3892 lines
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- *603537 - POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 4; KCNQ4
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<p>
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<span class="h4">*603537</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/603537">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<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 class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000117013;t=ENST00000347132" 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=9132" 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=603537" 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=ENSG00000117013;t=ENST00000347132" 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_004700,NM_172163,XM_017002792,XM_047434057,XR_007064876,XR_007064877" 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_004700" 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=603537" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=04641&isoform_id=04641_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/KCNQ4" 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/4262523,4262539,26638653,26638655,119627602,193786717,259016259,1034563253,2217272225,2462515320,2462515322" 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/P56696" 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=9132" 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=ENSG00000117013;t=ENST00000347132" 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=KCNQ4" 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=KCNQ4" 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+9132" 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/KCNQ4" 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:9132" 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/9132" 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=chr1&hgg_gene=ENST00000347132.10&hgg_start=40783787&hgg_end=40840452&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:6298" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/kcnq4" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603537[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 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=603537[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/ENSG00000117013" 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=KCNQ4" 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=KCNQ4" 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=KCNQ4" 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=KCNQ4&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/PA30076" 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:6298" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0033494.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1926803" 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/KCNQ4#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:1926803" 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/9132/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=9132" 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=WBGene00002233;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-120215-132" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:9132" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=KCNQ4&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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603537
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 4; KCNQ4
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY Q, MEMBER 4
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=KCNQ4" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNQ4</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/1/495?start=-3&limit=10&highlight=495">1p34.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:40783787-40840452&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'})">1:40,783,787-40,840,452</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</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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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover 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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<a href="/geneMap/1/495?start=-3&limit=10&highlight=495">
|
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1p34.2
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Deafness, autosomal dominant 2A
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</span>
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</td>
|
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<td>
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<span class="mim-font">
|
|
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<a href="/entry/600101"> 600101 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</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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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/603537" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603537" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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<p>Potassium channels regulate electrical signaling and the ionic composition of biologic fluids. KCNQ4 is a member of the voltage-gated potassium channel gene family and forms a homologous tetrameric structure (<a href="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" 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="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> cloned the KCNQ4 cDNA, which encodes a deduced polypeptide of 695 amino acids with a predicted mass of 77 kD. Its overall amino acid identity to KCNQ1 (<a href="/entry/607542">607542</a>), KCNQ2 (<a href="/entry/602235">602235</a>), and KCNQ3 (<a href="/entry/602232">602232</a>) is 38%, 44%, and 37%, respectively. KCNQ4 has 6 predicted transmembrane domains and a P loop between transmembrane domains S5 and S6. In potassium channels, which are tetramers of identical or homologous subunits, 4 of these highly conserved P loops combine to form the ion-selective pore. As with other KCNQ channels, KCNQ4 has a long predicted cytoplasmic C terminus that accounts for about half of the protein. KCNQ4 is expressed in the cochlea; sensory outer hair cells strongly expressed KCNQ4, whereas the inner hair cells appeared negative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" 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="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> determined the genomic structure of the KCNQ4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By FISH, <a href="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> mapped the gene to 1p34. Using a YAC contig of this region, they refined the localization within a region encompassing the autosomal dominant nonsyndromic deafness type 2 (DFNA2; <a href="/entry/600101">600101</a>) locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" 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 the mouse cochlea, the Kcnq4 transcript is found exclusively in the outer hair cells. Using specific antibodies, <a href="#6" class="mim-tip-reference" title="Kharkovets, T., Hardelin, J.-P., Safieddine, S., Schweizer, M., El-Amraoui, A., Petit, C., Jentsch, T. J. <strong>KCNQ4, a K(+) channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.</strong> Proc. Nat. Acad. Sci. 97: 4333-4338, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10760300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10760300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10760300[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.8.4333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10760300">Kharkovets et al. (2000)</a> showed that Kcnq4 is situated at the basal membrane of these sensory cells. In the vestibular organs, Kcnq4 is restricted to the type I hair cells and the afferent calyx-like nerve endings ensheathing these sensory cells. Kcnq4 is also expressed in neurons of many, but not all, nuclei of the central auditory pathway, and is absent from most other brain regions. It is present, for example, in the cochlear nuclei, the nuclei of the lateral lemniscus, and the inferior colliculus. <a href="#6" class="mim-tip-reference" title="Kharkovets, T., Hardelin, J.-P., Safieddine, S., Schweizer, M., El-Amraoui, A., Petit, C., Jentsch, T. J. <strong>KCNQ4, a K(+) channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.</strong> Proc. Nat. Acad. Sci. 97: 4333-4338, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10760300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10760300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10760300[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.8.4333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10760300">Kharkovets et al. (2000)</a> stated that this was the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of the gene in the mouse auditory system raises the possibility of a central component in DFNA2 hearing loss. An understanding of the pharmacologic modification of the ion channels mutant in DFNA2 might permit the development of new treatments that are selective for a sensory modality and perhaps even for the quality of perception (<a href="#12" class="mim-tip-reference" title="Trussell, L. <strong>Mutant ion channel in cochlear hair cells causes deafness.</strong> Proc. Nat. Acad. Sci. 97: 3786-3788, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10760249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10760249</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10760249[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.97.8.3786" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10760249">Trussell, 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10760300+10760249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By recording channel currents produced in cRNA-injected Xenopus oocytes, <a href="#17" class="mim-tip-reference" title="Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E. <strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong> Neuron 37: 963-975, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12670425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12670425</a>] [<a href="https://doi.org/10.1016/s0896-6273(03)00125-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12670425">Zhang et al. (2003)</a> found that phosphatidylinositol (4,5)-bisphosphate activated all members of the KCNQ channel family analyzed, including KCNQ4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12670425" 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>Kv7 channels have distinct assembly preferences that are controlled by their cytoplasmic C-terminal assembly domains, or A-domain tails. <a href="#4" class="mim-tip-reference" title="Howard, R. J., Clark, K. A., Holton, J. M., Minor, D. L. <strong>Structural insight into KCNQ (Kv7) channel assembly and channelopathy.</strong> Neuron 53: 663-675, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17329207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17329207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17329207[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.neuron.2007.02.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17329207">Howard et al. (2007)</a> determined the crystal structure of the C-terminal A-domain tail (residues 610 to 640) of Kv7.4 at 2.07-angstrom resolution. The overall structure of the A-domain tail was a tightly twisted left-handed 4-stranded coiled coil. The last 3 C-terminal residues formed a broad base and participated in crystal contacts with neighboring molecules in the crystal lattice. The surface of the A-domain tail complex was predominantly polar and had 2 distinct networks of side-chain salt bridges and hydrogen bonds. The 2 networks made interhelical contacts across helix interfaces. Analysis of the Kv7.4 A-domain tail in aqueous solution showed that it had an estimated helical content of 66% and was present as a tetramer, reflecting the crystal structure and the expected stoichiometry of KCNQ voltage-gated potassium channels. Sequence comparisons showed conservation of the coiled-coil motif in the A-domain tails of all 5 Kv7 subtypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17329207" 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="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> identified a heterozygous mutation (<a href="#0001">603537.0001</a>) in the pore region in exon 6 of the KCNQ4 gene in all affected members of a family segregating autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>). The mutation abolished the potassium currents of wildtype KCNQ4, on which it exerted a strong dominant-negative effect. <a href="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> concluded that KCNQ4-related hearing loss is intrinsic to outer hair cells. The authors also found that KCNQ4 formed heteromeric channels with KCNQ3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> analyzed the KCNQ4 gene in 5 previously reported families with DFNA2A, 3 from the Netherlands and Belgium (<a href="#14" class="mim-tip-reference" title="Van Camp, G., Coucke, P. J., Kunst, H., Schatteman, I., Van Velzen, D., Marres, H., van Ewijk, M., Declau, F., Van Hauwe, P., Meyers, J., Kenyon, J., Smith, S. D., Smith, R. J. H., Djelantik, B., Cremers, C. W. R. J., Van de Heyning, P. H., Willems, P. J. <strong>Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.</strong> Genomics 41: 70-74, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126484</a>] [<a href="https://doi.org/10.1006/geno.1997.4624" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9126484">Van Camp et al., 1997</a>) and 2 from Indonesia and the U.S. (<a href="#3" class="mim-tip-reference" title="Coucke, P., Van Camp, G., Djoyodiharjo, B., Smith, S. D., Frants, R. R., Padberg, G. W., Darby, J. K., Huizing, E. H., Cremers, C. W., Kimberling, W. J., Oostra, B. A., Van de Heyning, P. H., Willems, P. J. <strong>Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families.</strong> New Eng. J. Med. 331: 425-431, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8035838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8035838</a>] [<a href="https://doi.org/10.1056/NEJM199408183310702" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8035838">Coucke et al., 1994</a>). They found missense mutations altering conserved amino acids in 3 families and an inactivating deletion in a fourth family. No KCNQ4 mutation was found in the DFNA2A family of Indonesian origin. <a href="#15" class="mim-tip-reference" title="Van Hauwe, P., Coucke, P. J., Declau, F., Kunst, H., Ensink, R. J., Marres, H. A., Cremers, C. W. R. J., Djelantik, B., Smith, S. D., Kelley, P., Van de Heyning, P. H., Van Camp, G. <strong>Deafness linked to DFNA2: one locus but how many genes? (Letter)</strong> Nature Genet. 21: 263 only, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080176</a>] [<a href="https://doi.org/10.1038/6778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10080176">Van Hauwe et al. (1999)</a> analyzed the GJB3 gene in the same 5 families and found no mutations in any. <a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> concluded that at least 2 and possibly 3 genes responsible for hearing impairment are located close together on 1p34 and suggested that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10369879+8035838+10080176+9126484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Talebizadeh, Z., Kelley, P. M., Askew, J. W., Beisel, K. W., Smith, S. D. <strong>Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss.</strong> Hum. Mutat. 14: 493-501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10571947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10571947</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10571947">Talebizadeh et al. (1999)</a> described a leu281-to-ser missense mutation (<a href="#0006">603537.0006</a>) of the KCNQ4 gene in all cases of nonsyndromic dominant progressive hearing loss in a 5-generation American family. They also tested for KCNQ4 mutations in probands from 20 families with dominant nonsyndromic hearing loss and probands from 60 families with recessive nonsyndromic hearing loss; none of these patients showed a truncating mutation in KCNQ4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10571947" 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="#16" class="mim-tip-reference" title="Van Hauwe, P., Coucke, P. J., Ensink, R. J., Huygen, P., Cremers, C. W. R. J., Van Camp, G. <strong>Mutations in the KCNQ4 K(+) channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region.</strong> Am. J. Med. Genet. 93: 184-187, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10925378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10925378</a>] [<a href="https://doi.org/10.1002/1096-8628(20000731)93:3<184::aid-ajmg4>3.0.co;2-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10925378">Van Hauwe et al. (2000)</a> identified a leu274-to-his (<a href="#0007">603537.0007</a>) mutation in the KCNQ4 gene in affected members of another Dutch family with DFNA2A. Examination of the position of all known KCNQ4 mutations showed a clustering of mutations in the pore region of the gene, which is responsible for the ion selectivity of the channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10925378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a 4-generation Spanish family segregating autosomal dominant hearing loss, <a href="#9" class="mim-tip-reference" title="Mencia, A., Gonzalez-Nieto, D., Modamio-Hoybjor, S., Etxeberria, A., Aranguez, G., Salvador, N., del Castillo, I., Villarroel, A., Moreno, F., Barrio, L., Moreno-Pelayo, M. A. <strong>A novel KCNQ4 pore-region mutation (p.G296S) causes deafness by impairing cell-surface channel expression.</strong> Hum. Genet. 123: 41-53, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18030493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18030493</a>] [<a href="https://doi.org/10.1007/s00439-007-0447-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18030493">Mencia et al. (2008)</a> identified heterozygosity for a mutation (G296S; <a href="#0009">603537.0009</a>) in the KCNQ4 gene. Expression and functional studies demonstrated a strong dominant-negative effect on wildtype channel activity via a trafficking defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18030493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In electrophysiologic studies, <a href="#7" class="mim-tip-reference" title="Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N. <strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong> J. Biol. Chem. 286: 1517-1527, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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/10.1074/jbc.M110.179010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966080">Kim et al. (2011)</a> found that Chinese hamster ovary cells transfected with KCNQ4 mutants affecting the pore region (L274H, <a href="#0007">603537.0007</a>; W276S, <a href="#0002">603537.0002</a>; L281S, <a href="#0006">603537.0006</a>; G285C, <a href="#0004">603537.0004</a>; and G296S, <a href="#0009">603537.0009</a>) had no measurable outward currents compared to cells transfected with the wildtype protein. When coexpressed with wildtype, the mutant W276S protein caused a reduction in current density, consistent with a dominant-negative effect, although the gating properties of the channel were unchanged. Current suppression increased with decreasing wildtype:mutant ratio, consistent with the tetrameric structure of the channel. Most mutants also shortened the kinetics of deactivation. Similar studies with the G321S mutant (<a href="#0003">603537.0003</a>) at the C terminus showed similar effects as those in the pore channel. Immunohistochemical studies showed that none of the pore mutant proteins localized to the plasma membrane when expressed alone, indicating a trafficking defect and retention in the ER. However, coexpression with the wildtype protein resulted in some membrane expression. These findings indicated functional channel defects associated with pathogenic KCNQ4 mutations, but also suggested an interaction with the wildtype protein resulting in different effects. Finally, the results of <a href="#7" class="mim-tip-reference" title="Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N. <strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong> J. Biol. Chem. 286: 1517-1527, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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/10.1074/jbc.M110.179010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966080">Kim et al. (2011)</a> indicated that the F182L variant, identified in a Taiwanese patient with deafness (<a href="#10" class="mim-tip-reference" title="Su, C.-C., Yang, J.-J., Shieh, J.-C., Su, M.-C., Li, S.-Y. <strong>Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan.</strong> Audiol. Neurootol. 12: 20-26, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033161</a>] [<a href="https://doi.org/10.1159/000096154" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17033161">Su et al., 2007</a>) had normal cell surface expression and functional features, suggesting that it is not pathogenic. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17033161+20966080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937588 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937588;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a> identified a gly285-to-ser (GGC-to-AGC) mutation in heterozygous state. This mutation segregated with all affected members in the pedigree and was not found on 150 control Caucasian chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" 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="#7" class="mim-tip-reference" title="Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N. <strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong> J. Biol. Chem. 286: 1517-1527, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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/10.1074/jbc.M110.179010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966080">Kim et al. (2011)</a> referred to this mutation as resulting from an 853G-A transition in exon 6, resulting in a G285S substitution in the pore region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20966080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358277 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358277;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Dutch family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> identified an 827G-C transversion in exon 5 of the KCNQ4 gene resulting in a trp276-to-ser (W276S) mutation in the pore region of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369879" 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="Akita, J., Abe, S., Shinkawa, H., Kimberling, W. J., Usami, S. <strong>Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss: KCNQ4 is a gene responsible in Japanese.</strong> J. Hum. Genet. 46: 355-361, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11450843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11450843</a>] [<a href="https://doi.org/10.1007/s100380170053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11450843">Akita et al. (2001)</a> found this mutation in a Japanese family with deafness in 4 successive generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11450843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Van Camp, G., Coucke, P. J., Akita, J., Fransen, E., Abe, S., De Leenheer, E. M. R., Huygen, P. L. M., Cremers, C. W. R. J., Usami, S.-I. <strong>A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment.</strong> Hum. Mutat. 20: 15-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112653</a>] [<a href="https://doi.org/10.1002/humu.10096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112653">Van Camp et al. (2002)</a> described 2 additional families originating from Europe and Japan with the W276S mutation. They compared the disease-associated haplotype of the 3 W276S-bearing families using closely linked microsatellite markers and intragenic SNPS. <a href="#13" class="mim-tip-reference" title="Van Camp, G., Coucke, P. J., Akita, J., Fransen, E., Abe, S., De Leenheer, E. M. R., Huygen, P. L. M., Cremers, C. W. R. J., Usami, S.-I. <strong>A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment.</strong> Hum. Mutat. 20: 15-19, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112653</a>] [<a href="https://doi.org/10.1002/humu.10096" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12112653">Van Camp et al. (2002)</a> found differences between the haplotypes, excluding a single founder mutation for the families. Therefore, the W276S mutation has occurred 3 times independently, and most likely represents a hotspot for a mutation in the KCNQ4 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28939710 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28939710;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs28939710?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28939710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28939710" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006621 OR RCV001195307 OR RCV002512842" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006621, RCV001195307, RCV002512842" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006621...</a>
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<p>In a Dutch family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> identified a 961G-A transition in exon 7 of the KCNQ4 gene, which was predicted to produce a gly321-to-ser (G321S) change in the S6 transmembrane domain of the protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs28937588 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28937588;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28937588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs28937588" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a U.S. family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> identified an 853G-T transversion in exon 6 of the KCNQ4 gene, resulting in a gly285-to-cys (G285C) substitution. The same codon is involved in the gly285-to-ser mutation (G285S; <a href="#0001">603537.0001</a>) found in a French family by <a href="#8" class="mim-tip-reference" title="Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J. <strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong> Cell 96: 437-446, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10025409">Kubisch et al. (1999)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10369879+10025409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358271 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358271;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Belgian family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#2" class="mim-tip-reference" title="Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G. <strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong> Hum. Molec. Genet. 8: 1321-1328, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>] [<a href="https://doi.org/10.1093/hmg/8.7.1321" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369879">Coucke et al. (1999)</a> found deletion of 13 bp between nucleotide positions 211 and 224 of the KCNQ4 cDNA sequence. This deletion resulted in a frameshift after gly70, followed by 63 novel amino acids and a premature stop codon at amino acid position 134. The mutation was expected to yield a KCNQ4 protein that was truncated before the first transmembrane region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358278 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358278;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358278" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006624 OR RCV001567939" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006624, RCV001567939" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006624...</a>
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<p>In a 5-generation American family of Austrian origin in which 51 members had nonsyndromic dominant progressive hearing loss linked to the DFNA2A (<a href="/entry/600101">600101</a>) locus on 1p34, <a href="#11" class="mim-tip-reference" title="Talebizadeh, Z., Kelley, P. M., Askew, J. W., Beisel, K. W., Smith, S. D. <strong>Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss.</strong> Hum. Mutat. 14: 493-501, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10571947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10571947</a>] [<a href="https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10571947">Talebizadeh et al. (1999)</a> identified an 824T-C transition in the KCNQ4 gene, resulting in a leu281-to-ser (L281S) substitution. The mutation occurred in the pore region of the protein (<a href="#7" class="mim-tip-reference" title="Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N. <strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong> J. Biol. Chem. 286: 1517-1527, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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/10.1074/jbc.M110.179010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966080">Kim et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10571947+20966080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358276 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358276;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358276" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006625" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006625" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006625</a>
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<p><a href="#16" class="mim-tip-reference" title="Van Hauwe, P., Coucke, P. J., Ensink, R. J., Huygen, P., Cremers, C. W. R. J., Van Camp, G. <strong>Mutations in the KCNQ4 K(+) channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region.</strong> Am. J. Med. Genet. 93: 184-187, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10925378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10925378</a>] [<a href="https://doi.org/10.1002/1096-8628(20000731)93:3<184::aid-ajmg4>3.0.co;2-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10925378">Van Hauwe et al. (2000)</a> found a leu274-to-his (L274H) mutation in the KCNQ4 gene in affected members of a Dutch family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>). The mutation occurred in the pore region of the protein (<a href="#7" class="mim-tip-reference" title="Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N. <strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong> J. Biol. Chem. 286: 1517-1527, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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/10.1074/jbc.M110.179010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20966080">Kim et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10925378+20966080" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358272 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358272;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358272" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a Japanese family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#5" class="mim-tip-reference" title="Kamada, F., Kure, S., Kudo, T., Suzuki, Y., Oshima, T., Ichinohe, A., Kojima, K., Niihori, T., Kanno, J., Narumi, Y., Narisawa, A., Kato, K., Aoki, Y., Ikeda, K., Kobayashi, T., Matsubara, Y. <strong>A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.</strong> J. Hum. Genet. 51: 455-460, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596322</a>] [<a href="https://doi.org/10.1007/s10038-006-0384-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16596322">Kamada et al. (2006)</a> identified a heterozygous 1-bp deletion (211delC) in exon 1 of the KCNQ4 gene, resulting in a truncated protein without transmembrane domains. Affected individuals had late-onset (8 to 50 years) pure high-frequency hearing loss, which was less severe compared to previously reported patients with missense mutations in the KCNQ4 gene. <a href="#5" class="mim-tip-reference" title="Kamada, F., Kure, S., Kudo, T., Suzuki, Y., Oshima, T., Ichinohe, A., Kojima, K., Niihori, T., Kanno, J., Narumi, Y., Narisawa, A., Kato, K., Aoki, Y., Ikeda, K., Kobayashi, T., Matsubara, Y. <strong>A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.</strong> J. Hum. Genet. 51: 455-460, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596322</a>] [<a href="https://doi.org/10.1007/s10038-006-0384-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16596322">Kamada et al. (2006)</a> postulated different pathogenic mechanisms to explain the phenotypic differences: haploinsufficiency in deletion mutations and dominant-negative effects in missense mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16596322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80358279 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80358279;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80358279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80358279" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006627" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006627" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006627</a>
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<p>In affected members of a 4-generation Spanish family with autosomal dominant deafness (DFNA2A; <a href="/entry/600101">600101</a>), <a href="#9" class="mim-tip-reference" title="Mencia, A., Gonzalez-Nieto, D., Modamio-Hoybjor, S., Etxeberria, A., Aranguez, G., Salvador, N., del Castillo, I., Villarroel, A., Moreno, F., Barrio, L., Moreno-Pelayo, M. A. <strong>A novel KCNQ4 pore-region mutation (p.G296S) causes deafness by impairing cell-surface channel expression.</strong> Hum. Genet. 123: 41-53, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18030493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18030493</a>] [<a href="https://doi.org/10.1007/s00439-007-0447-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18030493">Mencia et al. (2008)</a> identified heterozygosity for an 886G-A transition in exon 6 of the KCNQ4 gene, resulting in a gly296-to-ser (G296S) substitution at a highly conserved residue in a stretch of 5 amino acids connecting the P-loop domain and the S6 segment in the pore region. The mutation was not found in 100 unrelated Spanish individuals with normal hearing. Expression and functional studies in Xenopus oocytes and transfected NIH-3T3 cells revealed that the G296S mutant exerts a strong dominant-negative effect on wildtype channel activity by causing a defect in trafficking of KCNQ4 channels to the cell surface membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18030493" 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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Akita, J., Abe, S., Shinkawa, H., Kimberling, W. J., Usami, S.
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<strong>Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss: KCNQ4 is a gene responsible in Japanese.</strong>
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J. Hum. Genet. 46: 355-361, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11450843/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11450843</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11450843" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s100380170053" target="_blank">Full Text</a>]
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Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G.
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<strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong>
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Hum. Molec. Genet. 8: 1321-1328, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Coucke, P., Van Camp, G., Djoyodiharjo, B., Smith, S. D., Frants, R. R., Padberg, G. W., Darby, J. K., Huizing, E. H., Cremers, C. W., Kimberling, W. J., Oostra, B. A., Van de Heyning, P. H., Willems, P. J.
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<strong>Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families.</strong>
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New Eng. J. Med. 331: 425-431, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8035838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8035838</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8035838" 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/10.1056/NEJM199408183310702" target="_blank">Full Text</a>]
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<strong>Structural insight into KCNQ (Kv7) channel assembly and channelopathy.</strong>
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Neuron 53: 663-675, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17329207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17329207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17329207[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=17329207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.neuron.2007.02.010" target="_blank">Full Text</a>]
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<a id="Kamada2006" class="mim-anchor"></a>
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Kamada, F., Kure, S., Kudo, T., Suzuki, Y., Oshima, T., Ichinohe, A., Kojima, K., Niihori, T., Kanno, J., Narumi, Y., Narisawa, A., Kato, K., Aoki, Y., Ikeda, K., Kobayashi, T., Matsubara, Y.
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<strong>A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.</strong>
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J. Hum. Genet. 51: 455-460, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16596322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16596322</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16596322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10038-006-0384-7" target="_blank">Full Text</a>]
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<a id="Kharkovets2000" class="mim-anchor"></a>
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Kharkovets, T., Hardelin, J.-P., Safieddine, S., Schweizer, M., El-Amraoui, A., Petit, C., Jentsch, T. J.
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<strong>KCNQ4, a K(+) channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.</strong>
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Proc. Nat. Acad. Sci. 97: 4333-4338, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10760300/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10760300</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10760300[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=10760300" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.97.8.4333" target="_blank">Full Text</a>]
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<a id="Kim2011" class="mim-anchor"></a>
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Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N.
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<strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong>
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J. Biol. Chem. 286: 1517-1527, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20966080/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20966080</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20966080[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=20966080" 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/10.1074/jbc.M110.179010" target="_blank">Full Text</a>]
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<a id="Kubisch1999" class="mim-anchor"></a>
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<div class="">
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Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J.
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<strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong>
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Cell 96: 437-446, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10025409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10025409</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10025409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80556-5" target="_blank">Full Text</a>]
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<a id="Mencia2008" class="mim-anchor"></a>
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Mencia, A., Gonzalez-Nieto, D., Modamio-Hoybjor, S., Etxeberria, A., Aranguez, G., Salvador, N., del Castillo, I., Villarroel, A., Moreno, F., Barrio, L., Moreno-Pelayo, M. A.
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<strong>A novel KCNQ4 pore-region mutation (p.G296S) causes deafness by impairing cell-surface channel expression.</strong>
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Hum. Genet. 123: 41-53, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18030493/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18030493</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18030493" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00439-007-0447-7" target="_blank">Full Text</a>]
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<a id="Su2007" class="mim-anchor"></a>
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Su, C.-C., Yang, J.-J., Shieh, J.-C., Su, M.-C., Li, S.-Y.
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<strong>Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan.</strong>
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Audiol. Neurootol. 12: 20-26, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17033161/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17033161</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17033161" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1159/000096154" target="_blank">Full Text</a>]
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<a id="Talebizadeh1999" class="mim-anchor"></a>
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Talebizadeh, Z., Kelley, P. M., Askew, J. W., Beisel, K. W., Smith, S. D.
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<strong>Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss.</strong>
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Hum. Mutat. 14: 493-501, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10571947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10571947</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10571947" 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/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P" target="_blank">Full Text</a>]
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<a id="Trussell2000" class="mim-anchor"></a>
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<div class="">
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Trussell, L.
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<strong>Mutant ion channel in cochlear hair cells causes deafness.</strong>
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Proc. Nat. Acad. Sci. 97: 3786-3788, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10760249/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10760249</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10760249[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=10760249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.97.8.3786" target="_blank">Full Text</a>]
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<a id="Van Camp2002" class="mim-anchor"></a>
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Van Camp, G., Coucke, P. J., Akita, J., Fransen, E., Abe, S., De Leenheer, E. M. R., Huygen, P. L. M., Cremers, C. W. R. J., Usami, S.-I.
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<strong>A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment.</strong>
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Hum. Mutat. 20: 15-19, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.10096" target="_blank">Full Text</a>]
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<a id="Van Camp1997" class="mim-anchor"></a>
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Van Camp, G., Coucke, P. J., Kunst, H., Schatteman, I., Van Velzen, D., Marres, H., van Ewijk, M., Declau, F., Van Hauwe, P., Meyers, J., Kenyon, J., Smith, S. D., Smith, R. J. H., Djelantik, B., Cremers, C. W. R. J., Van de Heyning, P. H., Willems, P. J.
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<strong>Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.</strong>
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Genomics 41: 70-74, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126484" 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.1997.4624" target="_blank">Full Text</a>]
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<a id="Van Hauwe1999" class="mim-anchor"></a>
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Van Hauwe, P., Coucke, P. J., Declau, F., Kunst, H., Ensink, R. J., Marres, H. A., Cremers, C. W. R. J., Djelantik, B., Smith, S. D., Kelley, P., Van de Heyning, P. H., Van Camp, G.
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<strong>Deafness linked to DFNA2: one locus but how many genes? (Letter)</strong>
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Nature Genet. 21: 263 only, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10080176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10080176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10080176" 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/10.1038/6778" target="_blank">Full Text</a>]
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Van Hauwe, P., Coucke, P. J., Ensink, R. J., Huygen, P., Cremers, C. W. R. J., Van Camp, G.
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<strong>Mutations in the KCNQ4 K(+) channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region.</strong>
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Am. J. Med. Genet. 93: 184-187, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10925378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10925378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10925378" 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/10.1002/1096-8628(20000731)93:3<184::aid-ajmg4>3.0.co;2-5" target="_blank">Full Text</a>]
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<a id="Zhang2003" class="mim-anchor"></a>
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Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E.
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<strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong>
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Neuron 37: 963-975, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12670425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12670425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12670425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(03)00125-9" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 10/12/2022
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 1/28/2011<br>Patricia A. Hartz - updated : 8/2/2010<br>Marla J. F. O'Neill - updated : 3/18/2008<br>Cassandra L. Kniffin - updated : 7/6/2006<br>Victor A. McKusick - updated : 10/22/2002<br>Victor A. McKusick - updated : 8/27/2002<br>Victor A. McKusick - updated : 7/18/2001<br>Victor A. McKusick - updated : 8/17/2000<br>Victor A. McKusick - updated : 12/21/1999<br>Victor A. McKusick - updated : 7/22/1999
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Creation Date:
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 2/16/1999
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 10/12/2022
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carol : 11/22/2019<br>carol : 11/21/2019<br>carol : 09/27/2016<br>carol : 05/30/2012<br>terry : 2/23/2011<br>wwang : 2/18/2011<br>ckniffin : 1/28/2011<br>mgross : 8/18/2010<br>terry : 8/2/2010<br>carol : 3/6/2009<br>ckniffin : 3/3/2009<br>terry : 12/2/2008<br>wwang : 3/26/2008<br>terry : 3/18/2008<br>wwang : 7/13/2006<br>ckniffin : 7/6/2006<br>ckniffin : 2/5/2003<br>tkritzer : 10/29/2002<br>tkritzer : 10/25/2002<br>terry : 10/22/2002<br>tkritzer : 9/10/2002<br>tkritzer : 8/29/2002<br>terry : 8/27/2002<br>terry : 3/25/2002<br>mcapotos : 8/10/2001<br>terry : 7/18/2001<br>carol : 8/29/2000<br>terry : 8/17/2000<br>terry : 8/17/2000<br>mcapotos : 8/3/2000<br>mcapotos : 1/19/2000<br>mcapotos : 1/11/2000<br>mcapotos : 1/7/2000<br>terry : 12/21/1999<br>jlewis : 8/11/1999<br>terry : 8/9/1999<br>terry : 7/22/1999<br>alopez : 2/26/1999<br>carol : 2/17/1999<br>mgross : 2/17/1999
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<span class="mim-font">
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<strong>*</strong> 603537
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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POTASSIUM CHANNEL, VOLTAGE-GATED, KQT-LIKE SUBFAMILY, MEMBER 4; KCNQ4
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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POTASSIUM CHANNEL, VOLTAGE-GATED, SUBFAMILY Q, MEMBER 4
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: KCNQ4</em></strong>
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</span>
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</p>
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<strong>
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<em>
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Cytogenetic location: 1p34.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 1:40,783,787-40,840,452 </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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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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1p34.2
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<span class="mim-font">
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Deafness, autosomal dominant 2A
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<span class="mim-font">
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600101
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<span class="mim-font">
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Autosomal dominant
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<span class="mim-font">
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<span class="mim-text-font">
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<p>Potassium channels regulate electrical signaling and the ionic composition of biologic fluids. KCNQ4 is a member of the voltage-gated potassium channel gene family and forms a homologous tetrameric structure (Kubisch et al., 1999). </p>
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</span>
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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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</h4>
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<span class="mim-text-font">
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<p>Kubisch et al. (1999) cloned the KCNQ4 cDNA, which encodes a deduced polypeptide of 695 amino acids with a predicted mass of 77 kD. Its overall amino acid identity to KCNQ1 (607542), KCNQ2 (602235), and KCNQ3 (602232) is 38%, 44%, and 37%, respectively. KCNQ4 has 6 predicted transmembrane domains and a P loop between transmembrane domains S5 and S6. In potassium channels, which are tetramers of identical or homologous subunits, 4 of these highly conserved P loops combine to form the ion-selective pore. As with other KCNQ channels, KCNQ4 has a long predicted cytoplasmic C terminus that accounts for about half of the protein. KCNQ4 is expressed in the cochlea; sensory outer hair cells strongly expressed KCNQ4, whereas the inner hair cells appeared negative. </p>
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<strong>Gene Structure</strong>
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<span class="mim-text-font">
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<p>Kubisch et al. (1999) determined the genomic structure of the KCNQ4 gene. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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</div>
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<span class="mim-text-font">
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<p>By FISH, Kubisch et al. (1999) mapped the gene to 1p34. Using a YAC contig of this region, they refined the localization within a region encompassing the autosomal dominant nonsyndromic deafness type 2 (DFNA2; 600101) locus. </p>
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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 class="mim-text-font">
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<p>In the mouse cochlea, the Kcnq4 transcript is found exclusively in the outer hair cells. Using specific antibodies, Kharkovets et al. (2000) showed that Kcnq4 is situated at the basal membrane of these sensory cells. In the vestibular organs, Kcnq4 is restricted to the type I hair cells and the afferent calyx-like nerve endings ensheathing these sensory cells. Kcnq4 is also expressed in neurons of many, but not all, nuclei of the central auditory pathway, and is absent from most other brain regions. It is present, for example, in the cochlear nuclei, the nuclei of the lateral lemniscus, and the inferior colliculus. Kharkovets et al. (2000) stated that this was the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of the gene in the mouse auditory system raises the possibility of a central component in DFNA2 hearing loss. An understanding of the pharmacologic modification of the ion channels mutant in DFNA2 might permit the development of new treatments that are selective for a sensory modality and perhaps even for the quality of perception (Trussell, 2000). </p><p>By recording channel currents produced in cRNA-injected Xenopus oocytes, Zhang et al. (2003) found that phosphatidylinositol (4,5)-bisphosphate activated all members of the KCNQ channel family analyzed, including KCNQ4. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</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>Kv7 channels have distinct assembly preferences that are controlled by their cytoplasmic C-terminal assembly domains, or A-domain tails. Howard et al. (2007) determined the crystal structure of the C-terminal A-domain tail (residues 610 to 640) of Kv7.4 at 2.07-angstrom resolution. The overall structure of the A-domain tail was a tightly twisted left-handed 4-stranded coiled coil. The last 3 C-terminal residues formed a broad base and participated in crystal contacts with neighboring molecules in the crystal lattice. The surface of the A-domain tail complex was predominantly polar and had 2 distinct networks of side-chain salt bridges and hydrogen bonds. The 2 networks made interhelical contacts across helix interfaces. Analysis of the Kv7.4 A-domain tail in aqueous solution showed that it had an estimated helical content of 66% and was present as a tetramer, reflecting the crystal structure and the expected stoichiometry of KCNQ voltage-gated potassium channels. Sequence comparisons showed conservation of the coiled-coil motif in the A-domain tails of all 5 Kv7 subtypes. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kubisch et al. (1999) identified a heterozygous mutation (603537.0001) in the pore region in exon 6 of the KCNQ4 gene in all affected members of a family segregating autosomal dominant deafness (DFNA2A; 600101). The mutation abolished the potassium currents of wildtype KCNQ4, on which it exerted a strong dominant-negative effect. Kubisch et al. (1999) concluded that KCNQ4-related hearing loss is intrinsic to outer hair cells. The authors also found that KCNQ4 formed heteromeric channels with KCNQ3. </p><p>Coucke et al. (1999) analyzed the KCNQ4 gene in 5 previously reported families with DFNA2A, 3 from the Netherlands and Belgium (Van Camp et al., 1997) and 2 from Indonesia and the U.S. (Coucke et al., 1994). They found missense mutations altering conserved amino acids in 3 families and an inactivating deletion in a fourth family. No KCNQ4 mutation was found in the DFNA2A family of Indonesian origin. Van Hauwe et al. (1999) analyzed the GJB3 gene in the same 5 families and found no mutations in any. Coucke et al. (1999) concluded that at least 2 and possibly 3 genes responsible for hearing impairment are located close together on 1p34 and suggested that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss. </p><p>Talebizadeh et al. (1999) described a leu281-to-ser missense mutation (603537.0006) of the KCNQ4 gene in all cases of nonsyndromic dominant progressive hearing loss in a 5-generation American family. They also tested for KCNQ4 mutations in probands from 20 families with dominant nonsyndromic hearing loss and probands from 60 families with recessive nonsyndromic hearing loss; none of these patients showed a truncating mutation in KCNQ4. </p><p>Van Hauwe et al. (2000) identified a leu274-to-his (603537.0007) mutation in the KCNQ4 gene in affected members of another Dutch family with DFNA2A. Examination of the position of all known KCNQ4 mutations showed a clustering of mutations in the pore region of the gene, which is responsible for the ion selectivity of the channel. </p><p>In affected members of a 4-generation Spanish family segregating autosomal dominant hearing loss, Mencia et al. (2008) identified heterozygosity for a mutation (G296S; 603537.0009) in the KCNQ4 gene. Expression and functional studies demonstrated a strong dominant-negative effect on wildtype channel activity via a trafficking defect. </p><p>In electrophysiologic studies, Kim et al. (2011) found that Chinese hamster ovary cells transfected with KCNQ4 mutants affecting the pore region (L274H, 603537.0007; W276S, 603537.0002; L281S, 603537.0006; G285C, 603537.0004; and G296S, 603537.0009) had no measurable outward currents compared to cells transfected with the wildtype protein. When coexpressed with wildtype, the mutant W276S protein caused a reduction in current density, consistent with a dominant-negative effect, although the gating properties of the channel were unchanged. Current suppression increased with decreasing wildtype:mutant ratio, consistent with the tetrameric structure of the channel. Most mutants also shortened the kinetics of deactivation. Similar studies with the G321S mutant (603537.0003) at the C terminus showed similar effects as those in the pore channel. Immunohistochemical studies showed that none of the pore mutant proteins localized to the plasma membrane when expressed alone, indicating a trafficking defect and retention in the ER. However, coexpression with the wildtype protein resulted in some membrane expression. These findings indicated functional channel defects associated with pathogenic KCNQ4 mutations, but also suggested an interaction with the wildtype protein resulting in different effects. Finally, the results of Kim et al. (2011) indicated that the F182L variant, identified in a Taiwanese patient with deafness (Su et al., 2007) had normal cell surface expression and functional features, suggesting that it is not pathogenic. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>9 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, GLY285SER
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<br />
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SNP: rs28937588,
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ClinVar: RCV000006619, RCV000211722, RCV000844633, RCV002512841
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<div>
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<span class="mim-text-font">
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<p>In a family with autosomal dominant deafness (DFNA2A; 600101), Kubisch et al. (1999) identified a gly285-to-ser (GGC-to-AGC) mutation in heterozygous state. This mutation segregated with all affected members in the pedigree and was not found on 150 control Caucasian chromosomes. </p><p>Kim et al. (2011) referred to this mutation as resulting from an 853G-A transition in exon 6, resulting in a G285S substitution in the pore region of the protein. </p>
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</span>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, TRP276SER
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<br />
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SNP: rs80358277,
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ClinVar: RCV000006620, RCV000211784, RCV001723546
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Dutch family with autosomal dominant deafness (DFNA2A; 600101), Coucke et al. (1999) identified an 827G-C transversion in exon 5 of the KCNQ4 gene resulting in a trp276-to-ser (W276S) mutation in the pore region of the protein. </p><p>Akita et al. (2001) found this mutation in a Japanese family with deafness in 4 successive generations. </p><p>Van Camp et al. (2002) described 2 additional families originating from Europe and Japan with the W276S mutation. They compared the disease-associated haplotype of the 3 W276S-bearing families using closely linked microsatellite markers and intragenic SNPS. Van Camp et al. (2002) found differences between the haplotypes, excluding a single founder mutation for the families. Therefore, the W276S mutation has occurred 3 times independently, and most likely represents a hotspot for a mutation in the KCNQ4 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, GLY321SER
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<br />
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SNP: rs28939710,
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gnomAD: rs28939710,
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ClinVar: RCV000006621, RCV001195307, RCV002512842
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Dutch family with autosomal dominant deafness (DFNA2A; 600101), Coucke et al. (1999) identified a 961G-A transition in exon 7 of the KCNQ4 gene, which was predicted to produce a gly321-to-ser (G321S) change in the S6 transmembrane domain of the protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, GLY285CYS
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<br />
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SNP: rs28937588,
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ClinVar: RCV000006622, RCV001851702
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a U.S. family with autosomal dominant deafness (DFNA2A; 600101), Coucke et al. (1999) identified an 853G-T transversion in exon 6 of the KCNQ4 gene, resulting in a gly285-to-cys (G285C) substitution. The same codon is involved in the gly285-to-ser mutation (G285S; 603537.0001) found in a French family by Kubisch et al. (1999). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, 13-BP DEL, NT211
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<br />
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SNP: rs80358271,
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ClinVar: RCV000006623
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Belgian family with autosomal dominant deafness (DFNA2A; 600101), Coucke et al. (1999) found deletion of 13 bp between nucleotide positions 211 and 224 of the KCNQ4 cDNA sequence. This deletion resulted in a frameshift after gly70, followed by 63 novel amino acids and a premature stop codon at amino acid position 134. The mutation was expected to yield a KCNQ4 protein that was truncated before the first transmembrane region. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 DEAFNESS, AUTOSOMAL DOMINANT 2A</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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KCNQ4, LEU281SER
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<br />
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SNP: rs80358278,
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ClinVar: RCV000006624, RCV001567939
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 5-generation American family of Austrian origin in which 51 members had nonsyndromic dominant progressive hearing loss linked to the DFNA2A (600101) locus on 1p34, Talebizadeh et al. (1999) identified an 824T-C transition in the KCNQ4 gene, resulting in a leu281-to-ser (L281S) substitution. The mutation occurred in the pore region of the protein (Kim et al., 2011). </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0007 DEAFNESS, AUTOSOMAL DOMINANT 2A</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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KCNQ4, LEU274HIS
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<br />
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SNP: rs80358276,
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ClinVar: RCV000006625
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Van Hauwe et al. (2000) found a leu274-to-his (L274H) mutation in the KCNQ4 gene in affected members of a Dutch family with autosomal dominant deafness (DFNA2A; 600101). The mutation occurred in the pore region of the protein (Kim et al., 2011). </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>.0008 DEAFNESS, AUTOSOMAL DOMINANT 2A</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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KCNQ4, 1-BP DEL, 211C
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<br />
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SNP: rs80358272,
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ClinVar: RCV000006626
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In affected members of a Japanese family with autosomal dominant deafness (DFNA2A; 600101), Kamada et al. (2006) identified a heterozygous 1-bp deletion (211delC) in exon 1 of the KCNQ4 gene, resulting in a truncated protein without transmembrane domains. Affected individuals had late-onset (8 to 50 years) pure high-frequency hearing loss, which was less severe compared to previously reported patients with missense mutations in the KCNQ4 gene. Kamada et al. (2006) postulated different pathogenic mechanisms to explain the phenotypic differences: haploinsufficiency in deletion mutations and dominant-negative effects in missense mutations. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 DEAFNESS, AUTOSOMAL DOMINANT 2A</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
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<div>
|
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<span class="mim-text-font">
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|
|
KCNQ4, GLY296SER
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<br />
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|
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SNP: rs80358279,
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|
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ClinVar: RCV000006627
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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 affected members of a 4-generation Spanish family with autosomal dominant deafness (DFNA2A; 600101), Mencia et al. (2008) identified heterozygosity for an 886G-A transition in exon 6 of the KCNQ4 gene, resulting in a gly296-to-ser (G296S) substitution at a highly conserved residue in a stretch of 5 amino acids connecting the P-loop domain and the S6 segment in the pore region. The mutation was not found in 100 unrelated Spanish individuals with normal hearing. Expression and functional studies in Xenopus oocytes and transfected NIH-3T3 cells revealed that the G296S mutant exerts a strong dominant-negative effect on wildtype channel activity by causing a defect in trafficking of KCNQ4 channels to the cell surface membrane. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
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<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Akita, J., Abe, S., Shinkawa, H., Kimberling, W. J., Usami, S.
|
|
<strong>Clinical and genetic features of nonsyndromic autosomal dominant sensorineural hearing loss: KCNQ4 is a gene responsible in Japanese.</strong>
|
|
J. Hum. Genet. 46: 355-361, 2001.
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|
|
[PubMed: 11450843]
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[Full Text: https://doi.org/10.1007/s100380170053]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Coucke, P. J., Van Hauwe, P., Kelley, P. M., Kunst, H., Schatteman, I., Van Velzen, D., Meyers, J., Ensink, R. J., Verstreken, M., Declau, F., Marres, H., Kastury, K., Bhasin, S., McGuirt, W. T., Smith, R. J. H., Cremers, C. W. R. J., Van de Heyning, P., Willems, P. J., Smith, S. D., Van Camp, G.
|
|
<strong>Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.</strong>
|
|
Hum. Molec. Genet. 8: 1321-1328, 1999.
|
|
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|
|
[PubMed: 10369879]
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|
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[Full Text: https://doi.org/10.1093/hmg/8.7.1321]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Coucke, P., Van Camp, G., Djoyodiharjo, B., Smith, S. D., Frants, R. R., Padberg, G. W., Darby, J. K., Huizing, E. H., Cremers, C. W., Kimberling, W. J., Oostra, B. A., Van de Heyning, P. H., Willems, P. J.
|
|
<strong>Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families.</strong>
|
|
New Eng. J. Med. 331: 425-431, 1994.
|
|
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|
|
[PubMed: 8035838]
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|
|
[Full Text: https://doi.org/10.1056/NEJM199408183310702]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Howard, R. J., Clark, K. A., Holton, J. M., Minor, D. L.
|
|
<strong>Structural insight into KCNQ (Kv7) channel assembly and channelopathy.</strong>
|
|
Neuron 53: 663-675, 2007.
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|
|
[PubMed: 17329207]
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|
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[Full Text: https://doi.org/10.1016/j.neuron.2007.02.010]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kamada, F., Kure, S., Kudo, T., Suzuki, Y., Oshima, T., Ichinohe, A., Kojima, K., Niihori, T., Kanno, J., Narumi, Y., Narisawa, A., Kato, K., Aoki, Y., Ikeda, K., Kobayashi, T., Matsubara, Y.
|
|
<strong>A novel KCNQ4 one-base deletion in a large pedigree with hearing loss: implication for the genotype-phenotype correlation.</strong>
|
|
J. Hum. Genet. 51: 455-460, 2006.
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[PubMed: 16596322]
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[Full Text: https://doi.org/10.1007/s10038-006-0384-7]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kharkovets, T., Hardelin, J.-P., Safieddine, S., Schweizer, M., El-Amraoui, A., Petit, C., Jentsch, T. J.
|
|
<strong>KCNQ4, a K(+) channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 4333-4338, 2000.
|
|
|
|
|
|
[PubMed: 10760300]
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|
|
[Full Text: https://doi.org/10.1073/pnas.97.8.4333]
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Kim, H. J., Lv, P., Sihn, C.-R., Yamoah, E. N.
|
|
<strong>Cellular and molecular mechanisms of autosomal dominant form of progressive hearing loss, DFNA2.</strong>
|
|
J. Biol. Chem. 286: 1517-1527, 2011.
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|
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[PubMed: 20966080]
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|
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|
|
[Full Text: https://doi.org/10.1074/jbc.M110.179010]
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|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kubisch, C., Schroeder, B. C., Friedrich, T., Lutjohann, B., El-Amraoui, A., Marlin, S., Petit, C., Jentsch, T. J.
|
|
<strong>KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness.</strong>
|
|
Cell 96: 437-446, 1999.
|
|
|
|
|
|
[PubMed: 10025409]
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|
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|
|
|
[Full Text: https://doi.org/10.1016/s0092-8674(00)80556-5]
|
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|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Mencia, A., Gonzalez-Nieto, D., Modamio-Hoybjor, S., Etxeberria, A., Aranguez, G., Salvador, N., del Castillo, I., Villarroel, A., Moreno, F., Barrio, L., Moreno-Pelayo, M. A.
|
|
<strong>A novel KCNQ4 pore-region mutation (p.G296S) causes deafness by impairing cell-surface channel expression.</strong>
|
|
Hum. Genet. 123: 41-53, 2008.
|
|
|
|
|
|
[PubMed: 18030493]
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|
|
[Full Text: https://doi.org/10.1007/s00439-007-0447-7]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Su, C.-C., Yang, J.-J., Shieh, J.-C., Su, M.-C., Li, S.-Y.
|
|
<strong>Identification of novel mutations in the KCNQ4 gene of patients with nonsyndromic deafness from Taiwan.</strong>
|
|
Audiol. Neurootol. 12: 20-26, 2007.
|
|
|
|
|
|
[PubMed: 17033161]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1159/000096154]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Talebizadeh, Z., Kelley, P. M., Askew, J. W., Beisel, K. W., Smith, S. D.
|
|
<strong>Novel mutation in the KCNQ4 gene in a large kindred with dominant progressive hearing loss.</strong>
|
|
Hum. Mutat. 14: 493-501, 1999.
|
|
|
|
|
|
[PubMed: 10571947]
|
|
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|
|
|
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(199912)14:6<493::AID-HUMU8>3.0.CO;2-P]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Trussell, L.
|
|
<strong>Mutant ion channel in cochlear hair cells causes deafness.</strong>
|
|
Proc. Nat. Acad. Sci. 97: 3786-3788, 2000.
|
|
|
|
|
|
[PubMed: 10760249]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.97.8.3786]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Camp, G., Coucke, P. J., Akita, J., Fransen, E., Abe, S., De Leenheer, E. M. R., Huygen, P. L. M., Cremers, C. W. R. J., Usami, S.-I.
|
|
<strong>A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment.</strong>
|
|
Hum. Mutat. 20: 15-19, 2002.
|
|
|
|
|
|
[PubMed: 12112653]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10096]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Camp, G., Coucke, P. J., Kunst, H., Schatteman, I., Van Velzen, D., Marres, H., van Ewijk, M., Declau, F., Van Hauwe, P., Meyers, J., Kenyon, J., Smith, S. D., Smith, R. J. H., Djelantik, B., Cremers, C. W. R. J., Van de Heyning, P. H., Willems, P. J.
|
|
<strong>Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.</strong>
|
|
Genomics 41: 70-74, 1997.
|
|
|
|
|
|
[PubMed: 9126484]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4624]
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Hauwe, P., Coucke, P. J., Declau, F., Kunst, H., Ensink, R. J., Marres, H. A., Cremers, C. W. R. J., Djelantik, B., Smith, S. D., Kelley, P., Van de Heyning, P. H., Van Camp, G.
|
|
<strong>Deafness linked to DFNA2: one locus but how many genes? (Letter)</strong>
|
|
Nature Genet. 21: 263 only, 1999.
|
|
|
|
|
|
[PubMed: 10080176]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/6778]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Van Hauwe, P., Coucke, P. J., Ensink, R. J., Huygen, P., Cremers, C. W. R. J., Van Camp, G.
|
|
<strong>Mutations in the KCNQ4 K(+) channel gene, responsible for autosomal dominant hearing loss, cluster in the channel pore region.</strong>
|
|
Am. J. Med. Genet. 93: 184-187, 2000.
|
|
|
|
|
|
[PubMed: 10925378]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/1096-8628(20000731)93:3<184::aid-ajmg4>3.0.co;2-5]
|
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|
|
</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M. B., Jin, T., Logothetis, D. E.
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<strong>PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents.</strong>
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Neuron 37: 963-975, 2003.
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[PubMed: 12670425]
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[Full Text: https://doi.org/10.1016/s0896-6273(03)00125-9]
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Bao Lige - updated : 10/12/2022<br>Cassandra L. Kniffin - updated : 1/28/2011<br>Patricia A. Hartz - updated : 8/2/2010<br>Marla J. F. O'Neill - updated : 3/18/2008<br>Cassandra L. Kniffin - updated : 7/6/2006<br>Victor A. McKusick - updated : 10/22/2002<br>Victor A. McKusick - updated : 8/27/2002<br>Victor A. McKusick - updated : 7/18/2001<br>Victor A. McKusick - updated : 8/17/2000<br>Victor A. McKusick - updated : 12/21/1999<br>Victor A. McKusick - updated : 7/22/1999
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