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Entry
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- *189907 - HNF1 HOMEOBOX B; HNF1B
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- OMIM
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</form>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*189907</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 role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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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="#geneStructure">Gene Structure</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="#geneFunction">Gene Function</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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</li>
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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>
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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/189907">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=ENSG00000275410;t=ENST00000617811" 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=6928" 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=189907" 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=ENSG00000275410;t=ENST00000617811" 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_000458,NM_001165923,NM_001304286,NM_001411100,XM_011525161,XM_011525162,XM_011525163,XM_011525164,XM_047436630,XM_047436631" 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_000458" 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=189907" 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=08926&isoform_id=08926_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/HNF1B" 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/414048,547664,2739348,4507397,6102951,17389340,30583091,49168628,119578006,119578007,158261285,194383754,194391020,260064065,304560920,304560922,304560924,304560926,747165384,767995702,767995704,767995706,767995708,2217313487,2217313490,2288627442,2462491241,2462491243,2462491245,2462491247,2462491249,2462491251,2462557193,2462557195,2462557197,2462557199,2462557201,2462557203,2462557205" 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/P35680" 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=6928" 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=ENSG00000275410;t=ENST00000617811" 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=HNF1B" 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=HNF1B" 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+6928" 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/HNF1B" 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:6928" 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/6928" 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=chr17&hgg_gene=ENST00000617811.5&hgg_start=37686431&hgg_end=37745059&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:11630" 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:11630" 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/hnf1b" 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=189907[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=189907[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/HNF1B/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/ENSG00000275410" 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=HNF1B" 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=HNF1B" 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=HNF1B" 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="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HNF1B&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/PA162391083" 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:11630" 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:98505" 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/HNF1B#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:98505" 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/6928/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://www.orthodb.org/?ncbi=6928" 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-020104-1" 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:6928" 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=HNF1B&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> 128667008, 253864004, 44054006, 609572000, 733471003<br />
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<strong>ICD10CM:</strong> E11<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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189907
|
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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 B; HNF1B
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TRANSCRIPTION FACTOR 2; TCF2<br />
|
|
TRANSCRIPTION FACTOR, LIVER-SPECIFIC, 3<br />
|
|
HEPATOCYTE NUCLEAR FACTOR-1-BETA<br />
|
|
HEPATIC NUCLEAR FACTOR-1-BETA<br />
|
|
HEPATOCYTE NUCLEAR FACTOR 2; HNF2
|
|
</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>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HNF1B" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HNF1B</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/17/459?start=-3&limit=10&highlight=459">17q12</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:37686431-37745059&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'})">17:37,686,431-37,745,059</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=144700,137920,125853" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/17/459?start=-3&limit=10&highlight=459">
|
|
17q12
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Renal cell carcinoma}
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/144700"> 144700 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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|
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</span>
|
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</td>
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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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<p>Hepatocyte nuclear factor-1-beta (HNF1B), also known as transcription factor-2 (TCF2), is a member of the homeodomain-containing superfamily of transcription factors (<a href="#2" class="mim-tip-reference" title="Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M. <strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong> Nucleic Acids Res. 19: 3553-3559, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677179</a>] [<a href="https://doi.org/10.1093/nar/19.13.3553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1677179">Bach et al., 1991</a>). Early expression of TCF2 is seen in the kidney, liver, bile ducts, thymus, genital tract, pancreas, lung, and gut. It can act either as a homodimer or as a heterodimer with HNF1A (<a href="/entry/142410">142410</a>) (<a href="#9" class="mim-tip-reference" title="Edghill, E. L., Bingham, C., Ellard, S., Hattersley, A. T. <strong>Mutations in hepatocyte nuclear factor-1-beta and their related phenotypes.</strong> J. Med. Genet. 43: 84-90, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15930087/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15930087</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15930087[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/10.1136/jmg.2005.032854" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15930087">Edghill et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1677179+15930087" 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="#1" class="mim-tip-reference" title="Abbott, C., Piaggio, G., Ammendola, R., Solomon, E., Povey, S., Gounari, F., De Simone, V., Cortese, R. <strong>Mapping of the gene TCF2 for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction.</strong> Genomics 8: 165-167, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2081590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2081590</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90239-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2081590">Abbott et al. (1990)</a> isolated and partially sequenced a human clone corresponding to the HNF1B gene, which they called LFB3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2081590" 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="#2" class="mim-tip-reference" title="Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M. <strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong> Nucleic Acids Res. 19: 3553-3559, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677179</a>] [<a href="https://doi.org/10.1093/nar/19.13.3553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1677179">Bach et al. (1991)</a> isolated a cDNA clone from a human liver library encoding a protein, designated HNF1B, that is highly homologous to HNF1A in 3 regions, including the homeodomain and the dimerization domain. They showed that this protein can heterodimerize with human HNF1A in vitro. Sequence comparison with a rat variant HNF1A identified the cDNA as the human homolog. HNF1B is a nuclear protein recognizing the same binding site as HNF1A. By Northern blot analysis, <a href="#2" class="mim-tip-reference" title="Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M. <strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong> Nucleic Acids Res. 19: 3553-3559, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677179</a>] [<a href="https://doi.org/10.1093/nar/19.13.3553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1677179">Bach et al. (1991)</a> showed that the HNF1B transcripts are present in differentiated human HepG2 hepatoma cells as well as in rat liver and that this transcript level is 10- to 20-fold lower than that of HNF1A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1677179" 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>The HNF1B gene contains 9 exons (<a href="#14" class="mim-tip-reference" title="Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B. N., Lindner, T., Yamagata, K., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Iwamoto, Y., Bell, G. I. <strong>Mutation in hepatocyte nuclear factor-1-beta gene (TCF2) associated with MODY. (Letter)</strong> Nature Genet. 17: 384-385, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398836</a>] [<a href="https://doi.org/10.1038/ng1297-384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398836">Horikawa et al., 1997</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398836" 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>By analysis of human/rodent somatic cell hybrids, <a href="#1" class="mim-tip-reference" title="Abbott, C., Piaggio, G., Ammendola, R., Solomon, E., Povey, S., Gounari, F., De Simone, V., Cortese, R. <strong>Mapping of the gene TCF2 for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction.</strong> Genomics 8: 165-167, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2081590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2081590</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90239-q" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2081590">Abbott et al. (1990)</a> mapped the TCF2 gene to chromosome 17q between the centromere and the breakpoint of acute promyelocytic leukemia, i.e., proximal to 17q22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2081590" 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="#2" class="mim-tip-reference" title="Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M. <strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong> Nucleic Acids Res. 19: 3553-3559, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677179</a>] [<a href="https://doi.org/10.1093/nar/19.13.3553" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1677179">Bach et al. (1991)</a> assigned the HNF1B gene to human chromosome 17 and mouse chromosome 11. The HNF1A gene maps to human chromosome 12 and mouse chromosome 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1677179" 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="#11" class="mim-tip-reference" title="Gudmundsson, J., Sulem, P., Steinthorsdottir, V., Bergthorsson, J. T., Thorleifsson, G., Manolescu, A., Rafnar, T., Gudbjartsson, D., Agnarsson, B. A., Baker, A., Sigurdsson, A., Benediktsdottir, K. R., and 63 others. <strong>Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.</strong> Nature Genet. 39: 977-983, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17603485/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17603485</a>] [<a href="https://doi.org/10.1038/ng2062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17603485">Gudmundsson et al. (2007)</a> noted that the HNF1B gene maps to chromosome 17q12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17603485" 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="#17" class="mim-tip-reference" title="Kolatsi-Joannou, M., Bingham, C., Ellard, S., Bulman, M. P., Allen, L. I. S., Hattersley, A. T., Woolf, A. S. <strong>Hepatocyte nuclear factor-1-beta: a new kindred with renal cysts and diabetes and gene expression in normal human development.</strong> J. Am. Soc. Nephrol. 12: 2175-2180, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11562418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11562418</a>] [<a href="https://doi.org/10.1681/ASN.V12102175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11562418">Kolatsi-Joannou et al. (2001)</a> detected TCF2 mRNA in liver, pancreas, stomach, and lung through 91 days' gestation in 6 terminated normal human fetuses. Renal metanephroi expressed the gene at preglomerular stages during metanephrogenesis. The expression was most prominent in medullary and cortical collecting duct branches, which are ureteric bud derivatives. TCF2 gene expression was not detected in mesenchymal tissues, suggesting that it plays a role in epithelial differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11562418" 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 genomewide chromatin immunoprecipitation and DNA microarray analysis and microarray analysis of mRNA expression, <a href="#20" class="mim-tip-reference" title="Ma, Z., Gong, Y., Patel, V., Karner, C. M., Fischer, E., Hiesberger, T., Carroll, T. J., Pontoglio, M., Igarashi, P. <strong>Mutations of HNF-1-beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.</strong> Proc. Nat. Acad. Sci. 104: 20386-20391, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18077349[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.0705957104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077349">Ma et al. (2007)</a> identified Socs3 (<a href="/entry/604176">604176</a>) as an Hnf1b target gene in mouse kidney. Hnf1b bound to the Socs3 promoter and repressed Socs3 transcription. Expression of Socs3 increased in Hnf1b-knockout mice and in renal epithelial cells expressing dominant-negative mutant Hnf1b. Increased levels of Socs3 inhibited Hgf (<a href="/entry/142409">142409</a>)-induced tubulogenesis by decreasing phosphorylation of Erk (see MAPK1; <a href="/entry/176948">176948</a>) and Stat3 (<a href="/entry/102582">102582</a>). Conversely, knockdown of Socs3 in renal epithelial cells expressing dominant-negative mutant Hnf1b rescued the defect in Hgf-induced tubulogenesis by restoring phosphorylation of Erk and Stat3. <a href="#20" class="mim-tip-reference" title="Ma, Z., Gong, Y., Patel, V., Karner, C. M., Fischer, E., Hiesberger, T., Carroll, T. J., Pontoglio, M., Igarashi, P. <strong>Mutations of HNF-1-beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.</strong> Proc. Nat. Acad. Sci. 104: 20386-20391, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18077349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18077349</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18077349[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.0705957104" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18077349">Ma et al. (2007)</a> concluded that HNF1B regulates renal tubulogenesis by controlling expression of SOC3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18077349" 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>By time-lapse microscopy of IMCD3 mouse renal cells expressing fluorescence-tagged Hnf1b, <a href="#27" class="mim-tip-reference" title="Verdeguer, F., Le Corre, S., Fischer, E., Callens, C., Garbay, S., Doyen, A., Igarashi, P., Terzi, F., Pontoglio, M. <strong>A mitotic transcriptional switch in polycystic kidney disease. (Letter)</strong> Nature Med. 16: 106-110, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966811[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/nm.2068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966811">Verdeguer et al. (2010)</a> found that, unlike the classical behavior of transcription factors, such as Hnf4a (<a href="/entry/600281">600281</a>), a substantial fraction of Hnf1b remained associated with mitotic chromatin and traveled with condensed chromosomes throughout mitosis. From these observations and data they obtained following conditional knockout of Hnf1b in mice (see ANIMAL MODEL), <a href="#27" class="mim-tip-reference" title="Verdeguer, F., Le Corre, S., Fischer, E., Callens, C., Garbay, S., Doyen, A., Igarashi, P., Terzi, F., Pontoglio, M. <strong>A mitotic transcriptional switch in polycystic kidney disease. (Letter)</strong> Nature Med. 16: 106-110, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966811[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/nm.2068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966811">Verdeguer et al. (2010)</a> hypothesized that HNF1B functions as both a classic transcriptional activator and as a bookmarking factor that marks target genes for rapid transcriptional reactivation after mitosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966811" 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="#18" class="mim-tip-reference" title="Kornfeld, J.-W., Baitzel, C., Konner, A. C., Nicholls, H. T., Vogt, M. C., Herrmanns, K., Scheja, L., Haumaitre, C., Wolf, A. M., Knippschild, U., Seibler, J., Cereghini, S., Heeren, J., Stoffel, M., Bruning, J. C. <strong>Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b.</strong> Nature 494: 111-115, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23389544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23389544</a>] [<a href="https://doi.org/10.1038/nature11793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23389544">Kornfeld et al. (2013)</a> found that inducible transgenic overexpression of Mir802 (<a href="/entry/616090">616090</a>) in mice caused impaired glucose tolerance and attenuated insulin sensitivity, whereas reduction of Mir802 expression improved glucose tolerance and insulin action. The authors identified Hnf1b as a target of Mir802-dependent silencing, and showed that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signaling, and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr (<a href="/entry/601007">601007</a>)(db/db) mice. <a href="#18" class="mim-tip-reference" title="Kornfeld, J.-W., Baitzel, C., Konner, A. C., Nicholls, H. T., Vogt, M. C., Herrmanns, K., Scheja, L., Haumaitre, C., Wolf, A. M., Knippschild, U., Seibler, J., Cereghini, S., Heeren, J., Stoffel, M., Bruning, J. C. <strong>Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b.</strong> Nature 494: 111-115, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23389544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23389544</a>] [<a href="https://doi.org/10.1038/nature11793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23389544">Kornfeld et al. (2013)</a> concluded that their study defined a critical role for deregulated expression of MIR802 in the development of obesity-associated impairment of glucose metabolism through targeting of HNF1B, and assigned HNF1B an unexpected role in the control of hepatic insulin sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23389544" 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><strong><em>Renal Cysts and Diabetes Syndrome</em></strong></p><p>
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In 2 Japanese sibs with a phenotype consistent with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#14" class="mim-tip-reference" title="Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B. N., Lindner, T., Yamagata, K., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Iwamoto, Y., Bell, G. I. <strong>Mutation in hepatocyte nuclear factor-1-beta gene (TCF2) associated with MODY. (Letter)</strong> Nature Genet. 17: 384-385, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398836</a>] [<a href="https://doi.org/10.1038/ng1297-384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398836">Horikawa et al. (1997)</a> identified a heterozygous mutation in the TCF2 gene (<a href="#0001">189907.0001</a>). The sibs developed diabetes mellitus at ages 10 and 15 years, respectively, consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). Although there was no report of renal appearance or histology, a nonspecific nephropathy was described. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398836" 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 affected members of a Norwegian family with renal cysts and diabetes syndrome, <a href="#19" class="mim-tip-reference" title="Lindner, T. H., Njolstad, P. R., Horikawa, Y., Bostad, L., Bell, G. I., Sovik, O. <strong>A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1-beta.</strong> Hum. Molec. Genet. 8: 2001-2008, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484768</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484768">Lindner et al. (1999)</a> identified a 75-bp deletion in exon 2 of the TCF2 gene (<a href="#0002">189907.0002</a>). <a href="#6" class="mim-tip-reference" title="Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T. <strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong> Kidney Int. 57: 898-907, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720943</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2000.057003898.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720943">Bingham et al. (2000)</a> identified a heterozygous 5-bp deletion in the TCF2 gene (<a href="#0003">189907.0003</a>) in a woman with renal cysts and diabetes syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10720943+10484768" 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="Bingham, C., Bulman, M. P., Ellard, S., Allen, L. I. S., Lipkin, G. W., van't Hoff, W. G., Woolf, A. S., Rizzoni, G., Novelli, G., Nicholls, A. J., Hattersley, A. T. <strong>Mutations in the hepatocyte nuclear factor-1-beta gene are associated with familial hypoplastic glomerulocystic kidney disease.</strong> Am. J. Hum. Genet. 68: 219-224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11085914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11085914</a>] [<a href="https://doi.org/10.1086/316945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11085914">Bingham et al. (2001)</a> identified 2 different heterozygous mutations in the TCF2 gene (<a href="#0004">189907.0004</a> and <a href="#0005">189907.0005</a>) in affected members of the families reported by <a href="#26" class="mim-tip-reference" title="Rizzoni, G., Loirat, C., Levy, M., Milanesi, C., Zachello, G., Mathieu, H. <strong>Familial hypoplastic glomerulocystic kidney: a new entity?</strong> Clin. Nephrol. 18: 263-268, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7151342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7151342</a>]" pmid="7151342">Rizzoni et al. (1982)</a> and <a href="#16" class="mim-tip-reference" title="Kaplan, B. S., Gordon, I., Pincott, J., Barratt, T. M. <strong>Familial hypoplastic glomerulocystic kidney disease: a definite entity with dominant inheritance.</strong> Am. J. Med. Genet. 34: 569-573, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2624270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2624270</a>] [<a href="https://doi.org/10.1002/ajmg.1320340423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2624270">Kaplan et al. (1989)</a> as having familial hypoplastic glomerulocystic kidney disease. All of the patients eventually developed diabetes mellitus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11085914+7151342+2624270" 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 8 probands and 5 offspring with renal cysts and diabetes syndrome, <a href="#4" class="mim-tip-reference" title="Bellanne-Chantelot, C., Chauveau, D., Gautier, J.-F., Dubois-Laforgue, D., Clauin, S., Beaufils, S., Wilhelm, J.-M., Boitard, C., Noel, L.-H., Velho, G., Timsit, J. <strong>Clinical spectrum associated with hepatocyte nuclear factor-1B mutations.</strong> Ann. Intern. Med. 140: 510-517, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15068978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15068978</a>] [<a href="https://doi.org/10.7326/0003-4819-140-7-200404060-00009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15068978">Bellanne-Chantelot et al. (2004)</a> identified 8 novel mutations in the TCF2 gene, all in the DNA-binding domain: 5 missense mutations (see, e.g., <a href="#0014">189907.0014</a>), 2 nonsense mutations, and 1 mutation in the splice donor site of intron 2 at the highly conserved +1 position. Cosegregation of the mutation and the phenotype was observed in 4 families; 2 mutations were de novo. The patients had various renal abnormalities and some also had genital tract abnormalities and pancreatic atrophy. Eleven patients had abnormal liver enzyme levels with normal liver function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15068978" 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="Barbacci, E., Chalkiadaki, A., Masdeu, C., Haumaitre, C., Lokmane, L., Loirat, C., Cloarec, S., Taliandis, I., Bellanne-Chantelot, C., Cereghini, S. <strong>HNF1-beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.</strong> Hum. Molec. Genet. 13: 3139-3149, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509593</a>] [<a href="https://doi.org/10.1093/hmg/ddh338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509593">Barbacci et al. (2004)</a> functionally characterized 5 missense mutations, 2 truncating mutations, and 1 frameshift deletion in different domains of the TCF2 protein. Truncation mutations, retaining the dimerization domain, displayed defective nuclear localization and weak dominant-negative activity when coexpressed with the wildtype protein. A frameshift mutation located within the C-terminal QSP-rich domain partially reduced transcriptional activity, whereas selective deletion of this domain abolished transactivation. All 5 missense mutations, which involved POU-specific and homeodomain residues, were correctly expressed and localized to the nucleus. Although having different effects on DNA-binding capacity that ranged from complete loss to mild reduction, these mutations exhibited severe reduction in transactivation capacity. The transcriptional impairment of mutations with weak or unaffected DNA-binding activity correlated with the loss of association with 1 of the histone-acetyltransferases CREBBP (<a href="/entry/600140">600140</a>) or PCAF (<a href="/entry/602303">602303</a>). In contrast to the transactivation potential of wildtype TCF2, which depends on the synergistic action of CREBBP and PCAF, the activity of these mutants was not increased by the synergistic action of these 2 coactivators or by treatment with a specific histone-deacetylase inhibitor. <a href="#3" class="mim-tip-reference" title="Barbacci, E., Chalkiadaki, A., Masdeu, C., Haumaitre, C., Lokmane, L., Loirat, C., Cloarec, S., Taliandis, I., Bellanne-Chantelot, C., Cereghini, S. <strong>HNF1-beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.</strong> Hum. Molec. Genet. 13: 3139-3149, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509593</a>] [<a href="https://doi.org/10.1093/hmg/ddh338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15509593">Barbacci et al. (2004)</a> concluded that the complex syndrome associated with TCF2 mutations arises from either defective DNA-binding or decreased transactivation function through impaired coactivator recruitment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15509593" 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="#12" class="mim-tip-reference" title="Harries, L. W., Bingham, C., Bellanne-Chantelot, C., Hattersley, A. T., Ellard, S. <strong>The position of premature termination codons in the hepatocyte nuclear factor--1 beta gene determines susceptibility to nonsense-mediated decay.</strong> Hum. Genet. 118: 214-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133182</a>] [<a href="https://doi.org/10.1007/s00439-005-0023-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16133182">Harries et al. (2005)</a> investigated the susceptibility to nonsense-mediated decay (NMD) of 6 truncating HNF1B mutations. Four of the 6 mutations showed evidence of NMD; 2 mutations, 1 of which was P159fsdelT (<a href="#0005">189907.0005</a>), produced transcripts unexpectedly immune to NMD. <a href="#12" class="mim-tip-reference" title="Harries, L. W., Bingham, C., Bellanne-Chantelot, C., Hattersley, A. T., Ellard, S. <strong>The position of premature termination codons in the hepatocyte nuclear factor--1 beta gene determines susceptibility to nonsense-mediated decay.</strong> Hum. Genet. 118: 214-224, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16133182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16133182</a>] [<a href="https://doi.org/10.1007/s00439-005-0023-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16133182">Harries et al. (2005)</a> concluded that truncating mutant transcripts of the HNF1B gene do not conform to the known rules governing NMD susceptibility, but instead demonstrate a previously unreported 5-prime to 3-prime polarity. They hypothesized that this may be due to reinitiation of translation downstream of the premature termination codon, thus providing a mechanism for the evasion of NMD, but that other factors such as the distance from the native initiation codon may play a part. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16133182" 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="#23" class="mim-tip-reference" title="Nakayama, M., Nozu, K., Goto, Y., Kamei, K., Ito, S., Sato, H., Emi, M., Nakanishi, K., Tsuchiya, S., Iijima, K. <strong>HNF1B alterations associated with congenital anomalies of the kidney and urinary tract.</strong> Pediat. Nephrol. 25: 1073-1079, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20155289/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20155289</a>] [<a href="https://doi.org/10.1007/s00467-010-1454-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20155289">Nakayama et al. (2010)</a> identified heterozygous pathogenic HNF1B mutations in 5 (10%) of 50 Japanese children with congenital anomalies of the kidney and urinary tract (CAKUT), including 2 with hypodysplastic kidneys and 3 with unilateral multicystic dysplastic kidneys. No mutations were found in 4 patients with a single kidney. There were 3 whole-gene deletions, 1 truncating mutation, and 1 missense mutation. The clinical spectrum of renal disease was variable, ranging in severity from unilateral disease and normal renal function to bilateral disease necessitating transplant. However, none of the patients had evidence of diabetes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20155289" 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>Susceptibility to Chromophobe Renal Cell Carcinoma</em></strong></p><p>
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<a href="#25" 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 inactivation. Biallelic HNF1B inactivation was found in 2 of 12 chromophobe renal carcinomas by association of 2 germline mutations (<a href="#0014">189907.0014</a> and <a href="#0015">189907.0015</a>, respectively) with somatic gene deletion. In these cases, expression of PKHD1 (<a href="/entry/606702">606702</a>) and uromodulin (UMOD; <a href="/entry/191845">191845</a>), 2 genes regulated by HNF1B, was turned off. 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 HNF1B, PKHD1, and UMOD. <a href="#25" 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 mutations of HNF1B may predispose to renal tumors and proposed that HNF1B may function as a tumor suppressor gene in chromophobe renal cell carcinogenesis through control of PKHD1 expression. <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>Possible Association with Prostate Cancer</em></strong></p><p>
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For information regarding a possible association of single-nucleotide polymorphisms (SNPs) in the HNF1B gene with susceptibility to prostate cancer, see HPC11 (<a href="/entry/611955">611955</a>).</p>
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<p><a href="#28" class="mim-tip-reference" title="Wild, W., Pogge von Strandmann, E., Nastos, A., Senkel, S., Lingott-Frieg, A., Bulman, M., Bingham, C., Ellard, S., Hattersley, A. T., Ryffel, G. U. <strong>The mutated human gene encoding hepatocyte nuclear factor 1-beta inhibits kidney formation in developing Xenopus embryos.</strong> Proc. Nat. Acad. Sci. 97: 4695-4700, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10758154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10758154</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10758154[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.080010897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10758154">Wild et al. (2000)</a> reported that the 5-bp deletion in the TCF2 gene reported by <a href="#6" class="mim-tip-reference" title="Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T. <strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong> Kidney Int. 57: 898-907, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720943</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2000.057003898.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720943">Bingham et al. (2000)</a> resulted in a truncated protein that retained the DNA-binding domain; 3 previously reported mutations lacked part of the DNA-binding domain. In transfection experiments, the 5-bp deletion was associated with nephron agenesis and acted as a gain-of-function mutation with increased transactivation potential. Expression of this mutated factor in Xenopus embryos led to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects were generated by overexpression of wildtype HNF1B, consistent with the gain-of-function property of the mutant. In contrast, introduction of the human 75-bp deletion HNF1B mutant, which was associated with a reduced number of nephrons and hypertrophy of the remaining ones and had impaired DNA binding, showed only a minor effect on pronephros development in Xenopus. Thus, the overexpression of both human mutants had a different effect on renal development in Xenopus, reflecting the variation in renal phenotype seen with these mutations. The findings implied that HNF1B not only is an early marker of kidney development but also is functionally involved in morphogenetic events, and that these processes can be investigated in lower vertebrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10720943+10758154" 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>During pancreatic organogenesis, endocrine cells arise from non-self-renewing progenitors that express Ngn3 (<a href="/entry/604882">604882</a>). <a href="#21" class="mim-tip-reference" title="Maestro, M. A., Boj, S. F., Luco, R. F., Pierreux, C. E., Cabedo, J., Servitja, J. M., German, M. S., Rousseau, G. G., Lemaigre, F. P., Ferrer, J. <strong>Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas.</strong> Hum. Molec. Genet. 12: 3307-3314, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570708</a>] [<a href="https://doi.org/10.1093/hmg/ddg355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570708">Maestro et al. (2003)</a> showed that from E13 to E18 (the embryonic stage during which the major burst of beta-cell neogenesis takes place) murine pancreatic duct cells express Hnf1b. Ngn3-positive cells at this stage invariably cluster with mitotically competent Hnf1b-positive cells and are often intercalated with these cells in the epithelium that lines the lumen of primitive ducts. Hnf1b expression is markedly reduced in early pancreatic epithelial cells of Hnf6 (ONECUT1; <a href="/entry/604164">604164</a>)-deficient mice, in which formation of Ngn3-positive cells is defective. <a href="#21" class="mim-tip-reference" title="Maestro, M. A., Boj, S. F., Luco, R. F., Pierreux, C. E., Cabedo, J., Servitja, J. M., German, M. S., Rousseau, G. G., Lemaigre, F. P., Ferrer, J. <strong>Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas.</strong> Hum. Molec. Genet. 12: 3307-3314, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14570708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14570708</a>] [<a href="https://doi.org/10.1093/hmg/ddg355" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14570708">Maestro et al. (2003)</a> suggested that Hnf1b plays a role in the genetic hierarchy regulating the generation of pancreatic endocrine cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14570708" 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="Hiesberger, T., Bai, Y., Shao, X., McNally, B. T., Sinclair, A. M., Tian, X., Somlo, S., Igarashi, P. <strong>Mutation of hepatocyte nuclear factor-1-beta inhibits Pkhd1 gene expression and produces renal cysts in mice.</strong> J. Clin. Invest. 113: 814-825, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15067314/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15067314</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15067314[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/10.1172/JCI20083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15067314">Hiesberger et al. (2004)</a> identified an evolutionarily conserved TCF2-binding site in the proximal promoter of the mouse Pkhd1 gene. Mutations in the human homolog (PKHD1; <a href="/entry/606702">606702</a>) cause autosomal recessive polycystic kidney disease (see <a href="/entry/263200">263200</a>). Wildtype Tcf2 and the structurally related Tcf1 were noted to bind specifically to the Pkhd1 promoter and activate gene transcription. Expression of a dominant-negative Tcf2 mutant inhibited Pkhd1 expression and produced renal cysts in transgenic mice. Pkhd1 transcripts were absent in the cells lining the cysts but were present in morphologically normal surrounding tubules. The authors concluded that TCF2 directly regulates the transcription of PKHD1 and that inhibition of PKHD1 gene expression may contribute to the formation of renal cysts in humans with MODY5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15067314" 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="Verdeguer, F., Le Corre, S., Fischer, E., Callens, C., Garbay, S., Doyen, A., Igarashi, P., Terzi, F., Pontoglio, M. <strong>A mitotic transcriptional switch in polycystic kidney disease. (Letter)</strong> Nature Med. 16: 106-110, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966811[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/nm.2068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966811">Verdeguer et al. (2010)</a> found that conditional knockout of Hnf1b expression in young mice led to the development of polycystic kidneys, whereas knockout on postnatal day 10 or later significantly delayed cyst development. Experiments with ischemia-reperfusion injury of adult wildtype and Hnf1b-knockout kidneys suggested that cyst formation following Hnf1b knockout required a background of rapid cell proliferation. In both developing kidney and regenerating adult kidney, Hnf1b knockout enhanced cell proliferation and distorted the orientation and synchronization of tubule cells required for tubule elongation, resulting in tubule dilation and cyst formation. <a href="#27" class="mim-tip-reference" title="Verdeguer, F., Le Corre, S., Fischer, E., Callens, C., Garbay, S., Doyen, A., Igarashi, P., Terzi, F., Pontoglio, M. <strong>A mitotic transcriptional switch in polycystic kidney disease. (Letter)</strong> Nature Med. 16: 106-110, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966811[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/nm.2068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966811">Verdeguer et al. (2010)</a> concluded that HNF1B is required to rapidly reactivate crucial target genes that orient rapidly proliferating cells toward tubule elongation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966811" 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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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=189907[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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<p>In 2 Japanese sibs with renal disease and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#14" class="mim-tip-reference" title="Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B. N., Lindner, T., Yamagata, K., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Iwamoto, Y., Bell, G. I. <strong>Mutation in hepatocyte nuclear factor-1-beta gene (TCF2) associated with MODY. (Letter)</strong> Nature Genet. 17: 384-385, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398836</a>] [<a href="https://doi.org/10.1038/ng1297-384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398836">Horikawa et al. (1997)</a> identified a heterozygous C-to-T transition in the TCF2 gene, resulting in an arg177-to-ter (R177X) substitution. The R177X mutation generated a truncated 176-residue protein with the NF2-dimerization and POU domains. This truncated protein did not stimulate transcription of a rat albumin promoter-linked reporter gene or inhibit the activity of wildtype TCF2, consistent with a loss of function. The 2 sibs had onset of diabetes at ages 10 and 15, respectively, consistent with a diagnosis of maturity-onset diabetes of the young type 5 (MODY5). Although both parents had late-onset diabetes, only the mother carried the TCF2 mutation. <a href="#14" class="mim-tip-reference" title="Horikawa, Y., Iwasaki, N., Hara, M., Furuta, H., Hinokio, Y., Cockburn, B. N., Lindner, T., Yamagata, K., Ogata, M., Tomonaga, O., Kuroki, H., Kasahara, T., Iwamoto, Y., Bell, G. I. <strong>Mutation in hepatocyte nuclear factor-1-beta gene (TCF2) associated with MODY. (Letter)</strong> Nature Genet. 17: 384-385, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9398836/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9398836</a>] [<a href="https://doi.org/10.1038/ng1297-384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9398836">Horikawa et al. (1997)</a> postulated that the early onset in the children reflected bilineal inheritance of 2 different diabetes susceptibility genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9398836" 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="mim-changed mim-change"><p>In affected members of a Norwegian family with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#19" class="mim-tip-reference" title="Lindner, T. H., Njolstad, P. R., Horikawa, Y., Bostad, L., Bell, G. I., Sovik, O. <strong>A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1-beta.</strong> Hum. Molec. Genet. 8: 2001-2008, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10484768/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10484768</a>] [<a href="https://doi.org/10.1093/hmg/8.11.2001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10484768">Lindner et al. (1999)</a> identified a 75-bp deletion spanning nucleotides 409 to 483 in exon 2 of the TCF2 gene (<a href="#0002">189907.0002</a>), resulting in the synthesis of a protein lacking amino acids arg137 to lys161. This deletion was located in the pseudo-POU region of TCF2, a region implicated in the specificity of DNA binding. Functional studies of the mutant TCF2 protein showed that it could not bind a TCF1 target sequence or stimulate transcription of the reporter gene, indicating that this was a loss-of-function mutation. Two of 4 female mutation carriers had vaginal aplasia and rudimentary uterus (mullerian aplasia; <a href="/entry/277000">277000</a>) in addition to diabetes and renal disease. The presence of internal genital malformations suggested that additional clinical features may be associated with TCF2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484768" 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></div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000787107" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000787107" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000787107</a>
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<div class="mim-changed mim-change"><p>In a woman with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#6" class="mim-tip-reference" title="Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T. <strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong> Kidney Int. 57: 898-907, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720943</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2000.057003898.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720943">Bingham et al. (2000)</a> identified a heterozygous 5-bp deletion in the TCF2 gene, which the authors designated P328L329fsdelCCTCT, resulting in a frameshift and premature termination of the protein. Her first pregnancy was terminated at 17 weeks following an ultrasound diagnosis of bilateral nonfunctioning cystic kidneys. Her first-born child had small multicystic, dysplastic kidneys with no normal nephrogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720943" 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></div>
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<p><a href="#28" class="mim-tip-reference" title="Wild, W., Pogge von Strandmann, E., Nastos, A., Senkel, S., Lingott-Frieg, A., Bulman, M., Bingham, C., Ellard, S., Hattersley, A. T., Ryffel, G. U. <strong>The mutated human gene encoding hepatocyte nuclear factor 1-beta inhibits kidney formation in developing Xenopus embryos.</strong> Proc. Nat. Acad. Sci. 97: 4695-4700, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10758154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10758154</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10758154[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.080010897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10758154">Wild et al. (2000)</a> demonstrated that the 5-bp deletion reported by <a href="#6" class="mim-tip-reference" title="Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T. <strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong> Kidney Int. 57: 898-907, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720943</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2000.057003898.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10720943">Bingham et al. (2000)</a> resulted in a truncated protein that retained the DNA-binding domain; 3 previously reported mutations lacked part of the DNA-binding domain. Transfection experiments showed that the 5-bp deletion was associated with nephron agenesis and acted as a gain-of-function mutation with increased transactivation potential. Expression of this mutated factor in Xenopus embryos led to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects were generated by overexpression of wildtype TCF2, consistent with the gain-of-function property of the mutant. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10720943+10758154" 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> rs121918671 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918671;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/rs121918671?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=rs121918671" 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=rs121918671" 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=RCV000013473 OR RCV004700225" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013473, RCV004700225" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013473...</a>
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<div class="mim-changed mim-change"><p>In 3 affected members of an Italian family with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#5" class="mim-tip-reference" title="Bingham, C., Bulman, M. P., Ellard, S., Allen, L. I. S., Lipkin, G. W., van't Hoff, W. G., Woolf, A. S., Rizzoni, G., Novelli, G., Nicholls, A. J., Hattersley, A. T. <strong>Mutations in the hepatocyte nuclear factor-1-beta gene are associated with familial hypoplastic glomerulocystic kidney disease.</strong> Am. J. Hum. Genet. 68: 219-224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11085914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11085914</a>] [<a href="https://doi.org/10.1086/316945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11085914">Bingham et al. (2001)</a> identified a heterozygous mutation in exon 1 of the TCF2 gene, resulting in a glu101-to-ter (E101X) substitution. The family was originally described by <a href="#26" class="mim-tip-reference" title="Rizzoni, G., Loirat, C., Levy, M., Milanesi, C., Zachello, G., Mathieu, H. <strong>Familial hypoplastic glomerulocystic kidney: a new entity?</strong> Clin. Nephrol. 18: 263-268, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7151342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7151342</a>]" pmid="7151342">Rizzoni et al. (1982)</a> as having familial hypoplastic glomerulocystic kidney disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11085914+7151342" 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></div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013474" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013474" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013474</a>
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<div class="mim-changed mim-change"><p>In affected members of a family with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#5" class="mim-tip-reference" title="Bingham, C., Bulman, M. P., Ellard, S., Allen, L. I. S., Lipkin, G. W., van't Hoff, W. G., Woolf, A. S., Rizzoni, G., Novelli, G., Nicholls, A. J., Hattersley, A. T. <strong>Mutations in the hepatocyte nuclear factor-1-beta gene are associated with familial hypoplastic glomerulocystic kidney disease.</strong> Am. J. Hum. Genet. 68: 219-224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11085914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11085914</a>] [<a href="https://doi.org/10.1086/316945" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11085914">Bingham et al. (2001)</a> identified a heterozygous 1-bp deletion (delT) in exon 2 of the TCF2 gene, predicted to result in a frameshift and premature termination of the protein at codon 160. The family had originally been reported by <a href="#16" class="mim-tip-reference" title="Kaplan, B. S., Gordon, I., Pincott, J., Barratt, T. M. <strong>Familial hypoplastic glomerulocystic kidney disease: a definite entity with dominant inheritance.</strong> Am. J. Med. Genet. 34: 569-573, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2624270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2624270</a>] [<a href="https://doi.org/10.1002/ajmg.1320340423" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2624270">Kaplan et al. (1989)</a> as having familial hypoplastic glomerulocystic kidney disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11085914+2624270" 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></div>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121918672 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918672;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=rs121918672" 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=rs121918672" 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=RCV000013475 OR RCV001328308 OR RCV002472930 OR RCV002496343 OR RCV004689416" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013475, RCV001328308, RCV002472930, RCV002496343, RCV004689416" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013475...</a>
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<div class="mim-changed mim-change"><p><a href="#10" class="mim-tip-reference" title="Furuta, H., Furuta, M., Sanke, T., Ekawa, K., Hanabusa, T., Nishi, M., Sasaki, H., Nanjo, K. <strong>Nonsense and missense mutations in the human hepatocyte nuclear factor-1-beta gene (TCF2) and their relation to type 2 diabetes in Japanese.</strong> J. Clin. Endocr. Metab. 87: 3859-3863, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12161522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12161522</a>] [<a href="https://doi.org/10.1210/jcem.87.8.8776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12161522">Furuta et al. (2002)</a> screened the HNF1B gene for mutations in a group of 126 unrelated Japanese patients with type 2 diabetes (<a href="/entry/125853">125853</a>) and a family history of at least 1 first-degree relative with diabetes. In a patient with diabetes diagnosed at 13 years of age, they found a C-to-T transition in exon 4 of the HNF1B gene, which resulted in an arg276-to-ter (R276X) amino acid substitution in the protein product. This patient had MODY5 misdiagnosed as common type 2 diabetes. He had small kidneys with multiple bilateral renal cysts and decreased urinary concentrating ability (RCAD; <a href="/entry/137920">137920</a>). Functional studies indicated that the mutant hepatocyte nuclear factor-1-beta was inactive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12161522" 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></div>
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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> rs121918673 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918673;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/rs121918673?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=rs121918673" 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=rs121918673" 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=RCV000013476 OR RCV001124747 OR RCV003153303" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013476, RCV001124747, RCV003153303" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013476...</a>
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<p>In a group of 126 unrelated Japanese patients with type 2 diabetes (T2D; <a href="/entry/125853">125853</a>) and a family history of at least 1 first-degree relative with diabetes, <a href="#10" class="mim-tip-reference" title="Furuta, H., Furuta, M., Sanke, T., Ekawa, K., Hanabusa, T., Nishi, M., Sasaki, H., Nanjo, K. <strong>Nonsense and missense mutations in the human hepatocyte nuclear factor-1-beta gene (TCF2) and their relation to type 2 diabetes in Japanese.</strong> J. Clin. Endocr. Metab. 87: 3859-3863, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12161522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12161522</a>] [<a href="https://doi.org/10.1210/jcem.87.8.8776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12161522">Furuta et al. (2002)</a> identified a C-to-G translation in exon 7 of the HNF1B gene, resulting in a ser465-to-arg (S465R) amino acid substitution, in a 50-year-old female diagnosed at 49 years of age. On screening a second group of 272 randomly selected patients with type 2 diabetes, they identified a second patient with the S465R mutation, a 68-year-old male whose diabetes was well controlled with diet therapy. Neither patient with the S465R mutation showed evidence of kidney disease. Functional studies indicated that the mutant protein exhibited a 22% reduction in activity compared with the wildtype protein. The S465R mutation may function in a dominant-negative manner. The authors concluded that the S465R mutation, found in 0.5% of patients with common type 2 diabetes examined, may thus be a rare genetic risk factor contributing to the development of type 2 diabetes rather than MODY5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12161522" 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>.0008 RENAL CYSTS AND DIABETES SYNDROME</strong>
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HNF1B, 1-BP INS, 1055A
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013477" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013477" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013477</a>
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<div class="mim-changed mim-change"><p>In a mother and son with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#17" class="mim-tip-reference" title="Kolatsi-Joannou, M., Bingham, C., Ellard, S., Bulman, M. P., Allen, L. I. S., Hattersley, A. T., Woolf, A. S. <strong>Hepatocyte nuclear factor-1-beta: a new kindred with renal cysts and diabetes and gene expression in normal human development.</strong> J. Am. Soc. Nephrol. 12: 2175-2180, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11562418/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11562418</a>] [<a href="https://doi.org/10.1681/ASN.V12102175" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11562418">Kolatsi-Joannou et al. (2001)</a> identified a heterozygous 1-bp insertion (1055insA) in exon 5 of the TCF2 gene, resulting in a frameshift and premature termination of the protein at codon 352. The son had congenital cystic kidneys and was normoglycemic at age 12 years; his mother developed gestational diabetes at age 24 years and later developed renal cysts. The mutant TCF2 protein was predicted to retain dimerization and DNA-binding domains, but to lack most of the transactivation domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11562418" 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></div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013478 OR RCV001794444 OR RCV002504781" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013478, RCV001794444, RCV002504781" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013478...</a>
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<div class="mim-changed mim-change"><p>In a mother and 2 daughters with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#15" class="mim-tip-reference" title="Iwasaki, N., Okabe, I., Momoi, M. Y., Ohashi, H., Ogata, M., Iwamoto, Y. <strong>Splice site mutation in the hepatocyte nuclear factor-1-beta gene, IVS2nt+1G-A, associated with maturity-onset diabetes of the young, renal dysplasia and bicornuate uterus. (Letter)</strong> Diabetologia 44: 387-391, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11317673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11317673</a>] [<a href="https://doi.org/10.1007/s001250051631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11317673">Iwasaki et al. (2001)</a> identified a heterozygous G-to-A transition in intron 2 of the TCF2 gene, resulting in a splice site mutation. The mother developed diabetes at age 27 years and the children at age 11 years. All had renal cysts, the mother had a bicornuate uterus, and 1 of the daughters had hyperuricemia. The mutation was not identified in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11317673" 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></div>
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<strong>.0010 RENAL CYSTS AND DIABETES SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013479 OR RCV002266902 OR RCV003390678" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013479, RCV002266902, RCV003390678" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013479...</a>
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<div class="mim-changed mim-change"><p>In affected members of a family with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#7" class="mim-tip-reference" title="Bingham, C., Ellard, S., van't Hoff, W. G., Simmonds, A., Marinaki, A. M., Badman, M. K., Winocour, P. H., Stride, A., Lockwood, C. R., Nicholls, A. J., Owen, K. R., Spyer, G., Peason, E. R., Hattersley, A. T. <strong>Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1-beta gene mutation.</strong> Kidney Int. 63: 1645-1651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12675839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12675839</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2003.00903.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12675839">Bingham et al. (2003)</a> identified a heterozygous splice site mutation in the TCF2 gene. The patients also showed juvenile hyperuricemic nephropathy and early-onset gout. <a href="#7" class="mim-tip-reference" title="Bingham, C., Ellard, S., van't Hoff, W. G., Simmonds, A., Marinaki, A. M., Badman, M. K., Winocour, P. H., Stride, A., Lockwood, C. R., Nicholls, A. J., Owen, K. R., Spyer, G., Peason, E. R., Hattersley, A. T. <strong>Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1-beta gene mutation.</strong> Kidney Int. 63: 1645-1651, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12675839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12675839</a>] [<a href="https://doi.org/10.1046/j.1523-1755.2003.00903.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12675839">Bingham et al. (2003)</a> concluded that hyperuricemia is a consistent feature of the disorder. A G-to-A transition in the same splice site position had been reported by <a href="#15" class="mim-tip-reference" title="Iwasaki, N., Okabe, I., Momoi, M. Y., Ohashi, H., Ogata, M., Iwamoto, Y. <strong>Splice site mutation in the hepatocyte nuclear factor-1-beta gene, IVS2nt+1G-A, associated with maturity-onset diabetes of the young, renal dysplasia and bicornuate uterus. (Letter)</strong> Diabetologia 44: 387-391, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11317673/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11317673</a>] [<a href="https://doi.org/10.1007/s001250051631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11317673">Iwasaki et al. (2001)</a>; see <a href="#0009">189907.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11317673+12675839" 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></div>
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<strong>.0011 RENAL CYSTS AND DIABETES SYNDROME</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">rs121918674 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918674;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=rs121918674" 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=rs121918674" 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=RCV000013480 OR RCV001551662" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013480, RCV001551662" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013480...</a>
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<div class="mim-changed mim-change"><p>In 2 sibs with discordant phenotypes of the renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#29" class="mim-tip-reference" title="Yorifuji, T., Kurokawa, K., Mamada, M., Imai, T., Kawai, M., Nishi, Y., Shishido, S., Hasegawa, Y., Nakahata, T. <strong>Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1-beta gene due to germline mosaicism.</strong> J. Clin. Endocr. Metab. 89: 2905-2908, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15181075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15181075</a>] [<a href="https://doi.org/10.1210/jc.2003-031828" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15181075">Yorifuji et al. (2004)</a> reported recurrence of a missense mutation in TCF2 in 2 sibs, ser148 to trp (S148W), caused by a C-to-G transversion at nucleotide 443 in exon 2. The first sib had neonatal diabetes mellitus and kidneys with only a few small cysts and normal renal function. The second had neonatal polycystic, dysplastic kidneys leading to early renal failure but only a transient episode of hyperglycemia, which resolved spontaneously. Both parents were clinically unaffected, and RFLP analysis showed that the mother was a low-level mosaic of normal and mutant TCF2, which suggested that the recurrence was caused by germline mosaicism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15181075" 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></div>
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<strong>.0013 RENAL CYSTS AND DIABETES SYNDROME</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013481" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013481" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013481</a>
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<div class="mim-changed mim-change"><p>In 3 affected members of a French family with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#8" class="mim-tip-reference" title="Carette, C., Vaury, C., Barthelemy, A., Clauin, S., Grunfeld, J.-P., Timsit, J., Bellanne-Chantelot, C. <strong>Exonic duplication of the hepatocyte nuclear factor-1-beta gene (transcription factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5.</strong> J. Clin. Endocr. Metab. 92: 2844-2847, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17440011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17440011</a>] [<a href="https://doi.org/10.1210/jc.2007-0286" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17440011">Carette et al. (2007)</a> identified duplication of exon 5 (gly349_M402dup) of the TCF2 gene. There was wide intrafamilial variability of the phenotype. The proband had hyperuricemic nephropathy and early gout, chronic renal failure, renal morphologic abnormalities, abnormal liver tests, and diabetes. His son had almost no clinical expression of the disease, whereas his grandson had a restricted but severe renal phenotype present from birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17440011" 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></div>
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<strong>.0014 RENAL CYSTS AND DIABETES SYNDROME</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">rs121918675 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918675;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=rs121918675" 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=rs121918675" 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=RCV000013482 OR RCV001659694 OR RCV002051783 OR RCV002466400 OR RCV002482860" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013482, RCV001659694, RCV002051783, RCV002466400, RCV002482860" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013482...</a>
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<div class="mim-changed mim-change"><p>In 54-year-old woman with renal cysts and diabetes syndrome (RCAD; <a href="/entry/137920">137920</a>), <a href="#4" class="mim-tip-reference" title="Bellanne-Chantelot, C., Chauveau, D., Gautier, J.-F., Dubois-Laforgue, D., Clauin, S., Beaufils, S., Wilhelm, J.-M., Boitard, C., Noel, L.-H., Velho, G., Timsit, J. <strong>Clinical spectrum associated with hepatocyte nuclear factor-1B mutations.</strong> Ann. Intern. Med. 140: 510-517, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15068978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15068978</a>] [<a href="https://doi.org/10.7326/0003-4819-140-7-200404060-00009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15068978">Bellanne-Chantelot et al. (2004)</a>, identified heterozygosity for a 494G-A transition in the HNF1B gene, resulting in an arg165-to-his (R165H) substitution. She was diagnosed with MODY5 at age 20 years and had renal cysts, reduced kidney size, and bicornuate uterus. At age 54, she was diagnosed with chromophobe renal carcinoma (<a href="/entry/144700">144700</a>). By mutation screening of tumor samples, <a href="#25" 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 biallelic inactivation resulting from the R165H mutation and a somatic gene deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15068978+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></div>
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<strong>.0015 RENAL CELL CARCINOMA, CHROMOPHOBE</strong>
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HNF1B, 1-BP DEL, 46C
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000013483 OR RCV000787258" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000013483, RCV000787258" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000013483...</a>
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<p>In a 37-year-old woman with chromophobe renal cell carcinoma (<a href="/entry/144700">144700</a>), <a href="#25" 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 a germline 1-bp deletion at nucleotide 46 (46delC) of the HNF1B gene, resulting in a frameshift and premature termination at codon 17. Mutation screening of tumor samples identified biallelic inactivation resulting from the 1-bp deletion and a somatic gene deletion. Following partial nephrectomy of the primary tumor, local recurrence of 5 renal tumors required radical nephrectomy. In the recurrent tumor specimens, HNF1B alterations were identical to the primary tumor. When evaluated for MODY5, the patient had no liver test abnormality or diabetes, but CT scan detected absence of the body and tail of the pancreas. Renal abnormalities were observed in 2 of her children, but no other relatives exhibited findings suggestive of MODY5. <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>.0016 REMOVED FROM DATABASE</strong>
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<a id="seeAlso" class="mim-anchor"></a>
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<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>See Also:</strong>
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<a href="#Menzel1998" class="mim-tip-reference" title="Menzel, R., Kaisaki, P. J., Rjasanowski, I., Heinke, P., Kerner, W., Menzel, S. <strong>A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1-alpha (HNF-1-alpha) gene.</strong> Diabet. Med. 15: 816-820, 1998.">Menzel et al. (1998)</a>; <a href="#Nishigori1998" class="mim-tip-reference" title="Nishigori, H., Yamada, S., Kohama, T., Tomura, H., Sho, K., Horikawa, Y., Bell, G. I., Takeuchi, T., Takeda, J. <strong>Frameshift mutation, A263fsinsGG, in the hepatocyte nuclear factor-1-beta gene associated with diabetes and renal dysfunction.</strong> Diabetes 47: 1354-1355, 1998.">Nishigori et al. (1998)</a>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Abbott1990" class="mim-anchor"></a>
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Abbott, C., Piaggio, G., Ammendola, R., Solomon, E., Povey, S., Gounari, F., De Simone, V., Cortese, R.
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<strong>Mapping of the gene TCF2 for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction.</strong>
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Genomics 8: 165-167, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2081590/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2081590</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2081590" 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/10.1016/0888-7543(90)90239-q" target="_blank">Full Text</a>]
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<a id="Bach1991" class="mim-anchor"></a>
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Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M.
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<strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong>
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Nucleic Acids Res. 19: 3553-3559, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1677179/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1677179</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1677179" 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/10.1093/nar/19.13.3553" target="_blank">Full Text</a>]
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<a id="Barbacci2004" class="mim-anchor"></a>
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Barbacci, E., Chalkiadaki, A., Masdeu, C., Haumaitre, C., Lokmane, L., Loirat, C., Cloarec, S., Taliandis, I., Bellanne-Chantelot, C., Cereghini, S.
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<strong>HNF1-beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.</strong>
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Hum. Molec. Genet. 13: 3139-3149, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15509593/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15509593</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15509593" 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/10.1093/hmg/ddh338" target="_blank">Full Text</a>]
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<a id="Bellanne-Chantelot2004" class="mim-anchor"></a>
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Bellanne-Chantelot, C., Chauveau, D., Gautier, J.-F., Dubois-Laforgue, D., Clauin, S., Beaufils, S., Wilhelm, J.-M., Boitard, C., Noel, L.-H., Velho, G., Timsit, J.
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<strong>Clinical spectrum associated with hepatocyte nuclear factor-1B mutations.</strong>
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Ann. Intern. Med. 140: 510-517, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15068978/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15068978</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15068978" 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/10.7326/0003-4819-140-7-200404060-00009" target="_blank">Full Text</a>]
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Bingham, C., Bulman, M. P., Ellard, S., Allen, L. I. S., Lipkin, G. W., van't Hoff, W. G., Woolf, A. S., Rizzoni, G., Novelli, G., Nicholls, A. J., Hattersley, A. T.
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<strong>Mutations in the hepatocyte nuclear factor-1-beta gene are associated with familial hypoplastic glomerulocystic kidney disease.</strong>
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Am. J. Hum. Genet. 68: 219-224, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11085914/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11085914</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11085914" 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/10.1086/316945" target="_blank">Full Text</a>]
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<a id="Bingham2000" class="mim-anchor"></a>
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Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T.
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<strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong>
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Kidney Int. 57: 898-907, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720943</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720943" 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/10.1046/j.1523-1755.2000.057003898.x" target="_blank">Full Text</a>]
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<a id="Bingham2003" class="mim-anchor"></a>
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Bingham, C., Ellard, S., van't Hoff, W. G., Simmonds, A., Marinaki, A. M., Badman, M. K., Winocour, P. H., Stride, A., Lockwood, C. R., Nicholls, A. J., Owen, K. R., Spyer, G., Peason, E. R., Hattersley, A. T.
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<strong>Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1-beta gene mutation.</strong>
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Kidney Int. 63: 1645-1651, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12675839/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12675839</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12675839" 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/10.1046/j.1523-1755.2003.00903.x" target="_blank">Full Text</a>]
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<a id="Carette2007" class="mim-anchor"></a>
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Carette, C., Vaury, C., Barthelemy, A., Clauin, S., Grunfeld, J.-P., Timsit, J., Bellanne-Chantelot, C.
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<strong>Exonic duplication of the hepatocyte nuclear factor-1-beta gene (transcription factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5.</strong>
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J. Clin. Endocr. Metab. 92: 2844-2847, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17440011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17440011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17440011" 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.2007-0286" target="_blank">Full Text</a>]
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<a id="Edghill2006" class="mim-anchor"></a>
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Edghill, E. L., Bingham, C., Ellard, S., Hattersley, A. T.
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<strong>Mutations in hepatocyte nuclear factor-1-beta and their related phenotypes.</strong>
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J. Med. Genet. 43: 84-90, 2006.
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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>]
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[<a href="https://doi.org/10.1093/hmg/ddi057" 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="26" class="mim-anchor"></a>
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<a id="Rizzoni1982" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Rizzoni, G., Loirat, C., Levy, M., Milanesi, C., Zachello, G., Mathieu, H.
|
|
<strong>Familial hypoplastic glomerulocystic kidney: a new entity?</strong>
|
|
Clin. Nephrol. 18: 263-268, 1982.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7151342/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7151342</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7151342" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</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="27" class="mim-anchor"></a>
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<a id="Verdeguer2010" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Verdeguer, F., Le Corre, S., Fischer, E., Callens, C., Garbay, S., Doyen, A., Igarashi, P., Terzi, F., Pontoglio, M.
|
|
<strong>A mitotic transcriptional switch in polycystic kidney disease. (Letter)</strong>
|
|
Nature Med. 16: 106-110, 2010.
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966811/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966811</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966811[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=19966811" 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/nm.2068" 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="28" class="mim-anchor"></a>
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<a id="Wild2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wild, W., Pogge von Strandmann, E., Nastos, A., Senkel, S., Lingott-Frieg, A., Bulman, M., Bingham, C., Ellard, S., Hattersley, A. T., Ryffel, G. U.
|
|
<strong>The mutated human gene encoding hepatocyte nuclear factor 1-beta inhibits kidney formation in developing Xenopus embryos.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 4695-4700, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10758154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10758154</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10758154[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=10758154" 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/10.1073/pnas.080010897" 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="29" class="mim-anchor"></a>
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<a id="Yorifuji2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yorifuji, T., Kurokawa, K., Mamada, M., Imai, T., Kawai, M., Nishi, Y., Shishido, S., Hasegawa, Y., Nakahata, T.
|
|
<strong>Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1-beta gene due to germline mosaicism.</strong>
|
|
J. Clin. Endocr. Metab. 89: 2905-2908, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15181075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15181075</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15181075" 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.2003-031828" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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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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<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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Cassandra L. Kniffin - updated : 4/2/2014
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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">
|
|
Marla J. F. O'Neill - updated : 3/14/2012<br>Patricia A. Hartz - updated : 2/4/2010<br>Ada Hamosh - updated : 1/16/2009<br>Patricia A. Hartz - updated : 4/18/2008<br>George E. Tiller - updated : 2/5/2008<br>John A. Phillips, III - updated : 1/23/2008<br>Marla J. F. O'Neill - updated : 10/24/2007<br>Victor A. McKusick - updated : 10/10/2007<br>George E. Tiller - updated : 5/21/2007<br>John A. Phillips, III - updated : 4/7/2006<br>Cassandra L. Kniffin - updated : 4/5/2006<br>Victor A. McKusick - updated : 2/14/2006<br>George E. Tiller - updated : 1/10/2006<br>Marla J. F. O'Neill - updated : 5/20/2004<br>Marla J. F. O'Neill - updated : 4/27/2004<br>John A. Phillips, III - updated : 1/21/2003<br>Ada Hamosh - updated : 10/18/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 6/15/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 12/2/1997
|
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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 : 3/27/1990
|
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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="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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carol : 02/26/2025
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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 : 02/26/2025<br>carol : 02/09/2021<br>alopez : 01/05/2015<br>carol : 4/8/2014<br>ckniffin : 4/2/2014<br>carol : 12/2/2013<br>carol : 9/5/2013<br>carol : 3/14/2012<br>alopez : 4/16/2010<br>mgross : 2/15/2010<br>terry : 2/4/2010<br>alopez : 1/21/2009<br>terry : 1/16/2009<br>carol : 9/23/2008<br>mgross : 4/18/2008<br>alopez : 4/17/2008<br>alopez : 4/16/2008<br>wwang : 2/7/2008<br>terry : 2/5/2008<br>carol : 1/23/2008<br>carol : 11/16/2007<br>wwang : 10/25/2007<br>terry : 10/24/2007<br>alopez : 10/15/2007<br>terry : 10/10/2007<br>wwang : 6/4/2007<br>terry : 5/21/2007<br>alopez : 4/7/2006<br>carol : 4/7/2006<br>ckniffin : 4/5/2006<br>alopez : 2/27/2006<br>terry : 2/14/2006<br>wwang : 2/9/2006<br>wwang : 1/30/2006<br>terry : 1/10/2006<br>carol : 5/24/2004<br>carol : 5/24/2004<br>terry : 5/20/2004<br>carol : 4/27/2004<br>terry : 3/19/2004<br>alopez : 1/21/2003<br>carol : 10/18/2001<br>joanna : 1/30/2001<br>carol : 1/24/2001<br>terry : 1/23/2001<br>carol : 8/28/2000<br>carol : 8/25/2000<br>mcapotos : 7/20/2000<br>mcapotos : 7/19/2000<br>mcapotos : 7/19/2000<br>carol : 7/19/2000<br>mcapotos : 7/17/2000<br>mcapotos : 7/12/2000<br>terry : 6/15/2000<br>alopez : 11/15/1999<br>psherman : 11/9/1999<br>alopez : 11/4/1999<br>mgross : 11/4/1999<br>terry : 10/25/1999<br>dkim : 7/21/1998<br>psherman : 3/16/1998<br>mark : 12/3/1997<br>jenny : 12/2/1997<br>terry : 11/25/1997<br>carol : 11/13/1992<br>carol : 10/22/1992<br>supermim : 3/16/1992<br>carol : 9/4/1991<br>carol : 9/6/1990<br>carol : 6/11/1990
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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">
|
|
<strong>*</strong> 189907
|
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</span>
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</h3>
|
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</div>
|
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|
<div>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
HNF1 HOMEOBOX B; HNF1B
|
|
|
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</span>
|
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</h3>
|
|
</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>
|
|
<span class="mim-font">
|
|
<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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TRANSCRIPTION FACTOR 2; TCF2<br />
|
|
TRANSCRIPTION FACTOR, LIVER-SPECIFIC, 3<br />
|
|
HEPATOCYTE NUCLEAR FACTOR-1-BETA<br />
|
|
HEPATIC NUCLEAR FACTOR-1-BETA<br />
|
|
HEPATOCYTE NUCLEAR FACTOR 2; HNF2
|
|
</span>
|
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</h4>
|
|
</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: HNF1B</em></strong>
|
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</span>
|
|
</p>
|
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</div>
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<div>
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<p>
|
|
<span class="mim-text-font">
|
|
|
|
<strong>SNOMEDCT:</strong> 128667008, 253864004, 44054006, 609572000, 733471003;
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|
|
<strong>ICD10CM:</strong> E11;
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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: 17q12
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 17:37,686,431-37,745,059 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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<div>
|
|
<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="3">
|
|
<span class="mim-font">
|
|
17q12
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
{Renal cell carcinoma}
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
144700
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Renal cysts and diabetes syndrome
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
137920
|
|
</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">
|
|
Type 2 diabetes mellitus
|
|
</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>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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<div>
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<br />
|
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</div>
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|
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|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
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|
<span class="mim-text-font">
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<p>Hepatocyte nuclear factor-1-beta (HNF1B), also known as transcription factor-2 (TCF2), is a member of the homeodomain-containing superfamily of transcription factors (Bach et al., 1991). Early expression of TCF2 is seen in the kidney, liver, bile ducts, thymus, genital tract, pancreas, lung, and gut. It can act either as a homodimer or as a heterodimer with HNF1A (142410) (Edghill et al., 2006). </p>
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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>Abbott et al. (1990) isolated and partially sequenced a human clone corresponding to the HNF1B gene, which they called LFB3. </p><p>Bach et al. (1991) isolated a cDNA clone from a human liver library encoding a protein, designated HNF1B, that is highly homologous to HNF1A in 3 regions, including the homeodomain and the dimerization domain. They showed that this protein can heterodimerize with human HNF1A in vitro. Sequence comparison with a rat variant HNF1A identified the cDNA as the human homolog. HNF1B is a nuclear protein recognizing the same binding site as HNF1A. By Northern blot analysis, Bach et al. (1991) showed that the HNF1B transcripts are present in differentiated human HepG2 hepatoma cells as well as in rat liver and that this transcript level is 10- to 20-fold lower than that of HNF1A. </p>
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</span>
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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>Gene Structure</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 HNF1B gene contains 9 exons (Horikawa et al., 1997). </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>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>By analysis of human/rodent somatic cell hybrids, Abbott et al. (1990) mapped the TCF2 gene to chromosome 17q between the centromere and the breakpoint of acute promyelocytic leukemia, i.e., proximal to 17q22. </p><p>Bach et al. (1991) assigned the HNF1B gene to human chromosome 17 and mouse chromosome 11. The HNF1A gene maps to human chromosome 12 and mouse chromosome 5. </p><p>Gudmundsson et al. (2007) noted that the HNF1B gene maps to chromosome 17q12. </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>Kolatsi-Joannou et al. (2001) detected TCF2 mRNA in liver, pancreas, stomach, and lung through 91 days' gestation in 6 terminated normal human fetuses. Renal metanephroi expressed the gene at preglomerular stages during metanephrogenesis. The expression was most prominent in medullary and cortical collecting duct branches, which are ureteric bud derivatives. TCF2 gene expression was not detected in mesenchymal tissues, suggesting that it plays a role in epithelial differentiation. </p><p>Using genomewide chromatin immunoprecipitation and DNA microarray analysis and microarray analysis of mRNA expression, Ma et al. (2007) identified Socs3 (604176) as an Hnf1b target gene in mouse kidney. Hnf1b bound to the Socs3 promoter and repressed Socs3 transcription. Expression of Socs3 increased in Hnf1b-knockout mice and in renal epithelial cells expressing dominant-negative mutant Hnf1b. Increased levels of Socs3 inhibited Hgf (142409)-induced tubulogenesis by decreasing phosphorylation of Erk (see MAPK1; 176948) and Stat3 (102582). Conversely, knockdown of Socs3 in renal epithelial cells expressing dominant-negative mutant Hnf1b rescued the defect in Hgf-induced tubulogenesis by restoring phosphorylation of Erk and Stat3. Ma et al. (2007) concluded that HNF1B regulates renal tubulogenesis by controlling expression of SOC3. </p><p>By time-lapse microscopy of IMCD3 mouse renal cells expressing fluorescence-tagged Hnf1b, Verdeguer et al. (2010) found that, unlike the classical behavior of transcription factors, such as Hnf4a (600281), a substantial fraction of Hnf1b remained associated with mitotic chromatin and traveled with condensed chromosomes throughout mitosis. From these observations and data they obtained following conditional knockout of Hnf1b in mice (see ANIMAL MODEL), Verdeguer et al. (2010) hypothesized that HNF1B functions as both a classic transcriptional activator and as a bookmarking factor that marks target genes for rapid transcriptional reactivation after mitosis. </p><p>Kornfeld et al. (2013) found that inducible transgenic overexpression of Mir802 (616090) in mice caused impaired glucose tolerance and attenuated insulin sensitivity, whereas reduction of Mir802 expression improved glucose tolerance and insulin action. The authors identified Hnf1b as a target of Mir802-dependent silencing, and showed that short hairpin RNA (shRNA)-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signaling, and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in Lepr (601007)(db/db) mice. Kornfeld et al. (2013) concluded that their study defined a critical role for deregulated expression of MIR802 in the development of obesity-associated impairment of glucose metabolism through targeting of HNF1B, and assigned HNF1B an unexpected role in the control of hepatic insulin sensitivity. </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>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><strong><em>Renal Cysts and Diabetes Syndrome</em></strong></p><p>
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In 2 Japanese sibs with a phenotype consistent with renal cysts and diabetes syndrome (RCAD; 137920), Horikawa et al. (1997) identified a heterozygous mutation in the TCF2 gene (189907.0001). The sibs developed diabetes mellitus at ages 10 and 15 years, respectively, consistent with a diagnosis of maturity-onset diabetes of the young (MODY5). Although there was no report of renal appearance or histology, a nonspecific nephropathy was described. </p><p>In affected members of a Norwegian family with renal cysts and diabetes syndrome, Lindner et al. (1999) identified a 75-bp deletion in exon 2 of the TCF2 gene (189907.0002). Bingham et al. (2000) identified a heterozygous 5-bp deletion in the TCF2 gene (189907.0003) in a woman with renal cysts and diabetes syndrome. </p><p>Bingham et al. (2001) identified 2 different heterozygous mutations in the TCF2 gene (189907.0004 and 189907.0005) in affected members of the families reported by Rizzoni et al. (1982) and Kaplan et al. (1989) as having familial hypoplastic glomerulocystic kidney disease. All of the patients eventually developed diabetes mellitus. </p><p>In 8 probands and 5 offspring with renal cysts and diabetes syndrome, Bellanne-Chantelot et al. (2004) identified 8 novel mutations in the TCF2 gene, all in the DNA-binding domain: 5 missense mutations (see, e.g., 189907.0014), 2 nonsense mutations, and 1 mutation in the splice donor site of intron 2 at the highly conserved +1 position. Cosegregation of the mutation and the phenotype was observed in 4 families; 2 mutations were de novo. The patients had various renal abnormalities and some also had genital tract abnormalities and pancreatic atrophy. Eleven patients had abnormal liver enzyme levels with normal liver function. </p><p>Barbacci et al. (2004) functionally characterized 5 missense mutations, 2 truncating mutations, and 1 frameshift deletion in different domains of the TCF2 protein. Truncation mutations, retaining the dimerization domain, displayed defective nuclear localization and weak dominant-negative activity when coexpressed with the wildtype protein. A frameshift mutation located within the C-terminal QSP-rich domain partially reduced transcriptional activity, whereas selective deletion of this domain abolished transactivation. All 5 missense mutations, which involved POU-specific and homeodomain residues, were correctly expressed and localized to the nucleus. Although having different effects on DNA-binding capacity that ranged from complete loss to mild reduction, these mutations exhibited severe reduction in transactivation capacity. The transcriptional impairment of mutations with weak or unaffected DNA-binding activity correlated with the loss of association with 1 of the histone-acetyltransferases CREBBP (600140) or PCAF (602303). In contrast to the transactivation potential of wildtype TCF2, which depends on the synergistic action of CREBBP and PCAF, the activity of these mutants was not increased by the synergistic action of these 2 coactivators or by treatment with a specific histone-deacetylase inhibitor. Barbacci et al. (2004) concluded that the complex syndrome associated with TCF2 mutations arises from either defective DNA-binding or decreased transactivation function through impaired coactivator recruitment. </p><p>Harries et al. (2005) investigated the susceptibility to nonsense-mediated decay (NMD) of 6 truncating HNF1B mutations. Four of the 6 mutations showed evidence of NMD; 2 mutations, 1 of which was P159fsdelT (189907.0005), produced transcripts unexpectedly immune to NMD. Harries et al. (2005) concluded that truncating mutant transcripts of the HNF1B gene do not conform to the known rules governing NMD susceptibility, but instead demonstrate a previously unreported 5-prime to 3-prime polarity. They hypothesized that this may be due to reinitiation of translation downstream of the premature termination codon, thus providing a mechanism for the evasion of NMD, but that other factors such as the distance from the native initiation codon may play a part. </p><p>Nakayama et al. (2010) identified heterozygous pathogenic HNF1B mutations in 5 (10%) of 50 Japanese children with congenital anomalies of the kidney and urinary tract (CAKUT), including 2 with hypodysplastic kidneys and 3 with unilateral multicystic dysplastic kidneys. No mutations were found in 4 patients with a single kidney. There were 3 whole-gene deletions, 1 truncating mutation, and 1 missense mutation. The clinical spectrum of renal disease was variable, ranging in severity from unilateral disease and normal renal function to bilateral disease necessitating transplant. However, none of the patients had evidence of diabetes. </p><p><strong><em>Susceptibility to Chromophobe Renal Cell Carcinoma</em></strong></p><p>
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Rebouissou et al. (2005) screened 35 renal neoplasms for HNF1A and HNF1B inactivation. Biallelic HNF1B inactivation was found in 2 of 12 chromophobe renal carcinomas by association of 2 germline mutations (189907.0014 and 189907.0015, respectively) with somatic gene deletion. In these cases, expression of PKHD1 (606702) and uromodulin (UMOD; 191845), 2 genes regulated by HNF1B, was turned off. 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 HNF1B, PKHD1, and UMOD. Rebouissou et al. (2005) suggested that germline mutations of HNF1B may predispose to renal tumors and proposed that HNF1B may function as a tumor suppressor gene in chromophobe renal cell carcinogenesis through control of PKHD1 expression. </p><p><strong><em>Possible Association with Prostate Cancer</em></strong></p><p>
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For information regarding a possible association of single-nucleotide polymorphisms (SNPs) in the HNF1B gene with susceptibility to prostate cancer, see HPC11 (611955).</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>Genotype/Phenotype Correlations</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>Wild et al. (2000) reported that the 5-bp deletion in the TCF2 gene reported by Bingham et al. (2000) resulted in a truncated protein that retained the DNA-binding domain; 3 previously reported mutations lacked part of the DNA-binding domain. In transfection experiments, the 5-bp deletion was associated with nephron agenesis and acted as a gain-of-function mutation with increased transactivation potential. Expression of this mutated factor in Xenopus embryos led to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects were generated by overexpression of wildtype HNF1B, consistent with the gain-of-function property of the mutant. In contrast, introduction of the human 75-bp deletion HNF1B mutant, which was associated with a reduced number of nephrons and hypertrophy of the remaining ones and had impaired DNA binding, showed only a minor effect on pronephros development in Xenopus. Thus, the overexpression of both human mutants had a different effect on renal development in Xenopus, reflecting the variation in renal phenotype seen with these mutations. The findings implied that HNF1B not only is an early marker of kidney development but also is functionally involved in morphogenetic events, and that these processes can be investigated in lower vertebrates. </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>Animal Model</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>During pancreatic organogenesis, endocrine cells arise from non-self-renewing progenitors that express Ngn3 (604882). Maestro et al. (2003) showed that from E13 to E18 (the embryonic stage during which the major burst of beta-cell neogenesis takes place) murine pancreatic duct cells express Hnf1b. Ngn3-positive cells at this stage invariably cluster with mitotically competent Hnf1b-positive cells and are often intercalated with these cells in the epithelium that lines the lumen of primitive ducts. Hnf1b expression is markedly reduced in early pancreatic epithelial cells of Hnf6 (ONECUT1; 604164)-deficient mice, in which formation of Ngn3-positive cells is defective. Maestro et al. (2003) suggested that Hnf1b plays a role in the genetic hierarchy regulating the generation of pancreatic endocrine cells. </p><p>Hiesberger et al. (2004) identified an evolutionarily conserved TCF2-binding site in the proximal promoter of the mouse Pkhd1 gene. Mutations in the human homolog (PKHD1; 606702) cause autosomal recessive polycystic kidney disease (see 263200). Wildtype Tcf2 and the structurally related Tcf1 were noted to bind specifically to the Pkhd1 promoter and activate gene transcription. Expression of a dominant-negative Tcf2 mutant inhibited Pkhd1 expression and produced renal cysts in transgenic mice. Pkhd1 transcripts were absent in the cells lining the cysts but were present in morphologically normal surrounding tubules. The authors concluded that TCF2 directly regulates the transcription of PKHD1 and that inhibition of PKHD1 gene expression may contribute to the formation of renal cysts in humans with MODY5. </p><p>Verdeguer et al. (2010) found that conditional knockout of Hnf1b expression in young mice led to the development of polycystic kidneys, whereas knockout on postnatal day 10 or later significantly delayed cyst development. Experiments with ischemia-reperfusion injury of adult wildtype and Hnf1b-knockout kidneys suggested that cyst formation following Hnf1b knockout required a background of rapid cell proliferation. In both developing kidney and regenerating adult kidney, Hnf1b knockout enhanced cell proliferation and distorted the orientation and synchronization of tubule cells required for tubule elongation, resulting in tubule dilation and cyst formation. Verdeguer et al. (2010) concluded that HNF1B is required to rapidly reactivate crucial target genes that orient rapidly proliferating cells toward tubule elongation. </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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<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>16 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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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 RENAL CYSTS AND DIABETES SYNDROME</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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HNF1B, ARG177TER
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<br />
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SNP: rs1800575,
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ClinVar: RCV000013470, RCV001851826, RCV002496342
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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 2 Japanese sibs with renal disease and diabetes syndrome (RCAD; 137920), Horikawa et al. (1997) identified a heterozygous C-to-T transition in the TCF2 gene, resulting in an arg177-to-ter (R177X) substitution. The R177X mutation generated a truncated 176-residue protein with the NF2-dimerization and POU domains. This truncated protein did not stimulate transcription of a rat albumin promoter-linked reporter gene or inhibit the activity of wildtype TCF2, consistent with a loss of function. The 2 sibs had onset of diabetes at ages 10 and 15, respectively, consistent with a diagnosis of maturity-onset diabetes of the young type 5 (MODY5). Although both parents had late-onset diabetes, only the mother carried the TCF2 mutation. Horikawa et al. (1997) postulated that the early onset in the children reflected bilineal inheritance of 2 different diabetes susceptibility genes. </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 RENAL CYSTS AND DIABETES SYNDROME</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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HNF1B, 75-BP DEL, NT409
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<br />
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ClinVar: RCV000787198
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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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<div class="mim-changed mim-change"><p>In affected members of a Norwegian family with renal cysts and diabetes syndrome (RCAD; 137920), Lindner et al. (1999) identified a 75-bp deletion spanning nucleotides 409 to 483 in exon 2 of the TCF2 gene (189907.0002), resulting in the synthesis of a protein lacking amino acids arg137 to lys161. This deletion was located in the pseudo-POU region of TCF2, a region implicated in the specificity of DNA binding. Functional studies of the mutant TCF2 protein showed that it could not bind a TCF1 target sequence or stimulate transcription of the reporter gene, indicating that this was a loss-of-function mutation. Two of 4 female mutation carriers had vaginal aplasia and rudimentary uterus (mullerian aplasia; 277000) in addition to diabetes and renal disease. The presence of internal genital malformations suggested that additional clinical features may be associated with TCF2 mutations. </p></div>
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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 RENAL CYSTS AND DIABETES SYNDROME</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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HNF1B, 5-BP DEL
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<br />
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ClinVar: RCV000787107
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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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<div class="mim-changed mim-change"><p>In a woman with renal cysts and diabetes syndrome (RCAD; 137920), Bingham et al. (2000) identified a heterozygous 5-bp deletion in the TCF2 gene, which the authors designated P328L329fsdelCCTCT, resulting in a frameshift and premature termination of the protein. Her first pregnancy was terminated at 17 weeks following an ultrasound diagnosis of bilateral nonfunctioning cystic kidneys. Her first-born child had small multicystic, dysplastic kidneys with no normal nephrogenesis. </p></div>
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<p>Wild et al. (2000) demonstrated that the 5-bp deletion reported by Bingham et al. (2000) resulted in a truncated protein that retained the DNA-binding domain; 3 previously reported mutations lacked part of the DNA-binding domain. Transfection experiments showed that the 5-bp deletion was associated with nephron agenesis and acted as a gain-of-function mutation with increased transactivation potential. Expression of this mutated factor in Xenopus embryos led to defective development and agenesis of the pronephros, the first kidney form of amphibians. Very similar defects were generated by overexpression of wildtype TCF2, consistent with the gain-of-function property of the mutant. </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 RENAL CYSTS AND DIABETES SYNDROME</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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HNF1B, GLU101TER
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<br />
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SNP: rs121918671,
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gnomAD: rs121918671,
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ClinVar: RCV000013473, RCV004700225
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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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<div class="mim-changed mim-change"><p>In 3 affected members of an Italian family with renal cysts and diabetes syndrome (RCAD; 137920), Bingham et al. (2001) identified a heterozygous mutation in exon 1 of the TCF2 gene, resulting in a glu101-to-ter (E101X) substitution. The family was originally described by Rizzoni et al. (1982) as having familial hypoplastic glomerulocystic kidney disease. </p></div>
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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>.0005 RENAL CYSTS AND DIABETES SYNDROME</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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HNF1B, 1-BP DEL
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<br />
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ClinVar: RCV000013474
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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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<div class="mim-changed mim-change"><p>In affected members of a family with renal cysts and diabetes syndrome (RCAD; 137920), Bingham et al. (2001) identified a heterozygous 1-bp deletion (delT) in exon 2 of the TCF2 gene, predicted to result in a frameshift and premature termination of the protein at codon 160. The family had originally been reported by Kaplan et al. (1989) as having familial hypoplastic glomerulocystic kidney disease. </p></div>
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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>.0006 RENAL CYSTS AND DIABETES SYNDROME</strong>
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</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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|
HNF1B, ARG276TER
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|
<br />
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|
SNP: rs121918672,
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|
ClinVar: RCV000013475, RCV001328308, RCV002472930, RCV002496343, RCV004689416
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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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|
<div class="mim-changed mim-change"><p>Furuta et al. (2002) screened the HNF1B gene for mutations in a group of 126 unrelated Japanese patients with type 2 diabetes (125853) and a family history of at least 1 first-degree relative with diabetes. In a patient with diabetes diagnosed at 13 years of age, they found a C-to-T transition in exon 4 of the HNF1B gene, which resulted in an arg276-to-ter (R276X) amino acid substitution in the protein product. This patient had MODY5 misdiagnosed as common type 2 diabetes. He had small kidneys with multiple bilateral renal cysts and decreased urinary concentrating ability (RCAD; 137920). Functional studies indicated that the mutant hepatocyte nuclear factor-1-beta was inactive. </p></div>
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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>.0007 TYPE 2 DIABETES MELLITUS</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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HNF1B, SER465ARG
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<br />
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SNP: rs121918673,
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gnomAD: rs121918673,
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ClinVar: RCV000013476, RCV001124747, RCV003153303
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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 group of 126 unrelated Japanese patients with type 2 diabetes (T2D; 125853) and a family history of at least 1 first-degree relative with diabetes, Furuta et al. (2002) identified a C-to-G translation in exon 7 of the HNF1B gene, resulting in a ser465-to-arg (S465R) amino acid substitution, in a 50-year-old female diagnosed at 49 years of age. On screening a second group of 272 randomly selected patients with type 2 diabetes, they identified a second patient with the S465R mutation, a 68-year-old male whose diabetes was well controlled with diet therapy. Neither patient with the S465R mutation showed evidence of kidney disease. Functional studies indicated that the mutant protein exhibited a 22% reduction in activity compared with the wildtype protein. The S465R mutation may function in a dominant-negative manner. The authors concluded that the S465R mutation, found in 0.5% of patients with common type 2 diabetes examined, may thus be a rare genetic risk factor contributing to the development of type 2 diabetes rather than MODY5. </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>.0008 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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HNF1B, 1-BP INS, 1055A
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<br />
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ClinVar: RCV000013477
|
|
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|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a mother and son with renal cysts and diabetes syndrome (RCAD; 137920), Kolatsi-Joannou et al. (2001) identified a heterozygous 1-bp insertion (1055insA) in exon 5 of the TCF2 gene, resulting in a frameshift and premature termination of the protein at codon 352. The son had congenital cystic kidneys and was normoglycemic at age 12 years; his mother developed gestational diabetes at age 24 years and later developed renal cysts. The mutant TCF2 protein was predicted to retain dimerization and DNA-binding domains, but to lack most of the transactivation domain. </p></div>
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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HNF1B, IVS2DS, G-A, +1
|
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<br />
|
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|
|
|
|
|
ClinVar: RCV000013478, RCV001794444, RCV002504781
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In a mother and 2 daughters with renal cysts and diabetes syndrome (RCAD; 137920), Iwasaki et al. (2001) identified a heterozygous G-to-A transition in intron 2 of the TCF2 gene, resulting in a splice site mutation. The mother developed diabetes at age 27 years and the children at age 11 years. All had renal cysts, the mother had a bicornuate uterus, and 1 of the daughters had hyperuricemia. The mutation was not identified in 100 control chromosomes. </p></div>
|
|
</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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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
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|
HNF1B, IVS2DS, G-T, +1
|
|
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|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000013479, RCV002266902, RCV003390678
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In affected members of a family with renal cysts and diabetes syndrome (RCAD; 137920), Bingham et al. (2003) identified a heterozygous splice site mutation in the TCF2 gene. The patients also showed juvenile hyperuricemic nephropathy and early-onset gout. Bingham et al. (2003) concluded that hyperuricemia is a consistent feature of the disorder. A G-to-A transition in the same splice site position had been reported by Iwasaki et al. (2001); see 189907.0009. </p></div>
|
|
</span>
|
|
</div>
|
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<div>
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|
<br />
|
|
</div>
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|
</div>
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<div>
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1B, SER148TRP
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|
|
<br />
|
|
|
|
SNP: rs121918674,
|
|
|
|
|
|
|
|
ClinVar: RCV000013480, RCV001551662
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In 2 sibs with discordant phenotypes of the renal cysts and diabetes syndrome (RCAD; 137920), Yorifuji et al. (2004) reported recurrence of a missense mutation in TCF2 in 2 sibs, ser148 to trp (S148W), caused by a C-to-G transversion at nucleotide 443 in exon 2. The first sib had neonatal diabetes mellitus and kidneys with only a few small cysts and normal renal function. The second had neonatal polycystic, dysplastic kidneys leading to early renal failure but only a transient episode of hyperglycemia, which resolved spontaneously. Both parents were clinically unaffected, and RFLP analysis showed that the mother was a low-level mosaic of normal and mutant TCF2, which suggested that the recurrence was caused by germline mosaicism. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0013 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1B, EX5DUP
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000013481
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In 3 affected members of a French family with renal cysts and diabetes syndrome (RCAD; 137920), Carette et al. (2007) identified duplication of exon 5 (gly349_M402dup) of the TCF2 gene. There was wide intrafamilial variability of the phenotype. The proband had hyperuricemic nephropathy and early gout, chronic renal failure, renal morphologic abnormalities, abnormal liver tests, and diabetes. His son had almost no clinical expression of the disease, whereas his grandson had a restricted but severe renal phenotype present from birth. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0014 RENAL CYSTS AND DIABETES SYNDROME</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1B, ARG165HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121918675,
|
|
|
|
|
|
|
|
ClinVar: RCV000013482, RCV001659694, RCV002051783, RCV002466400, RCV002482860
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<div class="mim-changed mim-change"><p>In 54-year-old woman with renal cysts and diabetes syndrome (RCAD; 137920), Bellanne-Chantelot et al. (2004), identified heterozygosity for a 494G-A transition in the HNF1B gene, resulting in an arg165-to-his (R165H) substitution. She was diagnosed with MODY5 at age 20 years and had renal cysts, reduced kidney size, and bicornuate uterus. At age 54, she was diagnosed with chromophobe renal carcinoma (144700). By mutation screening of tumor samples, Rebouissou et al. (2005) identified biallelic inactivation resulting from the R165H mutation and a somatic gene deletion. </p></div>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0015 RENAL CELL CARCINOMA, CHROMOPHOBE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HNF1B, 1-BP DEL, 46C
|
|
|
|
|
|
<br />
|
|
|
|
|
|
|
|
ClinVar: RCV000013483, RCV000787258
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 37-year-old woman with chromophobe renal cell carcinoma (144700), Rebouissou et al. (2005) identified a germline 1-bp deletion at nucleotide 46 (46delC) of the HNF1B gene, resulting in a frameshift and premature termination at codon 17. Mutation screening of tumor samples identified biallelic inactivation resulting from the 1-bp deletion and a somatic gene deletion. Following partial nephrectomy of the primary tumor, local recurrence of 5 renal tumors required radical nephrectomy. In the recurrent tumor specimens, HNF1B alterations were identical to the primary tumor. When evaluated for MODY5, the patient had no liver test abnormality or diabetes, but CT scan detected absence of the body and tail of the pancreas. Renal abnormalities were observed in 2 of her children, but no other relatives exhibited findings suggestive of MODY5. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0016 REMOVED FROM DATABASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
</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">
|
|
Menzel et al. (1998); Nishigori et al. (1998)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
|
|
<div>
|
|
<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Abbott, C., Piaggio, G., Ammendola, R., Solomon, E., Povey, S., Gounari, F., De Simone, V., Cortese, R.
|
|
<strong>Mapping of the gene TCF2 for the transcription factor LFB3 to human chromosome 17 by polymerase chain reaction.</strong>
|
|
Genomics 8: 165-167, 1990.
|
|
|
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|
|
[PubMed: 2081590]
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[Full Text: https://doi.org/10.1016/0888-7543(90)90239-q]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bach, I., Mattei, M.-G., Cereghini, S., Yaniv, M.
|
|
<strong>Two members of an HNF1 homeoprotein family are expressed in human liver.</strong>
|
|
Nucleic Acids Res. 19: 3553-3559, 1991.
|
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|
|
[PubMed: 1677179]
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[Full Text: https://doi.org/10.1093/nar/19.13.3553]
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Barbacci, E., Chalkiadaki, A., Masdeu, C., Haumaitre, C., Lokmane, L., Loirat, C., Cloarec, S., Taliandis, I., Bellanne-Chantelot, C., Cereghini, S.
|
|
<strong>HNF1-beta/TCF2 mutations impair transactivation potential through altered co-regulator recruitment.</strong>
|
|
Hum. Molec. Genet. 13: 3139-3149, 2004.
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[PubMed: 15509593]
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[Full Text: https://doi.org/10.1093/hmg/ddh338]
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</p>
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|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Bellanne-Chantelot, C., Chauveau, D., Gautier, J.-F., Dubois-Laforgue, D., Clauin, S., Beaufils, S., Wilhelm, J.-M., Boitard, C., Noel, L.-H., Velho, G., Timsit, J.
|
|
<strong>Clinical spectrum associated with hepatocyte nuclear factor-1B mutations.</strong>
|
|
Ann. Intern. Med. 140: 510-517, 2004.
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[PubMed: 15068978]
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[Full Text: https://doi.org/10.7326/0003-4819-140-7-200404060-00009]
|
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bingham, C., Bulman, M. P., Ellard, S., Allen, L. I. S., Lipkin, G. W., van't Hoff, W. G., Woolf, A. S., Rizzoni, G., Novelli, G., Nicholls, A. J., Hattersley, A. T.
|
|
<strong>Mutations in the hepatocyte nuclear factor-1-beta gene are associated with familial hypoplastic glomerulocystic kidney disease.</strong>
|
|
Am. J. Hum. Genet. 68: 219-224, 2001.
|
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|
|
[PubMed: 11085914]
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[Full Text: https://doi.org/10.1086/316945]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Bingham, C., Ellard, S., Allen, L., Bulman, M., Shepherd, M., Frayling, T., Berry, P. J., Clark, P. M., Lindner, T., Bell, G. I., Ryffel, G. U., Nicholls, A. J., Hattersley, A. T.
|
|
<strong>Abnormal nephron development associated with a frameshift mutation in the transcription factor hepatocyte nuclear factor-1-beta.</strong>
|
|
Kidney Int. 57: 898-907, 2000.
|
|
|
|
|
|
[PubMed: 10720943]
|
|
|
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|
|
[Full Text: https://doi.org/10.1046/j.1523-1755.2000.057003898.x]
|
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</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
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Cassandra L. Kniffin - updated : 4/2/2014<br>Marla J. F. O'Neill - updated : 3/14/2012<br>Patricia A. Hartz - updated : 2/4/2010<br>Ada Hamosh - updated : 1/16/2009<br>Patricia A. Hartz - updated : 4/18/2008<br>George E. Tiller - updated : 2/5/2008<br>John A. Phillips, III - updated : 1/23/2008<br>Marla J. F. O'Neill - updated : 10/24/2007<br>Victor A. McKusick - updated : 10/10/2007<br>George E. Tiller - updated : 5/21/2007<br>John A. Phillips, III - updated : 4/7/2006<br>Cassandra L. Kniffin - updated : 4/5/2006<br>Victor A. McKusick - updated : 2/14/2006<br>George E. Tiller - updated : 1/10/2006<br>Marla J. F. O'Neill - updated : 5/20/2004<br>Marla J. F. O'Neill - updated : 4/27/2004<br>John A. Phillips, III - updated : 1/21/2003<br>Ada Hamosh - updated : 10/18/2001<br>Victor A. McKusick - updated : 1/23/2001<br>Victor A. McKusick - updated : 6/15/2000<br>Victor A. McKusick - updated : 10/25/1999<br>Victor A. McKusick - updated : 12/2/1997
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Victor A. McKusick : 3/27/1990
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carol : 02/26/2025<br>carol : 02/26/2025<br>carol : 02/09/2021<br>alopez : 01/05/2015<br>carol : 4/8/2014<br>ckniffin : 4/2/2014<br>carol : 12/2/2013<br>carol : 9/5/2013<br>carol : 3/14/2012<br>alopez : 4/16/2010<br>mgross : 2/15/2010<br>terry : 2/4/2010<br>alopez : 1/21/2009<br>terry : 1/16/2009<br>carol : 9/23/2008<br>mgross : 4/18/2008<br>alopez : 4/17/2008<br>alopez : 4/16/2008<br>wwang : 2/7/2008<br>terry : 2/5/2008<br>carol : 1/23/2008<br>carol : 11/16/2007<br>wwang : 10/25/2007<br>terry : 10/24/2007<br>alopez : 10/15/2007<br>terry : 10/10/2007<br>wwang : 6/4/2007<br>terry : 5/21/2007<br>alopez : 4/7/2006<br>carol : 4/7/2006<br>ckniffin : 4/5/2006<br>alopez : 2/27/2006<br>terry : 2/14/2006<br>wwang : 2/9/2006<br>wwang : 1/30/2006<br>terry : 1/10/2006<br>carol : 5/24/2004<br>carol : 5/24/2004<br>terry : 5/20/2004<br>carol : 4/27/2004<br>terry : 3/19/2004<br>alopez : 1/21/2003<br>carol : 10/18/2001<br>joanna : 1/30/2001<br>carol : 1/24/2001<br>terry : 1/23/2001<br>carol : 8/28/2000<br>carol : 8/25/2000<br>mcapotos : 7/20/2000<br>mcapotos : 7/19/2000<br>mcapotos : 7/19/2000<br>carol : 7/19/2000<br>mcapotos : 7/17/2000<br>mcapotos : 7/12/2000<br>terry : 6/15/2000<br>alopez : 11/15/1999<br>psherman : 11/9/1999<br>alopez : 11/4/1999<br>mgross : 11/4/1999<br>terry : 10/25/1999<br>dkim : 7/21/1998<br>psherman : 3/16/1998<br>mark : 12/3/1997<br>jenny : 12/2/1997<br>terry : 11/25/1997<br>carol : 11/13/1992<br>carol : 10/22/1992<br>supermim : 3/16/1992<br>carol : 9/4/1991<br>carol : 9/6/1990<br>carol : 6/11/1990
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