3232 lines
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Entry
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- *603796 - POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 2; KCNE2
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<p>
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<span class="h4">*603796</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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<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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<a href="#mapping">Mapping</a>
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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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<a href="#animalModel">Animal Model</a>
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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/603796">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<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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</ul>
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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 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=ENSG00000159197;t=ENST00000290310" 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=9992" 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=603796" 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=ENSG00000159197;t=ENST00000290310" 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_172201" 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_172201" 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=603796" 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=04813&isoform_id=04813_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/KCNE2" 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/4704423,6685661,10121888,27436978,62740029,77632642,85567538,119630195,119630196,146048332" 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/Q9Y6J6" 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=9992" 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=ENSG00000159197;t=ENST00000290310" 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=KCNE2" 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=KCNE2" 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+9992" 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/KCNE2" 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:9992" 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/9992" 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=ENST00000290310.4&hgg_start=34364006&hgg_end=34371381&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:6242" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603796[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=603796[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/KCNE2/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/ENSG00000159197" 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=KCNE2" 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=KCNE2" 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=KCNE2" 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=KCNE2" title="Zhejiang University-Adinovo Center KCNE2 Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Zhejiang University-Adinov…</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>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=KCNE2&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/PA392" 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:6242" 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:1891123" 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/KCNE2#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:1891123" 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/9992/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=9992" 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>
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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:9992" 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=KCNE2&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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603796
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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 2; KCNE2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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MINIMUM POTASSIUM ION CHANNEL-RELATED PEPTIDE 1; MIRP1<br />
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MINK-RELATED PEPTIDE 1
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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=KCNE2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNE2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/21/79?start=-3&limit=10&highlight=79">21q22.11</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr21:34364006-34371381&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'})">21:34,364,006-34,371,381</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=611493,613693" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
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View Clinical Synopses
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</a>
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</span>
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
|
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<span class="mim-font">
|
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<a href="/geneMap/21/79?start=-3&limit=10&highlight=79">
|
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21q22.11
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Atrial fibrillation, familial, 4
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/611493"> 611493 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Long QT syndrome 6
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/613693"> 613693 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
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<p>KCNE2 belongs to a family of small auxiliary subunits of voltage-gated cation channels. It can assemble with multiple alpha subunits of voltage-gated cation channels and modulate their gating, conductance, and pharmacology. KCNE2 plays an important role in maintaining cardiac electrical stability (summary by <a href="#4" class="mim-tip-reference" title="Liu, W., Deng, J., Wang, G., Zhang, C., Luo, X., Yan, D., Su, Q., Liu, J. <strong>KCNE2 modulates cardiac L-type Ca(2+) channel.</strong> J. Molec. Cell. Cardiol. 72: 208-218, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24681347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24681347</a>] [<a href="https://doi.org/10.1016/j.yjmcc.2014.03.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24681347">Liu et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24681347" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> cloned and characterized KCNE2, a potassium channel gene encoding MinK-related peptide-1 (MiRP1), a small integral membrane subunit that assembles with the HERG gene product (KCNH2; <a href="/entry/152427">152427</a>), a pore-forming protein, to alter its function. Unlike channels formed only with HERG, mixed complexes resemble native cardiac I(Kr) channels in their gating, unitary conductance, regulation by potassium, and distinctive biphasic inhibition by the class III antiarrhythmic E-4031. MiRP1 is a small, 123-amino acid protein containing consensus sequences for 2 N-linked glycosylation sites (asn6 and asn29) and 2 protein kinase C-mediated phosphorylation sites (thr71 and ser74). Northern blot analysis detected MiRP1 expression in heart and muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> stated that the KCNE2 gene has been mapped to chromosome 21q22.1 (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AP000052" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AP000052</a>). They noted that KCNE1 (<a href="/entry/176261">176261</a>), the gene encoding MinK, was previously mapped to this site. The 2 genes are arrayed in opposite orientation, separated by 79 kb. Their open reading frames share 34% identity, and both are contained in a single exon. This suggests that the KCNE2 and KCNE1 genes are related through gene duplication and divergent evolution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" 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="#6" class="mim-tip-reference" title="Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., Abbott, G. W. <strong>Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.</strong> Nature Med. 15: 1186-1194, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767733[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19767733">Roepke et al. (2009)</a> demonstrated that both KCNE2 and KCNQ1 (<a href="/entry/607542">607542</a>) were expressed and partially colocalized in human and mouse thyroid glands with the basolaterally located Na(+)/I(-) symporter (NIS) that mediates active I(-) transport, the first step in thyroid hormone biosynthesis. Thyroid follicular epithelia in Kcne2 -/- mice showed abnormal architecture, and Kcne2-deficient thyrocytes were flattened and less abundant compared to wildtype. Using the rat thyroid-derived FRTL5 cell line, the authors detected endogenous expression of KCNQ1 and KCNE2 proteins that was upregulated by thyroid-stimulating hormone (TSH; see <a href="/entry/188540">188540</a>) or its major downstream effector cAMP in the cell membrane fraction. The authors identified a TSH-stimulated K(+) current in FRTL5 cells that bore the signature linear current-voltage relationship of KCNQ1-KCNE2 channels and was inhibited by a KCNQ1-specific antagonist. Kcne2 -/- pups nursing from Kcne2 -/- dams had an 87% reduction in thyroid I(-) accumulation compared to wildtype pups. <a href="#6" class="mim-tip-reference" title="Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., Abbott, G. W. <strong>Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.</strong> Nature Med. 15: 1186-1194, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767733[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19767733">Roepke et al. (2009)</a> concluded that the potassium channel subunits KCNQ1 and KCNE2 form a TSH-stimulated constitutively active thyrocyte K(+) channel that is required for normal thyroid hormone biosynthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19767733" 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 primary cultures of rat ventricular myocytes, <a href="#4" class="mim-tip-reference" title="Liu, W., Deng, J., Wang, G., Zhang, C., Luo, X., Yan, D., Su, Q., Liu, J. <strong>KCNE2 modulates cardiac L-type Ca(2+) channel.</strong> J. Molec. Cell. Cardiol. 72: 208-218, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24681347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24681347</a>] [<a href="https://doi.org/10.1016/j.yjmcc.2014.03.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24681347">Liu et al. (2014)</a> found that human KCNE2 coimmunoprecipitated with and colocalized with Cav1.2 (CACNA1C; <a href="/entry/114205">114205</a>), predominantly at transverse tubules. KCNE2 overexpression decreased Cav1.2 current magnitude and slightly altered its gating and kinetic properties, but it had no effect on Cav1.2 trafficking or membrane localization. Knockdown of endogenous Kcne2 increased Cav1.2-dependent calcium currents. KCNE2 copurified with the N-terminal inhibitory module of Cav1.2 and appeared to increase its inhibitory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24681347" 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>To assess the potential role of MiRP1 in disturbances of heart rhythm, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> screened 250 patients (20 with drug-induced arrhythmia and 230 with inherited or sporadic arrhythmias) with no mutations in the known arrhythmia genes KCNQ1 (<a href="/entry/607542">607542</a>), HERG, SCN5A (<a href="/entry/600163">600163</a>), and KCNE1. A control population of 1,010 individuals was also evaluated. Three missense mutations associated with long QT syndrome (LQT6; <a href="/entry/613693">613693</a>) and ventricular fibrillation were identified in the KCNE2 gene (<a href="#0001">603796.0001</a>-<a href="#0003">603796.0003</a>). In addition, in 18 of 1,260 individuals screened, an A-to-G polymorphism at nucleotide 22 produced a thr8-to-ala substitution in the putative extracellular domain of MiRP1. This change was found in 1 patient with quinidine-induced arrhythmia, 1 with inherited or sporadic arrhythmia, and 16 controls. Channels formed with mutant MiRP1 subunits and HERG showed slower activation, faster deactivation, and increased drug sensitivity. One variant (<a href="#0001">603796.0001</a>), associated with clarithromycin-induced arrhythmia, increases channel blockade by the antibiotic. A mechanism for acquired arrhythmia was revealed in which genetically based reduction in potassium currents remains clinically silent until combined with additional stressors. These findings support a theory for arrhythmogenesis that invokes superimposition of genetic and environmental factors acting in concert to diminish progressively the capacity of cardiac ion channels to terminate each action potential in normal fashion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="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, KCNE1, and KCNE2) 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="#8" 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="#8" 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="#5" 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; see, e.g., <a href="#0005">603796.0005</a>). <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>
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<p>In a canine model of ischemic cardiomyopathy, <a href="#3" class="mim-tip-reference" title="Jiang, M., Zhang, M., Tang, D. G., Clemo, H. F., Liu, J., Holwitt, D., Kasirajan, V., Pond, A. L., Wettwer, E., Tseng, G.-N. <strong>KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.</strong> Circulation 109: 1783-1788, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066947</a>] [<a href="https://doi.org/10.1161/01.CIR.0000124225.43852.50" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15066947">Jiang et al. (2004)</a> observed an increase in the rapid delayed rectifier current, I(Kr), density and a marked reduction in the KCNE2 protein level, although the protein level of KCNH2, the I(Kr) pore-forming alpha subunit, was not altered. <a href="#3" class="mim-tip-reference" title="Jiang, M., Zhang, M., Tang, D. G., Clemo, H. F., Liu, J., Holwitt, D., Kasirajan, V., Pond, A. L., Wettwer, E., Tseng, G.-N. <strong>KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.</strong> Circulation 109: 1783-1788, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066947</a>] [<a href="https://doi.org/10.1161/01.CIR.0000124225.43852.50" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15066947">Jiang et al. (2004)</a> suggested that in the canine ventricle, KCNE2 may associate with KCNH2 and suppress its current amplitude. In aging rat ventricle, the pacemaker current density was increased, and there was a significant increase in the Kcne2 protein level, whereas changes in the main alpha-subunit (HCN2; <a href="/entry/602781">602781</a>) of the pacemaker current channel were not significant. <a href="#3" class="mim-tip-reference" title="Jiang, M., Zhang, M., Tang, D. G., Clemo, H. F., Liu, J., Holwitt, D., Kasirajan, V., Pond, A. L., Wettwer, E., Tseng, G.-N. <strong>KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.</strong> Circulation 109: 1783-1788, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066947</a>] [<a href="https://doi.org/10.1161/01.CIR.0000124225.43852.50" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15066947">Jiang et al. (2004)</a> suggested that in aging rat ventricle, Kcne2 may associate with Hcn2 and enhance its current amplitude. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15066947" 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="Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., Abbott, G. W. <strong>Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.</strong> Nature Med. 15: 1186-1194, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767733[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19767733">Roepke et al. (2009)</a> performed targeted disruption of Kcne2 in mice and observed impaired thyroid iodide accumulation up to 8-fold, impaired maternal milk ejection, halved mild tetraiodothyronine (T4) content, and halved litter size. Kcne2-deficient mice had hypothyroidism, dwarfism, alopecia, goiter, and cardiac abnormalities including hypertrophy, fibrosis, and reduced fractional shortening. The alopecia, dwarfism, and cardiac abnormalities were alleviated by triiodothyroinine (T3) and T4 administration to pups, by supplementing dams with T4 before and after they gave birth, or by feeding the pups exclusively from Kcne2 +/+ dams; conversely, these symptoms were elicited in Kcne2 +/+ pups by feeding exclusively from Kcne2 -/- dams. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19767733" 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>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>5 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=603796[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 LONG QT SYNDROME 6, ACQUIRED, SUSCEPTIBILITY TO</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000006424 OR RCV000058370 OR RCV000170567 OR RCV000245955 OR RCV000990346 OR RCV001139400" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006424, RCV000058370, RCV000170567, RCV000245955, RCV000990346, RCV001139400" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006424...</a>
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<p>In a 76-year-old African American female with drug-induced arrhythmia, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> identified a 25C-G transversion in the KCNE2 gene, resulting in a gln9-to-glu (Q9E) substitution in the putative extracellular domain of MiRP1. This mutation was not identified in 1,010 control individuals. The patient had a history of high blood pressure, noninsulin-dependent diabetes, and stroke. Two baseline electrocardiograms showed QT intervals corrected for heart rate that were borderline prolonged (QTc = 460 ms) (<a href="/entry/613693">613693</a>). There was concentric left ventricular hypertrophy with mild to moderate diffuse hypokinesis but no ventricular dilatation. The patient was admitted to the hospital with pneumonia and treated with 500 mg of oral clarithromycin every 12 hours. After 2 doses of clarithromycin, electrocardiography showed a QTc of 540 ms. The patient developed torsade de pointes and ventricular fibrillation, requiring defibrillation. At the time, she was hypokalemic with a serum potassium level of 2.8 meq/l. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Ackerman, M. J., Tester, D. J., Jones, G. S., Will, M. L., Burrow, C. R., Curran, M. E. <strong>Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.</strong> Mayo Clin. Proc. 78: 1479-1487, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661677</a>] [<a href="https://doi.org/10.4065/78.12.1479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14661677">Ackerman et al. (2003)</a> identified the Q9E variant as a relatively common polymorphism present in 3% of black individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661677" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315447 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315447;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/rs74315447?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=rs74315447" 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=rs74315447" 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=RCV000006425 OR RCV000058360 OR RCV000212497 OR RCV000407848 OR RCV001841228 OR RCV002399310 OR RCV004772828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006425, RCV000058360, RCV000212497, RCV000407848, RCV001841228, RCV002399310, RCV004772828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006425...</a>
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<p>In a healthy 38-year-old Caucasian female, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> identified a T-to-C transition at nucleotide 161, resulting in a met54-to-thr substitution in the predicted transmembrane segment of MiRP1. This mutation was not identified in 1,010 control individuals. The patient had had ventricular fibrillation while jogging. Her resuscitation required defibrillation. The results from echocardiography and cardiac catheterization with electrophysiologic studies and right ventricular biopsy were normal. Subsequent electrocardiograms showed an atypical response to exercise with QTc intervals ranging from 390 to 500 ms (<a href="/entry/613693">613693</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs74315448 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315448;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/rs74315448?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=rs74315448" 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=rs74315448" 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 healthy 48-year-old Hispanic female with no history of torsade de pointes or ventricular fibrillation, <a href="#1" class="mim-tip-reference" title="Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N. <strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong> Cell 97: 175-187, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>] [<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10219239">Abbott et al. (1999)</a> identified a T-to-C transition at nucleotide 170, resulting in an ile57-to-thr substitution in the predicted transmembrane segment of MiRP1. The patient's resting electrocardiogram showed a prolonged QT interval (QTc = 470 ms) (<a href="/entry/613693">613693</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" 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>.0004 ATRIAL FIBRILLATION, FAMILIAL, 4</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> rs74315449 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs74315449;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/rs74315449?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=rs74315449" 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=rs74315449" 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=RCV000006427 OR RCV000058377 OR RCV000157256 OR RCV000490451 OR RCV000756281 OR RCV001080271 OR RCV004018576" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006427, RCV000058377, RCV000157256, RCV000490451, RCV000756281, RCV001080271, RCV004018576" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006427...</a>
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<p>In a study of 28 unrelated Chinese kindreds with atrial fibrillation (<a href="/entry/611493">611493</a>), <a href="#9" class="mim-tip-reference" title="Yang, Y., Xia, M., Jin, Q., Bendahhou, S., Shi, J., Chen, Y., Liang, B., Lin, J., Liu, Y., Liu, B., Zhou, Q., Zhang, D., and 11 others. <strong>Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.</strong> Am. J. Hum. Genet. 75: 899-905, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15368194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15368194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15368194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/425342" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15368194">Yang et al. (2004)</a> found that 2 of the probands had an arginine-to-cysteine change at codon 27 (R27C) of KCNE2, the beta-subunit of the KCNQ1-KCNE2 channel responsible for a background potassium current. The amino acid change resulted from a C-to-T transition at nucleotide position 79 from the translation initiation codon. The mutation was present in all affected members in the 2 kindreds and was absent in 462 healthy unrelated Chinese subjects. Similar to KCNQ1 S140G (<a href="/entry/607542#0032">607542.0032</a>), the KCNE2 R27C mutation had a gain-of-function effect on the KCNQ1-KCNE2 channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15368194" 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 expression in rat ventricular myocytes, <a href="#4" class="mim-tip-reference" title="Liu, W., Deng, J., Wang, G., Zhang, C., Luo, X., Yan, D., Su, Q., Liu, J. <strong>KCNE2 modulates cardiac L-type Ca(2+) channel.</strong> J. Molec. Cell. Cardiol. 72: 208-218, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24681347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24681347</a>] [<a href="https://doi.org/10.1016/j.yjmcc.2014.03.013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24681347">Liu et al. (2014)</a> found that human KCNE2 with the R27C substitution was more effective than wildtype in suppressing Cav1.2 (CACNA1C; <a href="/entry/114205">114205</a>)-dependent calcium currents. The mutation did not significantly change KCNE2 regulation of voltage-dependent activation and steady-stage voltage-dependent channel inactivation, nor did it alter expression of other calcium channel subunits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24681347" 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>.0005 LONG QT SYNDROME 3/6, DIGENIC</strong>
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KCNE2, PHE60LEU
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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> rs16991654 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs16991654;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/rs16991654?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=rs16991654" 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=rs16991654" 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=RCV000006428 OR RCV000058363" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000006428, RCV000058363" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000006428...</a>
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<p>In a 1-month-old male infant who had syncope, torsade de pointes, cardiac arrest, and a QTc of 460 ms (<a href="/entry/613693">613693</a>), <a href="#5" 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> identified biallelic digenic mutations: a 178C-T transition in exon 1 of the KCNE2 gene, resulting in a phe60-to-leu (F60L) substitution, and a missense mutation in the SCN5A gene (R1623Q; <a href="/entry/600163#0007">600163.0007</a>). <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>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
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<a id="Abbott1999" class="mim-anchor"></a>
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Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N.
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<strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong>
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Cell 97: 175-187, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10219239/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10219239</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10219239" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0092-8674(00)80728-x" target="_blank">Full Text</a>]
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<a id="Ackerman2003" class="mim-anchor"></a>
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Ackerman, M. J., Tester, D. J., Jones, G. S., Will, M. L., Burrow, C. R., Curran, M. E.
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<strong>Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.</strong>
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Mayo Clin. Proc. 78: 1479-1487, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14661677/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14661677</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14661677" 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/10.4065/78.12.1479" target="_blank">Full Text</a>]
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<a id="Jiang2004" class="mim-anchor"></a>
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Jiang, M., Zhang, M., Tang, D. G., Clemo, H. F., Liu, J., Holwitt, D., Kasirajan, V., Pond, A. L., Wettwer, E., Tseng, G.-N.
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<strong>KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.</strong>
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Circulation 109: 1783-1788, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15066947/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15066947</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15066947" 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/10.1161/01.CIR.0000124225.43852.50" target="_blank">Full Text</a>]
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<a id="Liu2014" class="mim-anchor"></a>
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Liu, W., Deng, J., Wang, G., Zhang, C., Luo, X., Yan, D., Su, Q., Liu, J.
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<strong>KCNE2 modulates cardiac L-type Ca(2+) channel.</strong>
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J. Molec. Cell. Cardiol. 72: 208-218, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24681347/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24681347</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24681347" 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.yjmcc.2014.03.013" target="_blank">Full Text</a>]
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<a id="Millat2006" class="mim-anchor"></a>
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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.
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<strong>Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome.</strong>
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Clin. Genet. 70: 214-227, 2006.
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[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://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'})">related citations</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 id="Roepke2009" class="mim-anchor"></a>
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Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., Abbott, G. W.
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<strong>Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.</strong>
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Nature Med. 15: 1186-1194, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19767733/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19767733</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19767733[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19767733" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nm.2029" target="_blank">Full Text</a>]
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<a id="Splawski2000" class="mim-anchor"></a>
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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.
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<strong>Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.</strong>
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Circulation 102: 1178-1185, 2000.
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[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://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'})">related citations</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 id="Tester2005" class="mim-anchor"></a>
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Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J.
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<strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong>
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Heart Rhythm 2: 507-517, 2005.
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[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://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'})">related citations</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 id="Yang2004" class="mim-anchor"></a>
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Yang, Y., Xia, M., Jin, Q., Bendahhou, S., Shi, J., Chen, Y., Liang, B., Lin, J., Liu, Y., Liu, B., Zhou, Q., Zhang, D., and 11 others.
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<strong>Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.</strong>
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Am. J. Hum. Genet. 75: 899-905, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15368194/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15368194</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15368194[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15368194" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/425342" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 02/17/2017
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Patricia A. Hartz - updated : 02/17/2017<br>Marla J. F. O'Neill - updated : 11/16/2009<br>Marla J. F. O'Neill - updated : 2/12/2008<br>Marla J. F. O'Neill - updated : 11/9/2006<br>Marla J. F. O'Neill - updated : 12/12/2005<br>Victor A. McKusick - updated : 11/1/2004
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 5/11/1999
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mgross : 02/17/2017
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mgross : 02/17/2017<br>carol : 01/14/2011<br>wwang : 11/17/2009<br>terry : 11/16/2009<br>wwang : 2/26/2008<br>terry : 2/12/2008<br>alopez : 10/3/2007<br>carol : 11/10/2006<br>carol : 11/9/2006<br>wwang : 12/12/2005<br>alopez : 11/4/2004<br>alopez : 11/4/2004<br>terry : 11/1/2004<br>carol : 3/17/2004<br>ckniffin : 2/5/2003<br>carol : 8/17/1999<br>terry : 8/13/1999<br>mgross : 5/12/1999
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<span class="mim-font">
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<strong>*</strong> 603796
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POTASSIUM CHANNEL, VOLTAGE-GATED, ISK-RELATED SUBFAMILY, MEMBER 2; KCNE2
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MINIMUM POTASSIUM ION CHANNEL-RELATED PEPTIDE 1; MIRP1<br />
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MINK-RELATED PEPTIDE 1
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: KCNE2</em></strong>
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Cytogenetic location: 21q22.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 21:34,364,006-34,371,381 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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21q22.11
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Atrial fibrillation, familial, 4
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<span class="mim-font">
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611493
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3
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Long QT syndrome 6
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613693
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Autosomal dominant
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3
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>KCNE2 belongs to a family of small auxiliary subunits of voltage-gated cation channels. It can assemble with multiple alpha subunits of voltage-gated cation channels and modulate their gating, conductance, and pharmacology. KCNE2 plays an important role in maintaining cardiac electrical stability (summary by Liu et al., 2014). </p>
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<strong>Cloning and Expression</strong>
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<p>Abbott et al. (1999) cloned and characterized KCNE2, a potassium channel gene encoding MinK-related peptide-1 (MiRP1), a small integral membrane subunit that assembles with the HERG gene product (KCNH2; 152427), a pore-forming protein, to alter its function. Unlike channels formed only with HERG, mixed complexes resemble native cardiac I(Kr) channels in their gating, unitary conductance, regulation by potassium, and distinctive biphasic inhibition by the class III antiarrhythmic E-4031. MiRP1 is a small, 123-amino acid protein containing consensus sequences for 2 N-linked glycosylation sites (asn6 and asn29) and 2 protein kinase C-mediated phosphorylation sites (thr71 and ser74). Northern blot analysis detected MiRP1 expression in heart and muscle. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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<span class="mim-text-font">
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<p>Abbott et al. (1999) stated that the KCNE2 gene has been mapped to chromosome 21q22.1 (GenBank AP000052). They noted that KCNE1 (176261), the gene encoding MinK, was previously mapped to this site. The 2 genes are arrayed in opposite orientation, separated by 79 kb. Their open reading frames share 34% identity, and both are contained in a single exon. This suggests that the KCNE2 and KCNE1 genes are related through gene duplication and divergent evolution. </p>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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<span class="mim-text-font">
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<p>Roepke et al. (2009) demonstrated that both KCNE2 and KCNQ1 (607542) were expressed and partially colocalized in human and mouse thyroid glands with the basolaterally located Na(+)/I(-) symporter (NIS) that mediates active I(-) transport, the first step in thyroid hormone biosynthesis. Thyroid follicular epithelia in Kcne2 -/- mice showed abnormal architecture, and Kcne2-deficient thyrocytes were flattened and less abundant compared to wildtype. Using the rat thyroid-derived FRTL5 cell line, the authors detected endogenous expression of KCNQ1 and KCNE2 proteins that was upregulated by thyroid-stimulating hormone (TSH; see 188540) or its major downstream effector cAMP in the cell membrane fraction. The authors identified a TSH-stimulated K(+) current in FRTL5 cells that bore the signature linear current-voltage relationship of KCNQ1-KCNE2 channels and was inhibited by a KCNQ1-specific antagonist. Kcne2 -/- pups nursing from Kcne2 -/- dams had an 87% reduction in thyroid I(-) accumulation compared to wildtype pups. Roepke et al. (2009) concluded that the potassium channel subunits KCNQ1 and KCNE2 form a TSH-stimulated constitutively active thyrocyte K(+) channel that is required for normal thyroid hormone biosynthesis. </p><p>Using primary cultures of rat ventricular myocytes, Liu et al. (2014) found that human KCNE2 coimmunoprecipitated with and colocalized with Cav1.2 (CACNA1C; 114205), predominantly at transverse tubules. KCNE2 overexpression decreased Cav1.2 current magnitude and slightly altered its gating and kinetic properties, but it had no effect on Cav1.2 trafficking or membrane localization. Knockdown of endogenous Kcne2 increased Cav1.2-dependent calcium currents. KCNE2 copurified with the N-terminal inhibitory module of Cav1.2 and appeared to increase its inhibitory function. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>To assess the potential role of MiRP1 in disturbances of heart rhythm, Abbott et al. (1999) screened 250 patients (20 with drug-induced arrhythmia and 230 with inherited or sporadic arrhythmias) with no mutations in the known arrhythmia genes KCNQ1 (607542), HERG, SCN5A (600163), and KCNE1. A control population of 1,010 individuals was also evaluated. Three missense mutations associated with long QT syndrome (LQT6; 613693) and ventricular fibrillation were identified in the KCNE2 gene (603796.0001-603796.0003). In addition, in 18 of 1,260 individuals screened, an A-to-G polymorphism at nucleotide 22 produced a thr8-to-ala substitution in the putative extracellular domain of MiRP1. This change was found in 1 patient with quinidine-induced arrhythmia, 1 with inherited or sporadic arrhythmia, and 16 controls. Channels formed with mutant MiRP1 subunits and HERG showed slower activation, faster deactivation, and increased drug sensitivity. One variant (603796.0001), associated with clarithromycin-induced arrhythmia, increases channel blockade by the antibiotic. A mechanism for acquired arrhythmia was revealed in which genetically based reduction in potassium currents remains clinically silent until combined with additional stressors. These findings support a theory for arrhythmogenesis that invokes superimposition of genetic and environmental factors acting in concert to diminish progressively the capacity of cardiac ion channels to terminate each action potential in normal fashion. </p><p>Splawski et al. (2000) screened 262 unrelated individuals with LQT syndrome for mutations in the 5 defined genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) 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>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; see, e.g., 603796.0005). </p>
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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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<span class="mim-text-font">
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<p>In a canine model of ischemic cardiomyopathy, Jiang et al. (2004) observed an increase in the rapid delayed rectifier current, I(Kr), density and a marked reduction in the KCNE2 protein level, although the protein level of KCNH2, the I(Kr) pore-forming alpha subunit, was not altered. Jiang et al. (2004) suggested that in the canine ventricle, KCNE2 may associate with KCNH2 and suppress its current amplitude. In aging rat ventricle, the pacemaker current density was increased, and there was a significant increase in the Kcne2 protein level, whereas changes in the main alpha-subunit (HCN2; 602781) of the pacemaker current channel were not significant. Jiang et al. (2004) suggested that in aging rat ventricle, Kcne2 may associate with Hcn2 and enhance its current amplitude. </p><p>Roepke et al. (2009) performed targeted disruption of Kcne2 in mice and observed impaired thyroid iodide accumulation up to 8-fold, impaired maternal milk ejection, halved mild tetraiodothyronine (T4) content, and halved litter size. Kcne2-deficient mice had hypothyroidism, dwarfism, alopecia, goiter, and cardiac abnormalities including hypertrophy, fibrosis, and reduced fractional shortening. The alopecia, dwarfism, and cardiac abnormalities were alleviated by triiodothyroinine (T3) and T4 administration to pups, by supplementing dams with T4 before and after they gave birth, or by feeding the pups exclusively from Kcne2 +/+ dams; conversely, these symptoms were elicited in Kcne2 +/+ pups by feeding exclusively from Kcne2 -/- dams. </p>
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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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</h4>
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<p />
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LONG QT SYNDROME 6, ACQUIRED, SUSCEPTIBILITY TO</strong>
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<span class="mim-text-font">
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KCNE2, GLN9GLU
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<br />
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SNP: rs16991652,
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gnomAD: rs16991652,
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ClinVar: RCV000006424, RCV000058370, RCV000170567, RCV000245955, RCV000990346, RCV001139400
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<p>In a 76-year-old African American female with drug-induced arrhythmia, Abbott et al. (1999) identified a 25C-G transversion in the KCNE2 gene, resulting in a gln9-to-glu (Q9E) substitution in the putative extracellular domain of MiRP1. This mutation was not identified in 1,010 control individuals. The patient had a history of high blood pressure, noninsulin-dependent diabetes, and stroke. Two baseline electrocardiograms showed QT intervals corrected for heart rate that were borderline prolonged (QTc = 460 ms) (613693). There was concentric left ventricular hypertrophy with mild to moderate diffuse hypokinesis but no ventricular dilatation. The patient was admitted to the hospital with pneumonia and treated with 500 mg of oral clarithromycin every 12 hours. After 2 doses of clarithromycin, electrocardiography showed a QTc of 540 ms. The patient developed torsade de pointes and ventricular fibrillation, requiring defibrillation. At the time, she was hypokalemic with a serum potassium level of 2.8 meq/l. </p><p>Ackerman et al. (2003) identified the Q9E variant as a relatively common polymorphism present in 3% of black individuals. </p>
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<span class="mim-font">
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<strong>.0002 LONG QT SYNDROME 6</strong>
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</span>
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KCNE2, MET54THR
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SNP: rs74315447,
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gnomAD: rs74315447,
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ClinVar: RCV000006425, RCV000058360, RCV000212497, RCV000407848, RCV001841228, RCV002399310, RCV004772828
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<p>In a healthy 38-year-old Caucasian female, Abbott et al. (1999) identified a T-to-C transition at nucleotide 161, resulting in a met54-to-thr substitution in the predicted transmembrane segment of MiRP1. This mutation was not identified in 1,010 control individuals. The patient had had ventricular fibrillation while jogging. Her resuscitation required defibrillation. The results from echocardiography and cardiac catheterization with electrophysiologic studies and right ventricular biopsy were normal. Subsequent electrocardiograms showed an atypical response to exercise with QTc intervals ranging from 390 to 500 ms (613693). </p>
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<span class="mim-font">
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<strong>.0003 LONG QT SYNDROME 6</strong>
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KCNE2, ILE57THR
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SNP: rs74315448,
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gnomAD: rs74315448,
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ClinVar: RCV000006426, RCV000058362, RCV000241603, RCV001139401, RCV001841229, RCV004532298
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<span class="mim-text-font">
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<p>In a healthy 48-year-old Hispanic female with no history of torsade de pointes or ventricular fibrillation, Abbott et al. (1999) identified a T-to-C transition at nucleotide 170, resulting in an ile57-to-thr substitution in the predicted transmembrane segment of MiRP1. The patient's resting electrocardiogram showed a prolonged QT interval (QTc = 470 ms) (613693). </p>
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<span class="mim-font">
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<strong>.0004 ATRIAL FIBRILLATION, FAMILIAL, 4</strong>
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<span class="mim-text-font">
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KCNE2, ARG27CYS
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<br />
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SNP: rs74315449,
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gnomAD: rs74315449,
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ClinVar: RCV000006427, RCV000058377, RCV000157256, RCV000490451, RCV000756281, RCV001080271, RCV004018576
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<p>In a study of 28 unrelated Chinese kindreds with atrial fibrillation (611493), Yang et al. (2004) found that 2 of the probands had an arginine-to-cysteine change at codon 27 (R27C) of KCNE2, the beta-subunit of the KCNQ1-KCNE2 channel responsible for a background potassium current. The amino acid change resulted from a C-to-T transition at nucleotide position 79 from the translation initiation codon. The mutation was present in all affected members in the 2 kindreds and was absent in 462 healthy unrelated Chinese subjects. Similar to KCNQ1 S140G (607542.0032), the KCNE2 R27C mutation had a gain-of-function effect on the KCNQ1-KCNE2 channel. </p><p>By expression in rat ventricular myocytes, Liu et al. (2014) found that human KCNE2 with the R27C substitution was more effective than wildtype in suppressing Cav1.2 (CACNA1C; 114205)-dependent calcium currents. The mutation did not significantly change KCNE2 regulation of voltage-dependent activation and steady-stage voltage-dependent channel inactivation, nor did it alter expression of other calcium channel subunits. </p>
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<h4>
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<span class="mim-font">
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<strong>.0005 LONG QT SYNDROME 3/6, DIGENIC</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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KCNE2, PHE60LEU
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<br />
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SNP: rs16991654,
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gnomAD: rs16991654,
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ClinVar: RCV000006428, RCV000058363
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<span class="mim-text-font">
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<p>In a 1-month-old male infant who had syncope, torsade de pointes, cardiac arrest, and a QTc of 460 ms (613693), Millat et al. (2006) identified biallelic digenic mutations: a 178C-T transition in exon 1 of the KCNE2 gene, resulting in a phe60-to-leu (F60L) substitution, and a missense mutation in the SCN5A gene (R1623Q; 600163.0007). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</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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<ol>
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<li>
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<p class="mim-text-font">
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Abbott, G. W., Sesti, F., Splawsky, I., Buck, M. E., Lehmann, M. H., Timothy, K. W., Keating, M. T., Goldstein, S. A. N.
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<strong>MiRP1 forms I(kr) potassium channels with HERG and is associated with cardiac arrhythmia.</strong>
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Cell 97: 175-187, 1999.
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[PubMed: 10219239]
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[Full Text: https://doi.org/10.1016/s0092-8674(00)80728-x]
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</p>
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</li>
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<p class="mim-text-font">
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Ackerman, M. J., Tester, D. J., Jones, G. S., Will, M. L., Burrow, C. R., Curran, M. E.
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<strong>Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.</strong>
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Mayo Clin. Proc. 78: 1479-1487, 2003.
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[PubMed: 14661677]
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[Full Text: https://doi.org/10.4065/78.12.1479]
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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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Jiang, M., Zhang, M., Tang, D. G., Clemo, H. F., Liu, J., Holwitt, D., Kasirajan, V., Pond, A. L., Wettwer, E., Tseng, G.-N.
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<strong>KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribute to electrical remodeling in diseased hearts.</strong>
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Circulation 109: 1783-1788, 2004.
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[PubMed: 15066947]
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[Full Text: https://doi.org/10.1161/01.CIR.0000124225.43852.50]
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</p>
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<li>
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<p class="mim-text-font">
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Liu, W., Deng, J., Wang, G., Zhang, C., Luo, X., Yan, D., Su, Q., Liu, J.
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<strong>KCNE2 modulates cardiac L-type Ca(2+) channel.</strong>
|
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J. Molec. Cell. Cardiol. 72: 208-218, 2014.
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[PubMed: 24681347]
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[Full Text: https://doi.org/10.1016/j.yjmcc.2014.03.013]
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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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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>
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Clin. Genet. 70: 214-227, 2006.
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[PubMed: 16922724]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2006.00671.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Roepke, T. K., King, E. C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D. J., Carrasco, N., Abbott, G. W.
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<strong>Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis.</strong>
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Nature Med. 15: 1186-1194, 2009.
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[PubMed: 19767733]
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[Full Text: https://doi.org/10.1038/nm.2029]
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</li>
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<li>
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<p class="mim-text-font">
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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.
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<strong>Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2.</strong>
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Circulation 102: 1178-1185, 2000.
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[PubMed: 10973849]
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[Full Text: https://doi.org/10.1161/01.cir.102.10.1178]
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<p class="mim-text-font">
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Tester, D. J., Will, M. L., Haglund, C. M., Ackerman, M. J.
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<strong>Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing.</strong>
|
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Heart Rhythm 2: 507-517, 2005.
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[PubMed: 15840476]
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[Full Text: https://doi.org/10.1016/j.hrthm.2005.01.020]
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<li>
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<p class="mim-text-font">
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Yang, Y., Xia, M., Jin, Q., Bendahhou, S., Shi, J., Chen, Y., Liang, B., Lin, J., Liu, Y., Liu, B., Zhou, Q., Zhang, D., and 11 others.
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<strong>Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.</strong>
|
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Am. J. Hum. Genet. 75: 899-905, 2004.
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[PubMed: 15368194]
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[Full Text: https://doi.org/10.1086/425342]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 02/17/2017<br>Patricia A. Hartz - updated : 02/17/2017<br>Marla J. F. O'Neill - updated : 11/16/2009<br>Marla J. F. O'Neill - updated : 2/12/2008<br>Marla J. F. O'Neill - updated : 11/9/2006<br>Marla J. F. O'Neill - updated : 12/12/2005<br>Victor A. McKusick - updated : 11/1/2004
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 5/11/1999
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mgross : 02/17/2017<br>mgross : 02/17/2017<br>carol : 01/14/2011<br>wwang : 11/17/2009<br>terry : 11/16/2009<br>wwang : 2/26/2008<br>terry : 2/12/2008<br>alopez : 10/3/2007<br>carol : 11/10/2006<br>carol : 11/9/2006<br>wwang : 12/12/2005<br>alopez : 11/4/2004<br>alopez : 11/4/2004<br>terry : 11/1/2004<br>carol : 3/17/2004<br>ckniffin : 2/5/2003<br>carol : 8/17/1999<br>terry : 8/13/1999<br>mgross : 5/12/1999
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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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