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Entry
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- *176261 - POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 1; KCNE1
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*176261</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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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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</li>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/176261">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000180509;t=ENST00000399286" 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=3753" 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=176261" 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=ENSG00000180509;t=ENST00000399286" 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_000219,NM_001127668,NM_001127669,NM_001127670,NM_001270402,NM_001270403,NM_001270404,NM_001270405,XM_047440764" 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_000219" 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=176261" 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=01442&isoform_id=01442_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/KCNE1" 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/116416,386838,452494,603451,4583499,22209087,49456471,55777836,59896110,59896112,60218915,119630188,146048327,152211817,152211819,152211821,154707787,154707789,154707791,154707793,189069287,189095237,189095239,189095241,194385608,393715100,393715102,393715104,393715106,2217337574,2462582494" 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/P15382" 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=3753" 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=ENSG00000180509;t=ENST00000399286" 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=KCNE1" 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=KCNE1" 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+3753" 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/KCNE1" 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:3753" 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/3753" 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=chr21&hgg_gene=ENST00000399286.3&hgg_start=34446688&hgg_end=34512210&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:6240" 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/kcne1" 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=176261[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=176261[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/KCNE1/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000180509" 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=KCNE1" 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=KCNE1" 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=KCNE1" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://databases.lovd.nl/genomed/home.php?select_db=KCNE1" title="Zhejiang University Center for Genetic and Genomic Medicine (ZJU-CGGM)" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Zhejiang University Center…</a></div><div style="margin-left: 0.5em;"><a href="http://www.fsm.it/cardmoc/" title="Gene Connection for the Heart" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Gene Connection for the He…</a></div><div style="margin-left: 0.5em;"><a href="http://www.ssi.dk/graphics/html/lqtsdb/lqtsdb.htm" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Long QT Syndrome Database</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=KCNE1" title="CCHMC - Human Genetics Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC - Human Genetics Mut…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=KCNE1&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/PA211" 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:6240" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96673" 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/KCNE1#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:96673" 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/3753/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=3753" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-141104-1" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3753" 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=KCNE1&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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176261
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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, ISK-RELATED SUBFAMILY, MEMBER 1; KCNE1
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</span>
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</h3>
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</div>
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<div>
|
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
ISK<br />
|
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MINIMAL POTASSIUM ION CHANNEL; MINK
|
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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=KCNE1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNE1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/21/80?start=-3&limit=10&highlight=80">21q22.12</a>
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr21:34446688-34512210&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'})">21:34,446,688-34,512,210</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=612347,613695" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/21/80?start=-3&limit=10&highlight=80">
|
|
21q22.12
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Jervell and Lange-Nielsen syndrome 2
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/612347"> 612347 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</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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<p>KCNE1 is an accessory beta subunit that assembles with the pore-forming alpha subunit KCNQ1 (<a href="/entry/607542">607542</a>) to form the slow delayed rectifier I(Ks) potassium channel, which is essential for cardiac function (summary by <a href="#15" class="mim-tip-reference" title="Osteen, J. D., Gonzalez, C., Sampson, K. J., Iyer, V., Rebolledo, S., Larsson, H. P., Kass, R. S. <strong>KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate.</strong> Proc. Nat. Acad. Sci. 107: 22710-22715, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149716[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.1016300108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21149716">Osteen et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21149716" 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>Potassium ion channels are essential to many cellular functions in both excitable and nonexcitable cells and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. By molecular cloning and sequence analysis of its genomic DNA, <a href="#14" class="mim-tip-reference" title="Murai, T., Kakizuka, A., Takumi, T., Ohkubo, H., Nakanishi, S. <strong>Molecular cloning and sequence analysis of human genomic DNA encoding a novel membrane protein which exhibits a slowly activating potassium channel activity.</strong> Biochem. Biophys. Res. Commun. 161: 176-181, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2730656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2730656</a>] [<a href="https://doi.org/10.1016/0006-291x(89)91577-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2730656">Murai et al. (1989)</a> deduced the amino acid sequence of a novel human membrane protein that induces selective potassium permeation by membrane depolarization. The protein consisted of 129 amino acid residues and shared structural characteristics with the rat counterpart. The transmembrane domain and its flanking C-terminal sequence were highly conserved between the human and rat sequences. The slowly activating potassium current elicited by the human protein on its expression in Xenopus oocytes was indistinguishable from that induced by the rat protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2730656" 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 genomic sequence analysis, <a href="#21" class="mim-tip-reference" title="Splawski, I., Shen, J., Timothy, K. W., Vincent, G. M., Lehmann, M. H., Keating, M. T. <strong>Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1.</strong> Genomics 51: 86-97, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9693036/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9693036</a>] [<a href="https://doi.org/10.1006/geno.1998.5361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9693036">Splawski et al. (1998)</a> determined that the KCNE1 gene contains 3 exons. The 2 introns are located in the 5-prime untranslated region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9693036" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using the human probe in the study of somatic cell hybrids, <a href="#11" class="mim-tip-reference" title="McPherson, J. D., Wasmuth, J. J., Chandy, K. G., Swanson, R., Dethlefs, B., Chandy, G., Wymore, R., Ghanshani, S. <strong>Chromosomal localization of 7 potassium channel genes. (Abstract)</strong> Cytogenet. Cell Genet. 58: 1979 only, 1991."None>McPherson et al. (1991)</a> mapped the KCNE1 gene to chromosome 21. <a href="#5" class="mim-tip-reference" title="Chevillard, C., Attali, B., Lesage, F., Fontes, M., Barhanin, J., Lazdunski, M., Mattei, M. G. <strong>Localization of a potassium channel gene (KCNE1) to 21q22.1-q22.2 by in situ hybridization and somatic cell hybridization.</strong> Genomics 15: 243-245, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432548</a>] [<a href="https://doi.org/10.1006/geno.1993.1051" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8432548">Chevillard et al. (1993)</a> confirmed the assignment to chromosome 21 by somatic cell hybridization and regionalized the assignment to 21q22.1-q22.2 by isotopic in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432548" 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 PCR analysis of 2 complete panels of human/rodent hybrid DNA, <a href="#8" class="mim-tip-reference" title="Malo, M. S., Srivastava, K., Ingram, V. M. <strong>Gene assignment by polymerase chain reaction: localization of the human potassium channel ISK gene to the Down's syndrome region of chromosome 21q22.1-q22.2.</strong> Gene 159: 273-275, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7622063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7622063</a>] [<a href="https://doi.org/10.1016/0378-1119(95)00102-c" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7622063">Malo et al. (1995)</a> mapped the KCNE1 gene to chromosome 21 with 100% concordance. PCR on DNA of a human chromosome 21 regional mapping panel sublocalized the gene to 21q22.1-q22.2, which also contains a putative Down syndrome (trisomy 21) region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7622063" 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>Through cotransfection studies using human KVLQT1 (KCNQ1; <a href="/entry/607542">607542</a>) and minK genes, <a href="#18" class="mim-tip-reference" title="Sanguinetti, M. C., Curran, M. E., Zou, A., Shen, J., Spector, P. S., Atkinson, D. L., Keating, M. T. <strong>Coassembly of K(v)LQT1 and minK (IsK) proteins to form cardiac I(Ks) potassium channel.</strong> Nature 384: 80-83, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900283/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900283</a>] [<a href="https://doi.org/10.1038/384080a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900283">Sanguinetti et al. (1996)</a> demonstrated that the KVLQT1 and minK protein products coassemble to form the cardiac I(Ks) channel. <a href="#2" class="mim-tip-reference" title="Barhanin, J., Lesage, F., Guillemare, E., Fink, M., Lazdunski, M., Romey, G. <strong>K(v)LQT1 and IsK (minK) proteins associate to form the I(Ks) cardiac potassium current.</strong> Nature 384: 78-80, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8900282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8900282</a>] [<a href="https://doi.org/10.1038/384078a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8900282">Barhanin et al. (1996)</a> expressed mouse KVLQT1 in COS cells and carried out electrophysiologic studies. They demonstrated that KVLQT1 encodes a subunit forming the important cardiac ion channel underlying the I(Ks) cardiac current. They observed also that the ISK was required to form the I(Ks) channel. <a href="#10" class="mim-tip-reference" title="McDonald, T. V., Yu, Z., Ming, Z., Palma, E., Meyers, M. B., Wang, K.-W., Goldstein, S. A. N., Fishman, G. I. <strong>A minK-HERG complex regulates the cardiac potassium current I(Kr).</strong> Nature 388: 289-292, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9230439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9230439</a>] [<a href="https://doi.org/10.1038/40882" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9230439">McDonald et al. (1997)</a> showed that the product of the KCNE1 gene, minK, forms a stable complex with HERG (KCNH2; <a href="/entry/152427">152427</a>) and this heteromultimerization regulates the rapidly activating cardiac delayed rectifier. They concluded that, through the formation of heteromeric channel complexes, minK is central to the control of the heart rate and rhythm. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9230439+8900282+8900283" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Marx, S. O., Kurokawa, J., Reiken, S., Motoike, H., D'Armiento, J., Marks, A. R., Kass, R. S. <strong>Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.</strong> Science 295: 496-499, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11799244/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11799244</a>] [<a href="https://doi.org/10.1126/science.1066843" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11799244">Marx et al. (2002)</a> demonstrated that beta-adrenergic receptor modulation of the slow outward potassium ion current (I-KS) requires targeting of cAMP-dependent protein kinase A (<a href="/entry/188830">188830</a>) and protein phosphatase 1 (PP1, e.g., <a href="/entry/176875">176875</a>) to KCNQ1 (<a href="/entry/607542">607542</a>) through the targeting protein yotiao (AKAP9; <a href="/entry/604001">604001</a>). Yotiao binds to KCNQ1 by a leucine zipper motif. Identification of the KCNQ1 macromolecular complex provides a mechanism for sympathetic nervous system modulation of cardiac action potential duration through I-KS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11799244" 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="#28" 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 KCNQ1/KCNE1 heterodimers. <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><p><a href="#12" class="mim-tip-reference" title="Melman, Y. F., Um, S. Y., Krumerman, A., Kagan, A., McDonald, T. V. <strong>KCNE1 binds to the KCNQ1 pore to regulate potassium channel activity.</strong> Neuron 42: 927-937, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15207237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15207237</a>] [<a href="https://doi.org/10.1016/j.neuron.2004.06.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15207237">Melman et al. (2004)</a> showed that KCNE1 and KCNE3 (<a href="/entry/604433">604433</a>) associate with an extended binding interface of KCNQ1 that includes structures within the channel pore and C terminus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15207237" 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="#15" class="mim-tip-reference" title="Osteen, J. D., Gonzalez, C., Sampson, K. J., Iyer, V., Rebolledo, S., Larsson, H. P., Kass, R. S. <strong>KCNE1 alters the voltage sensor movements necessary to open the KCNQ1 channel gate.</strong> Proc. Nat. Acad. Sci. 107: 22710-22715, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21149716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21149716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21149716[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.1016300108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21149716">Osteen et al. (2010)</a> found that coexpression of KCNE1 with KCNQ1 (<a href="/entry/607542">607542</a>) in Xenopus oocytes separated voltage dependence of KCNQ1/KCNE1 potassium channel opening and movement, suggesting an imposed requirement for movement of multiple voltage sensors before channel opening. The results indicated that KCNE1 modulates KCNQ1 to slow down activation of the KCNQ1/KCNE1 channel by altering the voltage sensor movements necessary to open the channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21149716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using Xenopus oocytes expressing human KCNQ1 in the presence or absence of KCNE1, <a href="#17" class="mim-tip-reference" title="Peng, G., Barro-Soria, R., Sampson, K. J., Larsson, H. P., Kass, R. S. <strong>Gating mechanisms underlying deactivation slowing by two KCNQ1 atrial fibrillation mutations.</strong> Sci. Rep. 7: 45911, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28383569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28383569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28383569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/srep45911" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28383569">Peng et al. (2017)</a> characterized 2 KCNQ1 gain-of-function mutations that cause atrial fibrillation, ser140 to gly (S140G; <a href="/entry/607542#0032">607542.0032</a>) and val141 to met (V141M; <a href="/entry/607542#0045">607542.0045</a>). In the absence of KCNE1, S140G, but not V141M, slowed voltage sensor movement, leading to indirect slowing of current deactivation. Slowing of voltage sensor deactivation by S140G in the absence of KCNE1 was independent of channel opening. When KCNE1 was coexpressed, S140G slowed both current deactivation and voltage sensor movement, whereas V141M slowed current deactivation without slowing voltage sensor movement. Slowing of voltage sensor deactivation by S140G in the presence of KCNE1 was dependent on channel opening. The authors proposed a molecular mechanism underlying the effects of the KCNQ1 mutations on channel gating and suggested that KCNE1 mediates changes in pore movement and voltage sensor-pore coupling to slow channel deactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28383569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Long QT Syndrome 5</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Lai, L.-P., Deng, C.-L., Moss, A. J., Kass, R. S., Liang, C. <strong>Polymorphism of the gene encoding a human minimal potassium ion channel (minK).</strong> Gene 151: 339-340, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7828904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7828904</a>] [<a href="https://doi.org/10.1016/0378-1119(94)90685-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7828904">Lai et al. (1994)</a>, who referred to the KCNE1 gene product as 'minimal potassium ion channel' (minK), described a polymorphism. An A-to-G substitution at position 112 resulted in a change from a ser codon (AGT) to a gly codon (GGT) and the creation of a new MspAI restriction site. Of the 32 alleles from 16 subjects studied, 25 had a G112 and 7 had an A112. No definite relationship to the long QT syndrome-1 (LQT1; <a href="/entry/192500">192500</a>) could be established. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7828904" 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>KCNE1 encodes beta subunits that coassemble with KVLQT1 alpha subunits. Ion-channel beta subunits are ancillary proteins that modulate the gating kinetics and enhance stability of multimeric channel complexes. Despite their functional importance, dysfunction of potassium channel beta subunits had not been associated with disease before the reports by <a href="#25" class="mim-tip-reference" title="Tyson, J., Tranebjaerg, L., Bellman, S., Wren, C., Taylor, J. F. N., Bathen, J., Aslaksen, B., Sorland, S. J., Lund, O., Malcolm, S., Pembrey, M., Bhattacharya, S., Bitner-Glindzicz, M. <strong>IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.</strong> Hum. Molec. Genet. 6: 2179-2185, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9328483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9328483</a>] [<a href="https://doi.org/10.1093/hmg/6.12.2179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9328483">Tyson et al. (1997)</a> and <a href="#22" class="mim-tip-reference" title="Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., Keating, M. T. <strong>Mutations in the hminK gene cause long QT syndrome and suppress I(Ks) function.</strong> Nature Genet. 17: 338-340, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354802</a>] [<a href="https://doi.org/10.1038/ng1197-338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354802">Splawski et al. (1997)</a>. <a href="#22" class="mim-tip-reference" title="Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., Keating, M. T. <strong>Mutations in the hminK gene cause long QT syndrome and suppress I(Ks) function.</strong> Nature Genet. 17: 338-340, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354802</a>] [<a href="https://doi.org/10.1038/ng1197-338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354802">Splawski et al. (1997)</a> identified KCNE1 missense mutations in affected members of 2 LQT5 families (<a href="#0003">176261.0003</a>-<a href="#0004">176261.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9328483+9354802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bianchi, L., Shen, Z., Dennis, A. T., Priori, S. G., Napolitano, C., Ronchetti, E., Bryskin, R., Schwartz, P. J., Brown, A. M. <strong>Cellular dysfunction of LQT5-minK mutants: abnormalities of I(Ks), I(Kr) and trafficking in long QT syndrome.</strong> Hum. Molec. Genet. 8: 1499-1507, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400998</a>] [<a href="https://doi.org/10.1093/hmg/8.8.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400998">Bianchi et al. (1999)</a>, who referred to the long QT syndrome produced by mutations in the KCNE1 gene as LQT5, used electrophysiologic and immunocytochemical methods to compare the cellular phenotypes of wildtype minK and 4 LQT5 mutants coexpressed with KVLQT1 in Xenopus oocytes and with HERG in HEK293 cells. They found that 3 mutants, V47F, W87R, and D76N (<a href="#0003">176261.0003</a>), were expressed at the cell surface, while one mutant, L51H, was not. Coexpression of V47F and W87R with KVLQT1 produced I(Ks) currents having altered gating and reduced amplitudes compared with wildtype minK; coexpression with L51H produced KVLQT1 current rather than I(Ks); and coexpression with D76N suppressed KVLQT1 current. V47F increased HERG current but to a lesser extent than wildtype minK, while L51H and W87R had no effect and D76N suppressed HERG current markedly. Thus, V47F interacted with both KVLQT1 and HERG; W87R interacted functionally with KVLQT1 but not with HERG; D76N suppressed both KVLQT1 and HERG; and L51H was processed improperly and interacted with neither channel. <a href="#3" class="mim-tip-reference" title="Bianchi, L., Shen, Z., Dennis, A. T., Priori, S. G., Napolitano, C., Ronchetti, E., Bryskin, R., Schwartz, P. J., Brown, A. M. <strong>Cellular dysfunction of LQT5-minK mutants: abnormalities of I(Ks), I(Kr) and trafficking in long QT syndrome.</strong> Hum. Molec. Genet. 8: 1499-1507, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10400998/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10400998</a>] [<a href="https://doi.org/10.1093/hmg/8.8.1499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10400998">Bianchi et al. (1999)</a> concluded that minK is a cofactor in the expression of both I(Ks) and I(Kr) and proposed that clinical manifestations of LQT5 may be complicated by differing effects of minK mutations on KVLQT1 and HERG. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10400998" 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="#20" class="mim-tip-reference" title="Splawski, I., Shen, J., Timothy, K. W., Lehmann, M. H., Priori, S., Robinson, J. L., Moss, A. J., Schwartz, P. J., Towbin, J. A., Vincent, G. M., Keating, M. T. <strong>Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.</strong> Circulation 102: 1178-1185, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10973849/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10973849</a>] [<a href="https://doi.org/10.1161/01.cir.102.10.1178" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10973849">Splawski et al. (2000)</a> screened 262 unrelated individuals with LQT syndrome for mutations in the 5 defined genes (KCNQ1; KCNH2; SCN5A, <a href="/entry/600163">600163</a>; KCNE1; and KCNE2 <a href="/entry/603796">603796</a>) and identified mutations in 177 individuals (68%). KCNQ1 and KCNH2 accounted for 87% of mutations (42% and 45%, respectively), and SCN5A, KCNE1, and KCNE2 for the remaining 13% (8%, 3%, and 2%, respectively). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10973849" 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="Paulussen, A. D. C., Gilissen, R. A. H. J., Armstrong, M., Doevendans, P. A., Verhasselt, P., Smeets, H. J. M., Schulze-Bahr, E., Haverkamp, W., Breithardt, G., Cohen, N., Aerssens, J. <strong>Genetic variations in KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients.</strong> J. Molec. Med. 82: 182-188, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14760488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14760488</a>] [<a href="https://doi.org/10.1007/s00109-003-0522-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14760488">Paulussen et al. (2004)</a> screened 5 congenital long QT syndrome-associated genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) in 32 individuals with drug-induced long QT syndrome and identified 3 heterozygous mutations in 4 patients that were not found in 32 healthy controls (see, e.g., <a href="#0005">176261.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14760488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#24" class="mim-tip-reference" title="Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J. <strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong> Heart Rhythm 2: 507-517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15840476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15840476</a>] [<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15840476">Tester et al. (2005)</a> analyzed 5 LQTS-associated cardiac channel genes in 541 consecutive unrelated patients with LQT syndrome (average QTc, 482 ms). In 272 (50%) patients, they identified 211 different pathogenic mutations, including 88 in KCNQ1, 89 in KCNH2, 32 in SCN5A, and 1 each in KCNE1 and KCNE2. Mutations considered pathogenic were absent in more than 1,400 reference alleles. Among the mutation-positive patients, 29 (11%) had 2 LQTS-causing mutations, of which 16 (8%) were in 2 different LQTS genes (biallelic digenic). <a href="#24" class="mim-tip-reference" title="Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J. <strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong> Heart Rhythm 2: 507-517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15840476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15840476</a>] [<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15840476">Tester et al. (2005)</a> noted that patients with multiple mutations were younger at diagnosis, but they did not discern any genotype/phenotype correlations associated with location or type of mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15840476" 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 44 unrelated patients with LQT syndrome, <a href="#13" class="mim-tip-reference" title="Millat, G., Chevalier, P., Restier-Miron, L., Da Costa, A., Bouvagnet, P., Kugener, B., Fayol, L., Gonzalez Armengod, C., Oddou, B., Chanavat, V., Froidefond, E., Perraudin, R., Rousson, R., Rodriguez-Lafrasse, C. <strong>Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.</strong> Clin. Genet. 70: 214-227, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922724</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00671.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16922724">Millat et al. (2006)</a> used DHLP chromatography to analyze the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes for mutations and SNPs. Most of the patients (84%) showed a complex molecular pattern, with an identified mutation associated with 1 or more SNPs located in several LQTS genes; 4 of the patients also had a second mutation in a different LQTS gene (biallelic digenic inheritance). <a href="#13" class="mim-tip-reference" title="Millat, G., Chevalier, P., Restier-Miron, L., Da Costa, A., Bouvagnet, P., Kugener, B., Fayol, L., Gonzalez Armengod, C., Oddou, B., Chanavat, V., Froidefond, E., Perraudin, R., Rousson, R., Rodriguez-Lafrasse, C. <strong>Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.</strong> Clin. Genet. 70: 214-227, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922724</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2006.00671.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16922724">Millat et al. (2006)</a> suggested that because double heterozygosity appears to be more common than expected, molecular diagnosis should be performed on all LQTS-related genes, even after a single mutation has been identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Jervell and Lange-Nielsen Syndrome</em></strong></p><p>
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The KCNE1 gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. The KVLQT1 gene is the site of mutations that cause either type 1 long QT syndrome or type 1 Jervell and Lange-Nielsen syndrome (JLNS1). <a href="#25" class="mim-tip-reference" title="Tyson, J., Tranebjaerg, L., Bellman, S., Wren, C., Taylor, J. F. N., Bathen, J., Aslaksen, B., Sorland, S. J., Lund, O., Malcolm, S., Pembrey, M., Bhattacharya, S., Bitner-Glindzicz, M. <strong>IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.</strong> Hum. Molec. Genet. 6: 2179-2185, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9328483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9328483</a>] [<a href="https://doi.org/10.1093/hmg/6.12.2179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9328483">Tyson et al. (1997)</a> described a family in which JLNS (JLNS2; <a href="/entry/612347">612347</a>) was due to homozygosity for a mutation in the KCNE1 gene. The phenotype was indistinguishable from that resulting from mutations in the KVLQT1 gene. <a href="#23" class="mim-tip-reference" title="Tesson, F., Donger, C., Denjoy, I., Berthet, M., Bennaceur, M., Petit, C., Coumel, P., Schwartz, K., Guicheney, P. <strong>Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome.</strong> J. Molec. Cell. Cardiol. 28: 2051-2055, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8899564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8899564</a>] [<a href="https://doi.org/10.1006/jmcc.1996.0198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8899564">Tesson et al. (1996)</a> had excluded the KCNE1 gene as the site of the mutation in the Jervell and Lange-Nielsen syndrome (JLNS1; <a href="/entry/220400">220400</a>) in 4 consanguineous families, using microsatellite markers of chromosome 21 as well as KCNE1 intragenic polymorphisms. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9328483+8899564" 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="#19" class="mim-tip-reference" title="Schulze-Bahr, E., Wang, Q., Wedekind, H., Haverkamp, W., Chen, Q., Sun, Y., Rubie, C., Hordt, M., Towbin, J. A., Borggrefe, M., Assmann, G., Qu, X., Somberg, J. C., Breithardt, G., Oberti, C., Funke, H. <strong>KCNE1 mutations cause Jervell and Lange-Nielsen syndrome. (Letter)</strong> Nature Genet. 17: 267-268, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354783</a>] [<a href="https://doi.org/10.1038/ng1197-267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354783">Schulze-Bahr et al. (1997)</a> found mutations in the KCNE1 gene in members of a Lebanese family with JLNS2 (e.g., <a href="#0002">176261.0002</a>). Three of 6 children had prolonged QT intervals and congenital bilateral deafness; 2 of the 3 had suffered from recurrent syncope since early childhood. Both parents and the 3 other sibs showed normal hearing and had QT durations within the normal range. Segregation analysis using microsatellite markers excluded linkage to the LQT1, LQT2 (<a href="/entry/613688">613688</a>), and LQT3 (<a href="/entry/603830">603830</a>) loci, located on 11p, 7q, and 3p, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a study of 218 Swedish noise-exposed male workers, <a href="#26" class="mim-tip-reference" title="Van Laer, L., Carlsson, P.-I., Ottschytsch, N., Bondeson, M.-L., Konings, A., Vandevelde, A., Dieltjens, N., Fransen, E., Snyders, D., Borg, E., Raes, A., Van Camp, G. <strong>The contribution of genes involved in potassium recycling in the inner ear to noise-induced hearing loss.</strong> Hum. Mutat. 27: 786-795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16823764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16823764</a>] [<a href="https://doi.org/10.1002/humu.20360" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16823764">Van Laer et al. (2006)</a> identified the asp85-to-asn variant in the KCNE1 gene (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1805128;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1805128</a>; <a href="#0005">176261.0005</a>) as the possible cause of susceptibility to noise-induced hearing loss (NIHL; <a href="/entry/613035">613035</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16823764" 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="#27" class="mim-tip-reference" title="Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C. <strong>Compound mutations: a common cause of severe long-QT syndrome.</strong> Circulation 109: 1834-1841, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>] [<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15051636">Westenskow et al. (2004)</a> analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 252 probands with long QT syndrome and identified 19 with biallelic mutations in LQTS genes, of whom 18 were either compound (monogenic) or double (digenic) heterozygotes and 1 was a homozygote. They also identified 1 patient who had triallelic digenic mutations (see <a href="#0005">176261.0005</a>). Compared with probands who had 1 or no identified mutation, probands with 2 mutations had longer QTc intervals (p less than 0.001) and were 3.5-fold more likely to undergo cardiac arrest (p less than 0.01). All 20 probands with 2 mutations had experienced cardiac events. <a href="#27" class="mim-tip-reference" title="Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C. <strong>Compound mutations: a common cause of severe long-QT syndrome.</strong> Circulation 109: 1834-1841, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>] [<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15051636">Westenskow et al. (2004)</a> concluded that biallelic mono- or digenic mutations (which the authors termed 'compound mutations') cause a severe phenotype and are relatively common in long QT syndrome. The authors noted that these findings support the concept of arrhythmia risk as a multi-hit process and suggested that genotype can be used to predict risk. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15051636" 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="#4" class="mim-tip-reference" title="Charpentier, F., Merot, J., Riochet, D., Le Marec, H., Escande, D. <strong>Adult KCNE1-knockout mice exhibit a mild cardiac cellular phenotype.</strong> Biochem. Biophys. Res. Commun. 251: 806-810, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790991</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9554" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790991">Charpentier et al. (1998)</a> investigated the cellular electrophysiologic characteristics of adult Kcne1-knockout mouse hearts by means of the standard microelectrode technique. Action potential parameters from the ventricular endocardium of Kcne1 -/- mice were indistinguishable from those of Kcne1 wildtype animals. In particular, Kcne1-deficient hearts did not exhibit prolonged repolarization. A specific blocker of ERG potassium channels consistently prolonged repolarization in Kcne1-wildtype but not in Kcne1-deficient hearts. By contrast, a specific blocker of KvLQT1 potassium channel produced comparable effects on repolarization in Kcne1 -/- and wildtype mice. These results suggested to <a href="#4" class="mim-tip-reference" title="Charpentier, F., Merot, J., Riochet, D., Le Marec, H., Escande, D. <strong>Adult KCNE1-knockout mice exhibit a mild cardiac cellular phenotype.</strong> Biochem. Biophys. Res. Commun. 251: 806-810, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790991</a>] [<a href="https://doi.org/10.1006/bbrc.1998.9554" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9790991">Charpentier et al. (1998)</a> that invalidation of the mouse Kcne1 gene leads to a mild cardiac phenotype at the cellular level. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790991" 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="Arrighi, I., Bloch-Faure, M., Grahammer, F., Bleich, M., Warth, R., Mengual, R., Drici, M.-D., Barhanin, J., Meneton, P. <strong>Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome.</strong> Proc. Nat. Acad. Sci. 98: 8792-8797, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11438691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11438691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11438691[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.141233398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11438691">Arrighi et al. (2001)</a> demonstrated altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome. The slowly activating delayed K+ current, known as I(Ks), is composed of pore-forming KCNQ1 (<a href="/entry/607542">607542</a>) and regulatory KCNE1 subunits, which are mutated in familial forms of cardiac long QT syndrome, LQT1 and LQT5, respectively. Because KCNQ1 and KCNE1 genes are also expressed in epithelial tissues, such as the kidneys and the intestine, <a href="#1" class="mim-tip-reference" title="Arrighi, I., Bloch-Faure, M., Grahammer, F., Bleich, M., Warth, R., Mengual, R., Drici, M.-D., Barhanin, J., Meneton, P. <strong>Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome.</strong> Proc. Nat. Acad. Sci. 98: 8792-8797, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11438691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11438691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11438691[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.141233398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11438691">Arrighi et al. (2001)</a> investigated the adaptation of Kcne1-deficient mice to different K+ and Na+ intakes. On a normal potassium diet, homozygous Kcne1 knockout-null mice exhibited signs of chronic volume depletion associated with fecal sodium and potassium ion wasting and had lower plasma potassium ion concentration and higher levels of aldosterone than wildtype mice. Although plasma aldosterone can be suppressed by low potassium diets or stimulated by low sodium diets, a high potassium diet provoked a tremendous increase of plasma aldosterone levels in the Kcne1 knockout-null mice as compared with wildtype mice despite lower plasma potassium. This exacerbated aldosterone production in the knockout mice was accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. <a href="#1" class="mim-tip-reference" title="Arrighi, I., Bloch-Faure, M., Grahammer, F., Bleich, M., Warth, R., Mengual, R., Drici, M.-D., Barhanin, J., Meneton, P. <strong>Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome.</strong> Proc. Nat. Acad. Sci. 98: 8792-8797, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11438691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11438691</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11438691[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.141233398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11438691">Arrighi et al. (2001)</a> found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulosa of adrenal glands where I(Ks) may directly participate in the control of aldosterone production by plasma K+. These results, which showed that KCNE1 and I(Ks) are involved in potassium homeostasis, may have important implications for patients with I(Ks)-related long QT syndrome, because hypokalemia is a well-known risk factor for the occurrence of torsade de pointes ventricular arrhythmia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11438691" 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">rs281865421 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs281865421;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=rs281865421" 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=rs281865421" 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 small consanguineous family, <a href="#25" class="mim-tip-reference" title="Tyson, J., Tranebjaerg, L., Bellman, S., Wren, C., Taylor, J. F. N., Bathen, J., Aslaksen, B., Sorland, S. J., Lund, O., Malcolm, S., Pembrey, M., Bhattacharya, S., Bitner-Glindzicz, M. <strong>IsK and KvLQT1: mutation in either of the two subunits of the slow component of the delayed rectifier potassium channel can cause Jervell and Lange-Nielsen syndrome.</strong> Hum. Molec. Genet. 6: 2179-2185, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9328483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9328483</a>] [<a href="https://doi.org/10.1093/hmg/6.12.2179" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9328483">Tyson et al. (1997)</a> used linkage to exclude the KVLQT1 gene (<a href="/entry/607542">607542</a>) as the site of the mutation causing Jervell and Lange-Nielsen syndrome (JLNS2; <a href="/entry/612347">612347</a>). The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the KCNE1 gene. Sequencing showed a homozygous mutation in that gene. The phenotype was indistinguishable from that caused by mutation in the other component of the delayed rectifier potassium channel, KVLQT1. The change in the KCNE1 gene that was present in homozygous state in this family consisted of alteration in 3 nucleotides in codons 59 and 60. Codon 59 was changed from ACC (thr) to CCC (pro) and codon 60 was changed from CTG (leu) to CCT (pro). Both of these changes occurred in the transmembrane region of the predicted protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9328483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 JERVELL AND LANGE-NIELSEN SYNDROME 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs28933384 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933384;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/rs28933384?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=rs28933384" 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=rs28933384" 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=RCV000014418 OR RCV000119076 OR RCV004777562" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014418, RCV000119076, RCV004777562" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014418...</a>
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<p>In 3 children from a Lebanese family who were affected with Jervell and Lange-Nielsen syndrome (<a href="/entry/612347">612347</a>), <a href="#19" class="mim-tip-reference" title="Schulze-Bahr, E., Wang, Q., Wedekind, H., Haverkamp, W., Chen, Q., Sun, Y., Rubie, C., Hordt, M., Towbin, J. A., Borggrefe, M., Assmann, G., Qu, X., Somberg, J. C., Breithardt, G., Oberti, C., Funke, H. <strong>KCNE1 mutations cause Jervell and Lange-Nielsen syndrome. (Letter)</strong> Nature Genet. 17: 267-268, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354783</a>] [<a href="https://doi.org/10.1038/ng1197-267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354783">Schulze-Bahr et al. (1997)</a> found compound heterozygosity for mutations in the KCNE1 gene: a thr7-to-ile substitution from a 20C-T transition inherited from the father, and an asp76-to-asn substitution from a 226G-A transition inherited from the mother (<a href="#0003">176261.0003</a>). The parents and 3 other sibs were heterozygous for one or the other mutation and were unaffected. These mutations were absent from 100 healthy unrelated individuals of the general population. The allele inherited from the father also included a gly38-to-ser polymorphism shown previously not to cause JLNS or LQT. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 JERVELL AND LANGE-NIELSEN SYNDROME 2</strong>
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LONG QT SYNDROME 5, INCLUDED
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KCNE1, ASP76ASN
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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> rs74315445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315445;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/rs74315445?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=rs74315445" 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=rs74315445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014419 OR RCV000014420 OR RCV000119080 OR RCV000148512 OR RCV000222568 OR RCV000243273 OR RCV000471399 OR RCV000606753 OR RCV000678806 OR RCV005054138" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014419, RCV000014420, RCV000119080, RCV000148512, RCV000222568, RCV000243273, RCV000471399, RCV000606753, RCV000678806, RCV005054138" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014419...</a>
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<p>By SSCP analyses using primers that spanned KCNE1, <a href="#22" class="mim-tip-reference" title="Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., Keating, M. T. <strong>Mutations in the hminK gene cause long QT syndrome and suppress I(Ks) function.</strong> Nature Genet. 17: 338-340, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354802</a>] [<a href="https://doi.org/10.1038/ng1197-338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354802">Splawski et al. (1997)</a> identified an anomalous conformer in affected members of a kindred with long QT syndrome-5 (<a href="/entry/613695">613695</a>). The DNA sequence analysis revealed a G-to-A transition at the first nucleotide of codon 76, causing an asp-to-asn substitution (D76N). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354802" 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="#19" class="mim-tip-reference" title="Schulze-Bahr, E., Wang, Q., Wedekind, H., Haverkamp, W., Chen, Q., Sun, Y., Rubie, C., Hordt, M., Towbin, J. A., Borggrefe, M., Assmann, G., Qu, X., Somberg, J. C., Breithardt, G., Oberti, C., Funke, H. <strong>KCNE1 mutations cause Jervell and Lange-Nielsen syndrome. (Letter)</strong> Nature Genet. 17: 267-268, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354783</a>] [<a href="https://doi.org/10.1038/ng1197-267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354783">Schulze-Bahr et al. (1997)</a> demonstrated the D76N mutation in compound heterozygotes with Jervell and Lange-Nielsen syndrome (JLNS2; <a href="/entry/612347">612347</a>); see <a href="#0002">176261.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354783" 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="#6" class="mim-tip-reference" title="Duggal, P., Vesely, M. R., Wattanasirichaigoon, D., Villafane, J., Kaushik, V., Beggs, A. H. <strong>Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome.</strong> Circulation 97: 142-146, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9445165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9445165</a>] [<a href="https://doi.org/10.1161/01.cir.97.2.142" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9445165">Duggal et al. (1998)</a> reported the same mutation in homozygous form in a young girl with congenital deafness, extreme QT prolongation, and recurrent syncope, who fulfilled the criteria for Jervell and Lange-Nielsen syndrome. Her mother and half sister, who were heterozygous for the D76N mutation, experienced syncope and partial hearing loss and had prolonged QT intervals. The authors commented that the heterozygous state was consistent with the Romano-Ward syndrome, also known to be caused by mutations in the KVLQT1 gene, and suggested that the KCNE1 gene represents a fifth long QT syndrome locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9445165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0004 LONG QT SYNDROME 5</strong>
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KCNE1, SER74LEU
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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> rs74315446 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315446;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/rs74315446?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=rs74315446" 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=rs74315446" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014421 OR RCV000119079 OR RCV000471661 OR RCV000603252 OR RCV002482866 OR RCV003318541 OR RCV004017244" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014421, RCV000119079, RCV000471661, RCV000603252, RCV002482866, RCV003318541, RCV004017244" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014421...</a>
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<span class="mim-text-font">
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<p>In affected members of a family with long QT syndrome-5 (<a href="/entry/613695">613695</a>), <a href="#22" class="mim-tip-reference" title="Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., Keating, M. T. <strong>Mutations in the hminK gene cause long QT syndrome and suppress I(Ks) function.</strong> Nature Genet. 17: 338-340, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9354802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9354802</a>] [<a href="https://doi.org/10.1038/ng1197-338" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9354802">Splawski et al. (1997)</a> identified a C-to-T transition in the second nucleotide of codon 74, leading to a substitution of serine for leucine (S74L). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9354802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0005 LONG QT SYNDROME 5, ACQUIRED, SUSCEPTIBILITY TO</strong>
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LONG QT SYNDROME 2/5, DIGENIC, INCLUDED
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<span class="mim-text-font">
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KCNE1, ASP85ASN
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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> rs1805128 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1805128;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/rs1805128?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=rs1805128" 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=rs1805128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014422 OR RCV000014423 OR RCV000035353 OR RCV000057858 OR RCV000157255 OR RCV000247942 OR RCV000399257 OR RCV000709727 OR RCV000852954 OR RCV001195103 OR RCV003224097" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014422, RCV000014423, RCV000035353, RCV000057858, RCV000157255, RCV000247942, RCV000399257, RCV000709727, RCV000852954, RCV001195103, RCV003224097" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014422...</a>
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<p><strong><em>Long QT Syndrome 5</em></strong></p><p>
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In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), <a href="#16" class="mim-tip-reference" title="Paulussen, A. D. C., Gilissen, R. A. H. J., Armstrong, M., Doevendans, P. A., Verhasselt, P., Smeets, H. J. M., Schulze-Bahr, E., Haverkamp, W., Breithardt, G., Cohen, N., Aerssens, J. <strong>Genetic variations in KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 in drug-induced long QT syndrome patients.</strong> J. Molec. Med. 82: 182-188, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14760488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14760488</a>] [<a href="https://doi.org/10.1007/s00109-003-0522-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14760488">Paulussen et al. (2004)</a> identified heterozygosity for a 253G-A transition in exon 3 of the KCNE1 gene, previously described by <a href="#23" class="mim-tip-reference" title="Tesson, F., Donger, C., Denjoy, I., Berthet, M., Bennaceur, M., Petit, C., Coumel, P., Schwartz, K., Guicheney, P. <strong>Exclusion of KCNE1 (IsK) as a candidate gene for Jervell and Lange-Nielsen syndrome.</strong> J. Molec. Cell. Cardiol. 28: 2051-2055, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8899564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8899564</a>] [<a href="https://doi.org/10.1006/jmcc.1996.0198" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8899564">Tesson et al. (1996)</a> as a polymorphism, resulting in an asp85-to-asn (D85N) substitution. Both subjects showed QTc prolongation compared to an electrocardiogram recorded prior to drug exposure (<a href="/entry/613695">613695</a>). The 85N variant was not found in 32 healthy controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8899564+14760488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a female patient who had a QTc of 460 ms and suffered cardiac arrest, <a href="#27" class="mim-tip-reference" title="Westenskow, P., Splawski, I., Timothy, K. W., Keating, M. T., Sanguinetti, M. C. <strong>Compound mutations: a common cause of severe long-QT syndrome.</strong> Circulation 109: 1834-1841, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15051636/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15051636</a>] [<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15051636">Westenskow et al. (2004)</a> identified triallelic digenic mutations: homozygosity for D85N in the KCNE1 gene, and heterozygosity for a missense mutation in the KCNH2 gene (<a href="/entry/152427#0021">152427.0021</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15051636" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a study of noise-induced hearing loss susceptibility (NIHL; <a href="/entry/613035">613035</a>) in 218 Swedish noise-exposed male workers, <a href="#26" class="mim-tip-reference" title="Van Laer, L., Carlsson, P.-I., Ottschytsch, N., Bondeson, M.-L., Konings, A., Vandevelde, A., Dieltjens, N., Fransen, E., Snyders, D., Borg, E., Raes, A., Van Camp, G. <strong>The contribution of genes involved in potassium recycling in the inner ear to noise-induced hearing loss.</strong> Hum. Mutat. 27: 786-795, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16823764/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16823764</a>] [<a href="https://doi.org/10.1002/humu.20360" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16823764">Van Laer et al. (2006)</a> genotyped 35 SNPs in 10 candidate genes involved in cell coupling and potassium recycling in the inner ear, and identified the 85N variant of KCNE1 in 5 of 104 noise-susceptible individuals and in none of 114 noise-resistant individuals (p = 0.023). Patch-clamp experiments in Chinese hamster ovary (CHO) cells showed a significant difference in current density and midpoint potential between 85N and wildtype channels. The authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16823764" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1038/384078a0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/8.8.1499" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9790991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9790991</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9790991" 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/bbrc.1998.9554" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8432548/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8432548</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8432548" 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.1993.1051" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0378-1119(94)90685-8" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15207237/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15207237</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15207237" 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.2004.06.001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2006.00671.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.1016300108" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s00109-003-0522-z" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng1197-267" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.cir.102.10.1178" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/geno.1998.5361" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/jmcc.1996.0198" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.hrthm.2005.01.020" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/6.12.2179" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20360" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.CIR.0000125524.34234.13" target="_blank">Full Text</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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Matthew B. Gross - updated : 10/12/2022
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Bao Lige - updated : 10/12/2022<br>Patricia A. Hartz - updated : 8/2/2010<br>Marla J. F. O'Neill - updated : 2/12/2008<br>Marla J. F. O'Neill - updated : 11/9/2006<br>Victor A. McKusick - updated : 8/24/2006<br>Patricia A. Hartz - updated : 5/12/2005<br>Ada Hamosh - updated : 1/22/2002<br>Victor A. McKusick - updated : 8/10/2001<br>Ada Hamosh - updated : 7/28/2000<br>Paul J. Converse - updated : 5/23/2000<br>Victor A. McKusick - updated : 8/13/1999<br>Paul Brennan - updated : 4/1/1998<br>Victor A. McKusick - updated : 11/19/1997<br>Victor A. McKusick - updated : 11/3/1997<br>Victor A. McKusick - updated : 10/27/1997<br>Victor A. McKusick - updated : 10/22/1997<br>Victor A. McKusick - updated : 9/10/1997<br>Moyra Smith - updated : 11/19/1996<br>Moyra Smith - updated : 11/15/1996
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Creation Date:
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Victor A. McKusick : 10/23/1991
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mgross : 10/12/2022
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mgross : 10/12/2022<br>carol : 08/09/2022<br>carol : 06/11/2019<br>carol : 01/28/2019<br>carol : 06/19/2015<br>carol : 12/11/2012<br>joanna : 7/10/2012<br>joanna : 7/9/2012<br>carol : 1/14/2011<br>carol : 1/13/2011<br>mgross : 8/18/2010<br>terry : 8/2/2010<br>wwang : 10/15/2009<br>ckniffin : 9/25/2009<br>alopez : 10/13/2008<br>alopez : 10/13/2008<br>wwang : 2/26/2008<br>terry : 2/12/2008<br>carol : 11/22/2006<br>carol : 11/10/2006<br>carol : 11/10/2006<br>carol : 11/9/2006<br>carol : 11/9/2006<br>alopez : 9/6/2006<br>terry : 8/24/2006<br>wwang : 5/20/2005<br>wwang : 5/16/2005<br>terry : 5/12/2005<br>terry : 3/16/2005<br>terry : 2/2/2005<br>joanna : 3/17/2004<br>ckniffin : 2/5/2003<br>alopez : 1/25/2002<br>terry : 1/22/2002<br>mcapotos : 8/15/2001<br>mcapotos : 8/14/2001<br>mcapotos : 8/10/2001<br>alopez : 8/1/2000<br>terry : 7/28/2000<br>carol : 5/23/2000<br>carol : 8/17/1999<br>terry : 8/13/1999<br>carol : 5/26/1999<br>carol : 5/25/1999<br>alopez : 1/28/1999<br>terry : 8/7/1998<br>carol : 4/1/1998<br>jenny : 11/26/1997<br>terry : 11/19/1997<br>mark : 11/4/1997<br>terry : 11/3/1997<br>terry : 10/28/1997<br>mark : 10/28/1997<br>terry : 10/28/1997<br>terry : 10/27/1997<br>terry : 10/24/1997<br>terry : 10/22/1997<br>terry : 9/16/1997<br>terry : 9/16/1997<br>terry : 9/10/1997<br>mark : 12/3/1996<br>terry : 11/19/1996<br>mark : 11/19/1996<br>mark : 11/15/1996<br>mark : 10/13/1995<br>carol : 2/17/1993<br>supermim : 3/16/1992<br>carol : 3/10/1992<br>carol : 3/8/1992<br>carol : 2/23/1992
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<strong>*</strong> 176261
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POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 1; KCNE1
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ISK<br />
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MINIMAL POTASSIUM ION CHANNEL; MINK
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<strong><em>HGNC Approved Gene Symbol: KCNE1</em></strong>
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Cytogenetic location: 21q22.12
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Genomic coordinates <span class="small">(GRCh38)</span> : 21:34,446,688-34,512,210 </span>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Phenotype
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21q22.12
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Jervell and Lange-Nielsen syndrome 2
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612347
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Autosomal recessive
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Long QT syndrome 5
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613695
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Autosomal dominant
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>KCNE1 is an accessory beta subunit that assembles with the pore-forming alpha subunit KCNQ1 (607542) to form the slow delayed rectifier I(Ks) potassium channel, which is essential for cardiac function (summary by Osteen et al., 2010). </p>
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<strong>Cloning and Expression</strong>
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<p>Potassium ion channels are essential to many cellular functions in both excitable and nonexcitable cells and show a high degree of diversity, varying in their electrophysiologic and pharmacologic properties. By molecular cloning and sequence analysis of its genomic DNA, Murai et al. (1989) deduced the amino acid sequence of a novel human membrane protein that induces selective potassium permeation by membrane depolarization. The protein consisted of 129 amino acid residues and shared structural characteristics with the rat counterpart. The transmembrane domain and its flanking C-terminal sequence were highly conserved between the human and rat sequences. The slowly activating potassium current elicited by the human protein on its expression in Xenopus oocytes was indistinguishable from that induced by the rat protein. </p>
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<strong>Gene Structure</strong>
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<p>By genomic sequence analysis, Splawski et al. (1998) determined that the KCNE1 gene contains 3 exons. The 2 introns are located in the 5-prime untranslated region. </p>
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<strong>Mapping</strong>
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<p>Using the human probe in the study of somatic cell hybrids, McPherson et al. (1991) mapped the KCNE1 gene to chromosome 21. Chevillard et al. (1993) confirmed the assignment to chromosome 21 by somatic cell hybridization and regionalized the assignment to 21q22.1-q22.2 by isotopic in situ hybridization. </p><p>By PCR analysis of 2 complete panels of human/rodent hybrid DNA, Malo et al. (1995) mapped the KCNE1 gene to chromosome 21 with 100% concordance. PCR on DNA of a human chromosome 21 regional mapping panel sublocalized the gene to 21q22.1-q22.2, which also contains a putative Down syndrome (trisomy 21) region. </p>
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<strong>Gene Function</strong>
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<p>Through cotransfection studies using human KVLQT1 (KCNQ1; 607542) and minK genes, Sanguinetti et al. (1996) demonstrated that the KVLQT1 and minK protein products coassemble to form the cardiac I(Ks) channel. Barhanin et al. (1996) expressed mouse KVLQT1 in COS cells and carried out electrophysiologic studies. They demonstrated that KVLQT1 encodes a subunit forming the important cardiac ion channel underlying the I(Ks) cardiac current. They observed also that the ISK was required to form the I(Ks) channel. McDonald et al. (1997) showed that the product of the KCNE1 gene, minK, forms a stable complex with HERG (KCNH2; 152427) and this heteromultimerization regulates the rapidly activating cardiac delayed rectifier. They concluded that, through the formation of heteromeric channel complexes, minK is central to the control of the heart rate and rhythm. </p><p>Marx et al. (2002) demonstrated that beta-adrenergic receptor modulation of the slow outward potassium ion current (I-KS) requires targeting of cAMP-dependent protein kinase A (188830) and protein phosphatase 1 (PP1, e.g., 176875) to KCNQ1 (607542) through the targeting protein yotiao (AKAP9; 604001). Yotiao binds to KCNQ1 by a leucine zipper motif. Identification of the KCNQ1 macromolecular complex provides a mechanism for sympathetic nervous system modulation of cardiac action potential duration through I-KS. </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 KCNQ1/KCNE1 heterodimers. </p><p>Melman et al. (2004) showed that KCNE1 and KCNE3 (604433) associate with an extended binding interface of KCNQ1 that includes structures within the channel pore and C terminus. </p><p>Osteen et al. (2010) found that coexpression of KCNE1 with KCNQ1 (607542) in Xenopus oocytes separated voltage dependence of KCNQ1/KCNE1 potassium channel opening and movement, suggesting an imposed requirement for movement of multiple voltage sensors before channel opening. The results indicated that KCNE1 modulates KCNQ1 to slow down activation of the KCNQ1/KCNE1 channel by altering the voltage sensor movements necessary to open the channel. </p><p>Using Xenopus oocytes expressing human KCNQ1 in the presence or absence of KCNE1, Peng et al. (2017) characterized 2 KCNQ1 gain-of-function mutations that cause atrial fibrillation, ser140 to gly (S140G; 607542.0032) and val141 to met (V141M; 607542.0045). In the absence of KCNE1, S140G, but not V141M, slowed voltage sensor movement, leading to indirect slowing of current deactivation. Slowing of voltage sensor deactivation by S140G in the absence of KCNE1 was independent of channel opening. When KCNE1 was coexpressed, S140G slowed both current deactivation and voltage sensor movement, whereas V141M slowed current deactivation without slowing voltage sensor movement. Slowing of voltage sensor deactivation by S140G in the presence of KCNE1 was dependent on channel opening. The authors proposed a molecular mechanism underlying the effects of the KCNQ1 mutations on channel gating and suggested that KCNE1 mediates changes in pore movement and voltage sensor-pore coupling to slow channel deactivation. </p>
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<strong>Molecular Genetics</strong>
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<p><strong><em>Long QT Syndrome 5</em></strong></p><p>
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Lai et al. (1994), who referred to the KCNE1 gene product as 'minimal potassium ion channel' (minK), described a polymorphism. An A-to-G substitution at position 112 resulted in a change from a ser codon (AGT) to a gly codon (GGT) and the creation of a new MspAI restriction site. Of the 32 alleles from 16 subjects studied, 25 had a G112 and 7 had an A112. No definite relationship to the long QT syndrome-1 (LQT1; 192500) could be established. </p><p>KCNE1 encodes beta subunits that coassemble with KVLQT1 alpha subunits. Ion-channel beta subunits are ancillary proteins that modulate the gating kinetics and enhance stability of multimeric channel complexes. Despite their functional importance, dysfunction of potassium channel beta subunits had not been associated with disease before the reports by Tyson et al. (1997) and Splawski et al. (1997). Splawski et al. (1997) identified KCNE1 missense mutations in affected members of 2 LQT5 families (176261.0003-176261.0004). </p><p>Bianchi et al. (1999), who referred to the long QT syndrome produced by mutations in the KCNE1 gene as LQT5, used electrophysiologic and immunocytochemical methods to compare the cellular phenotypes of wildtype minK and 4 LQT5 mutants coexpressed with KVLQT1 in Xenopus oocytes and with HERG in HEK293 cells. They found that 3 mutants, V47F, W87R, and D76N (176261.0003), were expressed at the cell surface, while one mutant, L51H, was not. Coexpression of V47F and W87R with KVLQT1 produced I(Ks) currents having altered gating and reduced amplitudes compared with wildtype minK; coexpression with L51H produced KVLQT1 current rather than I(Ks); and coexpression with D76N suppressed KVLQT1 current. V47F increased HERG current but to a lesser extent than wildtype minK, while L51H and W87R had no effect and D76N suppressed HERG current markedly. Thus, V47F interacted with both KVLQT1 and HERG; W87R interacted functionally with KVLQT1 but not with HERG; D76N suppressed both KVLQT1 and HERG; and L51H was processed improperly and interacted with neither channel. Bianchi et al. (1999) concluded that minK is a cofactor in the expression of both I(Ks) and I(Kr) and proposed that clinical manifestations of LQT5 may be complicated by differing effects of minK mutations on KVLQT1 and HERG. </p><p>Splawski et al. (2000) screened 262 unrelated individuals with LQT syndrome for mutations in the 5 defined genes (KCNQ1; KCNH2; SCN5A, 600163; KCNE1; and KCNE2 603796) and identified mutations in 177 individuals (68%). KCNQ1 and KCNH2 accounted for 87% of mutations (42% and 45%, respectively), and SCN5A, KCNE1, and KCNE2 for the remaining 13% (8%, 3%, and 2%, respectively). </p><p>Paulussen et al. (2004) screened 5 congenital long QT syndrome-associated genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) in 32 individuals with drug-induced long QT syndrome and identified 3 heterozygous mutations in 4 patients that were not found in 32 healthy controls (see, e.g., 176261.0005). </p><p>Tester et al. (2005) analyzed 5 LQTS-associated cardiac channel genes in 541 consecutive unrelated patients with LQT syndrome (average QTc, 482 ms). In 272 (50%) patients, they identified 211 different pathogenic mutations, including 88 in KCNQ1, 89 in KCNH2, 32 in SCN5A, and 1 each in KCNE1 and KCNE2. Mutations considered pathogenic were absent in more than 1,400 reference alleles. Among the mutation-positive patients, 29 (11%) had 2 LQTS-causing mutations, of which 16 (8%) were in 2 different LQTS genes (biallelic digenic). Tester et al. (2005) noted that patients with multiple mutations were younger at diagnosis, but they did not discern any genotype/phenotype correlations associated with location or type of mutation. </p><p>In 44 unrelated patients with LQT syndrome, Millat et al. (2006) used DHLP chromatography to analyze the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes for mutations and SNPs. Most of the patients (84%) showed a complex molecular pattern, with an identified mutation associated with 1 or more SNPs located in several LQTS genes; 4 of the patients also had a second mutation in a different LQTS gene (biallelic digenic inheritance). Millat et al. (2006) suggested that because double heterozygosity appears to be more common than expected, molecular diagnosis should be performed on all LQTS-related genes, even after a single mutation has been identified. </p><p><strong><em>Jervell and Lange-Nielsen Syndrome</em></strong></p><p>
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The KCNE1 gene encodes a transmembrane protein known to associate with the product of the KVLQT1 gene to form the delayed rectifier potassium channel. The KVLQT1 gene is the site of mutations that cause either type 1 long QT syndrome or type 1 Jervell and Lange-Nielsen syndrome (JLNS1). Tyson et al. (1997) described a family in which JLNS (JLNS2; 612347) was due to homozygosity for a mutation in the KCNE1 gene. The phenotype was indistinguishable from that resulting from mutations in the KVLQT1 gene. Tesson et al. (1996) had excluded the KCNE1 gene as the site of the mutation in the Jervell and Lange-Nielsen syndrome (JLNS1; 220400) in 4 consanguineous families, using microsatellite markers of chromosome 21 as well as KCNE1 intragenic polymorphisms. </p><p>Schulze-Bahr et al. (1997) found mutations in the KCNE1 gene in members of a Lebanese family with JLNS2 (e.g., 176261.0002). Three of 6 children had prolonged QT intervals and congenital bilateral deafness; 2 of the 3 had suffered from recurrent syncope since early childhood. Both parents and the 3 other sibs showed normal hearing and had QT durations within the normal range. Segregation analysis using microsatellite markers excluded linkage to the LQT1, LQT2 (613688), and LQT3 (603830) loci, located on 11p, 7q, and 3p, respectively. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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In a study of 218 Swedish noise-exposed male workers, Van Laer et al. (2006) identified the asp85-to-asn variant in the KCNE1 gene (rs1805128; 176261.0005) as the possible cause of susceptibility to noise-induced hearing loss (NIHL; 613035). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Westenskow et al. (2004) analyzed the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes in 252 probands with long QT syndrome and identified 19 with biallelic mutations in LQTS genes, of whom 18 were either compound (monogenic) or double (digenic) heterozygotes and 1 was a homozygote. They also identified 1 patient who had triallelic digenic mutations (see 176261.0005). Compared with probands who had 1 or no identified mutation, probands with 2 mutations had longer QTc intervals (p less than 0.001) and were 3.5-fold more likely to undergo cardiac arrest (p less than 0.01). All 20 probands with 2 mutations had experienced cardiac events. Westenskow et al. (2004) concluded that biallelic mono- or digenic mutations (which the authors termed 'compound mutations') cause a severe phenotype and are relatively common in long QT syndrome. The authors noted that these findings support the concept of arrhythmia risk as a multi-hit process and suggested that genotype can be used to predict risk. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Charpentier et al. (1998) investigated the cellular electrophysiologic characteristics of adult Kcne1-knockout mouse hearts by means of the standard microelectrode technique. Action potential parameters from the ventricular endocardium of Kcne1 -/- mice were indistinguishable from those of Kcne1 wildtype animals. In particular, Kcne1-deficient hearts did not exhibit prolonged repolarization. A specific blocker of ERG potassium channels consistently prolonged repolarization in Kcne1-wildtype but not in Kcne1-deficient hearts. By contrast, a specific blocker of KvLQT1 potassium channel produced comparable effects on repolarization in Kcne1 -/- and wildtype mice. These results suggested to Charpentier et al. (1998) that invalidation of the mouse Kcne1 gene leads to a mild cardiac phenotype at the cellular level. </p><p>Arrighi et al. (2001) demonstrated altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome. The slowly activating delayed K+ current, known as I(Ks), is composed of pore-forming KCNQ1 (607542) and regulatory KCNE1 subunits, which are mutated in familial forms of cardiac long QT syndrome, LQT1 and LQT5, respectively. Because KCNQ1 and KCNE1 genes are also expressed in epithelial tissues, such as the kidneys and the intestine, Arrighi et al. (2001) investigated the adaptation of Kcne1-deficient mice to different K+ and Na+ intakes. On a normal potassium diet, homozygous Kcne1 knockout-null mice exhibited signs of chronic volume depletion associated with fecal sodium and potassium ion wasting and had lower plasma potassium ion concentration and higher levels of aldosterone than wildtype mice. Although plasma aldosterone can be suppressed by low potassium diets or stimulated by low sodium diets, a high potassium diet provoked a tremendous increase of plasma aldosterone levels in the Kcne1 knockout-null mice as compared with wildtype mice despite lower plasma potassium. This exacerbated aldosterone production in the knockout mice was accompanied by an abnormally high plasma renin concentration, which could partly explain the hyperaldosteronism. Arrighi et al. (2001) found that KCNE1 and KCNQ1 mRNAs are expressed in the zona glomerulosa of adrenal glands where I(Ks) may directly participate in the control of aldosterone production by plasma K+. These results, which showed that KCNE1 and I(Ks) are involved in potassium homeostasis, may have important implications for patients with I(Ks)-related long QT syndrome, because hypokalemia is a well-known risk factor for the occurrence of torsade de pointes ventricular arrhythmia. </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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<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>5 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 JERVELL AND LANGE-NIELSEN SYNDROME 2</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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KCNE1, THR59PRO AND LEU60PRO
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<br />
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SNP: rs281865421,
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ClinVar: RCV000014417, RCV001244610, RCV001588813, RCV002476967
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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 small consanguineous family, Tyson et al. (1997) used linkage to exclude the KVLQT1 gene (607542) as the site of the mutation causing Jervell and Lange-Nielsen syndrome (JLNS2; 612347). The affected children in this family were homozygous by descent for markers on chromosome 21, in a region containing the KCNE1 gene. Sequencing showed a homozygous mutation in that gene. The phenotype was indistinguishable from that caused by mutation in the other component of the delayed rectifier potassium channel, KVLQT1. The change in the KCNE1 gene that was present in homozygous state in this family consisted of alteration in 3 nucleotides in codons 59 and 60. Codon 59 was changed from ACC (thr) to CCC (pro) and codon 60 was changed from CTG (leu) to CCT (pro). Both of these changes occurred in the transmembrane region of the predicted 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>.0002 JERVELL AND LANGE-NIELSEN SYNDROME 2</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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KCNE1, THR7ILE
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<br />
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SNP: rs28933384,
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gnomAD: rs28933384,
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ClinVar: RCV000014418, RCV000119076, RCV004777562
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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 3 children from a Lebanese family who were affected with Jervell and Lange-Nielsen syndrome (612347), Schulze-Bahr et al. (1997) found compound heterozygosity for mutations in the KCNE1 gene: a thr7-to-ile substitution from a 20C-T transition inherited from the father, and an asp76-to-asn substitution from a 226G-A transition inherited from the mother (176261.0003). The parents and 3 other sibs were heterozygous for one or the other mutation and were unaffected. These mutations were absent from 100 healthy unrelated individuals of the general population. The allele inherited from the father also included a gly38-to-ser polymorphism shown previously not to cause JLNS or LQT. </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 JERVELL AND LANGE-NIELSEN SYNDROME 2</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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LONG QT SYNDROME 5, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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KCNE1, ASP76ASN
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<br />
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SNP: rs74315445,
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gnomAD: rs74315445,
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ClinVar: RCV000014419, RCV000014420, RCV000119080, RCV000148512, RCV000222568, RCV000243273, RCV000471399, RCV000606753, RCV000678806, RCV005054138
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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>By SSCP analyses using primers that spanned KCNE1, Splawski et al. (1997) identified an anomalous conformer in affected members of a kindred with long QT syndrome-5 (613695). The DNA sequence analysis revealed a G-to-A transition at the first nucleotide of codon 76, causing an asp-to-asn substitution (D76N). </p><p>Schulze-Bahr et al. (1997) demonstrated the D76N mutation in compound heterozygotes with Jervell and Lange-Nielsen syndrome (JLNS2; 612347); see 176261.0002. </p><p>Duggal et al. (1998) reported the same mutation in homozygous form in a young girl with congenital deafness, extreme QT prolongation, and recurrent syncope, who fulfilled the criteria for Jervell and Lange-Nielsen syndrome. Her mother and half sister, who were heterozygous for the D76N mutation, experienced syncope and partial hearing loss and had prolonged QT intervals. The authors commented that the heterozygous state was consistent with the Romano-Ward syndrome, also known to be caused by mutations in the KVLQT1 gene, and suggested that the KCNE1 gene represents a fifth long QT syndrome locus. </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>.0004 LONG QT SYNDROME 5</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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KCNE1, SER74LEU
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<br />
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SNP: rs74315446,
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gnomAD: rs74315446,
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|
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ClinVar: RCV000014421, RCV000119079, RCV000471661, RCV000603252, RCV002482866, RCV003318541, RCV004017244
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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 family with long QT syndrome-5 (613695), Splawski et al. (1997) identified a C-to-T transition in the second nucleotide of codon 74, leading to a substitution of serine for leucine (S74L). </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LONG QT SYNDROME 5, ACQUIRED, SUSCEPTIBILITY TO</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
LONG QT SYNDROME 2/5, DIGENIC, INCLUDED
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
KCNE1, ASP85ASN
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs1805128,
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|
|
|
gnomAD: rs1805128,
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|
|
|
|
ClinVar: RCV000014422, RCV000014423, RCV000035353, RCV000057858, RCV000157255, RCV000247942, RCV000399257, RCV000709727, RCV000852954, RCV001195103, RCV003224097
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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 />
|
|
<p><strong><em>Long QT Syndrome 5</em></strong></p><p>
|
|
In a 71-year-old man and an unrelated 81-year-old female with drug-induced torsade de pointes (quinidine and sotolol, respectively), Paulussen et al. (2004) identified heterozygosity for a 253G-A transition in exon 3 of the KCNE1 gene, previously described by Tesson et al. (1996) as a polymorphism, resulting in an asp85-to-asn (D85N) substitution. Both subjects showed QTc prolongation compared to an electrocardiogram recorded prior to drug exposure (613695). The 85N variant was not found in 32 healthy controls. </p><p>In a female patient who had a QTc of 460 ms and suffered cardiac arrest, Westenskow et al. (2004) identified triallelic digenic mutations: homozygosity for D85N in the KCNE1 gene, and heterozygosity for a missense mutation in the KCNH2 gene (152427.0021). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
In a study of noise-induced hearing loss susceptibility (NIHL; 613035) in 218 Swedish noise-exposed male workers, Van Laer et al. (2006) genotyped 35 SNPs in 10 candidate genes involved in cell coupling and potassium recycling in the inner ear, and identified the 85N variant of KCNE1 in 5 of 104 noise-susceptible individuals and in none of 114 noise-resistant individuals (p = 0.023). Patch-clamp experiments in Chinese hamster ovary (CHO) cells showed a significant difference in current density and midpoint potential between 85N and wildtype channels. The authors suggested that further studies were necessary before KCNE1 D85N could be designated as a causative SNP. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
|
<ol>
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<li>
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<p class="mim-text-font">
|
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Arrighi, I., Bloch-Faure, M., Grahammer, F., Bleich, M., Warth, R., Mengual, R., Drici, M.-D., Barhanin, J., Meneton, P.
|
|
<strong>Altered potassium balance and aldosterone secretion in a mouse model of human congenital long QT syndrome.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 8792-8797, 2001.
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[PubMed: 11438691]
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[Full Text: https://doi.org/10.1073/pnas.141233398]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Barhanin, J., Lesage, F., Guillemare, E., Fink, M., Lazdunski, M., Romey, G.
|
|
<strong>K(v)LQT1 and IsK (minK) proteins associate to form the I(Ks) cardiac potassium current.</strong>
|
|
Nature 384: 78-80, 1996.
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[PubMed: 8900282]
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[Full Text: https://doi.org/10.1038/384078a0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Bianchi, L., Shen, Z., Dennis, A. T., Priori, S. G., Napolitano, C., Ronchetti, E., Bryskin, R., Schwartz, P. J., Brown, A. M.
|
|
<strong>Cellular dysfunction of LQT5-minK mutants: abnormalities of I(Ks), I(Kr) and trafficking in long QT syndrome.</strong>
|
|
Hum. Molec. Genet. 8: 1499-1507, 1999.
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[PubMed: 10400998]
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[Full Text: https://doi.org/10.1093/hmg/8.8.1499]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Charpentier, F., Merot, J., Riochet, D., Le Marec, H., Escande, D.
|
|
<strong>Adult KCNE1-knockout mice exhibit a mild cardiac cellular phenotype.</strong>
|
|
Biochem. Biophys. Res. Commun. 251: 806-810, 1998.
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[PubMed: 9790991]
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[Full Text: https://doi.org/10.1006/bbrc.1998.9554]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chevillard, C., Attali, B., Lesage, F., Fontes, M., Barhanin, J., Lazdunski, M., Mattei, M. G.
|
|
<strong>Localization of a potassium channel gene (KCNE1) to 21q22.1-q22.2 by in situ hybridization and somatic cell hybridization.</strong>
|
|
Genomics 15: 243-245, 1993.
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[PubMed: 8432548]
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[Full Text: https://doi.org/10.1006/geno.1993.1051]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Duggal, P., Vesely, M. R., Wattanasirichaigoon, D., Villafane, J., Kaushik, V., Beggs, A. H.
|
|
<strong>Mutation of the gene for IsK associated with both Jervell and Lange-Nielsen and Romano-Ward forms of long-QT syndrome.</strong>
|
|
Circulation 97: 142-146, 1998.
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[PubMed: 9445165]
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[Full Text: https://doi.org/10.1161/01.cir.97.2.142]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Lai, L.-P., Deng, C.-L., Moss, A. J., Kass, R. S., Liang, C.
|
|
<strong>Polymorphism of the gene encoding a human minimal potassium ion channel (minK).</strong>
|
|
Gene 151: 339-340, 1994.
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|
|
[PubMed: 7828904]
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[Full Text: https://doi.org/10.1016/0378-1119(94)90685-8]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Malo, M. S., Srivastava, K., Ingram, V. M.
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|
<strong>Gene assignment by polymerase chain reaction: localization of the human potassium channel ISK gene to the Down's syndrome region of chromosome 21q22.1-q22.2.</strong>
|
|
Gene 159: 273-275, 1995.
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|
[PubMed: 7622063]
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[Full Text: https://doi.org/10.1016/0378-1119(95)00102-c]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Marx, S. O., Kurokawa, J., Reiken, S., Motoike, H., D'Armiento, J., Marks, A. R., Kass, R. S.
|
|
<strong>Requirement of a macromolecular signaling complex for beta adrenergic receptor modulation of the KCNQ1-KCNE1 potassium channel.</strong>
|
|
Science 295: 496-499, 2002.
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[PubMed: 11799244]
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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