosegregation of liver adenoma with diabetes mellitus in a large family (Foster et al., 1978). Bluteau et al. (2002) suggested the results of their studies indicated that individuals with MODY could benefit from liver monitoring to detect early tumor occurrence, and individuals with liver adenomas, especially those with a family history of the same condition, should be tested for diabetes. </p><p>To elucidate the function of a molecular hotspot, Chi et al. (2002) cocrystallized human HNF1A amino acids 83 to 279 with a high-affinity promoter and solved the structure of the complex. Two identical protein molecules were bound to the promoter. Each contained a homeodomain (POU-H) and a second domain structurally similar to POU-specific (POU-S) domains that was not predicted on the basis of amino acid sequence. Atypical elements in both domains created a stable interface that further distinguished HNF1A from other flexible POU-homeodomain proteins. Chi et al. (2002) determined that 76% of MODY3-associated missense mutations in HNF1A occur in the region encompassing amino acids 98 to 272, which includes the POU-H and POU-S domains and a nuclear localization signal. They subdivided these mutations according to functional classes predicted to affect DNA binding, POU-S/POU-H domain interactions, protein stability, and nuclear localization. The largest class affected DNA binding, either through direct interactions or indirectly by perturbing local environment. </p><p>To estimate the prevalence of MODY3 in Norwegian diabetic pedigrees, Bjorkhaug et al. (2003) screened a total of 130 families for HNF1A mutations; 42 families with clinical MODY, 75 with suspected MODY, and 13 pedigrees with multiplex type 1 diabetes (IDDM). Twenty-two families with clinical MODY, 15 families with suspected MODY, and 1 family with type 1 diabetes multiplex harbored HNF1A mutations. Thus, in about half of Norwegian families with clinical MODY, mutations in the HNF1A gene could be detected. Eight of the 18 different mutations identified were novel. Haplotypes were determined for recurrent mutations, indicating a founder effect in Norway for the hotspot mutation P291fsinsC (142410.0001) and possibly also for P112L (142410.0015) and R131W (142410.0016). Two mutant HNF1A proteins were unable to bind DNA and at least 5 mutants showed defective nuclear translocation. Transcriptional activation was reduced for most of the MODY3-associated mutants. Accordingly, the functional studies of HNF1A mutants indicated that beta-cell dysfunction in MODY3 is caused by loss-of-function mechanisms like reduced DNA binding, impaired transcriptional activation, and defects in subcellular localization. </p><p>Johansen et al. (2005) examined the prevalence and nature of mutations in the 3 common MODY genes HNF4A (600281), GCK (138079), and TCF1 in Danish patients with a clinical diagnosis of MODY and determined metabolic differences in probands with and without mutations in HNF4A, GCK, and TCF1. They identified 29 different mutations in 38 MODY families. Fifteen of the mutations were novel. The variants segregated with diabetes within the families, and none of the variants were found in 100 normal Danish chromosomes. Their findings suggested a relative prevalence of 3% of MODY1 (125850) (2 different mutations in 2 families), 10% of MODY2 (7 in 8), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY. No significant differences in biochemical and anthropometric measurements were observed at baseline examinations. Forty-nine percent of the families carried mutations in the 3 examined MODY genes. </p><p>Rebouissou et al. (2005) screened 35 renal neoplasms for HNF1A and HNF1B (189907) inactivation. In 2 of 13 clear cell renal carcinomas, the authors found a monoallelic germline mutation (142410.0001 and 142410.0022) of HNF1A with no associated suppression of target mRNA expression. In normal and tumor renal tissues, there was a network of transcription factors differentially regulated in tumor subtypes. There was a related cluster of coregulated genes associating HNF1A, HNF4A, FABP1 (134650), and UGT2B7 (600068). Rebouissou et al. (2005) suggested that germline mutation of HNF1A may predispose to renal tumors. </p><p>Ridker et al. (2008) performed a multistage genomewide association study of CRP (123260) levels and found significant association with 7 loci, 1 of which was HNF1A. Reiner et al. (2008) reported an association between common variants of the HNF1A gene and plasma CRP concentrations in 2 independent populations of older adults. </p><p><strong><em>Penetrance of HNF1A Mutations in Diabetes</em></strong></p><p>
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Mirshahi et al. (2022) comprehensively assessed the penetrance and prevalence of pathogenic variants in HNF1A, HNF4A, and GCK that account for more than 80% of monogenic diabetes. Mirshahi et al. (2022) analyzed clinical and genetic data from 1,742 clinically referred probands, 2,194 family members, clinically unselected individuals from a US health system-based cohort of 132,194 individuals, and a UK population-based cohort of 198,748 individuals, and found that 1 in 1,500 individuals harbor a pathogenic variant in one of these genes. The penetrance of pathogenic GCK variants was similar (89 to 97%) across all cohorts. The penetrance of diabetes for HNF1A and HNF4A pathogenic variants was substantially lower in the clinically unselected individuals compared to clinically referred probands and was dependent on the setting (32% in the population, 49% in the health system cohort, 86% in a family member, and 98% in probands for HNF1A). The relative risk of diabetes was similar across the clinically unselected cohorts, highlighting the role of environment/ other genetic factors. The authors suggested that for HNF1A and HNF4A, genetic interpretation and counseling should be tailored to the setting in which a pathogenic monogenic variant was identified. GCK is an exception with near-complete penetrance in all settings. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cytogenetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Liver adenomas are benign tumors at risk of malignant transformation. In a genomewide search for loss of heterozygosity (LOH) associated with liver adenomas, Bluteau et al. (2002) found a deletion in 12q in 5 of 10 adenomas. In most cases, LOH at 12q was the only recurrent genetic alteration observed, suggesting the presence of a tumor-suppressor gene in that region. A minimal common region of deletion was defined in 12q24 that included the TCF1 gene. Bluteau et al. (2002) found biallelic inactivation of TCF1 in 10 of 16 screened adenomas, and heterozygous germline mutations were present in 3 affected individuals. Furthermore, 2 well-differentiated hepatocellular carcinomas occurring in normal liver, out of 30 HCCs screened, contained somatic biallelic mutations. These results indicated that inactivation of TCF1, whether sporadic or associated with MODY3, is an important genetic event in the occurrence of human liver adenomas, and may be an early step in the development of some hepatocellular carcinomas. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Gonzalez et al. (1990) found that newborn mice homozygous for a 1.2-cM deletion of chromosome 7 do not show the increased activity of CYP2E (124040), which is regulated by the transcription factor Hnf1. They suggested that the deleted region of chromosome 7 contains a gene encoding a transacting factor that is epistatic in a regulatory cascade that includes Hnf1 gene expression. </p><p>Pontoglio et al. (1996) found that mice with inactivation of the Hnf1 gene through homologous recombination failed to thrive and died around weaning after a progressive wasting syndrome with marked liver enlargement. The transcription rate of genes such as albumin and alpha-1-antitrypsin was reduced, while the gene coding the phenylalanine hydroxylase (612349) was totally silent, giving rise to phenylketonuria. Mutant mice also suffered from severe Fanconi syndrome (see 227650) caused by renal proximal tubular dysfunction. The resulting massive urinary glucose lost led to energy and water wasting. Pontoglio et al. (1996) commented that Hnf1-deficient mice may provide a model for human renal Fanconi syndrome. </p><p>Shih et al. (2001) explored the molecular basis for the hypercholesterolemia of Tcf1 -/- mice using oligonucleotide microchip expression analysis. Shih et al. (2001) demonstrated that Tcf1 -/- mice have a defect in bile acid transport, increased bile acid and liver cholesterol synthesis, and impaired high-density lipoprotein (HDL) metabolism. Tcf1 -/- liver has decreased expression of the basolateral membrane bile acid transporters Slc10a1 (182396), Slc21a3 (602883), and Slc21a5, leading to impaired portal bile acid uptake and elevated plasma bile acid concentrations. In intestine and kidneys, Tcf1 -/- mice lack expression of the ileal bile acid transporter (Slc10a2; 601295), resulting in increased fecal and urinary bile acid excretion. Tcf1 protein also regulates transcription of Nr1h4 (603826), encoding the farnesoid X receptor-1 (Fxr1), thereby leading to reduced expression of small heterodimer partner-1 (Shp1; 604630) and repression of Cyp7a1 (118455), the rate-limiting enzyme in the classic bile acid biosynthesis pathway. In addition, hepatocyte bile acid storage protein is absent from Tcf1 -/- mice. Increased plasma cholesterol of Tcf1 -/- mice resides predominantly in large buoyant HDL particles. This is most likely due to reduced activity of the HDL-catabolic enzyme hepatic lipase (151670) and increased expression of HDL-cholesterol esterifying enzyme lecithin:cholesterol acyltransferase (LCAT; 606967). Shih et al. (2001) concluded that TCF1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid in HDL-cholesterol metabolism. </p><p>Hiraiwa et al. (2001) investigated whether there is a molecular link between HNF1A deficiency and function of the G6Pase (602671) system. Transactivation studies revealed that HNF1A is required for transcription of the G6PT gene. Hepatic G6PT mRNA levels and microsomal G6P transport activity are also markedly reduced in Hnf1a -/- mice as compared with Hnf1a +/+ and Hnf1a +/- littermates. On the other hand, hepatic G6Pase mRNA expression and activity are upregulated in Hnf1a -/- mice, consistent with observations that G6Pase expression is increased in diabetic animals. Taken together, these results strongly suggest that metabolic abnormalities in Hnf1a-null mice are caused in part by G6PT deficiency and by perturbations of the G6Pase system. </p><p>Huang et al. (2011) demonstrated the direct induction of functional hepatocyte-like (induced hepatocyte, iHep) cells from mouse tail-tip fibroblasts by transduction of Gata4 (600576), Hnf1-alpha, and Foxa3 (602295) and inactivation of p19(Arf) (600160). iHep cells showed typical epithelial morphology, expressed hepatic genes, and acquired hepatocyte functions. Notably, transplanted iHep cells repopulated the livers of fumarylacetoacetate hydrolase-deficient (Fah-null; see 613871) mice and rescued almost half of recipients from death by restoring liver functions. </p>
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<h4>
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<span class="mim-font">
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<strong>Nomenclature</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Although the symbol TCF1 (transcription factor-1) is used in the literature for this gene, its official designation is HNF1A. It should not be confused with the TCF7 gene (189908), which has also been referred to as TCF1 (T cell-specific transcription factor-1) in the literature.</p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>22 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HEPATIC ADENOMA, SOMATIC, INCLUDED<br />
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RENAL CELL CARCINOMA, CLEAR CELL, INCLUDED<br />
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TYPE 1 DIABETES MELLITUS 20, INCLUDED
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</span>
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</div>
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<span class="mim-text-font">
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HNF1A, 1-BP INS, 872C
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<br />
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SNP: rs587776825,
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ClinVar: RCV000016062, RCV000016063, RCV000022617, RCV000117225, RCV000490055, RCV001255183, RCV001506982, RCV002221997, RCV003445070
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p />
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<p><strong><em>Maturity-Onset Diabetes of the Young, Type 3</em></strong></p><p>
|
|
In a patient from an Edinburgh pedigree with MODY3 (600496), Yamagata et al. (1996) found in exon 4 of the TCF1 gene an insertion of a cytosine at codon 291 (pro), resulting in a frameshift and synthesis of a truncated mutant protein of 315 amino acids. This mutation was present in all affected members and no unaffected members of this family. It was not found on screening 55 healthy nondiabetic white subjects. </p><p>Using a rapid screening PCR method for frameshift mutations in the HNF1A gene in the screening of 60 MODY probands defined according to strict diagnostic criteria, Frayling et al. (1997) detected mutations in 11 (18%); the insertion mutation accounted for 13% of the MODY cases. </p><p>Ellard (2000) stated that the C insertion in the poly(C) tract of exon 4 had been reported in 22 of the 116 families with MODY3 worldwide who were identified by the finding of a mutation in the TCF1 gene. The total number of different mutations described was 65. </p><p>Bjorkhaug et al. (2003) found the P291fsinsC mutation in 9 families, 8 of Norwegian origin. Microsatellite analysis data suggested that in 7 of these families the mutant allele had a common origin. </p><p><strong><em>Hepatic Adenoma</em></strong></p><p>
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|
In studies of hepatic adenomas (142330) demonstrating biallelic inactivation of TCF1, Bluteau et al. (2002) observed the pro291fsX316 frameshift mutation (142410.0001) in heterozygous state in the tumor tissue of 2 individuals, one with multiple adenoma and the other with hepatocellular carcinoma (114550). </p><p><strong><em>Renal Cell Carcinoma</em></strong></p><p>
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|
In a 78-year-old man with clear cell renal carcinoma (see 144700), Rebouissou et al. (2005) identified heterozygosity for the 872insC mutation. Mutation screening of a tumor sample detected the germline mutation without mutation/deletion of the second allele. The man was diagnosed with diabetes mellitus in his sixth decade that was controlled by diet and oral hypoglycemic agents. No relatives had a diagnosis of renal carcinoma or diabetes. </p><p><strong><em>Type 1 Diabetes Mellitus 20</em></strong></p><p>
|
|
In a Japanese subject with type 1 diabetes mellitus (T1D20; 612520) in whom insulin treatment was begun when hyperglycemia and ketonuria were noticed at 15 years of age, Yamada et al. (1997) identified a heterozygous frameshift mutation of codon pro291 resulting from insertion of a C in a poly(C) tract. (They designated this mutation P291fsinsC.) The mutation was predicted to result in a mutant truncated protein of 340 amino acids. The same mutation had been observed in British, German, and Finnish MODY families (Byrne et al., 1996; Yamagata et al., 1996; Kaisaki et al., 1997). Thus, Yamada et al. (1997) concluded that this site in exon 4 of the HNF1A gene appears to be a mutation hotspot. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, PRO447LEU
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<br />
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SNP: rs137853236,
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gnomAD: rs137853236,
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ClinVar: RCV000016065, RCV000713784, RCV000762891, RCV001526899, RCV001810399
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In their family A, Yamagata et al. (1996) found that MODY3 (600496) was associated with a single amino acid substitution in exon 7 of the TCF1 gene: codon 447 was changed from CCG (pro) to CTG (leu). </p><p>Hansen et al. (1997) found this mutation in a glucose-tolerant lean male who had relatives with MODY. He showed a low insulin secretion rate during oral glucose tolerance test (OGTT), but a 2-fold increase in pancreatic beta-cell response after intravenous glucose and a 2.5- to 4-fold increase in beta-cell response after either intravenous tolbutamide or intravenous glucagon loads. Hansen et al. (1997) concluded that early stages in the pathogenesis of MODY3 caused by the P447L mutation may be characterized by hyperexcitability of beta-cells to intravenous secretagogues. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, 1-BP DEL
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<br />
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SNP: rs2135842335,
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ClinVar: RCV000016066
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a family in which 4 members of 3 generations had MODY3 (600496), Vaxillaire et al. (1997) found deletion of a guanine from codon glycine-292 (G292fsdelG) resulting in frameshift in the TCF1 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, TYR122CYS
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<br />
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SNP: rs137853237,
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ClinVar: RCV000016067, RCV001384610, RCV001794449, RCV002464065
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a family with multiple members with MODY3 (600496) in 3 generations, Vaxillaire et al. (1997) found a TAC-to-TGC transition in codon 122 of the TCF1 gene, predicted to cause an amino acid change from tyrosine to cysteine (Y122C). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0005 TYPE 1 DIABETES MELLITUS 20</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, ARG272HIS
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<br />
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SNP: rs137853238,
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ClinVar: RCV000016068, RCV000255916, RCV000445525, RCV002051786, RCV002288493, RCV004752708
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a Japanese subject who developed type 1 diabetes mellitus (T1D20; 612520) 1 year after the diagnosis of T2D at 8 years of age, Yamada et al. (1997) identified heterozygosity for an arg272-to-his (R272H) mutation in the DNA binding domain of the HNF1A gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0006 TYPE 1 DIABETES MELLITUS 20</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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|
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HNF1A, ARG583GLY
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<br />
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SNP: rs137853239,
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gnomAD: rs137853239,
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ClinVar: RCV000016069, RCV000030492, RCV002514104, RCV004699116
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Japanese patient with sudden-onset type 1 diabetes (T1D20; 612520) at 20 years of age, Yamada et al. (1997) identified heterozygosity for an arg583-to-gly (R583G) mutation in the transactivation domain of HNF1A. When first diagnosed there was marked hyperglycemia and 'absolute' insulin deficiency, prompting the initiation of insulin therapy. Control of blood glucose levels by exogenous insulin was poor, and complications of diabetes (proliferative retinopathy, cataracts, and sensorimotor neuropathy) developed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
HNF1A, A-C, -58, PROMOTER
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<br />
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|
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SNP: rs2135818776,
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|
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ClinVar: RCV000016070, RCV001794450, RCV002225265
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|
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</span>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>Gragnoli et al. (1997) found an A-to-C substitution at nucleotide -58 of the promoter region of the HNF1A gene that cosegregated with MODY3 (600496). This mutation is located in a highly conserved region of the promoter and disrupted the binding site for the transcription factor HNF-4-alpha (600281), mutations in the gene encoding HNF-4-alpha being another cause of MODY (MODY1; 125850). This result demonstrated that decreased levels of HNF1-alpha per se can cause MODY. Moreover, it indicated that both the promoter and the coding regions of the HNF1A gene should be screened for mutations in subjects thought to have MODY. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 TYPE 2 DIABETES MELLITUS, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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|
|
HNF1A, GLY319SER
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|
<br />
|
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|
|
SNP: rs137853240,
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|
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|
|
gnomAD: rs137853240,
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|
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ClinVar: RCV000016071, RCV003230366
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|
|
|
|
|
</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Hegele et al. (1999) identified a gly319-to-ser (G319S) variant in the HNF1A gene in Ontario Oji-Cree with early-onset type 2 diabetes (125853). G319S is in the proline II-rich domain of the trans-activation site of HNF1A and alters a glycine residue that is conserved throughout evolution. S319 was absent from 990 alleles from 6 other ethnic groups, suggesting that it is private for Oji-Cree. The S319 allele was more prevalent in diabetic than in nondiabetic Oji-Cree (0.209 vs 0.087; P = 0.000001). S319/S319 homozygotes and S319/G319 heterozygotes, respectively, had odds ratios for type 2 diabetes of 4.00 (95% CI, 2.65-6.03) and 1.97 (95% CI, 1.44-2.70) compared with G319/G319 homozygotes. There was a significant difference in the mean age of onset of type 2 diabetes, with G319/G319, S319/G319, and S319/S319 subjects being affected in the fifth, fourth, and third decades of life, respectively. Among nondiabetic subjects, S319/G319 heterozygotes had significantly lower plasma insulin than G319/G319 homozygotes. The authors concluded that the G319S variant is associated with a distinct form of type 2 diabetes, characterized by onset at an earlier age, lower body mass, and a higher postchallenge plasma glucose. </p><p>That the majority of Oji-Cree subjects with diabetes did not have the HNF1A S319 variant suggested to Hegele et al. (2000) that there might be other genetic determinants of diabetes susceptibility. In the course of sequencing candidate genes in diabetic subjects who were homozygous for HNF1A G319/G319, they found that some subjects had the PPARG A12 variant (601487.0002). PPARG A12 was strongly associated with type 2 diabetes in women, but not in men. The authors concluded that, when taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least 2 genes are involved in determining susceptibility to the disease in this population. </p><p>Triggs-Raine et al. (2002) stated that Oji-Cree type 2 diabetes does not resemble MODY, because affected Oji-Cree subjects are obese and insulin-resistant with elevated plasma insulin concentrations, which clearly were insufficient to prevent diabetes onset. They evaluated the in vitro function of HNF1A G319S both to confirm that the mutation had a functional effect and to determine whether this effect was distinct from those of the complete loss-of-function or dominant-negative mutations seen in the MODY3 phenotype. They also evaluated the impact of the HNF1A G319S mutation on the dynamics of type 2 diabetes onset in the whole Sandy Lake Oji-Cree community. They found that the G319S mutation reduced the in vitro ability of HNF1-alpha to activate transcription by approximately 50%, with no effect on DNA binding or protein stability. There was no evidence of a dominant-negative effect of the mutant protein. Disease onset showed significant differences according to G319S genotype when gauged by the age at which half the subjects had become diabetic. Each dose of G319S accelerated median disease onset by approximately 7 years. Thus, the transactivation-deficient HNF1A G319S mutation affects the dynamics of disease onset. The demonstration of a functional consequence for the G319S mutation provided a mechanistic basis for its strong association with Oji-Cree type 2 diabetes and its unparalleled specificity for diabetes prediction in these people, in whom diabetes presents a significant public health problem. The finding also showed that HNF1A mutations can be associated with typical adult-onset insulin-resistant obesity-related diabetes in addition to maturity-onset diabetes of the young. Triggs-Raine et al. (2002) stated that in the Oji-Cree, HNF1A G319S behaves as a susceptibility allele for type 2 diabetes. Among nondiabetic Oji-Cree, fasting plasma insulin concentration was reduced significantly in HNF1A G319S carriers, suggesting that the partial impairment of function is tolerated when there is no insulin resistance. However, among Oji-Cree with type 2 diabetes, both carriers and noncarriers of the mutation had elevated plasma insulin concentration compared with nondiabetic Oji-Cree. The stress of obesity-induced insulin resistance seemed to expose the partial defect in HNF1A G319S carriers, causing expression of the disease. </p>
|
|
</span>
|
|
</div>
|
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<div>
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<br />
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</div>
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</div>
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<div>
|
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, THR620ILE
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|
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|
|
|
<br />
|
|
|
|
SNP: rs137853241,
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|
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|
|
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|
|
ClinVar: RCV000016072, RCV002250352, RCV002298445
|
|
|
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|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Miedzybrodzka et al. (1999) described a family in which a thr620-to-ile substitution in transcription factor-1 was found in all members affected by MODY (600496). The mutation was not fully penetrant, as 2 family members aged 87 and 46 had the mutation but did not have diabetes. The severity and age at diagnosis of diabetes varied widely within the family, and most presented over the age of 25. Miedzybrodzka et al. (1999) suggested that TCF1 mutation screening should be considered in any family with autosomal dominant inheritance of diabetes where one member has presented with diabetes before the age of 25. </p>
|
|
</span>
|
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</div>
|
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
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|
HNF1A, 1-BP DEL, -119G, PROMOTER
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|
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<br />
|
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|
|
SNP: rs754470733,
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|
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gnomAD: rs754470733,
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ClinVar: RCV000016073
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>Godart et al. (2000) observed a promoter mutation, -119delG, of the TCF1 gene that segregated with MODY3 (600496) in a diabetic family. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 INSULIN RESISTANCE, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
SERUM HDL CHOLESTEROL LEVEL, MODIFIER OF, INCLUDED
|
|
</span>
|
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</div>
|
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<div>
|
|
<span class="mim-text-font">
|
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|
|
HNF1A, ILE27LEU
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|
|
|
<br />
|
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|
|
SNP: rs1169288,
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|
|
|
gnomAD: rs1169288,
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|
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|
|
ClinVar: RCV000016074, RCV000016075, RCV000117233, RCV000710268, RCV000988920, RCV002226650, RCV002415417, RCV003315502
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>Chiu et al. (2000) examined the relationship between the ile27-to-leu (I27L) polymorphism of HNF1-alpha and insulin sensitivity (see 125853) and beta-cell function assessed by a hyperglycemic clamp. This study included 52 healthy glucose-tolerant and normotensive subjects (age, 19 to 40 years; body mass index, 17.58-35.61 kg/m2; waist/hip ratio, 0.65-1.03). Chiu et al. (2000) identified 19 LL subjects, 24 IL subjects, and 9 II subjects. The LL group had the highest postchallenge insulin levels at 30 and 90 min (P = 0.038 and P = 0.015, respectively) and also the highest insulin area under curve (P = 0.009) among the 3 genotypes. The LL group was more insulin resistant than the IL and II groups (P = 0.042 for insulin sensitivity index). After adjusting for age, gender, obesity, and ethnicity, the I27L polymorphism was an independent determinant of the insulin sensitivity index (P = 0.001). However, it had no impact on either the first or second phase insulin response. The authors concluded that the I27L polymorphism is associated with insulin resistance, but not beta-cell function. The mechanism of this association is unclear, but HNF1-alpha may play a role in regulating hepatic glucose metabolism. </p><p>Babaya et al. (2003) studied the relationship of the HNF1A gene polymorphism I27L with lipid parameters, in particular with serum HDL cholesterol level, in 356 unrelated Japanese men. Though no significant difference was observed in total cholesterol and triglyceride levels among the 3 genotypes, the serum HDL cholesterol level was significantly associated with the genotype (P less than 0.01). Subjects with the II genotype had low serum HDL cholesterol levels, and those with the LL genotype had high serum HDL cholesterol levels. The authors concluded that the HNF1A gene locus is associated with serum HDL cholesterol level and suggested that the I27 allele is a risk marker for atherosclerosis. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0012 TYPE 1 DIABETES MELLITUS 20</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, 1-BP DEL, 142G
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<br />
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SNP: rs1566092470,
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ClinVar: RCV000016076, RCV002221998, RCV002326678
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Yoshiuchi et al. (2001) identified a 142delG frameshift mutation in the TCF1 gene in a family with a strong history of type 1 diabetes (T1D20; 612520). The expression of the mutant protein was not detected in COS-7 cells by Western blot analysis after transfection of the mutant cDNA. According to the authors, this was the first case of an unstable mutant HNF1-alpha protein. Reporter gene analysis indicated that the mutant protein had no transactivation activity in HeLa and other cells. Haploinsufficiency for the TCF1 gene may lead to severe forms of diabetes resembling type I diabetes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0013 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, GLY574SER
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<br />
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SNP: rs1169305,
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gnomAD: rs1169305,
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ClinVar: RCV000016077, RCV000438436, RCV000861653, RCV003894808
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>This mutation was found by Collet et al. (2002) to be prevalent in African individuals with diabetes (600496). </p><p>In an individual who had had a liver-tumor resection and had familial diabetes, Bluteau et al. (2002) found a gly574-to-ser (G574S) mutation in the TCF1 gene. The hepatocellular carcinoma in this case had developed in an adenoma (142330). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0014 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, ARG583GLN
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<br />
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SNP: rs137853242,
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gnomAD: rs137853242,
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ClinVar: RCV000016078, RCV000455019, RCV000658670, RCV002408468, RCV002467498, RCV003924838
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>Bluteau et al. (2002) found a heterozygous germline mutation, arg583 to gln (R583Q), in an individual with a hyperplastic liver tumor (142330) who had had liver-tumor resection and had familial diabetes (600496). The substitution involved a highly conserved amino acid. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0015 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, PRO112LEU
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<br />
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SNP: rs137853243,
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|
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gnomAD: rs137853243,
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ClinVar: RCV000016080, RCV000517471, RCV002221999
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a 3-generation Norwegian family with MODY3 (600496), Bjorkhaug et al. (2000) found a C-to-T transition at nucleotide 358 in exon 2 of the HNF1A gene, leading to a pro112-to-leu (P112L) amino acid substitution, in all 3 affected members. The phenotype in this family was mild with mild fasting and postprandial hyperglycemia easily controlled by diet only. Diabetes-associated late complications were not observed. P112L mutant protein demonstrated a significantly reduced ability to bind a high affinity HNF1 binding site and to activate transcription. Immunolocalization studies in HeLa cells showed that P112L mutant protein was correctly targeted to the nucleus. Bjorkhaug et al. (2000) concluded that the P112L mutation seems to impair pancreatic beta-cell function by loss-of-function mechanisms. </p><p>Xu et al. (2002) found the HNF1A P112L mutation in a southern Chinese MODY family. </p><p>Bjorkhaug et al. (2003) found evidence for possible founder effect of the P112L mutation in the Norwegian population. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HNF1A, ARG131TRP
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<br />
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|
|
SNP: rs137853244,
|
|
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|
|
|
|
|
ClinVar: RCV000016081, RCV000441594, RCV001794451, RCV002464066
|
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|
|
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Bjorkhaug et al. (2003) found a C-to-T transition in exon 2 of the HNF1A gene, resulting in an arg131-to-trp (R131W) amino acid substitution, in 5 Norwegian families with MODY3 (600496). This mutation had been reported in families from North America and Great Britain. Haplotype analysis indicated possible founder effect for the Norwegian families. Immunofluorescence studies demonstrated incorrect localization and accumulation of protein in both cytoplasm and nucleus. The R131W mutant protein displayed 10 to 15% of binding activity of wildtype and levels of transcription activation close to 50% of wildtype. </p>
|
|
</span>
|
|
</div>
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0017 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, 4-BP DEL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2135839114,
|
|
|
|
|
|
|
|
ClinVar: RCV000016082
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian family with MODY3 (600496), Bjorkhaug et al. (2003) detected a novel 4-bp deletion in exon 3 of the HNF1A gene (T196fsdelCCAA). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0018 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, IVS3, G-A, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1463923467,
|
|
|
|
|
|
gnomAD: rs1463923467,
|
|
|
|
|
|
ClinVar: RCV000016079, RCV002463589
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian proband with MODY3 (600496), Bjorkhaug et al. (2003) found a novel splice site mutation in intron 3 of the HNF1A gene, IVS3-1G-A. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0019 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, ALA276ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853245,
|
|
|
|
|
|
gnomAD: rs137853245,
|
|
|
|
|
|
ClinVar: RCV000016083, RCV000521190, RCV001248962, RCV002254266
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian proband with MODY3 (600496), Bjorkhaug et al. (2003) detected a novel C-to-A transversion in exon 4 of the HNF1A gene resulting in an arg276-to-asp (A276D) amino acid substitution. Mutant protein was targeted to both nucleus and cytoplasm of transfected cells in immunofluorescence assays. DNA binding ability of 30 to 40% of wildtype could be detected; no significant reduction in transcription activation could be demonstrated. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0020 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, 2-BP DEL, AG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2135847417,
|
|
|
|
|
|
|
|
ClinVar: RCV000016084
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 members of a Norwegian family with MODY3 (600496), Bjorkhaug et al. (2003) found a novel 2-bp deletion in exon 7 of the HNF1A gene (S445fsdelAG). Mutant protein was targeted to both nucleus and cytoplasm of transfected cells in immunofluorescence assays. DNA binding ability of 30 to 40% of wildtype could be detected; no significant reduction in transcription activation could be demonstrated. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0021 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, SER531THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853246,
|
|
|
|
|
|
gnomAD: rs137853246,
|
|
|
|
|
|
ClinVar: RCV000016085, RCV001810400
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Norwegian proband with MODY3 (600496), Bjorkhaug et al. (2003) detected a novel G-to-C transversion in exon 8 of the HNF1A gene, leading to a ser531-to-thr (S531T) amino acid substitution. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0022 MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
RENAL CELL CARCINOMA, CLEAR CELL, INCLUDED<br />
|
|
RENAL CELL CARCINOMA, CHROMOPHOBE, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1A, GLY92ASP
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs137853247,
|
|
|
|
|
|
gnomAD: rs137853247,
|
|
|
|
|
|
ClinVar: RCV000016086, RCV000016087, RCV000016088, RCV000503110, RCV000763797, RCV000835061, RCV001810401, RCV002371772, RCV004752709
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Maturity-Onset Diabetes of the Young, Type 3</em></strong></p><p>
|
|
In a French family with MODY3 (600496), Chevre et al. (1998) identified heterozygosity for a 92G-A transition in exon 1 of the HNF1A gene, resulting in a gly31-to-asp (G31D) substitution in the dimerization domain of the protein. </p><p><strong><em>Renal Cell Carcinoma</em></strong></p><p>
|
|
In a 76-year-old woman with both clear cell and chromophobe renal carcinomas (see 144700), Rebouissou et al. (2005) identified heterozygosity for the G31D mutation. Mutation screening of the tumor samples detected only the germline G31D mutation. The renal carcinomas manifested in the same kidney with a single renal cyst in the other kidney. None of her relatives had a history of diabetes or renal carcinoma. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
De Simone et al. (1991); Mendel et al. (1991); Rey-Campos et al.
|
|
(1991)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Babaya, N., Ikegami, H., Fujisawa, T., Nojima, K., Itoi-Babaya, M., Inoue, K., Nakura, J., Abe, M., Yamamoto, M., Jin, J. J., Wu, Z., Miki, T., Fukuda, M., Ogihara, T.
|
|
<strong>Association of I27L polymorphism of hepatocyte nuclear factor-1-alpha gene with high-density lipoprotein cholesterol level.</strong>
|
|
J. Clin. Endocr. Metab. 88: 2548-2551, 2003.
|
|
|
|
|
|
[PubMed: 12788852]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-021891]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Bach, I., Galcheva-Gargova, Z., Mattei, M.-G., Simon-Chazottes, D., Guenet, J.-L., Cereghini, S., Yaniv, M.
|
|
<strong>Cloning of human hepatic nuclear factor 1 (HNF1) and chromosomal localization of its gene in man and mouse.</strong>
|
|
Genomics 8: 155-164, 1990.
|
|
|
|
|
|
[PubMed: 1707031]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90238-p]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bjorkhaug, L., Sagen, J. V., Thorsby, P., Sovik, O., Molven, A., Njolstad, P. R.
|
|
<strong>Hepatocyte nuclear factor-1a gene mutations and diabetes in Norway.</strong>
|
|
J. Clin. Endocr. Metab. 88: 920-931, 2003.
|
|
|
|
|
|
[PubMed: 12574234]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2002-020945]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bjorkhaug, L., Ye, H., Horikawa, Y., Sovik, O., Molven, A., Njolstad, P. R.
|
|
<strong>MODY associated with two novel hepatocyte nuclear factor-1-alpha loss-of-function mutations (P112L and Q466X).</strong>
|
|
Biochem. Biophys. Res. Commun. 279: 792-798, 2000.
|
|
|
|
|
|
[PubMed: 11162430]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/bbrc.2000.4024]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bluteau, O., Jeannot, E., Bioulac-Sage, P., Marques, J. M., Blanc, J.-F., Bui, H., Beaudoin, J.-C., Franco, D., Balabaud, C., Laurent-Puig, P., Zucman-Rossi, J.
|
|
<strong>Bi-allelic inactivation of TCF1 in hepatic adenomas.</strong>
|
|
Nature Genet. 32: 312-315, 2002.
|
|
|
|
|
|
[PubMed: 12355088]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1001]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Byrne, M. M., Sturis, J., Menzel, S., Yamagata, K., Fajans, S. S., Dronsfield, M. J., Bain, S. C., Hattersley, A. T., Velho, G., Froguel, P., Bell, G. I., Polonsky, K. S.
|
|
<strong>Altered insulin secretory responses to glucose in diabetic and nondiabetic subjects with mutations in the diabetes susceptibility gene MODY3 on chromosome 12.</strong>
|
|
Diabetes 45: 1503-1510, 1996.
|
|
|
|
|
|
[PubMed: 8866553]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.45.11.1503]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chevre, J. C., Hani, E. H., Boutin, P., Vaxillaire, M., Blanche, H., Vionnet, N., Pardini, V. C., Timsit, J., Larger, E., Charpentier, G., Beckers, D., Maes, M., Bellanne-Chantelot, C., Velho, C., Froguel, P.
|
|
<strong>Mutation screening in 18 Caucasian families suggest the existence of other MODY genes.</strong>
|
|
Diabetologia 41: 1017-1023, 1998.
|
|
|
|
|
|
[PubMed: 9754819]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s001250051025]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chi, Y.-I., Frantz, J. D., Oh, B.-C., Hansen, L., Dhe-Paganon, S., Shoelson, S. E.
|
|
<strong>Diabetes mutations delineate an atypical POU domain in HNF-1-alpha.</strong>
|
|
Molec. Cell 10: 1129-1137, 2002.
|
|
|
|
|
|
[PubMed: 12453420]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s1097-2765(02)00704-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chiu, K. C., Chuang, L.-M., Ryu, J. M., Tsai, G. P., Saad, M. F.
|
|
<strong>The I27L amino acid polymorphism of hepatic nuclear factor-1-alpha is associated with insulin resistance.</strong>
|
|
J. Clin. Endocr. Metab. 85: 2178-2183, 2000.
|
|
|
|
|
|
[PubMed: 10852449]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.6.6618]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Collet, C., Ducorps, M, Mayaudon, H., Dupuy, O., Ceppa, F., Boutin, P., Froguel, P., Bauduceau, B.
|
|
<strong>Prevalence of the missense mutation Gly574Ser in the hepatocyte nuclear factor-1-alpha in Africans with diabetes.</strong>
|
|
Diabetes Metab. 28: 39-44, 2002.
|
|
|
|
|
|
[PubMed: 11938027]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Courtois, G., Morgan, J. G., Campbell, L. A., Fourel, G., Crabtree, G. R.
|
|
<strong>Interaction of a liver-specific nuclear factor with the fibrinogen and alpha-1-antitrypsin promoters.</strong>
|
|
Science 238: 688-692, 1987.
|
|
|
|
|
|
[PubMed: 3499668]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.3499668]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
De Simone, V., De Magistris, L., Lazzaro, D., Gerstner, J., Monaci, P., Nicosia, A., Cortese, R.
|
|
<strong>LFB3, a heterodimer-forming homeoprotein of the LFB1 family, is expressed in specialized epithelia.</strong>
|
|
EMBO J. 10: 1435-1443, 1991.
|
|
|
|
|
|
[PubMed: 1673925]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1991.tb07664.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ellard, S.
|
|
<strong>Hepatocyte nuclear factor 1 alpha (HNF-1-alpha) mutations in maturity-onset diabetes of the young.</strong>
|
|
Hum. Mutat. 16: 377-385, 2000.
|
|
|
|
|
|
[PubMed: 11058894]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1098-1004(200011)16:5<377::AID-HUMU1>3.0.CO;2-2]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fajans, S. S., Bell, G. I., Polonsky, K. S.
|
|
<strong>Molecular mechanisms and clinical pathophysiology of maturity-onset diabetes of the young.</strong>
|
|
New Eng. J. Med. 345: 971-980, 2001.
|
|
|
|
|
|
[PubMed: 11575290]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJMra002168]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Foster, J. H., Donohue, T. A., Berman, M. M.
|
|
<strong>Familial liver-cell adenomas and diabetes mellitus.</strong>
|
|
New Eng. J. Med. 299: 239-241, 1978.
|
|
|
|
|
|
[PubMed: 207987]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1056/NEJM197808032990508]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frayling, T. M., Bulman, M. P., Appleton, M., Hattersley, A. T., Ellard, S.
|
|
<strong>A rapid screening method for hepatocyte nuclear factor 1 alpha frameshift mutations; prevalence in maturity-onset diabetes of the young and late-onset non-insulin dependent diabetes.</strong>
|
|
Hum. Genet. 101: 351-354, 1997.
|
|
|
|
|
|
[PubMed: 9439666]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s004390050640]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Frayling, T. M., Bulman, M. P., Ellard, S., Appleton, M., Dronsfield, M. J., Mackie, A. D. R., Baird, J. D., Kaisaki, P. J., Yamagata, K., Bell, G. I., Bain, S. C., Hattersley, A. T.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.</strong>
|
|
Diabetes 46: 720-725, 1997.
|
|
|
|
|
|
[PubMed: 9075818]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.46.4.720]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Godart, F., Bellanne-Chantelot, C., Clauin, S., Gragnoli, C., Abderrahmani, A., Blanche, H., Boutin, P., Chevre, J. C., Froguel, P., Bailleul, B.
|
|
<strong>Identification of seven novel nucleotide variants in the hepatocyte nuclear factor-1-alpha (TCF1) promoter region in MODY patients.</strong>
|
|
Hum. Mutat. 15: 173-180, 2000.
|
|
|
|
|
|
[PubMed: 10649494]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(200002)15:2<173::AID-HUMU6>3.0.CO;2-W]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gonzalez, F. J., Liu, S.-Y., Kozak, C. A., Nebert, D. W.
|
|
<strong>Decreased Hnf-1 gene expression in mice homozygous for a 1.2-centimorgan deletion on chromosome 7.</strong>
|
|
DNA Cell Biol. 9: 771-776, 1990.
|
|
|
|
|
|
[PubMed: 2264930]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1089/dna.1990.9.771]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gragnoli, C., Lindner, T., Cockburn, B. N., Kaisaki, P. J., Gragnoli, F., Marozzi, G., Bell, G. I.
|
|
<strong>Maturity-onset diabetes of the young due to a mutation in the hepatocyte nuclear factor-4-alpha binding site in the promoter of the hepatocyte nuclear factor-1-alpha gene.</strong>
|
|
Diabetes 46: 1648-1651, 1997.
|
|
|
|
|
|
[PubMed: 9313764]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diacare.46.10.1648]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hansen, T., Eiberg, H., Rouard, M., Vaxillaire, M., Moller, A. M., Rasmussen, S. K., Fridberg, M., Urhammer, S. A., Holst, J. J., Almind, K., Echwald, S. M., Hansen, L., Bell, G. I., Pedersen, O.
|
|
<strong>Novel MODY3 mutations in the hepatocyte nuclear factor-1-alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation.</strong>
|
|
Diabetes 46: 726-730, 1997.
|
|
|
|
|
|
[PubMed: 9075819]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.46.4.726]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Hanley, A. J. G., Zinman, B.
|
|
<strong>The hepatic nuclear factor-1-alpha G319S variant is associated with early-onset type 2 diabetes in Canadian Oji-Cree.</strong>
|
|
J. Clin. Endocr. Metab. 84: 1077-1082, 1999.
|
|
|
|
|
|
[PubMed: 10084598]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.84.3.5528]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hegele, R. A., Cao, H., Harris, S. B., Zinman, B., Hanley, A. J. G., Anderson, C. M.
|
|
<strong>Peroxisome proliferator-activated receptor-gamma-2 P12A and type 2 diabetes in Canadian Oji-Cree.</strong>
|
|
J. Clin. Endocr. Metab. 85: 2014-2019, 2000.
|
|
|
|
|
|
[PubMed: 10843190]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.85.5.6610]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hiraiwa, H., Pan, C.-J., Lin, B., Akiyama, T. E., Gonzalez, F. J., Chou, J. Y.
|
|
<strong>A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1-alpha-null mice.</strong>
|
|
J. Biol. Chem. 276: 7963-7967, 2001.
|
|
|
|
|
|
[PubMed: 11121425]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M010523200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hua, Q.-X., Zhao, M., Narayana, N., Nakagawa, S. H., Jia, W., Weiss, M. A.
|
|
<strong>Diabetes-associated mutations in a beta-cell transcription factor destabilize an antiparallel 'mini-zipper' in a dimerization interface.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 1999-2004, 2000. Note: Erratum: Proc. Nat. Acad. Sci. 98: 13472 only, 2001.
|
|
|
|
|
|
[PubMed: 10696112]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.97.5.1999]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Huang, P., He, Z., Ji, S., Sun, H., Xiang, D., Liu, C., Hu, Y., Wang, X., Hui, L.
|
|
<strong>Induction of functional hepatocyte-like cells from mouse fibroblasts by defined factors.</strong>
|
|
Nature 475: 386-389, 2011.
|
|
|
|
|
|
[PubMed: 21562492]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature10116]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Johansen, A., Ek, J., Mortensen, H. B., Pedersen, O., Hansen, T.
|
|
<strong>Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.</strong>
|
|
J. Clin. Endocr. Metab. 90: 4607-4614, 2005.
|
|
|
|
|
|
[PubMed: 15928245]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2005-0196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kaisaki, P. J., Menzel, S., Lindner, T., Oda, N., Rjasanowski, I., Sahm, J., Meincke, G., Schulze, J., Schmechel, H., Petzold, C., Ledermann, H. M., Sachse, G., Boriraj, V. V., Menzel, R., Kerner, W., Turner, R. C., Yamagata, K., Bell, G. I.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.</strong>
|
|
Diabetes 46: 528-535, 1997. Note: Erratum: Diabetes 46: 1239 only, 1997.
|
|
|
|
|
|
[PubMed: 9032114]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diab.46.3.528]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kuo, C. J., Conley, P. B., Hsieh, C.-L., Francke, U., Crabtree, G. R.
|
|
<strong>Molecular cloning, functional expression, and chromosomal localization of mouse hepatocyte nuclear factor 1.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 9838-9842, 1990.
|
|
|
|
|
|
[PubMed: 2263635]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.87.24.9838]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mendel, D. B., Hansen, L. P., Graves, M. K., Conley, P. B., Crabtree, G. R.
|
|
<strong>HNF-1-alpha and HNF-1-beta (vHNF-1) share dimerization and homeo domains, but not activation domains, and form heterodimers in vitro.</strong>
|
|
Genes Dev. 5: 1042-1056, 1991.
|
|
|
|
|
|
[PubMed: 2044952]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1101/gad.5.6.1042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mendel, D. B., Khavari, P. A., Conley, P. B., Graves, M. K., Hansen, L. P., Admon, A., Crabtree, G. R.
|
|
<strong>Characterization of a cofactor that regulates dimerization of a mammalian homeodomain protein.</strong>
|
|
Science 254: 1762-1767, 1991.
|
|
|
|
|
|
[PubMed: 1763325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1763325]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Miedzybrodzka, Z., Hattersley, A. T., Ellard, S., Pearson, D., de Silva, D., Harvey, R., Haites, N.
|
|
<strong>Non-penetrance in a MODY 3 family with a mutation in the hepatic nuclear factor 1a gene: implications for predictive testing.</strong>
|
|
Europ. J. Hum. Genet. 7: 729-732, 1999.
|
|
|
|
|
|
[PubMed: 10482964]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5200358]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mirshahi, U. L., Colclough, K., Wright, C. F., Wood, A. R., Beaumont, R. N., Tyrrell, J., Laver, T. W., Stahl, R., Golden, A., Goehringer, J. M, Geisinger-Regeneron DiscovEHR Collaboration, Frayling, T. F., Hattersley, A. T., Carey, D. J., Weedon, M. N., Patel, K. A.
|
|
<strong>Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.</strong>
|
|
Am. J. Hum. Genet. 109: 2018-2028, 2022.
|
|
|
|
|
|
[PubMed: 36257325]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2022.09.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odom, D. T., Dowell, R. D., Jacobsen, E. S., Gordon, W., Danford, T. W., MacIsaac, K. D., Rolfe, P. A., Conboy, C. M., Gifford, D. K., Fraenkel, E.
|
|
<strong>Tissue-specific transcriptional regulation has diverged significantly between human and mouse.</strong>
|
|
Nature Genet. 39: 730-732, 2007.
|
|
|
|
|
|
[PubMed: 17529977]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng2047]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Odom, D. T., Zizlsperger, N., Gordon, D. B., Bell, G. W., Rinaldi, N. J., Murray, H. L., Volkert, T. L., Schreiber, J., Rolfe, P. A., Gifford, D. K., Fraenkel, E., Bell, G. I., Young, R. A.
|
|
<strong>Control of pancreas and liver gene expression by HNF transcription factors.</strong>
|
|
Science 303: 1378-1381, 2004.
|
|
|
|
|
|
[PubMed: 14988562]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1089769]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Pontoglio, M., Barra, J., Hadchouel, M., Doyen, A., Kress, C., Bach, J. P., Babinet, C., Yaniv, M.
|
|
<strong>Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria, and renal Fanconi syndrome.</strong>
|
|
Cell 84: 575-585, 1996.
|
|
|
|
|
|
[PubMed: 8598044]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)81033-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rebouissou, S., Vasiliu, V., Thomas, C., Bellanne-Chantelot, C., Bui, H., Chretien, Y., Timsit, J., Rosty, C., Laurent-Puig, P., Chauveau, D., Zucman-Rossi, J.
|
|
<strong>Germline hepatocyte nuclear factor 1-alpha and 1-beta mutations in renal cell carcinomas.</strong>
|
|
Hum. Molec. Genet. 14: 603-614, 2005.
|
|
|
|
|
|
[PubMed: 15649945]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddi057]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Reiner, A. P., Barber, M. J., Guan, Y., Ridker, P. M., Lange, L. A., Chasman, D. I., Walston, J. D., Cooper, G. M., Jenny, N. S., Rieder, M. J., Durda, J. P., Smith, J. D., Novembre, J., Tracy, R. P., Rotter, J. I., Stephens, M., Nickerson, D. A., Krauss, R. M.
|
|
<strong>Polymorphisms of the HNF1A gene encoding hepatocyte nuclear factor-1-alpha are associated with C-reactive protein.</strong>
|
|
Am. J. Hum. Genet. 82: 1193-1201, 2008.
|
|
|
|
|
|
[PubMed: 18439552]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2008.03.017]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rey-Campos, J., Chouard, T., Yaniv, M., Cereghini, S.
|
|
<strong>vHNF1 is a homeoprotein that activates transcription and forms heterodimers with HNF1.</strong>
|
|
EMBO J. 10: 1445-1457, 1991.
|
|
|
|
|
|
[PubMed: 1673926]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/j.1460-2075.1991.tb07665.x]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Ridker, P. M., Pare, G., Parker, A., Zee, R. Y. L., Danik, J. S., Buring, J. E., Kwiatkowski, D., Cook, N. R., Miletich, J. P., Chasman, D. I.
|
|
<strong>Loci related to metabolic syndrome pathways including LEPR, HNF1A, IL6R, and GCKR associate with plasma C-reactive protein: the Women's Genome Health Study.</strong>
|
|
Am. J. Hum. Genet. 82: 1185-1192, 2008.
|
|
|
|
|
|
[PubMed: 18439548]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2008.03.015]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Shih, D. Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B. L., Suchy, F. J., Shefer, S., Bollileni, J. S., Gonzalez, F. J., Breslow, J. L., Stoffel, M.
|
|
<strong>Hepatocyte nuclear factor-1-alpha is an essential regulator of bile acid and plasma cholesterol metabolism.</strong>
|
|
Nature Genet. 27: 375-382, 2001.
|
|
|
|
|
|
[PubMed: 11279518]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/86871]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Szpirer, C., Riviere, M., Cortese, R., Nakamura, T., Islam, M. Q., Levan, G., Szpirer, J.
|
|
<strong>Chromosomal localization in man and rat of the genes encoding the liver-enriched transcription factors C/EBP, DBP, and HNF1/LFB-1 (CEBP, DBP, and transcription factor 1, TCF1, respectively) and of the hepatocyte growth factor/scatter factor gene (HGF).</strong>
|
|
Genomics 13: 293-300, 1992.
|
|
|
|
|
|
[PubMed: 1535333]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(92)90245-n]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Triggs-Raine, B. L., Kirkpatrick, R. D., Kelly, S. L., Norquay, L. D., Cattini, P. A., Yamagata, K., Hanley, A. J. G., Zinman, B., Harris, S. B., Barrett, P. H., Hegele, R. A.
|
|
<strong>HNF1-alpha G319S, a transactivation-deficient mutant, is associated with altered dynamics of diabetes onset in an Oji-Cree community.</strong>
|
|
Proc. Nat. Acad. Sci. 99: 4614-4619, 2002.
|
|
|
|
|
|
[PubMed: 11904371]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.062059799]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Hansen, T., Ekstrom, C. T., Eiberg, H., Pederson, O.
|
|
<strong>The Ala/Val98 polymorphism of the hepatocyte nuclear factor-1-alpha gene contributes to the interindividual variation in serum C-peptide response during an oral glucose tolerance test: evidence from studies of 231 glucose-tolerant first degree relatives of type 2 diabetic probands.</strong>
|
|
J. Clin. Endocr. Metab. 83: 4506-4509, 1998.
|
|
|
|
|
|
[PubMed: 9851800]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.12.5359]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Moller, A. M., Nyholm, B., Ekstrom, C. T., Eiberg, H., Clausen, J. O., Hansen, T., Pedersen, O., Schmitz, O.
|
|
<strong>The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1-alpha gene on estimates of the pancreatic beta-cell function in Caucasian glucose-tolerant first-degree relatives of type 2 diabetic patients.</strong>
|
|
J. Clin. Endocr. Metab. 83: 3992-3995, 1998.
|
|
|
|
|
|
[PubMed: 9814481]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1210/jcem.83.11.5228]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Urhammer, S. A., Rasmussen, S. K., Kaisaki, P. J., Oda, N., Yamagata, K., Moller, A. M., Fridberg, M., Hansen, L., Hansen, T., Bell, G. I., Pedersen, O.
|
|
<strong>Genetic variation in the hepatocyte nuclear factor-1-alpha gene in Danish Caucasians with late-onset NIDDM.</strong>
|
|
Diabetologia 40: 473-475, 1997.
|
|
|
|
|
|
[PubMed: 9112026]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s001250050703]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
van Wering, H. M., Huibregtse, I. L., van der Zwan, S. M., de Bie, M. S., Dowling, L. N., Boudreau, F., Rings, E. H. H. M., Grand, R. J., Krasinski, S. D.
|
|
<strong>Physical interaction between GATA-5 and hepatocyte nuclear factor-1-alpha results in synergistic activation of the human lactase-phlorizin hydrolase promoter.</strong>
|
|
J. Biol. Chem. 277: 27659-27667, 2002.
|
|
|
|
|
|
[PubMed: 12011060]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M203645200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Vaxillaire, M., Rouard, M., Yamagata, K., Oda, N., Kaisaki, P. J., Boriraj, V. V., Chevre, J.-C., Boccio, V., Cox, R. D., Lathrop, G. M., Dussoix, P., Philippe, J., Timsit, J., Charpentier, G., Velho, G., Bell, G. I., Froguel, P.
|
|
<strong>Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3).</strong>
|
|
Hum. Molec. Genet. 6: 583-586, 1997.
|
|
|
|
|
|
[PubMed: 9097962]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/6.4.583]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Xu, J. Y., Chan, V., Zhang, W. Y., Wat, N. M. S., Lam, K. S. L.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in Chinese MODY families: prevalence and functional analysis.</strong>
|
|
Diabetologia 45: 744-746, 2002.
|
|
|
|
|
|
[PubMed: 12107757]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s00125-002-0814-9]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamada, S., Nishigori, H., Onda, H., Utsugi, T., Yanagawa, T., Maruyama, T., Onigata, K., Nagashima, K., Nagai, R., Morikawa, A., Takeuchi, T., Takeda, J.
|
|
<strong>Identification of mutations in the hepatocyte nuclear factor (HNF)-1-alpha gene in Japanese subjects with IDDM.</strong>
|
|
Diabetes 46: 1643-1647, 1997.
|
|
|
|
|
|
[PubMed: 9313763]
|
|
|
|
|
|
[Full Text: https://doi.org/10.2337/diacare.46.10.1643]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yamagata, K., Oda, N., Kalsaki, P. J., Menzel, S., Furuta, H., Vaxillaire, M., Southam, L., Cox, R. D., Lathrop, G. M., Borhaj, V. V., Chen, X., Cox, N. J., Oda, Y., Yano, H., Le Beau, M. M., Yamada, S., Nishigori, H., Takeda, J., Fajans, S. S., Hattersley, A. T., Iwasaki, N., Hansen, T., Pedersen, O., Polonsky, K. S., Turner, R. C., Velho, G., Chevre, J.-C., Froguel, P., Bell, G. I.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-alpha gene in maturity-onset diabetes of the young (MODY3).</strong>
|
|
Nature 384: 455-457, 1996.
|
|
|
|
|
|
[PubMed: 8945470]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/384455a0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Yoshiuchi, I., Yamagata, K., Yoshimoto, M., Zhu, Q., Yang, Q., Nammo, T., Uenaka, R., Kinoshita, E., Hanafusa, T., Miyagawa, J., Matsuzawa, Y.
|
|
<strong>Analysis of a non-functional HNF-1-alpha (TCF1) mutation in Japanese subjects with familial type 1 diabetes.</strong>
|
|
Hum. Mutat. 18: 345-351, 2001.
|
|
|
|
|
|
[PubMed: 11668618]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.1196]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
</ol>
|
|
|
|
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|
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|
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<span class="text-nowrap mim-text-font">
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Contributors:
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<span class="mim-text-font">
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Ada Hamosh - updated : 01/17/2023<br>Ada Hamosh - updated : 8/4/2011<br>Marla J. F. O'Neill - updated : 4/19/2010<br>Marla J. F. O'Neill - updated : 6/10/2008<br>George E. Tiller - updated : 2/5/2008<br>Patricia A. Hartz - updated : 10/3/2007<br>Patricia A. Hartz - updated : 8/3/2007<br>John A. Phillips, III - updated : 10/19/2006<br>Ada Hamosh - updated : 6/10/2004<br>John A. Phillips, III - updated : 2/10/2004<br>John A. Phillips, III - updated : 8/21/2003<br>Stylianos E. Antonarakis - updated : 5/5/2003<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 9/25/2002<br>Victor A. McKusick - updated : 2/15/2002<br>Ada Hamosh - updated : 10/18/2001<br>John A. Phillips, III - updated : 9/25/2001<br>Ada Hamosh - updated : 4/23/2001<br>Ada Hamosh - updated : 3/28/2001<br>John A. Phillips, III - updated : 2/12/2001<br>Victor A. McKusick - updated : 11/29/2000<br>John A. Phillips, III - updated : 8/9/2000<br>Victor A. McKusick - updated : 2/22/2000<br>Victor A. McKusick - updated : 11/8/1999<br>John A. Phillips, III - updated : 9/29/1999<br>John A. Phillips, III - updated : 3/24/1999<br>Victor A. McKusick - updated : 2/13/1998<br>Victor A. McKusick - updated : 2/11/1998<br>Victor A. McKusick - updated : 8/12/1997<br>Victor A. McKusick - updated : 8/7/1997<br>Victor A. McKusick - updated : 4/24/1997
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Victor A. McKusick : 11/13/1987
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