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<title>
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Entry
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- *601093 - FORKHEAD BOX I1; FOXI1
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- OMIM
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</ul>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</ul>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<div id="mimAlertBanner">
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*601093</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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</li>
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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>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/601093">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>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000168269;t=ENST00000306268" 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=2299" 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=601093" 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=ENSG00000168269;t=ENST00000306268" 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_012188,NM_144769,XR_941092" 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_012188" 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=601093" 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
|
|
</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=03057&isoform_id=03057_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/FOXI1" 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/563168,1911185,21618327,21618329,51872085,119581893,119581894,127796533,150421552,158257784,306569445,306569447,306569449,306569451,306569453,306569455,306569457,306569459,306569461,306569463,306569465,306569467,306569469,306569471,306569473,306569475,306569477,306569479,306569481,306569483,306569485,306569487,306569489,306569491,306569493,306569495,306569497,306569499,306569501,306569503,306569505,306569507,306569509,306569511,306569513,306569515,306569517,306569519,306569521,306569523,306569525,306569527,306569529,306569531,306569533,306569535,306569537,306569539,306569541,306569543,306569545,306569547,306569549,306569551,306569553,306569555,306569557,306569559,306569561,306569563,306569565,306569567,306569569,306569571,306569573,306569575,306569577,306569579,306569581,306569583,306569585,306569587,306569589,306569591,306569593,306569595,306569597,306569599,306569601,306569603,306569605,306569607,306569609,306569611,306569613,306569615,306569617,306569619,306569621,306569623,306569625,306569627,306569629,306569631,306569633,306569635,306569637,306569639,306569641,306569643,306569645,306569647,306569649,306569651,306569653,306569655,306569657,306569659,306569661,306569663,306569665,306569667,306569669,306569671,306569673,306569675,306569677,306569679,306569681,306569683" 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/Q12951" 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=2299" 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=ENSG00000168269;t=ENST00000306268" 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=FOXI1" 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=FOXI1" 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+2299" 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/FOXI1" 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:2299" 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/2299" 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=chr5&hgg_gene=ENST00000306268.8&hgg_start=170105897&hgg_end=170109737&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/genes/HGNC:3815" 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=601093[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=601093[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://gnomad.broadinstitute.org/gene/ENSG00000168269" 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=FOXI1" 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=FOXI1" 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=FOXI1" 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=FOXI1&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/PA28232" 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:3815" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1096329" 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/FOXI1#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:1096329" 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/2299/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=2299" 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=WBGene00001438;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-030505-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<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=FOXI1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
|
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 70348004<br />
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<strong>ICD10CM:</strong> E07.1<br />
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">ICD+</a>
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</div>
|
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
|
<span class="text-danger"><strong>*</strong></span>
|
|
601093
|
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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>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
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|
FORKHEAD BOX I1; FOXI1
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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">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
FORKHEAD, DROSOPHILA, HOMOLOG-LIKE 10; FKHL10<br />
|
|
FKH10<br />
|
|
FORKHEAD-RELATED ACTIVATOR 6; FREAC6
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</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=FOXI1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">FOXI1</a></em></strong>
|
|
</span>
|
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</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/5/751?start=-3&limit=10&highlight=751">5q35.1</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:170105897-170109737&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'})">5:170,105,897-170,109,737</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
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<p>FKH10 is a member of the forkhead family of winged helix transcription regulators. The forkhead family is distinguished by a characteristic 100-amino acid motif that was originally identified in Drosophila (see <a href="/entry/164874">164874</a>). <a href="#7" class="mim-tip-reference" title="Pierrou, S., Hellqvist, M., Samuelsson, L., Enerback, S., Carlsson, P. <strong>Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.</strong> EMBO J. 13: 5002-5012, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7957066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7957066</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06827.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7957066">Pierrou et al. (1994)</a> identified 7 human genes containing a forkhead domain and designated them forkhead related activators (FREAC) 1 through 7. Northern blot analysis revealed that the FREAC6, or FKHL10, gene is expressed as a 2.3-kb mRNA only in kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7957066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S., Carlsson, P. <strong>Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).</strong> Genomics 30: 464-469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8825632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8825632</a>] [<a href="https://doi.org/10.1006/geno.1995.1266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8825632">Larsson et al. (1995)</a> showed that human FKHL10 is expressed in the adult and fetal kidney, whereas 15 other tissues (which did not include any inner ear-derived samples) were negative. Kidney-specific expression had been observed also in the mouse. Although Fkh10 may play a role in the kidney during later stages of development, it may be a minor, or perhaps redundant, role, as no kidney dysfunction was observed in homozygous knockout mice. On the contrary, Fkh10 appears to be unique in the sense that it is an early otic vesicle-specific gene necessary for the development of both cochlea and vestibulum. These findings implicated Fkh10 as an early regulator necessary for development of both cochlea and vestibulum and identified its human homolog, FKHL10, as a candidate deafness gene at 5q34. The phenotype described by <a href="#4" class="mim-tip-reference" title="Hulander, M., Wurst, W., Carlsson, P., Enerback, S. <strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong> Nature Genet. 20: 374-376, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843211</a>] [<a href="https://doi.org/10.1038/3850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843211">Hulander et al. (1998)</a> resembles a group of human congenital inner ear malformations called 'common cavity.' <a href="#4" class="mim-tip-reference" title="Hulander, M., Wurst, W., Carlsson, P., Enerback, S. <strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong> Nature Genet. 20: 374-376, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843211</a>] [<a href="https://doi.org/10.1038/3850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843211">Hulander et al. (1998)</a> proposed that mutations in FKH10 may cause a 'common cavity' phenotype in humans. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8825632+9843211" 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="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> demonstrated that FOXI1 is a transcription factor for SLC26A4 (<a href="/entry/605646">605646</a>) and identified and characterized a key transcriptional regulatory element in the SLC26A4 promoter that binds FOXI1. The SLC26A4 cis element consists of 2 FOXI1 binding sites, FBS1 and FBS2, arranged head to head. Both binding sites and this specific orientation are required for FOXI1-mediated transcriptional activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17503324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using single-cell RNA sequencing and in vivo lineage tracing to study the composition and hierarchy of the mouse tracheal epithelium, <a href="#6" class="mim-tip-reference" title="Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., Rogel, N., Burgin, G., and 17 others. <strong>A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.</strong> Nature 560: 319-324, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069044</a>] [<a href="https://doi.org/10.1038/s41586-018-0393-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069044">Montoro et al. (2018)</a> identified a rare cell type, the Foxi1-positive pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that they termed 'hillocks'; and disease-relevant subsets of tuft and goblet cells. <a href="#6" class="mim-tip-reference" title="Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., Rogel, N., Burgin, G., and 17 others. <strong>A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.</strong> Nature 560: 319-324, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069044</a>] [<a href="https://doi.org/10.1038/s41586-018-0393-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069044">Montoro et al. (2018)</a> developed 'pulse-seq,' combining single-cell RNA-seq and lineage tracing, to show that tuft, neuroendocrine, and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the CFTR (<a href="/entry/602421">602421</a>) in both mouse and human. Knockout of Foxi1 in mouse ionocytes caused loss of Cftr expression and disrupted airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis (<a href="/entry/219700">219700</a>). <a href="#6" class="mim-tip-reference" title="Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., Rogel, N., Burgin, G., and 17 others. <strong>A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.</strong> Nature 560: 319-324, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069044</a>] [<a href="https://doi.org/10.1038/s41586-018-0393-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069044">Montoro et al. (2018)</a> concluded that by associating cell type-specific expression programs with key disease genes, they had established a new cellular narrative for airway disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30069044" 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="#8" class="mim-tip-reference" title="Plasschaert, L. W., Zilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., Jaffe, A. B. <strong>A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.</strong> Nature 560: 377-381, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069046</a>] [<a href="https://doi.org/10.1038/s41586-018-0394-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069046">Plasschaert et al. (2018)</a> performed single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behavior in homeostasis and regeneration. The analysis revealed cell states that represent known and novel cell populations, delineated their heterogeneity, and identified distinct differentiation trajectories during homeostasis and tissue repair. In addition, <a href="#8" class="mim-tip-reference" title="Plasschaert, L. W., Zilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., Jaffe, A. B. <strong>A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.</strong> Nature 560: 377-381, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069046</a>] [<a href="https://doi.org/10.1038/s41586-018-0394-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069046">Plasschaert et al. (2018)</a> identified a novel, rare cell type that they called the 'pulmonary ionocyte,' which coexpresses FOXI1, multiple subunits of the vacuolar-type H(+)-ATPase (V-ATPase), and CFTR. Using immunofluorescence, modulation of signaling pathways, and electrophysiology, <a href="#8" class="mim-tip-reference" title="Plasschaert, L. W., Zilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., Jaffe, A. B. <strong>A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.</strong> Nature 560: 377-381, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069046</a>] [<a href="https://doi.org/10.1038/s41586-018-0394-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30069046">Plasschaert et al. (2018)</a> showed that Notch signaling (see <a href="/entry/190198">190198</a>) is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30069046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S., Carlsson, P. <strong>Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).</strong> Genomics 30: 464-469, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8825632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8825632</a>] [<a href="https://doi.org/10.1006/geno.1995.1266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8825632">Larsson et al. (1995)</a> mapped the FKHL10 gene to 5q34 by fluorescence in situ hybridization and somatic cell hybrid analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8825632" 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>Genes encoding forkhead proteins are instrumental during embryogenesis in mammals, in particular during development of the nervous system. <a href="#4" class="mim-tip-reference" title="Hulander, M., Wurst, W., Carlsson, P., Enerback, S. <strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong> Nature Genet. 20: 374-376, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843211</a>] [<a href="https://doi.org/10.1038/3850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843211">Hulander et al. (1998)</a> reported that mice with a targeted disruption of the Fkh10 locus exhibited circling behavior, poor swimming ability, and abnormal reaching response, all common findings in mice with vestibular dysfunction. These animals also failed to elicit a Preyer reflex in response to a suprathreshold auditory stimulation, as seen in mice with profound hearing impairment. Histologic examination of the inner ear revealed a gross structural malformation of the vestibulum as well as of the cochlea. These structures were replaced by a single irregular cavity in which neither proper semicircular ducts nor cochlea could be identified. <a href="#4" class="mim-tip-reference" title="Hulander, M., Wurst, W., Carlsson, P., Enerback, S. <strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong> Nature Genet. 20: 374-376, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843211</a>] [<a href="https://doi.org/10.1038/3850" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9843211">Hulander et al. (1998)</a> also showed that at 9.5 days postcoitum, Fkh10 was exclusively expressed in the otic vesicle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Blomqvist, S. R., Vidarsson, H., Fitzgerald, S., Johansson, B. R., Ollerstam, A., Brown, R., Persson, A. E. G., Bergstrom, G., Enerback, S. <strong>Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1.</strong> J. Clin. Invest. 113: 1560-1570, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15173882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15173882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15173882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI20665" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15173882">Blomqvist et al. (2004)</a> found that whereas macro- and microscopic kidney development appeared normal in Fkhl10-null mice, electron microscopy revealed an altered ultrastructure of cells lining the distal nephron. Northern blot analyses, cRNA in situ hybridizations, and immunohistochemistry demonstrated complete loss of expression of several anion transporters, proton pumps, and anion exchange proteins expressed by intercalated cells of the collecting ducts. The normal renal epithelium with its 2 major cell types, principal and intercalated cells, had been replaced by a single cell type positive for both principal and intercalated cell markers. The null mice were unable to acidify urine and had a lowered systemic buffer capacity and overt acidosis compared to their wildtype littermates. <a href="#1" class="mim-tip-reference" title="Blomqvist, S. R., Vidarsson, H., Fitzgerald, S., Johansson, B. R., Ollerstam, A., Brown, R., Persson, A. E. G., Bergstrom, G., Enerback, S. <strong>Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1.</strong> J. Clin. Invest. 113: 1560-1570, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15173882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15173882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15173882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI20665" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15173882">Blomqvist et al. (2004)</a> concluded that Fkhl10-null mice develop distal renal tubular acidosis due to altered cellular composition of the distal nephron epithelium, which lacks the proper gene expression pattern needed for maintaining adequate acid-base homeostasis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15173882" 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>Mice homozygous for the targeted deletion of Foxi1 have a phenotype that includes cochlear dysplasia and enlarged vestibular aqueduct (<a href="#3" class="mim-tip-reference" title="Hulander, M., Kiernan, A. E., Blomqvist, S. R., Carlsson, P., Samuelsson, E. J., Johansson, B. R., Steel, K. P., Enerback, S. <strong>Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice.</strong> Development 130: 2013-2025, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12642503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12642503</a>] [<a href="https://doi.org/10.1242/dev.00376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12642503">Hulander et al., 2003</a>). Also included in the Foxi1 -/- mouse phenotype are male infertility and distal renal tubular acidosis (Blomqvist et al. (<a href="#1" class="mim-tip-reference" title="Blomqvist, S. R., Vidarsson, H., Fitzgerald, S., Johansson, B. R., Ollerstam, A., Brown, R., Persson, A. E. G., Bergstrom, G., Enerback, S. <strong>Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1.</strong> J. Clin. Invest. 113: 1560-1570, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15173882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15173882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15173882[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI20665" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15173882">2004</a>, <a href="#2" class="mim-tip-reference" title="Blomqvist, S. R., Vidarsson, H., Soder, O., Enerback, S. <strong>Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.</strong> EMBO J. 25: 4131-4141, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16932748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16932748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16932748[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.7601272" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16932748">2006</a>)), 2 abnormalities that had not been reported in humans with Pendred syndrome or enlarged vestibular aqueduct. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16932748+15173882+12642503" 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>Recessive mutations in the anion transporter gene SLC26A4 (<a href="/entry/605646">605646</a>) are known to be responsible for Pendred syndrome (<a href="/entry/274600">274600</a>) and for nonsyndromic hearing loss associated with enlarged vestibular aqueduct (DFNB4; <a href="/entry/600791">600791</a>). However, a large percentage of patients with these phenotypes lack mutations in the SLC26A4 coding region in one or both alleles. <a href="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> identified and characterized a key transcriptional regulatory element in the SLC26A4 promoter that binds FOXI1, which is a transcriptional activator of SLC26A4. They found 9 patients with Pendred syndrome or nonsyndromic EVA who were heterozygous for a novel -103T-C mutation (<a href="/entry/605646#0027">605646.0027</a>) in this regulatory element, which interfered with FOXI1 binding and completely abolished FOXI1-mediated transcriptional activation. They also identified 2 Pendred and 4 EVA patients with heterozygous mutations in FOXI1 that compromised its ability to activate SLC26A4 transcription; 1 of the EVA patients was a double heterozygote who also carried a heterozygous mutation in the SLC26A4 gene (see <a href="/entry/605646#0028">605646.0028</a> and <a href="#0001">601093.0001</a>). This finding was consistent with their observation that EVA occurs in the mouse mutant doubly heterozygous for mutations in these 2 genes, and the results supported a dosage-dependent model for the molecular pathogenesis of Pendred syndrome and nonsyndromic EVA that involves SLC26A4 and its transcriptional regulatory machinery. Mutations in many transcription factors had been shown to lead to nonsyndromic or syndromic hearing impairment, but the FOXI1/SLC26A4 connection was the first identification of a specific downstream target gene; <a href="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> stated the this was the first example of digenic inheritance to be verified as a cause of human deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17503324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> described a patient with enlarged vestibular aqueduct as the basis of nonsyndromic hearing loss (DFNB4; <a href="/entry/600791">600791</a>) in whom the combination of a heterozygous glu29-to-gln (E29Q) mutation of SLC26A4 (<a href="/entry/605646#0028">605646.0028</a>) and a gly258-to-glu (G258E) mutation of FOXI1 was responsible. Each unaffected parent was heterozygous for 1 of the mutations, and her unaffected sister carried only the E29Q mutation in SLC26A4. <a href="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> concluded that this was the first example of digenic inheritance to be verified as a cause of human deafness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17503324" 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>In 2 families given a diagnosis of DFNB4 with EVA (<a href="/entry/600791">600791</a>), <a href="#9" class="mim-tip-reference" title="Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H. <strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong> Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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/10.1086/518314" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17503324">Yang et al. (2007)</a> found heterozygosity for an arg267-to-gln change (R267Q) in the FOXI1 protein. Although both of these families were classified by the authors as 'nonsyndromic EVA,' in one of them goiter reminiscent of Pendred syndrome (<a href="/entry/274600">274600</a>) was noted. Both alleles of the SLC26A4 gene (<a href="/entry/605646">605646</a>) were wildtype. The R267Q mutation showed significantly decreased luciferase activation in promoter-reporter assays, suggesting that this variant compromised FOXI1 transactivation ability of SLC26A4 expression and was causally related to disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17503324" 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>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Blomqvist2004" class="mim-anchor"></a>
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Blomqvist, S. R., Vidarsson, H., Fitzgerald, S., Johansson, B. R., Ollerstam, A., Brown, R., Persson, A. E. G., Bergstrom, G., Enerback, S.
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<strong>Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1.</strong>
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|
J. Clin. Invest. 113: 1560-1570, 2004.
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15173882/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15173882</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15173882[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=15173882" 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/10.1172/JCI20665" target="_blank">Full Text</a>]
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Blomqvist, S. R., Vidarsson, H., Soder, O., Enerback, S.
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<strong>Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.</strong>
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|
EMBO J. 25: 4131-4141, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16932748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16932748</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16932748[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=16932748" 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.7601272" target="_blank">Full Text</a>]
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<a id="Hulander2003" class="mim-anchor"></a>
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Hulander, M., Kiernan, A. E., Blomqvist, S. R., Carlsson, P., Samuelsson, E. J., Johansson, B. R., Steel, K. P., Enerback, S.
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<strong>Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice.</strong>
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Development 130: 2013-2025, 2003.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12642503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12642503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12642503" 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/10.1242/dev.00376" target="_blank">Full Text</a>]
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Hulander, M., Wurst, W., Carlsson, P., Enerback, S.
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<strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong>
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Nature Genet. 20: 374-376, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9843211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9843211</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9843211" 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/10.1038/3850" target="_blank">Full Text</a>]
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Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S., Carlsson, P.
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<strong>Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).</strong>
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Genomics 30: 464-469, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8825632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8825632</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8825632" 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/10.1006/geno.1995.1266" target="_blank">Full Text</a>]
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Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., Rogel, N., Burgin, G., and 17 others.
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<strong>A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.</strong>
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Nature 560: 319-324, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069044</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30069044" 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/s41586-018-0393-7" target="_blank">Full Text</a>]
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Pierrou, S., Hellqvist, M., Samuelsson, L., Enerback, S., Carlsson, P.
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<strong>Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.</strong>
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EMBO J. 13: 5002-5012, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7957066/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7957066</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7957066" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/j.1460-2075.1994.tb06827.x" target="_blank">Full Text</a>]
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<a id="Plasschaert2018" class="mim-anchor"></a>
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Plasschaert, L. W., Zilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., Jaffe, A. B.
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<strong>A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.</strong>
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Nature 560: 377-381, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30069046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30069046</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30069046" 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/s41586-018-0394-6" target="_blank">Full Text</a>]
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Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H.
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<strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong>
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Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17503324/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17503324</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17503324[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=17503324" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/518314" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 09/21/2018
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Marla J. F. O'Neill - updated : 8/9/2007<br>Victor A. McKusick - updated : 5/23/2007<br>Marla J. F. O'Neill - updated : 6/22/2004<br>Victor A. McKusick - updated : 11/24/1998<br>Rebekah S. Rasooly - updated : 11/4/1998
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Alan F. Scott : 2/26/1996
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alopez : 09/21/2018
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terry : 12/21/2012<br>alopez : 6/13/2012<br>ckniffin : 6/12/2012<br>alopez : 10/27/2009<br>alopez : 10/27/2009<br>alopez : 10/13/2009<br>alopez : 8/9/2007<br>alopez : 5/23/2007<br>terry : 5/23/2007<br>terry : 4/5/2005<br>carol : 6/23/2004<br>carol : 6/22/2004<br>terry : 6/22/2004<br>alopez : 12/1/1998<br>alopez : 12/1/1998<br>terry : 11/24/1998<br>alopez : 11/4/1998<br>dkim : 10/12/1998<br>mark : 1/10/1998<br>mark : 2/26/1996
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<strong>*</strong> 601093
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FORKHEAD BOX I1; FOXI1
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FORKHEAD, DROSOPHILA, HOMOLOG-LIKE 10; FKHL10<br />
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FKH10<br />
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FORKHEAD-RELATED ACTIVATOR 6; FREAC6
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<strong><em>HGNC Approved Gene Symbol: FOXI1</em></strong>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 70348004;
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<strong>ICD10CM:</strong> E07.1;
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</span>
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</p>
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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: 5q35.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:170,105,897-170,109,737 </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="1">
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<span class="mim-font">
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5q35.1
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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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Enlarged vestibular aqueduct
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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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600791
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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 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>FKH10 is a member of the forkhead family of winged helix transcription regulators. The forkhead family is distinguished by a characteristic 100-amino acid motif that was originally identified in Drosophila (see 164874). Pierrou et al. (1994) identified 7 human genes containing a forkhead domain and designated them forkhead related activators (FREAC) 1 through 7. Northern blot analysis revealed that the FREAC6, or FKHL10, gene is expressed as a 2.3-kb mRNA only in kidney. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Larsson et al. (1995) showed that human FKHL10 is expressed in the adult and fetal kidney, whereas 15 other tissues (which did not include any inner ear-derived samples) were negative. Kidney-specific expression had been observed also in the mouse. Although Fkh10 may play a role in the kidney during later stages of development, it may be a minor, or perhaps redundant, role, as no kidney dysfunction was observed in homozygous knockout mice. On the contrary, Fkh10 appears to be unique in the sense that it is an early otic vesicle-specific gene necessary for the development of both cochlea and vestibulum. These findings implicated Fkh10 as an early regulator necessary for development of both cochlea and vestibulum and identified its human homolog, FKHL10, as a candidate deafness gene at 5q34. The phenotype described by Hulander et al. (1998) resembles a group of human congenital inner ear malformations called 'common cavity.' Hulander et al. (1998) proposed that mutations in FKH10 may cause a 'common cavity' phenotype in humans. </p><p>Yang et al. (2007) demonstrated that FOXI1 is a transcription factor for SLC26A4 (605646) and identified and characterized a key transcriptional regulatory element in the SLC26A4 promoter that binds FOXI1. The SLC26A4 cis element consists of 2 FOXI1 binding sites, FBS1 and FBS2, arranged head to head. Both binding sites and this specific orientation are required for FOXI1-mediated transcriptional activation. </p><p>Using single-cell RNA sequencing and in vivo lineage tracing to study the composition and hierarchy of the mouse tracheal epithelium, Montoro et al. (2018) identified a rare cell type, the Foxi1-positive pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that they termed 'hillocks'; and disease-relevant subsets of tuft and goblet cells. Montoro et al. (2018) developed 'pulse-seq,' combining single-cell RNA-seq and lineage tracing, to show that tuft, neuroendocrine, and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the CFTR (602421) in both mouse and human. Knockout of Foxi1 in mouse ionocytes caused loss of Cftr expression and disrupted airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis (219700). Montoro et al. (2018) concluded that by associating cell type-specific expression programs with key disease genes, they had established a new cellular narrative for airway disease. </p><p>Plasschaert et al. (2018) performed single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behavior in homeostasis and regeneration. The analysis revealed cell states that represent known and novel cell populations, delineated their heterogeneity, and identified distinct differentiation trajectories during homeostasis and tissue repair. In addition, Plasschaert et al. (2018) identified a novel, rare cell type that they called the 'pulmonary ionocyte,' which coexpresses FOXI1, multiple subunits of the vacuolar-type H(+)-ATPase (V-ATPase), and CFTR. Using immunofluorescence, modulation of signaling pathways, and electrophysiology, Plasschaert et al. (2018) showed that Notch signaling (see 190198) is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium. </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>Larsson et al. (1995) mapped the FKHL10 gene to 5q34 by fluorescence in situ hybridization and somatic cell hybrid analysis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Genes encoding forkhead proteins are instrumental during embryogenesis in mammals, in particular during development of the nervous system. Hulander et al. (1998) reported that mice with a targeted disruption of the Fkh10 locus exhibited circling behavior, poor swimming ability, and abnormal reaching response, all common findings in mice with vestibular dysfunction. These animals also failed to elicit a Preyer reflex in response to a suprathreshold auditory stimulation, as seen in mice with profound hearing impairment. Histologic examination of the inner ear revealed a gross structural malformation of the vestibulum as well as of the cochlea. These structures were replaced by a single irregular cavity in which neither proper semicircular ducts nor cochlea could be identified. Hulander et al. (1998) also showed that at 9.5 days postcoitum, Fkh10 was exclusively expressed in the otic vesicle. </p><p>Blomqvist et al. (2004) found that whereas macro- and microscopic kidney development appeared normal in Fkhl10-null mice, electron microscopy revealed an altered ultrastructure of cells lining the distal nephron. Northern blot analyses, cRNA in situ hybridizations, and immunohistochemistry demonstrated complete loss of expression of several anion transporters, proton pumps, and anion exchange proteins expressed by intercalated cells of the collecting ducts. The normal renal epithelium with its 2 major cell types, principal and intercalated cells, had been replaced by a single cell type positive for both principal and intercalated cell markers. The null mice were unable to acidify urine and had a lowered systemic buffer capacity and overt acidosis compared to their wildtype littermates. Blomqvist et al. (2004) concluded that Fkhl10-null mice develop distal renal tubular acidosis due to altered cellular composition of the distal nephron epithelium, which lacks the proper gene expression pattern needed for maintaining adequate acid-base homeostasis. </p><p>Mice homozygous for the targeted deletion of Foxi1 have a phenotype that includes cochlear dysplasia and enlarged vestibular aqueduct (Hulander et al., 2003). Also included in the Foxi1 -/- mouse phenotype are male infertility and distal renal tubular acidosis (Blomqvist et al. (2004, 2006)), 2 abnormalities that had not been reported in humans with Pendred syndrome or enlarged vestibular aqueduct. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Recessive mutations in the anion transporter gene SLC26A4 (605646) are known to be responsible for Pendred syndrome (274600) and for nonsyndromic hearing loss associated with enlarged vestibular aqueduct (DFNB4; 600791). However, a large percentage of patients with these phenotypes lack mutations in the SLC26A4 coding region in one or both alleles. Yang et al. (2007) identified and characterized a key transcriptional regulatory element in the SLC26A4 promoter that binds FOXI1, which is a transcriptional activator of SLC26A4. They found 9 patients with Pendred syndrome or nonsyndromic EVA who were heterozygous for a novel -103T-C mutation (605646.0027) in this regulatory element, which interfered with FOXI1 binding and completely abolished FOXI1-mediated transcriptional activation. They also identified 2 Pendred and 4 EVA patients with heterozygous mutations in FOXI1 that compromised its ability to activate SLC26A4 transcription; 1 of the EVA patients was a double heterozygote who also carried a heterozygous mutation in the SLC26A4 gene (see 605646.0028 and 601093.0001). This finding was consistent with their observation that EVA occurs in the mouse mutant doubly heterozygous for mutations in these 2 genes, and the results supported a dosage-dependent model for the molecular pathogenesis of Pendred syndrome and nonsyndromic EVA that involves SLC26A4 and its transcriptional regulatory machinery. Mutations in many transcription factors had been shown to lead to nonsyndromic or syndromic hearing impairment, but the FOXI1/SLC26A4 connection was the first identification of a specific downstream target gene; Yang et al. (2007) stated the this was the first example of digenic inheritance to be verified as a cause of human deafness. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>2 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
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|
|
<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT, DIGENIC</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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|
|
FOXI1, GLY258GLU
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<br />
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|
|
SNP: rs121909340,
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|
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gnomAD: rs121909340,
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|
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ClinVar: RCV000008964, RCV000729912, RCV002490341
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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>Yang et al. (2007) described a patient with enlarged vestibular aqueduct as the basis of nonsyndromic hearing loss (DFNB4; 600791) in whom the combination of a heterozygous glu29-to-gln (E29Q) mutation of SLC26A4 (605646.0028) and a gly258-to-glu (G258E) mutation of FOXI1 was responsible. Each unaffected parent was heterozygous for 1 of the mutations, and her unaffected sister carried only the E29Q mutation in SLC26A4. Yang et al. (2007) concluded that this was the first example of digenic inheritance to be verified as a cause of human deafness. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 4, WITH ENLARGED VESTIBULAR AQUEDUCT</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
PENDRED SYNDROME, 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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FOXI1, ARG267GLN
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<br />
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|
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SNP: rs121909341,
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gnomAD: rs121909341,
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ClinVar: RCV000008965, RCV000008966
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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 families given a diagnosis of DFNB4 with EVA (600791), Yang et al. (2007) found heterozygosity for an arg267-to-gln change (R267Q) in the FOXI1 protein. Although both of these families were classified by the authors as 'nonsyndromic EVA,' in one of them goiter reminiscent of Pendred syndrome (274600) was noted. Both alleles of the SLC26A4 gene (605646) were wildtype. The R267Q mutation showed significantly decreased luciferase activation in promoter-reporter assays, suggesting that this variant compromised FOXI1 transactivation ability of SLC26A4 expression and was causally related to disease. </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>REFERENCES</strong>
|
|
</span>
|
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</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Blomqvist, S. R., Vidarsson, H., Fitzgerald, S., Johansson, B. R., Ollerstam, A., Brown, R., Persson, A. E. G., Bergstrom, G., Enerback, S.
|
|
<strong>Distal renal tubular acidosis in mice that lack the forkhead transcription factor Foxi1.</strong>
|
|
J. Clin. Invest. 113: 1560-1570, 2004.
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[PubMed: 15173882]
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[Full Text: https://doi.org/10.1172/JCI20665]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Blomqvist, S. R., Vidarsson, H., Soder, O., Enerback, S.
|
|
<strong>Epididymal expression of the forkhead transcription factor Foxi1 is required for male fertility.</strong>
|
|
EMBO J. 25: 4131-4141, 2006.
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[PubMed: 16932748]
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[Full Text: https://doi.org/10.1038/sj.emboj.7601272]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Hulander, M., Kiernan, A. E., Blomqvist, S. R., Carlsson, P., Samuelsson, E. J., Johansson, B. R., Steel, K. P., Enerback, S.
|
|
<strong>Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice.</strong>
|
|
Development 130: 2013-2025, 2003.
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|
[PubMed: 12642503]
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[Full Text: https://doi.org/10.1242/dev.00376]
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</p>
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|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hulander, M., Wurst, W., Carlsson, P., Enerback, S.
|
|
<strong>The winged helix transcription factor Fkh10 is required for normal development of the inner ear.</strong>
|
|
Nature Genet. 20: 374-376, 1998.
|
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|
[PubMed: 9843211]
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[Full Text: https://doi.org/10.1038/3850]
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</p>
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|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Larsson, C., Hellqvist, M., Pierrou, S., White, I., Enerback, S., Carlsson, P.
|
|
<strong>Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).</strong>
|
|
Genomics 30: 464-469, 1995.
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[PubMed: 8825632]
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[Full Text: https://doi.org/10.1006/geno.1995.1266]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Montoro, D. T., Haber, A. L., Biton, M., Vinarsky, V., Lin, B., Birket, S. E., Yuan, F., Chen, S., Leung, H. M., Villoria, J., Rogel, N., Burgin, G., and 17 others.
|
|
<strong>A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.</strong>
|
|
Nature 560: 319-324, 2018.
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|
[PubMed: 30069044]
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[Full Text: https://doi.org/10.1038/s41586-018-0393-7]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Pierrou, S., Hellqvist, M., Samuelsson, L., Enerback, S., Carlsson, P.
|
|
<strong>Cloning and characterization of seven human forkhead proteins: binding site specificity and DNA bending.</strong>
|
|
EMBO J. 13: 5002-5012, 1994.
|
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|
[PubMed: 7957066]
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[Full Text: https://doi.org/10.1002/j.1460-2075.1994.tb06827.x]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Plasschaert, L. W., Zilionis, R., Choo-Wing, R., Savova, V., Knehr, J., Roma, G., Klein, A. M., Jaffe, A. B.
|
|
<strong>A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.</strong>
|
|
Nature 560: 377-381, 2018.
|
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|
[PubMed: 30069046]
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[Full Text: https://doi.org/10.1038/s41586-018-0394-6]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Yang, T., Vidarsson, H., Rodrigo-Blomqvist, S., Rosengren, S. S., Enerback, S., Smith, R. J. H.
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<strong>Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4).</strong>
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Am. J. Hum. Genet. 80: 1055-1063, 2007. Note: Erratum: Am. J. Hum. Genet. 81: 634 only, 2007.
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[PubMed: 17503324]
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[Full Text: https://doi.org/10.1086/518314]
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Ada Hamosh - updated : 09/21/2018<br>Marla J. F. O'Neill - updated : 8/9/2007<br>Victor A. McKusick - updated : 5/23/2007<br>Marla J. F. O'Neill - updated : 6/22/2004<br>Victor A. McKusick - updated : 11/24/1998<br>Rebekah S. Rasooly - updated : 11/4/1998
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Alan F. Scott : 2/26/1996
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