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Entry
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- *600480 - TRANSCRIPTION FACTOR 12; TCF12
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600480</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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<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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<a href="#cloning">Cloning and Expression</a>
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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="#cytogenetics">Cytogenetics</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="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600480">Table View</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 role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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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 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">
|
|
<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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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000140262;t=ENST00000333725" 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=6938" 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=600480" 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=ENSG00000140262;t=ENST00000333725" 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_001306219,NM_001306220,NM_001322151,NM_001322152,NM_001322154,NM_001322156,NM_001322157,NM_001322158,NM_001322159,NM_001322161,NM_001322162,NM_001322164,NM_001322165,NM_003205,NM_207036,NM_207037,NM_207038,NM_207040,XM_011521959,XM_011521960,XM_011521961,XM_011521962,XM_011521963,XM_011521966,XM_011521969,XM_017022520,XM_047432971,XM_047432972,XM_047432973,XM_047432974,XM_047432975,XM_047432976,XM_047432977,XM_047432978" 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_207037" 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=600480" 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=02725&isoform_id=02725_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/TCF12" 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/183930,184445,184448,1708332,4507391,9049977,29792012,30268206,31874026,33413338,46370080,46370082,46370084,46370086,119597917,119597918,119597919,119597920,119597921,119597922,119597923,194378100,194379012,194380390,194381038,194381172,194384300,767985127,767985129,767985131,767985133,767985135,767985142,767985148,808154262,808154264,1015809671,1015809673,1015809681,1015809719,1015809721,1015809770,1015809782,1015809792,1015809798,1015809802,1015809804,1034591666,2217302410,2217302413,2217302416,2217302418,2217302420,2217302423,2217302425,2217302428,2462545609,2462545611,2462545613,2462545615,2462545617,2462545619,2462545621,2462545623,2462545625,2462545627,2462545629,2462545631,2462545633,2462545635,2462545637,2462545639" 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/Q99081" 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=6938" 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=ENSG00000140262;t=ENST00000333725" 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=TCF12" 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=TCF12" 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+6938" 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/TCF12" 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:6938" 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/6938" 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=chr15&hgg_gene=ENST00000333725.10&hgg_start=56918090&hgg_end=57291310&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:11623" 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:11623" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=600480[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=600480[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/TCF12/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/ENSG00000140262" 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=TCF12" 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=TCF12" 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=TCF12" 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=TCF12&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/PA36381" 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:11623" 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://flybase.org/reports/FBgn0267821.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:101877" 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/TCF12#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:101877" 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/6938/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=6938" 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://wormbase.org/db/gene/gene?name=WBGene00001949;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040516-11" 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">
|
|
<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://reactome.org/content/query?q=TCF12&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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</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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600480
|
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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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TRANSCRIPTION FACTOR 12; TCF12
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
|
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</p>
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</div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
HELIX-LOOP-HELIX TRANSCRIPTION FACTOR 4; HTF4
|
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</span>
|
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</h4>
|
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</div>
|
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</div>
|
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<div>
|
|
<br />
|
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</div>
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<div>
|
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<a id="includedTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
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<span class="h3 mim-font">
|
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TCF12/NR4A3 FUSION GENE, INCLUDED
|
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</span>
|
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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>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TCF12" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TCF12</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/15/242?start=-3&limit=10&highlight=242">15q21.3</a>
|
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:56918090-57291310&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'})">15:56,918,090-57,291,310</a> </span>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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View Clinical Synopses
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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15q21.3
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Craniosynostosis 3
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<a href="/entry/615314"> 615314 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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Hypogonadotropic hypogonadism 26 with or without anosmia
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<a href="/entry/619718"> 619718 </a>
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>, <abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/600480" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/600480" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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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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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<a id="cloning" class="mim-anchor"></a>
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<h4 href="#mimCloningFold" id="mimCloningToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimCloningToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Cloning and Expression</strong>
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<p><a href="#11" class="mim-tip-reference" title="Zhang, Y., Babin, J., Feldhaus, A. L., Singh, H., Sharp, P. A., Bina, M. <strong>HTF4: a new human helix-loop-helix protein.</strong> Nucleic Acids Res. 19: 4555 only, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1886779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1886779</a>] [<a href="https://doi.org/10.1093/nar/19.16.4555" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1886779">Zhang et al. (1991)</a> obtained a partial cDNA for HTF4 which predicted a protein that is a member of the class A basic helix-loop-helix (bHLH) family. The same cDNA, designated HEB, was cloned by <a href="#5" class="mim-tip-reference" title="Hu, J.-S., Olson, E. N., Kingston, R. E. <strong>HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.</strong> Molec. Cell. Biol. 12: 1031-1042, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1312219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1312219</a>] [<a href="https://doi.org/10.1128/mcb.12.3.1031-1042.1992" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1312219">Hu et al. (1992)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1312219+1886779" 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="Gan, T.-I., Rowen, L., Nesbitt, R., Roe, B. A., Wu, H., Hu, P., Yao, Z., Kim, U.-J., O'Sickey, T., Bina, M. <strong>Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4.</strong> Cytogenet. Genome Res. 98: 245-248, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826747</a>] [<a href="https://doi.org/10.1159/000071042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12826747">Gan et al. (2002)</a> identified 3 TCF12 variants that result from alternative splicing and differential exon utilization. Two of the variants differ in the 5-prime untranslated region but encode identical proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12826747" 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="#10" class="mim-tip-reference" title="Wang, D., Claus, C. L., Vaccarelli, G., Braunstein, M., Schmitt, T. M., Zuniga-Pflucker, J. C., Rothenberg, E. V., Anderson, M. K. <strong>The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors.</strong> J. Immun. 177: 109-119, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16785505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16785505</a>] [<a href="https://doi.org/10.4049/jimmunol.177.1.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16785505">Wang et al. (2006)</a> noted that E2A (TCF3; <a href="/entry/147141">147141</a>) homodimers are essential for early B-cell development, whereas HEB/E2A heterodimers are dominant during T-cell development. By screening a mouse pro-T-cell cDNA library, followed by database analysis, they identified a novel HEB variant, which they termed HEBAlt. HEBAlt includes the bHLH domain and activation domain-2 (AD2) of canonical HEB (HEBCan), but it replaces AD1 with an alternative domain homologous to the N-terminal region of the ITF2A variant of ITF2 (TCF4; <a href="/entry/602272">602272</a>). The alternative domain of HEBAlt is well conserved in vertebrates. RT-PCR analysis showed that HebAlt was expressed only in the double-negative stages of mouse thymocyte development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16785505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<br />
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<a id="geneStructure" class="mim-anchor"></a>
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<h4 href="#mimGeneStructureFold" id="mimGeneStructureToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimGeneStructureToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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<p><a href="#3" class="mim-tip-reference" title="Gan, T.-I., Rowen, L., Nesbitt, R., Roe, B. A., Wu, H., Hu, P., Yao, Z., Kim, U.-J., O'Sickey, T., Bina, M. <strong>Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4.</strong> Cytogenet. Genome Res. 98: 245-248, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826747</a>] [<a href="https://doi.org/10.1159/000071042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12826747">Gan et al. (2002)</a> determined that the TCF12 gene contains 21 exons and spans about 370 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12826747" 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 id="mapping" class="mim-anchor"></a>
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<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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<p><a href="#13" class="mim-tip-reference" title="Zhang, Y., Flejter, W. L., Barcroft, C. L., Riviere, M., Szpirer, J., Szpirer, C., Bina, M. <strong>Localization of the human HTF4 transcription factors 4 gene (TCF12) to chromosome 15q21.</strong> Cytogenet. Cell Genet. 68: 235-238, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842744</a>] [<a href="https://doi.org/10.1159/000133921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842744">Zhang et al. (1995)</a> used a panel of somatic cell hybrids to map HTF4 to chromosome 15. By fluorescence in situ hybridization, they further localized the gene to 15q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7842744" 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>TCF12/NR4A3 Fusion Gene</em></strong></p><p>
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By spectral karyotyping, <a href="#9" class="mim-tip-reference" title="Sjogren, H., Wedell, B., Meis-Kindblom, J. M., Kindblom, L.-G., Stenman, G. <strong>Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21).</strong> Cancer Res. 60: 6832-6835, 2000. Note: Erratum: Cancer Res. 61: 2339 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11156374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11156374</a>]" pmid="11156374">Sjogren et al. (2000)</a> identified a reciprocal t(9;15)(q22;q21) translocation in cells obtained from a tumor with characteristics of extraskeletal myxoid chondrosarcoma (<a href="/entry/612237">612237</a>). The translocation produced a chimeric transcript encoding a protein in which the first 108 amino acids of the N terminus of TCF12 were fused in-frame upstream of the entire NR4A3 (<a href="/entry/600542">600542</a>) sequence. The N-terminal TCF12 sequence included in the fusion product contains potential phosphorylation and N-glycosylation sites. <a href="#3" class="mim-tip-reference" title="Gan, T.-I., Rowen, L., Nesbitt, R., Roe, B. A., Wu, H., Hu, P., Yao, Z., Kim, U.-J., O'Sickey, T., Bina, M. <strong>Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4.</strong> Cytogenet. Genome Res. 98: 245-248, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826747</a>] [<a href="https://doi.org/10.1159/000071042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12826747">Gan et al. (2002)</a> determined that intron 5 of the TCF12 gene was the region involved in the translocation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12826747+11156374" 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>Based on studies of the mouse and chicken cDNAs, <a href="#12" class="mim-tip-reference" title="Zhang, Y., Bina, M. <strong>The nucleotide sequence of the human transcription factor HTF4a cDNA.</strong> DNA Seq. 2: 397-403, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1446075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1446075</a>] [<a href="https://doi.org/10.3109/10425179209020819" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1446075">Zhang and Bina (1992)</a> proposed that transcripts of HTF4 can be differentially spliced to yield distinct but related proteins which are evolutionarily similar to the products of the E2A gene. In vitro assays had shown that HTF4 can form heterodimers with other bHLH proteins of class A (e.g., the E2A proteins; see <a href="/entry/147141">147141</a>) and class B (e.g., the myogenic factors; MYF3, <a href="/entry/159970">159970</a>; MYF5, <a href="/entry/159990">159990</a>; and MYF6, <a href="/entry/159991">159991</a>), as well as the inhibitor of DNA binding (ID1; <a href="/entry/600349">600349</a>) and stem cell leukemia hematopoietic transcription factor (TAL1; <a href="/entry/187040">187040</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1446075" 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 DNA binding assays, (<a href="#2" class="mim-tip-reference" title="Doyle, K., Zhang, Y., Baer, R., Bina, M. <strong>Distinguishable patterns of protein-DNA interactions involving complexes of basic helix-loop-helix proteins.</strong> J. Biol. Chem. 269: 12099-12105, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163514</a>]" pmid="8163514">Doyle et al., 1994</a>) found that complexes of HTF4 with the myogenic factors have a relatively high affinity for the E box motifs of the mE2 (CACGTG) and kappa E2/muE5 (CACCTG) types, whereas heterodimers of HTF4 and TAL1 interact poorly. They suggested that these results and those obtained from transient expression studies indicated that leukemogenesis caused by TAL1 might include a pathway where TAL1 would act as a negative regulator of gene expression by forming a complex with class A bHLH proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163514" 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 Northern blot analysis, <a href="#13" class="mim-tip-reference" title="Zhang, Y., Flejter, W. L., Barcroft, C. L., Riviere, M., Szpirer, J., Szpirer, C., Bina, M. <strong>Localization of the human HTF4 transcription factors 4 gene (TCF12) to chromosome 15q21.</strong> Cytogenet. Cell Genet. 68: 235-238, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842744</a>] [<a href="https://doi.org/10.1159/000133921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842744">Zhang et al. (1995)</a> showed that TCF12 is expressed at varying levels in many human cell lines and tissues. High levels of transcription in Jurkat cells supported the view that TCF12 gene products may play a central role in T-cell regulation (<a href="#5" class="mim-tip-reference" title="Hu, J.-S., Olson, E. N., Kingston, R. E. <strong>HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.</strong> Molec. Cell. Biol. 12: 1031-1042, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1312219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1312219</a>] [<a href="https://doi.org/10.1128/mcb.12.3.1031-1042.1992" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1312219">Hu et al., 1992</a>; <a href="#7" class="mim-tip-reference" title="Sawada, S., Littman, D. R. <strong>A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines.</strong> Molec. Cell. Biol. 13: 5620-5628, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8355705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8355705</a>] [<a href="https://doi.org/10.1128/mcb.13.9.5620-5628.1993" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8355705">Sawada and Littman, 1993</a>; <a href="#2" class="mim-tip-reference" title="Doyle, K., Zhang, Y., Baer, R., Bina, M. <strong>Distinguishable patterns of protein-DNA interactions involving complexes of basic helix-loop-helix proteins.</strong> J. Biol. Chem. 269: 12099-12105, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163514</a>]" pmid="8163514">Doyle et al., 1994</a>), and detection of the mRNA in human heart and skeletal muscle supported a role for TCF12 in myogenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8355705+7842744+1312219+8163514" 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="#10" class="mim-tip-reference" title="Wang, D., Claus, C. L., Vaccarelli, G., Braunstein, M., Schmitt, T. M., Zuniga-Pflucker, J. C., Rothenberg, E. V., Anderson, M. K. <strong>The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors.</strong> J. Immun. 177: 109-119, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16785505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16785505</a>] [<a href="https://doi.org/10.4049/jimmunol.177.1.109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16785505">Wang et al. (2006)</a> found that HEBAlt specifically bound to an E box motif. HEBAlt mRNA was upregulated synergistically by HEBCan activity and Delta (see <a href="/entry/606582">606582</a>)-Notch (see <a href="/entry/190198">190198</a>) signaling. Further experiments demonstrated that HEBAlt and HEBCan are functionally distinct transcription factors, with HEBAlt specifically required for efficient generation of early T-cell precursors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16785505" 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="#4" class="mim-tip-reference" title="Goardon, N., Lambert, J. A., Rodriguez, P., Nissaire, P., Herblot, S., Thibault, P., Dumenil, D., Strouboulis, J., Romeo, P.-H., Hoang, T. <strong>ETO2 coordinates cellular proliferation and differentiation during erythropoiesis.</strong> EMBO J. 25: 357-366, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407974</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407974[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/sj.emboj.7600934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407974">Goardon et al. (2006)</a> found that ETO2 (CBFA2T3; <a href="/entry/603870">603870</a>) copurified with TAL1 complexes in human and mouse erythroleukemia cells. Protein pull-down assays revealed that ETO2 interacted with E2A and HEB within the TAL1 complex, but not with TAL1 itself. ETO2 also interacted with E2A in erythroid cells independent of the TAL1 complex. Reporter gene assays revealed that ETO2 repressed the transcriptional activity of the complex. The ETO2 content in TAL1 complexes was high during the proliferative phase in erythroid cells. In contrast, ETO2 was downregulated upon terminal differentiation, concomitant with appearance of histone modifications associated with gene activation and expression of glycophorin A (GPA; <a href="/entry/617922">617922</a>) and band 4.2 (EPB42; <a href="/entry/177070">177070</a>), which are markers of erythrocyte maturation. Knockdown of ETO2 via small interfering RNA induced growth arrest and differentiation in human and mouse erythroid progenitors. <a href="#4" class="mim-tip-reference" title="Goardon, N., Lambert, J. A., Rodriguez, P., Nissaire, P., Herblot, S., Thibault, P., Dumenil, D., Strouboulis, J., Romeo, P.-H., Hoang, T. <strong>ETO2 coordinates cellular proliferation and differentiation during erythropoiesis.</strong> EMBO J. 25: 357-366, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407974</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407974[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/sj.emboj.7600934" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16407974">Goardon et al. (2006)</a> concluded that ETO2 is required for expansion of erythroid progenitors, but that it is dispensable for terminal maturation. They proposed that the stoichiometry of ETO2 with the TAL1 complex controls the transition from erythroid progenitor expansion to terminal differentiation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16407974" 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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By exome sequencing of 347 DNA samples from unrelated individuals with craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for 36 different mutations in the TCF12 gene (see, e.g., <a href="#0001">600480.0001</a>-<a href="#0007">600480.0007</a>) in 38 families. The mutations occurred predominantly in patients with coronal synostosis, accounting for 32% and 10% of individuals with bilateral and unilateral pathology, respectively; 2 patients had both coronal and sagittal synostosis and 2 patients had only sagittal synostosis. In 36 families tested, the TCF12 mutation was shown to have arisen de novo. In 23 families, cascade testing identified 34 additional mutation-positive individuals, only 16 of whom had craniosynostosis or other relevant features, indicating substantial (53%) nonpenetrance. The mutations identified in TCF12 included 15 frameshift, 14 nonsense, 7 splicing, and 2 missense changes, suggesting a loss-of-function mechanism. All but 1 were located between exons 10 and 19; no genotype-phenotype correlation was detected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a cohort of 182 Spanish probands with craniosynostosis, <a href="#6" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> screened 7 craniosynostosis-associated genes and identified 5 patients with coronal or multisutural involvement who had mutations in the TCF12 gene (see, e.g., <a href="#0001">600480.0001</a> and <a href="#0008">600480.0008</a>). The authors noted that 4 of the 5 Spanish probands were initially referred for Saethre-Chotzen syndrome (SCS; <a href="/entry/101400">101400</a>) and 1 for Muenke syndrome (MNKES; <a href="/entry/602849">602849</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25271085" 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>Hypogonadotropic Hypogonadism 26</em></strong></p><p>
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In 13 patients from 12 families with hypogonadotropic hypogonadism with anosmia (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified heterozygosity for frameshift or splice-site mutations in the TCF12 gene (see, e.g., <a href="#0002">600480.0002</a> and <a href="#0009">600480.0009</a>-<a href="#0011">600480.0011</a>). The mutations were confirmed by Sanger sequencing and segregated with incomplete penetrance in the 5 families for which data was available; none was found in public variant databases. Craniosynostosis was present in 3 of the families, including in 1 of the probands (see <a href="#0011">600480.0011</a>). Using GeneMatcher, the authors also identified a consanguineous Pakistani family in which the proband exhibited bilateral coronal synostosis as well as hypogonadotropic hypogonadism; he was homozygous for a 1-bp deletion in TCF12 (<a href="#0012">600480.0012</a>) for which his unaffected parents were heterozygous. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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>Using targeted morpholino injections, <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> transiently suppressed tcf12 in zebrafish larvae. Immunostaining of larval batches at 2 days postfertilization (dpf) revealed a dose-dependent significant reduction in the length of the terminal nerve axons, which provide the scaffold for migrating GnRH neurons towards the hypothalamus. In addition, there was a significant reduction in the size of the olfactory bulb. Coinjection of human wildtype TCF12 resulted in significant restoration of terminal nerve axon length and olfactory bulb size in 2-dpf larvae. Analysis of morpholino-injected GnRH3 GFP transgenic zebrafish embryos showed GnRH3 reporter cell disorganization, including dispersed localization of individual cells and unilateral asymmetry. Quantification of the area marked by GPF, a proxy for the number of GnRH neurons, showed a significant reduction in morphants versus controls. CRISPR/Cas9-mediated genome editing of the tcf12 locus in GnRH3 GFP transgenic zebrafish confirmed the findings. The authors also observed that tcf12 morphants or mutants showed attenuation of the orthologous expression of tcf3a/b (TCF3; <a href="/entry/147141">147141</a>), encoding a binding partner of TCF12, and stub1 (<a href="/entry/607207">607207</a>), a gene that is associated with a syndromic form of HH and that also maps to a TCF12 affinity network. Expression of STUB1 was sufficient to significantly rescue tcf12-induced GnRH neuronal patterning defects. The authors concluded that tcf12 is involved in the GnRH axis development in zebrafish and likely plays a role in patterning of GNRH3 neurons as well as in regulating expression of multiple genes involved in the establishment of the GnRH axis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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">rs886037636 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037636;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=rs886037636" 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=rs886037636" 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=RCV000049324 OR RCV002272047" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049324, RCV002272047" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049324...</a>
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<p>In a father and son and an unrelated man with craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a c.842C-G transversion (c.842C-G, VAR NM_207040.1) in exon 11 of the TCF12 gene, resulting in a ser281-to-ter (S281X) substitution. The mutation arose de novo in the sporadic case. The father had left coronal synostosis whereas his son had right coronal synostosis, and the unrelated man had bicoronal craniosynostosis. Additional features included corneal abnormalities in the father and a small mass near the pineal gland in the son; the sporadic patient had low anterior hairline, incomplete descent of testes, mild learning disabilities, and mild ventriculomegaly, and also required an additional surgical procedure to correct supraorbital retrusion. <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> noted that the son and the sporadic patient had previously been given a clinical diagnosis of Saethre-Chotzen syndrome (SCS; <a href="/entry/101400">101400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Spanish proband (patient 2) with plagiocephaly resulting from synostosis of the left coronal suture, <a href="#6" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> identified heterozygosity for the S281X substitution in the TCF12 gene. The mutation was not found in the unaffected parents or unaffected brother. Other features in the proband included flat and asymmetric face, autism, delayed language, and bilateral sensorineural hearing loss. Brain MRI showed lateral ventricular asymmetry. The patient had initially been given a clinical diagnosis of SCS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25271085" 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">rs886037637 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037637;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=rs886037637" 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=rs886037637" 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=RCV000049325 OR RCV001569383 OR RCV001818229" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049325, RCV001569383, RCV001818229" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049325...</a>
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In the male probands from 2 unrelated families with craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a 1-bp duplication (c.1491dupT, NM_207040.1) in exon 17 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Val498CysfsTer12). One proband had bicoronal synostosis, whereas the other had right coronal synostosis; they inherited the mutation from their unaffected father and mother, respectively. RT-PCR of mRNA from patient blood samples showed lower expression of the mutant allele compared to wildtype, consistent with nonsense-mediated decay; the mutant-to-wildtype allele ratio was lower in the affected individuals than in the unaffected carriers. Additional features in the proband with bicoronal synostosis included dental crowding, bilateral transverse palmar creases, and hallux valgus; the other proband was tall and also had a right transverse palmar crease, flat thumbs, hallux valgus, and vertical strabismus, and he required an additional surgical procedure at 18 years of age. Brain scan was normal in both probands. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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>Hypogonadotropic Hypogonadism 26 with Anosmia</em></strong></p><p>
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In a 32-year-old man (family III) with hypogonadotropic hypogonadism and anosmia (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified heterozygosity for the c.1491dup mutation in the TCF12 gene. The duplication was inherited from his father, who had only anosmia; the variant was not found in his unaffected mother or brother, or in public variant databases. Analysis of transcript levels in proband lymphoblastoid cell lines (LCLs) revealed a significant reduction of TCF12 mRNA; the results were validated by immunoblotting whole-cell protein lysates from the same LCLs, which showed a similar reduction in wildtype protein compared to control. Blot image signal enhancement revealed only trace amounts of truncated protein in the expected size. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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> rs398122381 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs398122381;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/rs398122381?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=rs398122381" 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=rs398122381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 cousins with craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a c.722C-G transversion (c.722C-G, NM_207040.1) in exon 10 of the TCF12 gene, resulting in a ser241-to-ter (S241X) substitution. The 22-year-old female cousin had right coronal as well as sagittal synostosis, whereas the 27-year-old male cousin had only sagittal synostosis; the mutations were inherited from their unaffected mother and father, respectively. Both patients had mild learning disability. Other features in the woman included blepharoptosis requiring repair, strabismus, midface hypoplasia, class I dental malocclusion, brachydactyly, and camptodactyly of digits 3 and 5, and she required additional surgery for contour correction of the supraorbital rim and forehead. Other features in the man included partial sclerosis of both coronal sutures on plain radiography and a class II-1 malocclusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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">rs886037638 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037638;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=rs886037638" 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=rs886037638" 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=RCV000049327" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049327" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049327</a>
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<p>In a father and 2 sons with craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a 1-bp deletion (c.1646delA, 207040.1) in exon 18 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Lys549ArgfsTer14). The 48-year-old father and his 9-year-old son had right coronal synostosis, whereas the 13-year-old son had sagittal synostosis. Brain scan in the 2 boys showed slightly enlarged lateral ventricles in both, as well as a Chiari I malformation in the older boy. Additional features in the father and older boy included bilateral transverse palmar creases and brachydactyly of the hands; the son was also diagnosed with Asperger syndrome. The younger son, who was autistic, also had deafness and relapsing respiratory tract infections. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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">rs886037639 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037639;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=rs886037639" 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=rs886037639" 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=RCV000049328" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049328" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049328</a>
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<p>In a 3.3-year-old boy with bicoronal and sagittal craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a de novo c.1963G-T transversion (c.1963G-T, NM_207040.1) in exon 19 of the TCF12 gene, resulting in a glu655-to-ter (E655X) substitution. The mutation was not found in either parent. The patient had a normal brain scan and normal neurodevelopment, and no additional features were reported. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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">rs886037640 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037640;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=rs886037640" 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=rs886037640" 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=RCV000049329 OR RCV004794355" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049329, RCV004794355" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049329...</a>
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<p>In a 3.6-year-old girl and her maternal aunt who had bicoronal craniosynostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a G-C transversion (c.1035+3G-C, NM_207040.1) in intron 12 of the TCF12 gene, which was shown by RT-PCR of patient mRNA to cause skipping of exon 12. There was lower expression of the mutant allele compared to wildtype, consistent with nonsense-mediated decay. The mutation was also present in the girl's unaffected mother and maternal grandmother; the authors noted that there was relatively less skipped product present in blood samples from the affected girl than in her unaffected relatives. The affected girl had a normal brain scan and mild language delay, and she required further surgery 2 years after initial posterior release. Additional features in the affected aunt included mild brachydactyly of toes, severe early-onset rheumatoid arthritis, and Crohn disease, and she required speech therapy. The unaffected maternal grandmother also had rheumatoid arthritis; serum screening of the mother, aunt, and maternal grandmother showed normal indices of immune function. The 2 affected individuals had been clinically diagnosed with Saethre-Chotzen syndrome (<a href="/entry/101400">101400</a>), but no mutations were found in the TWIST1 gene (<a href="/entry/601622">601622</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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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TCF12, GLN638GLU
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs886037641 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037641;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=rs886037641" 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=rs886037641" 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=RCV000049330" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000049330" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000049330</a>
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<p>In a 14-year-old girl with bicoronal craniosynostosis and her affected mother, in whom the involved sutures were not determined (CRS3; <a href="/entry/615314">615314</a>), <a href="#8" class="mim-tip-reference" title="Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others. <strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong> Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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/ng.2531" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23354436">Sharma et al. (2013)</a> identified heterozygosity for a c.1912C-G transversion (c.1912C-G, NM_207040.1) in exon 19 of the TCF12 gene, resulting in a gln638-to-glu (Q638E) substitution at a highly conserved residue in the bHLH domain, a domain required for dimerization. In a transactivation assay, the combination of native TCF12 and TWIST proteins had a synergistic effect on activation relative to the activity of either protein alone; this effect was 65% lower with the Q638E mutation compared to wildtype. The daughter had a normal brain scan, and both affected individuals had normal neurodevelopment; the mother also had bilateral blepharoptosis, but no additional features were reported in the daughter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23354436" 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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TCF12, IVS10AS, A-G, -2
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs2151925569 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2151925569;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=rs2151925569" 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=rs2151925569" 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=RCV001822091" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001822091" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001822091</a>
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<p>In a Spanish child (patient 3) with turribrachycephaly due to bilateral coronal and left lambdoid suture synostosis (CRS3; <a href="/entry/615314">615314</a>), <a href="#6" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> identified heterozygosity for a splice site mutation (c.826-2A-G, NM_207037.1) in intron 10 of the TCF12 gene. The mutation was not found in the proband's unaffected parents. Additional features in the proband included flat face, frontal asymmetry, hypertelorism, downslanting palpebral fissures, and dysmorphic ears. The authors noted that the patient was initially given a clinical diagnosis of Saethre-Chotzen syndrome (SCS; <a href="/entry/101400">101400</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25271085" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA</strong>
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TCF12, 1-BP DUP, NT1528
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<p>In 2 male cousins (family I) with hypogonadotropic hypogonadism and anosmia (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified heterozygosity for a 1-bp duplication (c.1528dup, NM_207036.1) in exon 17 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Thr510AsnfsTer12). The duplication was also present in the apparently unaffected father of the proband and in the cousin's anosmic mother; it was not found in 5 other unaffected family members tested or in the dbSNP138, 1000 Genomes Project, NHLBI ESP, ExAC, and gnomAD databases. An uncle who was reported to have craniosynostosis was unavailable for clinical evaluation or DNA testing. Analysis of transcript levels in proband lymphoblastoid cell lines (LCLs) revealed a significant reduction of TCF12 mRNA; the results were validated by immunoblotting whole-cell protein lysates from the same LCLs, which showed a similar reduction in wildtype protein compared to control. Blot image signal enhancement revealed only trace amounts of truncated protein in the expected size. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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">rs2152019859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2152019859;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=rs2152019859" 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=rs2152019859" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male proband (family VII) with hypogonadotropic hypogonadism and anosmia (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified heterozygosity for a 1-bp duplication (c.1270dup, NM_207036.1) in exon 16 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Met424AsnfsTer10). The duplication was inherited from the proband's unaffected father and was also present in his brother, who had craniosynostosis but not HH; the mutation not found in public variant databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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">rs2151917567 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2151917567;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=rs2151917567" 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=rs2151917567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 19-year-old Spanish man (family XII) with hypogonadotropic hypogonadism and anosmia (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified heterozygosity for a de novo 1-bp duplication (c.596dup, NM_207036.1) in exon 9 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Asn200LysfsTer4). The patient, who also had plagiocephaly due to unilateral coronal synostosis, was originally reported as part of a craniosynostosis cohort by <a href="#6" class="mim-tip-reference" title="Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E. <strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong> Europ. J. Hum. Genet. 23: 907-914, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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/ejhg.2014.205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25271085">Paumard-Hernandez et al. (2015)</a> (patient 1). The mutation was not found in his unaffected parents or brother, or in public variant databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25271085+32620954" 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">rs2151710940 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2151710940;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=rs2151710940" 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=rs2151710940" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 6-year-old Pakistani boy (family XIII) with hypogonadotropic hypogonadism (HH26; <a href="/entry/619718">619718</a>), <a href="#1" class="mim-tip-reference" title="Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others. <strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong> Hum. Molec. Genet. 29: 2435-2450, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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/10.1093/hmg/ddaa120" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32620954">Davis et al. (2020)</a> identified homozygosity for a 1-bp deletion (c.445del, NM_207036.1) in exon 7 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Ser149GlnfsTer96). The patient, who also had bilateral coronal suture synostosis, could not be tested for olfaction due to his young age and intellectual disability. His unaffected consanguineous parents were heterozygous for the deletion, which was not found in public variant databases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32620954" 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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Hum. Molec. Genet. 29: 2435-2450, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32620954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32620954</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32620954[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=32620954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Distinguishable patterns of protein-DNA interactions involving complexes of basic helix-loop-helix proteins.</strong>
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J. Biol. Chem. 269: 12099-12105, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163514/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163514</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163514" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Gan, T.-I., Rowen, L., Nesbitt, R., Roe, B. A., Wu, H., Hu, P., Yao, Z., Kim, U.-J., O'Sickey, T., Bina, M.
|
|
<strong>Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4.</strong>
|
|
Cytogenet. Genome Res. 98: 245-248, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12826747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12826747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12826747" 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/10.1159/000071042" target="_blank">Full Text</a>]
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<a id="Goardon2006" class="mim-anchor"></a>
|
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<div class="">
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Goardon, N., Lambert, J. A., Rodriguez, P., Nissaire, P., Herblot, S., Thibault, P., Dumenil, D., Strouboulis, J., Romeo, P.-H., Hoang, T.
|
|
<strong>ETO2 coordinates cellular proliferation and differentiation during erythropoiesis.</strong>
|
|
EMBO J. 25: 357-366, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16407974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16407974</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16407974[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=16407974" 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/sj.emboj.7600934" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Hu1992" class="mim-anchor"></a>
|
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<div class="">
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<p class="mim-text-font">
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Hu, J.-S., Olson, E. N., Kingston, R. E.
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<strong>HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.</strong>
|
|
Molec. Cell. Biol. 12: 1031-1042, 1992.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1312219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1312219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1312219" 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/10.1128/mcb.12.3.1031-1042.1992" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Paumard-Hernandez2015" class="mim-anchor"></a>
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<div class="">
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Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong>
|
|
Europ. J. Hum. Genet. 23: 907-914, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25271085/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25271085</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25271085[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=25271085" 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/ejhg.2014.205" target="_blank">Full Text</a>]
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<a id="Sawada1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sawada, S., Littman, D. R.
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<strong>A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines.</strong>
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Molec. Cell. Biol. 13: 5620-5628, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8355705/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8355705</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8355705" 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/10.1128/mcb.13.9.5620-5628.1993" target="_blank">Full Text</a>]
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<a id="Sharma2013" class="mim-anchor"></a>
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Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others.
|
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<strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong>
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Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23354436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23354436</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23354436[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=23354436" 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/ng.2531" target="_blank">Full Text</a>]
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<a id="Sjogren2000" class="mim-anchor"></a>
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Sjogren, H., Wedell, B., Meis-Kindblom, J. M., Kindblom, L.-G., Stenman, G.
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<strong>Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21).</strong>
|
|
Cancer Res. 60: 6832-6835, 2000. Note: Erratum: Cancer Res. 61: 2339 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11156374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11156374</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11156374" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Wang2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wang, D., Claus, C. L., Vaccarelli, G., Braunstein, M., Schmitt, T. M., Zuniga-Pflucker, J. C., Rothenberg, E. V., Anderson, M. K.
|
|
<strong>The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors.</strong>
|
|
J. Immun. 177: 109-119, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16785505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16785505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16785505" 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/10.4049/jimmunol.177.1.109" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Zhang1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Y., Babin, J., Feldhaus, A. L., Singh, H., Sharp, P. A., Bina, M.
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<strong>HTF4: a new human helix-loop-helix protein.</strong>
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Nucleic Acids Res. 19: 4555 only, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1886779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1886779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1886779" 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/19.16.4555" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Zhang1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zhang, Y., Bina, M.
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<strong>The nucleotide sequence of the human transcription factor HTF4a cDNA.</strong>
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DNA Seq. 2: 397-403, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1446075/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1446075</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1446075" 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/10.3109/10425179209020819" target="_blank">Full Text</a>]
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<a id="Zhang1995" class="mim-anchor"></a>
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<div class="">
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Zhang, Y., Flejter, W. L., Barcroft, C. L., Riviere, M., Szpirer, J., Szpirer, C., Bina, M.
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<strong>Localization of the human HTF4 transcription factors 4 gene (TCF12) to chromosome 15q21.</strong>
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Cytogenet. Cell Genet. 68: 235-238, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842744/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842744</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7842744" 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/10.1159/000133921" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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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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Marla J. F. O'Neill - updated : 01/25/2022
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 7/18/2013<br>Patricia A. Hartz - updated : 6/8/2012<br>Cassandra L. Kniffin - updated : 8/14/2008<br>Paul J. Converse - updated : 4/4/2007<br>Patricia A. Hartz - updated : 9/5/2003<br>Victor A. McKusick - updated : 6/25/2003
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Creation Date:
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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 : 4/4/1995
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carol : 01/26/2022
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<span class="mim-text-font">
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carol : 01/25/2022<br>carol : 06/18/2019<br>mgross : 03/29/2018<br>alopez : 11/01/2013<br>carol : 7/18/2013<br>alopez : 8/7/2012<br>mgross : 6/8/2012<br>ckniffin : 8/14/2008<br>mgross : 4/5/2007<br>terry : 4/4/2007<br>mgross : 9/5/2003<br>carol : 7/16/2003<br>tkritzer : 7/14/2003<br>terry : 6/25/2003<br>terry : 6/18/1998<br>psherman : 3/16/1998<br>alopez : 1/13/1998<br>joanna : 4/30/1997<br>jenny : 4/4/1997<br>mark : 11/1/1995<br>mark : 4/4/1995
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<strong>*</strong> 600480
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<h3>
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<span class="mim-font">
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TRANSCRIPTION FACTOR 12; TCF12
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<em>Alternative titles; symbols</em>
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<h4>
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HELIX-LOOP-HELIX TRANSCRIPTION FACTOR 4; HTF4
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<span class="mim-font">
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Other entities represented in this entry:
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<span class="h3 mim-font">
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TCF12/NR4A3 FUSION GENE, INCLUDED
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TCF12</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 15q21.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:56,918,090-57,291,310 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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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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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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15q21.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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Craniosynostosis 3
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</span>
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</td>
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<td>
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<span class="mim-font">
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615314
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Hypogonadotropic hypogonadism 26 with or without anosmia
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</span>
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</td>
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<td>
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<span class="mim-font">
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619718
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant; Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Zhang et al. (1991) obtained a partial cDNA for HTF4 which predicted a protein that is a member of the class A basic helix-loop-helix (bHLH) family. The same cDNA, designated HEB, was cloned by Hu et al. (1992). </p><p>Gan et al. (2002) identified 3 TCF12 variants that result from alternative splicing and differential exon utilization. Two of the variants differ in the 5-prime untranslated region but encode identical proteins. </p><p>Wang et al. (2006) noted that E2A (TCF3; 147141) homodimers are essential for early B-cell development, whereas HEB/E2A heterodimers are dominant during T-cell development. By screening a mouse pro-T-cell cDNA library, followed by database analysis, they identified a novel HEB variant, which they termed HEBAlt. HEBAlt includes the bHLH domain and activation domain-2 (AD2) of canonical HEB (HEBCan), but it replaces AD1 with an alternative domain homologous to the N-terminal region of the ITF2A variant of ITF2 (TCF4; 602272). The alternative domain of HEBAlt is well conserved in vertebrates. RT-PCR analysis showed that HebAlt was expressed only in the double-negative stages of mouse thymocyte development. </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 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>Gan et al. (2002) determined that the TCF12 gene contains 21 exons and spans about 370 kb. </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>Zhang et al. (1995) used a panel of somatic cell hybrids to map HTF4 to chromosome 15. By fluorescence in situ hybridization, they further localized the gene to 15q21. </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>Cytogenetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>TCF12/NR4A3 Fusion Gene</em></strong></p><p>
|
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By spectral karyotyping, Sjogren et al. (2000) identified a reciprocal t(9;15)(q22;q21) translocation in cells obtained from a tumor with characteristics of extraskeletal myxoid chondrosarcoma (612237). The translocation produced a chimeric transcript encoding a protein in which the first 108 amino acids of the N terminus of TCF12 were fused in-frame upstream of the entire NR4A3 (600542) sequence. The N-terminal TCF12 sequence included in the fusion product contains potential phosphorylation and N-glycosylation sites. Gan et al. (2002) determined that intron 5 of the TCF12 gene was the region involved in the translocation. </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">
|
|
<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>Based on studies of the mouse and chicken cDNAs, Zhang and Bina (1992) proposed that transcripts of HTF4 can be differentially spliced to yield distinct but related proteins which are evolutionarily similar to the products of the E2A gene. In vitro assays had shown that HTF4 can form heterodimers with other bHLH proteins of class A (e.g., the E2A proteins; see 147141) and class B (e.g., the myogenic factors; MYF3, 159970; MYF5, 159990; and MYF6, 159991), as well as the inhibitor of DNA binding (ID1; 600349) and stem cell leukemia hematopoietic transcription factor (TAL1; 187040). </p><p>In DNA binding assays, (Doyle et al., 1994) found that complexes of HTF4 with the myogenic factors have a relatively high affinity for the E box motifs of the mE2 (CACGTG) and kappa E2/muE5 (CACCTG) types, whereas heterodimers of HTF4 and TAL1 interact poorly. They suggested that these results and those obtained from transient expression studies indicated that leukemogenesis caused by TAL1 might include a pathway where TAL1 would act as a negative regulator of gene expression by forming a complex with class A bHLH proteins. </p><p>By Northern blot analysis, Zhang et al. (1995) showed that TCF12 is expressed at varying levels in many human cell lines and tissues. High levels of transcription in Jurkat cells supported the view that TCF12 gene products may play a central role in T-cell regulation (Hu et al., 1992; Sawada and Littman, 1993; Doyle et al., 1994), and detection of the mRNA in human heart and skeletal muscle supported a role for TCF12 in myogenesis. </p><p>Wang et al. (2006) found that HEBAlt specifically bound to an E box motif. HEBAlt mRNA was upregulated synergistically by HEBCan activity and Delta (see 606582)-Notch (see 190198) signaling. Further experiments demonstrated that HEBAlt and HEBCan are functionally distinct transcription factors, with HEBAlt specifically required for efficient generation of early T-cell precursors. </p><p>Goardon et al. (2006) found that ETO2 (CBFA2T3; 603870) copurified with TAL1 complexes in human and mouse erythroleukemia cells. Protein pull-down assays revealed that ETO2 interacted with E2A and HEB within the TAL1 complex, but not with TAL1 itself. ETO2 also interacted with E2A in erythroid cells independent of the TAL1 complex. Reporter gene assays revealed that ETO2 repressed the transcriptional activity of the complex. The ETO2 content in TAL1 complexes was high during the proliferative phase in erythroid cells. In contrast, ETO2 was downregulated upon terminal differentiation, concomitant with appearance of histone modifications associated with gene activation and expression of glycophorin A (GPA; 617922) and band 4.2 (EPB42; 177070), which are markers of erythrocyte maturation. Knockdown of ETO2 via small interfering RNA induced growth arrest and differentiation in human and mouse erythroid progenitors. Goardon et al. (2006) concluded that ETO2 is required for expansion of erythroid progenitors, but that it is dispensable for terminal maturation. They proposed that the stoichiometry of ETO2 with the TAL1 complex controls the transition from erythroid progenitor expansion to terminal differentiation. </p>
|
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</span>
|
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<div>
|
|
<br />
|
|
</div>
|
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|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
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|
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|
|
<span class="mim-text-font">
|
|
<p><strong><em>Craniosynostosis 3</em></strong></p><p>
|
|
By exome sequencing of 347 DNA samples from unrelated individuals with craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for 36 different mutations in the TCF12 gene (see, e.g., 600480.0001-600480.0007) in 38 families. The mutations occurred predominantly in patients with coronal synostosis, accounting for 32% and 10% of individuals with bilateral and unilateral pathology, respectively; 2 patients had both coronal and sagittal synostosis and 2 patients had only sagittal synostosis. In 36 families tested, the TCF12 mutation was shown to have arisen de novo. In 23 families, cascade testing identified 34 additional mutation-positive individuals, only 16 of whom had craniosynostosis or other relevant features, indicating substantial (53%) nonpenetrance. The mutations identified in TCF12 included 15 frameshift, 14 nonsense, 7 splicing, and 2 missense changes, suggesting a loss-of-function mechanism. All but 1 were located between exons 10 and 19; no genotype-phenotype correlation was detected. </p><p>In a cohort of 182 Spanish probands with craniosynostosis, Paumard-Hernandez et al. (2015) screened 7 craniosynostosis-associated genes and identified 5 patients with coronal or multisutural involvement who had mutations in the TCF12 gene (see, e.g., 600480.0001 and 600480.0008). The authors noted that 4 of the 5 Spanish probands were initially referred for Saethre-Chotzen syndrome (SCS; 101400) and 1 for Muenke syndrome (MNKES; 602849). </p><p><strong><em>Hypogonadotropic Hypogonadism 26</em></strong></p><p>
|
|
In 13 patients from 12 families with hypogonadotropic hypogonadism with anosmia (HH26; 619718), Davis et al. (2020) identified heterozygosity for frameshift or splice-site mutations in the TCF12 gene (see, e.g., 600480.0002 and 600480.0009-600480.0011). The mutations were confirmed by Sanger sequencing and segregated with incomplete penetrance in the 5 families for which data was available; none was found in public variant databases. Craniosynostosis was present in 3 of the families, including in 1 of the probands (see 600480.0011). Using GeneMatcher, the authors also identified a consanguineous Pakistani family in which the proband exhibited bilateral coronal synostosis as well as hypogonadotropic hypogonadism; he was homozygous for a 1-bp deletion in TCF12 (600480.0012) for which his unaffected parents were heterozygous. </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">
|
|
<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">
|
|
<p>Using targeted morpholino injections, Davis et al. (2020) transiently suppressed tcf12 in zebrafish larvae. Immunostaining of larval batches at 2 days postfertilization (dpf) revealed a dose-dependent significant reduction in the length of the terminal nerve axons, which provide the scaffold for migrating GnRH neurons towards the hypothalamus. In addition, there was a significant reduction in the size of the olfactory bulb. Coinjection of human wildtype TCF12 resulted in significant restoration of terminal nerve axon length and olfactory bulb size in 2-dpf larvae. Analysis of morpholino-injected GnRH3 GFP transgenic zebrafish embryos showed GnRH3 reporter cell disorganization, including dispersed localization of individual cells and unilateral asymmetry. Quantification of the area marked by GPF, a proxy for the number of GnRH neurons, showed a significant reduction in morphants versus controls. CRISPR/Cas9-mediated genome editing of the tcf12 locus in GnRH3 GFP transgenic zebrafish confirmed the findings. The authors also observed that tcf12 morphants or mutants showed attenuation of the orthologous expression of tcf3a/b (TCF3; 147141), encoding a binding partner of TCF12, and stub1 (607207), a gene that is associated with a syndromic form of HH and that also maps to a TCF12 affinity network. Expression of STUB1 was sufficient to significantly rescue tcf12-induced GnRH neuronal patterning defects. The authors concluded that tcf12 is involved in the GnRH axis development in zebrafish and likely plays a role in patterning of GNRH3 neurons as well as in regulating expression of multiple genes involved in the establishment of the GnRH axis. </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>
|
|
</span>
|
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<strong>12 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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|
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<div>
|
|
<h4>
|
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<span class="mim-font">
|
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<strong>.0001 CRANIOSYNOSTOSIS 3</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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TCF12, SER281TER
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<br />
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SNP: rs886037636,
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ClinVar: RCV000049324, RCV002272047
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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 father and son and an unrelated man with craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a c.842C-G transversion (c.842C-G, VAR NM_207040.1) in exon 11 of the TCF12 gene, resulting in a ser281-to-ter (S281X) substitution. The mutation arose de novo in the sporadic case. The father had left coronal synostosis whereas his son had right coronal synostosis, and the unrelated man had bicoronal craniosynostosis. Additional features included corneal abnormalities in the father and a small mass near the pineal gland in the son; the sporadic patient had low anterior hairline, incomplete descent of testes, mild learning disabilities, and mild ventriculomegaly, and also required an additional surgical procedure to correct supraorbital retrusion. Sharma et al. (2013) noted that the son and the sporadic patient had previously been given a clinical diagnosis of Saethre-Chotzen syndrome (SCS; 101400). </p><p>In a Spanish proband (patient 2) with plagiocephaly resulting from synostosis of the left coronal suture, Paumard-Hernandez et al. (2015) identified heterozygosity for the S281X substitution in the TCF12 gene. The mutation was not found in the unaffected parents or unaffected brother. Other features in the proband included flat and asymmetric face, autism, delayed language, and bilateral sensorineural hearing loss. Brain MRI showed lateral ventricular asymmetry. The patient had initially been given a clinical diagnosis of SCS. </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 CRANIOSYNOSTOSIS 3</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA, INCLUDED
|
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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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TCF12, 1-BP DUP, 1491T
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<br />
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SNP: rs886037637,
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|
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ClinVar: RCV000049325, RCV001569383, RCV001818229
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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 />
|
|
<p><strong><em>Craniosynostosis 3</em></strong></p><p>
|
|
In the male probands from 2 unrelated families with craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a 1-bp duplication (c.1491dupT, NM_207040.1) in exon 17 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Val498CysfsTer12). One proband had bicoronal synostosis, whereas the other had right coronal synostosis; they inherited the mutation from their unaffected father and mother, respectively. RT-PCR of mRNA from patient blood samples showed lower expression of the mutant allele compared to wildtype, consistent with nonsense-mediated decay; the mutant-to-wildtype allele ratio was lower in the affected individuals than in the unaffected carriers. Additional features in the proband with bicoronal synostosis included dental crowding, bilateral transverse palmar creases, and hallux valgus; the other proband was tall and also had a right transverse palmar crease, flat thumbs, hallux valgus, and vertical strabismus, and he required an additional surgical procedure at 18 years of age. Brain scan was normal in both probands. </p><p><strong><em>Hypogonadotropic Hypogonadism 26 with Anosmia</em></strong></p><p>
|
|
In a 32-year-old man (family III) with hypogonadotropic hypogonadism and anosmia (HH26; 619718), Davis et al. (2020) identified heterozygosity for the c.1491dup mutation in the TCF12 gene. The duplication was inherited from his father, who had only anosmia; the variant was not found in his unaffected mother or brother, or in public variant databases. Analysis of transcript levels in proband lymphoblastoid cell lines (LCLs) revealed a significant reduction of TCF12 mRNA; the results were validated by immunoblotting whole-cell protein lysates from the same LCLs, which showed a similar reduction in wildtype protein compared to control. Blot image signal enhancement revealed only trace amounts of truncated protein in the expected size. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 CRANIOSYNOSTOSIS 3</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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TCF12, SER241TER
|
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<br />
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|
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SNP: rs398122381,
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gnomAD: rs398122381,
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ClinVar: RCV000049326
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 cousins with craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a c.722C-G transversion (c.722C-G, NM_207040.1) in exon 10 of the TCF12 gene, resulting in a ser241-to-ter (S241X) substitution. The 22-year-old female cousin had right coronal as well as sagittal synostosis, whereas the 27-year-old male cousin had only sagittal synostosis; the mutations were inherited from their unaffected mother and father, respectively. Both patients had mild learning disability. Other features in the woman included blepharoptosis requiring repair, strabismus, midface hypoplasia, class I dental malocclusion, brachydactyly, and camptodactyly of digits 3 and 5, and she required additional surgery for contour correction of the supraorbital rim and forehead. Other features in the man included partial sclerosis of both coronal sutures on plain radiography and a class II-1 malocclusion. </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 CRANIOSYNOSTOSIS 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TCF12, 1-BP DEL, 1646A
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<br />
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SNP: rs886037638,
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ClinVar: RCV000049327
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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 father and 2 sons with craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a 1-bp deletion (c.1646delA, 207040.1) in exon 18 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Lys549ArgfsTer14). The 48-year-old father and his 9-year-old son had right coronal synostosis, whereas the 13-year-old son had sagittal synostosis. Brain scan in the 2 boys showed slightly enlarged lateral ventricles in both, as well as a Chiari I malformation in the older boy. Additional features in the father and older boy included bilateral transverse palmar creases and brachydactyly of the hands; the son was also diagnosed with Asperger syndrome. The younger son, who was autistic, also had deafness and relapsing respiratory tract infections. </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>.0005 CRANIOSYNOSTOSIS 3</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TCF12, GLU656TER
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<br />
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SNP: rs886037639,
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ClinVar: RCV000049328
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 3.3-year-old boy with bicoronal and sagittal craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a de novo c.1963G-T transversion (c.1963G-T, NM_207040.1) in exon 19 of the TCF12 gene, resulting in a glu655-to-ter (E655X) substitution. The mutation was not found in either parent. The patient had a normal brain scan and normal neurodevelopment, and no additional features were reported. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>.0006 CRANIOSYNOSTOSIS 3</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TCF12, IVS12DS, G-C, +1
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<br />
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SNP: rs886037640,
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ClinVar: RCV000049329, RCV004794355
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 3.6-year-old girl and her maternal aunt who had bicoronal craniosynostosis (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a G-C transversion (c.1035+3G-C, NM_207040.1) in intron 12 of the TCF12 gene, which was shown by RT-PCR of patient mRNA to cause skipping of exon 12. There was lower expression of the mutant allele compared to wildtype, consistent with nonsense-mediated decay. The mutation was also present in the girl's unaffected mother and maternal grandmother; the authors noted that there was relatively less skipped product present in blood samples from the affected girl than in her unaffected relatives. The affected girl had a normal brain scan and mild language delay, and she required further surgery 2 years after initial posterior release. Additional features in the affected aunt included mild brachydactyly of toes, severe early-onset rheumatoid arthritis, and Crohn disease, and she required speech therapy. The unaffected maternal grandmother also had rheumatoid arthritis; serum screening of the mother, aunt, and maternal grandmother showed normal indices of immune function. The 2 affected individuals had been clinically diagnosed with Saethre-Chotzen syndrome (101400), but no mutations were found in the TWIST1 gene (601622). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 CRANIOSYNOSTOSIS 3</strong>
|
|
</span>
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|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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TCF12, GLN638GLU
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<br />
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SNP: rs886037641,
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|
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ClinVar: RCV000049330
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 14-year-old girl with bicoronal craniosynostosis and her affected mother, in whom the involved sutures were not determined (CRS3; 615314), Sharma et al. (2013) identified heterozygosity for a c.1912C-G transversion (c.1912C-G, NM_207040.1) in exon 19 of the TCF12 gene, resulting in a gln638-to-glu (Q638E) substitution at a highly conserved residue in the bHLH domain, a domain required for dimerization. In a transactivation assay, the combination of native TCF12 and TWIST proteins had a synergistic effect on activation relative to the activity of either protein alone; this effect was 65% lower with the Q638E mutation compared to wildtype. The daughter had a normal brain scan, and both affected individuals had normal neurodevelopment; the mother also had bilateral blepharoptosis, but no additional features were reported in the daughter. </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 CRANIOSYNOSTOSIS 3</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
TCF12, IVS10AS, A-G, -2
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|
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<br />
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|
|
|
SNP: rs2151925569,
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|
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|
|
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|
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ClinVar: RCV001822091
|
|
|
|
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Spanish child (patient 3) with turribrachycephaly due to bilateral coronal and left lambdoid suture synostosis (CRS3; 615314), Paumard-Hernandez et al. (2015) identified heterozygosity for a splice site mutation (c.826-2A-G, NM_207037.1) in intron 10 of the TCF12 gene. The mutation was not found in the proband's unaffected parents. Additional features in the proband included flat face, frontal asymmetry, hypertelorism, downslanting palpebral fissures, and dysmorphic ears. The authors noted that the patient was initially given a clinical diagnosis of Saethre-Chotzen syndrome (SCS; 101400). </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<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 HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TCF12, 1-BP DUP, NT1528
|
|
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|
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<br />
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|
|
SNP: rs2152056837,
|
|
|
|
|
|
|
|
ClinVar: RCV001822092
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 male cousins (family I) with hypogonadotropic hypogonadism and anosmia (HH26; 619718), Davis et al. (2020) identified heterozygosity for a 1-bp duplication (c.1528dup, NM_207036.1) in exon 17 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Thr510AsnfsTer12). The duplication was also present in the apparently unaffected father of the proband and in the cousin's anosmic mother; it was not found in 5 other unaffected family members tested or in the dbSNP138, 1000 Genomes Project, NHLBI ESP, ExAC, and gnomAD databases. An uncle who was reported to have craniosynostosis was unavailable for clinical evaluation or DNA testing. Analysis of transcript levels in proband lymphoblastoid cell lines (LCLs) revealed a significant reduction of TCF12 mRNA; the results were validated by immunoblotting whole-cell protein lysates from the same LCLs, which showed a similar reduction in wildtype protein compared to control. Blot image signal enhancement revealed only trace amounts of truncated protein in the expected size. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TCF12, 1-BP DUP, NT1270
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2152019859,
|
|
|
|
|
|
|
|
ClinVar: RCV001822093
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male proband (family VII) with hypogonadotropic hypogonadism and anosmia (HH26; 619718), Davis et al. (2020) identified heterozygosity for a 1-bp duplication (c.1270dup, NM_207036.1) in exon 16 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Met424AsnfsTer10). The duplication was inherited from the proband's unaffected father and was also present in his brother, who had craniosynostosis but not HH; the mutation not found in public variant databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TCF12, 1-BP DUP, NT596
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2151917567,
|
|
|
|
|
|
|
|
ClinVar: RCV001822094
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 19-year-old Spanish man (family XII) with hypogonadotropic hypogonadism and anosmia (HH26; 619718), Davis et al. (2020) identified heterozygosity for a de novo 1-bp duplication (c.596dup, NM_207036.1) in exon 9 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Asn200LysfsTer4). The patient, who also had plagiocephaly due to unilateral coronal synostosis, was originally reported as part of a craniosynostosis cohort by Paumard-Hernandez et al. (2015) (patient 1). The mutation was not found in his unaffected parents or brother, or in public variant databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 HYPOGONADOTROPIC HYPOGONADISM 26 WITH ANOSMIA</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TCF12, 1-BP DEL, NT445
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2151710940,
|
|
|
|
|
|
|
|
ClinVar: RCV001822095
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Pakistani boy (family XIII) with hypogonadotropic hypogonadism (HH26; 619718), Davis et al. (2020) identified homozygosity for a 1-bp deletion (c.445del, NM_207036.1) in exon 7 of the TCF12 gene, causing a frameshift predicted to result in a premature termination codon (Ser149GlnfsTer96). The patient, who also had bilateral coronal suture synostosis, could not be tested for olfaction due to his young age and intellectual disability. His unaffected consanguineous parents were heterozygous for the deletion, which was not found in public variant databases. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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|
<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
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</span>
|
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</h4>
|
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<div>
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<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
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<p class="mim-text-font">
|
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Davis, E. E., Balasubramanian, R., Kupchinsky, Z. A., Keefe, D. L., Jr., Plummer, L., Khan, K., Meczekalski, B., Heath, K. E., Lopez-Gonzalez, V., Ballesta-Martinez, M. J., Margabanthu, G., Price, S., and 12 others.
|
|
<strong>TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci.</strong>
|
|
Hum. Molec. Genet. 29: 2435-2450, 2020.
|
|
|
|
|
|
[PubMed: 32620954]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddaa120]
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Doyle, K., Zhang, Y., Baer, R., Bina, M.
|
|
<strong>Distinguishable patterns of protein-DNA interactions involving complexes of basic helix-loop-helix proteins.</strong>
|
|
J. Biol. Chem. 269: 12099-12105, 1994.
|
|
|
|
|
|
[PubMed: 8163514]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
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<p class="mim-text-font">
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Gan, T.-I., Rowen, L., Nesbitt, R., Roe, B. A., Wu, H., Hu, P., Yao, Z., Kim, U.-J., O'Sickey, T., Bina, M.
|
|
<strong>Genomic organization of human TCF12 gene and spliced mRNA variants producing isoforms of transcription factor HTF4.</strong>
|
|
Cytogenet. Genome Res. 98: 245-248, 2002.
|
|
|
|
|
|
[PubMed: 12826747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000071042]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
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<p class="mim-text-font">
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Goardon, N., Lambert, J. A., Rodriguez, P., Nissaire, P., Herblot, S., Thibault, P., Dumenil, D., Strouboulis, J., Romeo, P.-H., Hoang, T.
|
|
<strong>ETO2 coordinates cellular proliferation and differentiation during erythropoiesis.</strong>
|
|
EMBO J. 25: 357-366, 2006.
|
|
|
|
|
|
[PubMed: 16407974]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.emboj.7600934]
|
|
|
|
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</p>
|
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</li>
|
|
|
|
<li>
|
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<p class="mim-text-font">
|
|
Hu, J.-S., Olson, E. N., Kingston, R. E.
|
|
<strong>HEB, a helix-loop-helix protein related to E2A and ITF2 that can modulate the DNA-binding ability of myogenic regulatory factors.</strong>
|
|
Molec. Cell. Biol. 12: 1031-1042, 1992.
|
|
|
|
|
|
[PubMed: 1312219]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1128/mcb.12.3.1031-1042.1992]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Paumard-Hernandez, B., Berges-Soria, J., Barroso, E., Rivera-Pedroza, C. I., Perez-Carrizosa, V., Benito-Sanz, S., Lopez-Messa, E., Santos, F., Garcia-Recuero, I. I., Romance, A., Ballesta-Martinez, M. J., Lopez-Gonzalez, V., Campos-Barros, A., Cruz, J., Guillen-Navarro, E., Sanchez del Pozo, J., Lapunzina, P., Garcia-Minaur, S., Heath, K. E.
|
|
<strong>Expanding the mutation spectrum in 182 Spanish probands with craniosynostosis: identification and characterization of novel TCF12 variants.</strong>
|
|
Europ. J. Hum. Genet. 23: 907-914, 2015.
|
|
|
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|
|
[PubMed: 25271085]
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|
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[Full Text: https://doi.org/10.1038/ejhg.2014.205]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Sawada, S., Littman, D. R.
|
|
<strong>A heterodimer of HEB and an E12-related protein interacts with the CD4 enhancer and regulates its activity in T-cell lines.</strong>
|
|
Molec. Cell. Biol. 13: 5620-5628, 1993.
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[PubMed: 8355705]
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[Full Text: https://doi.org/10.1128/mcb.13.9.5620-5628.1993]
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</p>
|
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</li>
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<li>
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<p class="mim-text-font">
|
|
Sharma, V. P., Fenwick, A. L., Brockop, M. S., McGowan, S. J., Goos, J. A. C., Hoogeboom, A. J. M., Brady, A. F., Jeelani, N. O., Lynch, S. A., Mulliken, J. B., Murray, D. J., Phipps, J. M., and 15 others.
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<strong>Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.</strong>
|
|
Nature Genet. 45: 304-307, 2013. Note: Erratum: Nature Genet. 45: 1261 only, 2013.
|
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|
|
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[PubMed: 23354436]
|
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|
|
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[Full Text: https://doi.org/10.1038/ng.2531]
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Sjogren, H., Wedell, B., Meis-Kindblom, J. M., Kindblom, L.-G., Stenman, G.
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<strong>Fusion of the NH2-terminal domain of the basic helix-loop-helix protein TCF12 to TEC in extraskeletal myxoid chondrosarcoma with translocation t(9;15)(q22;q21).</strong>
|
|
Cancer Res. 60: 6832-6835, 2000. Note: Erratum: Cancer Res. 61: 2339 only, 2001.
|
|
|
|
|
|
[PubMed: 11156374]
|
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|
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</p>
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<li>
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Wang, D., Claus, C. L., Vaccarelli, G., Braunstein, M., Schmitt, T. M., Zuniga-Pflucker, J. C., Rothenberg, E. V., Anderson, M. K.
|
|
<strong>The basic helix-loop-helix transcription factor HEBAlt is expressed in pro-T cells and enhances the generation of T cell precursors.</strong>
|
|
J. Immun. 177: 109-119, 2006.
|
|
|
|
|
|
[PubMed: 16785505]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.177.1.109]
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</li>
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Zhang, Y., Babin, J., Feldhaus, A. L., Singh, H., Sharp, P. A., Bina, M.
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<strong>HTF4: a new human helix-loop-helix protein.</strong>
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|
Nucleic Acids Res. 19: 4555 only, 1991.
|
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[PubMed: 1886779]
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[Full Text: https://doi.org/10.1093/nar/19.16.4555]
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</p>
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</li>
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Zhang, Y., Bina, M.
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<strong>The nucleotide sequence of the human transcription factor HTF4a cDNA.</strong>
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DNA Seq. 2: 397-403, 1992.
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[PubMed: 1446075]
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[Full Text: https://doi.org/10.3109/10425179209020819]
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</p>
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Zhang, Y., Flejter, W. L., Barcroft, C. L., Riviere, M., Szpirer, J., Szpirer, C., Bina, M.
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<strong>Localization of the human HTF4 transcription factors 4 gene (TCF12) to chromosome 15q21.</strong>
|
|
Cytogenet. Cell Genet. 68: 235-238, 1995.
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[PubMed: 7842744]
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[Full Text: https://doi.org/10.1159/000133921]
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Marla J. F. O'Neill - updated : 01/25/2022<br>Marla J. F. O'Neill - updated : 7/18/2013<br>Patricia A. Hartz - updated : 6/8/2012<br>Cassandra L. Kniffin - updated : 8/14/2008<br>Paul J. Converse - updated : 4/4/2007<br>Patricia A. Hartz - updated : 9/5/2003<br>Victor A. McKusick - updated : 6/25/2003
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Victor A. McKusick : 4/4/1995
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