5127 lines
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- *176260 - POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 1; KCNA1
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- OMIM
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<p>
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<span class="h4">*176260</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<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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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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 role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/176260">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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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 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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<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=ENSG00000111262;t=ENST00000382545" 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=3736" 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=176260" 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="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=ENSG00000111262;t=ENST00000382545" 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_000217" 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_000217" 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=176260" 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 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=08885&isoform_id=08885_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/KCNA1" 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/186663,75517240,85567378,119395748,119609239,223590092" 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/Q09470" 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=3736" 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=ENSG00000111262;t=ENST00000382545" 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=KCNA1" 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=KCNA1" 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+3736" 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/KCNA1" 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:3736" 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/3736" 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=chr12&hgg_gene=ENST00000382545.5&hgg_start=4909905&hgg_end=4918256&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:6218" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/kcna1" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=176260[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=176260[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/KCNA1/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/ENSG00000111262" 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.gwascentral.org/search?q=KCNA1" 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=KCNA1" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=KCNA1&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/PA30019" 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:6218" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0003380.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:96654" 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/KCNA1#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:96654" 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/3736/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=3736" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00014261;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-110408-15" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=KCNA1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 421182009<br />
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">ICD+</a>
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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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176260
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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, SHAKER-RELATED SUBFAMILY, MEMBER 1; KCNA1
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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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|
MK1, MOUSE, HOMOLOG OF<br />
|
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KV1.1
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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=KCNA1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">KCNA1</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>
|
|
Cytogenetic location: <a href="/geneMap/12/41?start=-3&limit=10&highlight=41">12p13.32</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:4909905-4918256&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'})">12:4,909,905-4,918,256</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
|
<a href="/geneMap/12/41?start=-3&limit=10&highlight=41">
|
|
12p13.32
|
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</a>
|
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</span>
|
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</td>
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<td>
|
|
<span class="mim-font">
|
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Episodic ataxia/myokymia syndrome
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/160120"> 160120 </a>
|
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|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<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">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/176260" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/176260" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
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<p>Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Present in all eukaryotic cells, their diverse functions include maintaining membrane potential, regulating cell volume, and modulating electrical excitability in neurons. The delayed rectifier function of potassium channels allows nerve cells to efficiently repolarize following an action potential. In Drosophila, 4 sequence-related K+ channel genes--Shaker, Shaw, Shab, and Shal--have been identified. Each has been shown to have a human homolog (<a href="#8" class="mim-tip-reference" title="Chandy, K. G., Williams, C. B., Spencer, R. H., Aguilar, B. A., Ghanshani, S., Tempel, B. L., Gutman, G. A. <strong>A family of three mouse potassium channel genes with intronless coding regions.</strong> Science 247: 973-975, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2305265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2305265</a>] [<a href="https://doi.org/10.1126/science.2305265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2305265">Chandy et al., 1990</a>; <a href="#22" class="mim-tip-reference" title="McPherson, J. D., Wasmuth, J. J., Chandy, K. G., Swanson, R., Dethlefs, B., Chandy, G., Wymore, R., Ghanshani, S. <strong>Chromosomal localization of 7 potassium channel genes. (Abstract)</strong> Cytogenet. Cell Genet. 58: 1979, 1991."None>McPherson et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2305265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By PCR of genomic DNA with primers based on regions conserved between Drosophila Shaker and a mouse voltage-gated potassium channel, <a href="#26" class="mim-tip-reference" title="Ramaswami, M., Gautam, M., Kamb, A., Rudy, B., Tanouye, M. A., Mathew, M. K. <strong>Human potassium channel genes: molecular cloning and functional expression.</strong> Molec. Cell. Neurosci. 1: 214-223, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19912772/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19912772</a>] [<a href="https://doi.org/10.1016/1044-7431(90)90004-n" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19912772">Ramaswami et al. (1990)</a> isolated fragments of several related human genes. They used the fragments to screen cDNA libraries and cloned cDNAs encoding several potassium channels that they designated HuKI (KCNA1), HuKII (KCNA4; <a href="/entry/176266">176266</a>), HuKIV (KCNA2; <a href="/entry/176262">176262</a>), and HuKV (KCNA6; <a href="/entry/176257">176257</a>). Like other Shaker-class potassium channels, the predicted 495-amino acid KCNA1 protein contains 6 hydrophobic segments, a positively charged region called S4 between hydrophobic segments 3 and 4, and a leucine zipper. KCNA1 shares 98% amino acid identity with its rat homolog, RCK1. When expressed in Xenopus oocytes, KCNA1, KCNA4, and KCNA2 exhibited different voltage dependence, kinetics, and sensitivity to pharmacologic potassium channel blockers. KCNA1 and KCNA2 were noninactivating channels and resembled delayed rectifiers, while KCNA4 was rapidly inactivating. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19912772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. W., Knoers, N. V., Hoenderop, J. G., Bindels, R. J. <strong>A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia.</strong> J. Clin. Invest. 119: 936-942, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19307729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19307729</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19307729[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI36948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19307729">Glaudemans et al. (2009)</a> demonstrated the presence of Kv1.1 channels in the superficial cortex of mouse kidney. Using serial kidney sections, they showed that Kv1.1 channels colocalize with the epithelial magnesium channel TRPM6 (<a href="/entry/607009">607009</a>) in the distal convoluted tubule. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19307729" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Chandy, K. G., Williams, C. B., Spencer, R. H., Aguilar, B. A., Ghanshani, S., Tempel, B. L., Gutman, G. A. <strong>A family of three mouse potassium channel genes with intronless coding regions.</strong> Science 247: 973-975, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2305265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2305265</a>] [<a href="https://doi.org/10.1126/science.2305265" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2305265">Chandy et al. (1990)</a> demonstrated that 3 closely related potassium channel genes, MK1, MK2, and MK3, are located at separate sites in the genome of the mouse. These genes, encoding subunits of voltage-dependent K+ channels, are homologous to the Drosophila Shaker gene. <a href="#22" class="mim-tip-reference" title="McPherson, J. D., Wasmuth, J. J., Chandy, K. G., Swanson, R., Dethlefs, B., Chandy, G., Wymore, R., Ghanshani, S. <strong>Chromosomal localization of 7 potassium channel genes. (Abstract)</strong> Cytogenet. Cell Genet. 58: 1979, 1991."None>McPherson et al. (1991)</a> mapped member 1 of the Shaker-related subfamily of K+ channel genes (the homolog of MK1) to human chromosome 12 by study of somatic cell hybrids. <a href="#12" class="mim-tip-reference" title="Curran, M. E., Landes, G. M., Keating, M. T. <strong>Molecular cloning, characterization, and genomic localization of a human potassium channel gene.</strong> Genomics 12: 729-737, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1349297/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1349297</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90302-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1349297">Curran et al. (1992)</a> mapped the KCNA1 gene to chromosome 12 by use of human-rodent somatic cell panels and narrowed the localization to the distal short arm by in situ hybridization. Linkage studies had shown a maximum lod score of 2.72 at a recombination fraction of 0.05 between KCNA1 and the von Willebrand locus (VWF; <a href="/entry/613160">613160</a>). Using interspecific backcrosses between Mus musculus and Mus spretus, <a href="#19" class="mim-tip-reference" title="Klocke, R., Roberds, S. L., Tamkun, M. M., Gronemeier, M., Augustin, A., Albrecht, B., Pongs, O., Jockusch, H. <strong>Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal.</strong> Genomics 18: 568-574, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7905852/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7905852</a>] [<a href="https://doi.org/10.1016/s0888-7543(05)80358-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7905852">Klocke et al. (1993)</a> mapped the Kcna1, Kcna5 (<a href="/entry/176267">176267</a>), and Kcna6 genes to mouse chromosome 6, close to the homolog of TPI1 (<a href="/entry/190450">190450</a>), which is located on 12p13 in the human. <a href="#2" class="mim-tip-reference" title="Albrecht, B., Weber, K., Pongs, O. <strong>Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13.</strong> Receptors Channels 3: 213-220, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8821794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8821794</a>]" pmid="8821794">Albrecht et al. (1995)</a> determined that a 300-kb cluster on chromosome 12p13 contains the human KCNA6, KCNA1, and KCNA5 genes arranged in tandem. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7905852+8821794+1349297+2305265" 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="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> injected Xenopus oocytes with cDNAs corresponding to 6 different mutations associated with autosomal dominant myokymia with episodic ataxia, also known as episodic ataxia type 1 (EA1; <a href="/entry/160120">160120</a>). They demonstrated that coassembly of one or more episodic ataxia subunits with a wildtype subunit can alter channel function, giving a dominant-negative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Larsson, H. P., Elinder, F. <strong>A conserved glutamate is important for slow inactivation in K(+) channels.</strong> Neuron 27: 573-583, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055439</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)00067-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055439">Larsson and Elinder (2000)</a> investigated the role of conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). <a href="#20" class="mim-tip-reference" title="Larsson, H. P., Elinder, F. <strong>A conserved glutamate is important for slow inactivation in K(+) channels.</strong> Neuron 27: 573-583, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055439</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)00067-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11055439">Larsson and Elinder (2000)</a> could lock the channel in 2 different conformations by disulfide-linking 418C to 2 different cysteines, introduced in the Pore-S6 (P-S6) loop. Their results suggested that E418 normally stabilizes the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055439" 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="#31" class="mim-tip-reference" title="Zhou, M., Morais-Cabral, J. H., Mann, S., MacKinnon, R. <strong>Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.</strong> Nature 411: 657-661, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11395760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11395760</a>] [<a href="https://doi.org/10.1038/35079500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11395760">Zhou et al. (2001)</a> showed that the central cavity and inner pore of the Shaker type potassium channel form the receptor site for both the inactivation gate and small-molecule inhibitors. <a href="#31" class="mim-tip-reference" title="Zhou, M., Morais-Cabral, J. H., Mann, S., MacKinnon, R. <strong>Potassium channel receptor site for the inactivation gate and quaternary amine inhibitors.</strong> Nature 411: 657-661, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11395760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11395760</a>] [<a href="https://doi.org/10.1038/35079500" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11395760">Zhou et al. (2001)</a> proposed that inactivation occurs by a sequential reaction in which the gate binds initially to the cytoplasmic channel surface and then enters the pore as an extended peptide. This mechanism accounts for the functional properties of potassium channel inactivation and indicates that the cavity may be the site of action for certain drugs that alter cation channel function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11395760" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Gu, C., Jan, Y. N., Jan, L. Y. <strong>A conserved domain in axonal targeting of Kv1 (Shaker) voltage-gated potassium channels.</strong> Science 301: 646-649, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12893943/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12893943</a>] [<a href="https://doi.org/10.1126/science.1086998" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12893943">Gu et al. (2003)</a> found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 (<a href="/entry/186940">186940</a>) or dendritic transferrin receptor (TFR; <a href="/entry/190010">190010</a>), T1 domains from Kv1.1, Kv1.2, and Kv1.4 promoted their axonal surface expression. Moreover, mutations in the T1 domain of Kv1.2 that eliminated association with Kv-beta-2 (<a href="/entry/601142">601142</a>) compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. The authors concluded that proper association of Kv-beta with the Kv1 T1 domain is essential for axonal targeting. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12893943" 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>The combinatorial association between distinct alpha and beta subunits is thought to determine whether Kv channels function as noninactivating delayed rectifiers or as rapidly inactivating A-type channels. <a href="#24" class="mim-tip-reference" title="Oliver, D., Lien, C.-C., Soom, M., Baukrowitz, T., Jonas, P., Fakler, B. <strong>Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.</strong> Science 304: 265-270, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15031437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15031437</a>] [<a href="https://doi.org/10.1126/science.1094113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15031437">Oliver et al. (2004)</a> showed that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides, particularly phosphatidylinositol-4,5-bisphosphate (PIP2), remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. <a href="#24" class="mim-tip-reference" title="Oliver, D., Lien, C.-C., Soom, M., Baukrowitz, T., Jonas, P., Fakler, B. <strong>Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.</strong> Science 304: 265-270, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15031437/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15031437</a>] [<a href="https://doi.org/10.1126/science.1094113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15031437">Oliver et al. (2004)</a> concluded that the bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15031437" 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="#25" class="mim-tip-reference" title="Raab-Graham, K. F., Haddick, P. C. G., Jan, Y. N., Jan, L. Y. <strong>Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.</strong> Science 314: 144-148, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17023663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17023663</a>] [<a href="https://doi.org/10.1126/science.1131693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17023663">Raab-Graham et al. (2006)</a> found that the mTOR (<a href="/entry/601231">601231</a>) inhibitor rapamycin increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photoconvertible fluorescence protein Kaede as a reporter for local synthesis, <a href="#25" class="mim-tip-reference" title="Raab-Graham, K. F., Haddick, P. C. G., Jan, Y. N., Jan, L. Y. <strong>Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.</strong> Science 314: 144-148, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17023663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17023663</a>] [<a href="https://doi.org/10.1126/science.1131693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17023663">Raab-Graham et al. (2006)</a> observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-D-aspartate (NMDA) glutamate receptor (see <a href="/entry/138251">138251</a>). Thus, <a href="#25" class="mim-tip-reference" title="Raab-Graham, K. F., Haddick, P. C. G., Jan, Y. N., Jan, L. Y. <strong>Activity- and mTOR-dependent suppression of Kv1.1 channel mRNA translation in dendrites.</strong> Science 314: 144-148, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17023663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17023663</a>] [<a href="https://doi.org/10.1126/science.1131693" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17023663">Raab-Graham et al. (2006)</a> concluded that synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17023663" 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="#27" class="mim-tip-reference" title="Sanders, S. S., Hernandez, L. M., Soh, H., Karnam, S., Walikonis, R. S., Tzingounis, A. V., Thomas, G. M. <strong>The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment.</strong> eLife 9: e56058, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33185190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33185190</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33185190[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/10.7554/eLife.56058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33185190">Sanders et al. (2020)</a> found that developmental expression profiles of the palmitoyl acyltranserase (PAT) Zdhhc14 (<a href="/entry/619295">619295</a>) in rat hippocampal neurons were almost identical to those of Kv1-type potassium channels. Zdhhc14 functioned as a major neuronal PAT for Kv1.1, Kv1.2, and Kv1.4 in neurons and was required for axon initial segment (AIS) targeting of these channel subunits. As Zdhhc14 localized predominantly to Golgi, palmitoylation of Kv1 channel subunits took place in Golgi apparatus of hippocampal neurons, rather than directly at the AIS. Additionally, knockout analysis revealed that loss of Zdhhc14 reduced outward currents, which were likely mediated by voltage-dependent potassium channels, and increased action potential firing in rat hippocampal neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33185190" 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="#13" class="mim-tip-reference" title="Doyle, D. A., Morais-Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., MacKinnon, R. <strong>The structure of the potassium channel: molecular basis of K+ conduction and selectivity.</strong> Science 280: 69-77, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9525859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9525859</a>] [<a href="https://doi.org/10.1126/science.280.5360.69" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9525859">Doyle et al. (1998)</a> determined the atomic structure of the Streptomyces lividans KcsA potassium channel pore by means of x-ray crystallography. However, serious doubts were raised concerning whether the prokaryotic potassium channel pore actually represents those of eukaryotes. <a href="#21" class="mim-tip-reference" title="Lu, Z., Klem, A. M., Ramu, Y. <strong>Ion conduction pore is conserved among potassium channels.</strong> Nature 413: 809-813, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11677598/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11677598</a>] [<a href="https://doi.org/10.1038/35101535" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11677598">Lu et al. (2001)</a> addressed this issue by substituting the prokaryotic potassium channel pore into eukaryotic voltage-gated and inward-rectifier (see <a href="/entry/600681">600681</a>) potassium channels. The resulting chimeras retained the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among potassium channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9525859+11677598" 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="#32" class="mim-tip-reference" title="Zhou, Y., Morais-Cabral, J. H., Kaufman, A., MacKinnon, R. <strong>Chemistry of ion coordination and hydration revealed by a K(+) channel-Fab complex at 2.0 angstrom resolution.</strong> Nature 414: 43-48, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11689936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11689936</a>] [<a href="https://doi.org/10.1038/35102009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11689936">Zhou et al. (2001)</a> determined the chemistry of ion coordination and hydration of the KcsA potassium channel pore at 2-angstrom resolution. <a href="#23" class="mim-tip-reference" title="Morais-Cabral, J. H., Zhou, Y., MacKinnon, R. <strong>Energetic optimization of ion conduction rate by the K(+) selectivity filter.</strong> Nature 414: 37-42, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11689935/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11689935</a>] [<a href="https://doi.org/10.1038/35102000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11689935">Morais-Cabral et al. (2001)</a> further determined the energetic optimization by the potassium selectivity filter. <a href="#4" class="mim-tip-reference" title="Berneche, S., Roux, B. <strong>Energetics of ion conduction through the K(+) channel.</strong> Nature 414: 73-77, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11689945/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11689945</a>] [<a href="https://doi.org/10.1038/35102067" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11689945">Berneche and Roux (2001)</a> performed molecular dynamics free energy simulations on the basis of the x-ray structure of the KcsA potassium channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11689945+11689935+11689936" 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="#17" class="mim-tip-reference" title="Gubitosi-Klug, R. A., Mancuso, D. J., Gross, R. W. <strong>The human Kv1.1 channel is palmitoylated, modulating voltage sensing: identification of a palmitoylation consensus sequence.</strong> Proc. Nat. Acad. Sci. 102: 5964-5968, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15837928/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15837928</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15837928[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0501999102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15837928">Gubitosi-Klug et al. (2005)</a> determined that human Kv1.1 is palmitoylated at cys243. This palmitoylation modulated voltage sensing by Kv1.1 and facilitated its dynamic interactions with surrounding lipids during voltage-induced conformational changes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15837928" 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 the Shaker potassium channel, mutation of the first charged residue of the S4 helix to a smaller uncharged residue makes the voltage-sensing domain permeable to ions ('omega current') in the resting conformation ('S4 down'). <a href="#30" class="mim-tip-reference" title="Tombola, F., Pathak, M. M., Gorostiza, P., Isacoff, E. Y. <strong>The twisted ion-permeation pathway of a resting voltage-sensing domain.</strong> Nature 445: 546-549, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17187057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17187057</a>] [<a href="https://doi.org/10.1038/nature05396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17187057">Tombola et al. (2007)</a> performed a structure-guided perturbation analysis of the omega conductance to map its voltage-sensing domain permeation pathway. <a href="#30" class="mim-tip-reference" title="Tombola, F., Pathak, M. M., Gorostiza, P., Isacoff, E. Y. <strong>The twisted ion-permeation pathway of a resting voltage-sensing domain.</strong> Nature 445: 546-549, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17187057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17187057</a>] [<a href="https://doi.org/10.1038/nature05396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17187057">Tombola et al. (2007)</a> found that there are 4 omega pores per channel, which is consistent with 1 conduction path per voltage-sensing domain. Permeating ions from the extracellular medium enter the voltage-sensing domain at its peripheral junction with the pore domain, and then plunge into the core of the voltage-sending domain in a curved conduction pathway. <a href="#30" class="mim-tip-reference" title="Tombola, F., Pathak, M. M., Gorostiza, P., Isacoff, E. Y. <strong>The twisted ion-permeation pathway of a resting voltage-sensing domain.</strong> Nature 445: 546-549, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17187057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17187057</a>] [<a href="https://doi.org/10.1038/nature05396" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17187057">Tombola et al. (2007)</a> concluded that their results provided a model of the resting conformation of the voltage-sensing domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17187057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="Cuello, L. G., Jogini, V., Cortes, D. M., Pan, A. C., Gagnon, D. G., Dalmas, O., Cordero-Morales, J. F., Chakrapani, S., Roux, B., Perozo, E. <strong>Structural basis for the coupling between activation and inactivation gates in K+ channels.</strong> Nature 466: 272-275, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20613845/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20613845</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20613845[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/nature09136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20613845">Cuello et al. (2010)</a> identified the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the nonconductive C-type inactivated state of the KcsA potassium channel. Analysis of a series of KcsA open structures suggested that, as a consequence of the hinge bending and rotation of the transmembrane-2 helix, the aromatic ring of phe103 tilts toward thr74 and thr75 in the pore-helix and toward ile100 in the neighboring subunit. This allows the network of hydrogen bonds among trp67, glu71, and asp80 to destabilize the selectivity filter, allowing entry to its nonconductive conformation. Mutations at position 103 had a size-dependent effect on gating kinetics: small side-chain substitutions F103A and F103C severely impaired inactivation kinetics, whereas larger side-chain substitutions, such as F103W, had more subtle effects. This finding suggested that the allosteric coupling between the inner helical bundle and the selectivity filter might rely on straightforward mechanical deformation propagated through a network of steric contacts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20613845" 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="#7" class="mim-tip-reference" title="Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M. <strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong> Nature Genet. 8: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842011</a>] [<a href="https://doi.org/10.1038/ng1094-136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842011">Browne et al. (1994)</a> performed mutation analysis of the KCNA1 coding region in 4 families with myokymia (rippling of muscles) with episodic ataxia (<a href="/entry/160120">160120</a>). They found 4 different missense mutations present in heterozygous state (<a href="#0001">176260.0001</a>-<a href="#0004">176260.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7842011" 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>For a comprehensive review of episodic ataxia type 1 and its causative mutations, see <a href="#5" class="mim-tip-reference" title="Brandt, T., Strupp, M. <strong>Episodic ataxia type 1 and 2 (familial periodic ataxia/vertigo).</strong> Audiol. Neurootol. 2: 373-383, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9390841/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9390841</a>] [<a href="https://doi.org/10.1159/000259262" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9390841">Brandt and Strupp (1997)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9390841" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 5-generation Brazilian family segregating autosomal dominant hypomagnesemia and myokymia mapping to chromosome 12q, <a href="#15" class="mim-tip-reference" title="Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. W., Knoers, N. V., Hoenderop, J. G., Bindels, R. J. <strong>A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia.</strong> J. Clin. Invest. 119: 936-942, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19307729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19307729</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19307729[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI36948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19307729">Glaudemans et al. (2009)</a> identified a heterozygous missense mutation in the KCNA1 gene (N255D; <a href="/entry/176250#0015">176250.0015</a>) that segregated with disease and was not found in 100 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19307729" 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="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> identified 4 families with different neurologic phenotypes, including seizures and myokymia, isolated myokymia, severe drug-resistant EA1, and typical drug-responsive EA1, each of which carried a different heterozygous mutation in the KCNA1 gene (<a href="#0008">176260.0008</a>, <a href="#0010">176260.0010</a>-<a href="#0012">176260.0012</a>). Functional expression studies of the mutations expressed in Xenopus oocytes revealed that the mutations impaired the channel function via different mechanisms, and <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> concluded that there may be a genotype/phenotype correlation (see each allelic variant for details). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11026449" 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="#29" class="mim-tip-reference" title="Smart, S. L., Lopantsev, V., Zhang, C. L., Robbins, C. A., Wang, H., Chiu, S. Y., Schwartzkroin, P. A., Messing, A., Tempel, B. L. <strong>Deletion of the K(V)1.1 potassium channel causes epilepsy in mice.</strong> Neuron 20: 809-819, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9581771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9581771</a>] [<a href="https://doi.org/10.1016/s0896-6273(00)81018-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9581771">Smart et al. (1998)</a> found that Kcna1-null mice displayed frequent spontaneous seizures and that these seizures correlated on the cellular level with alterations in hippocampal excitability and nerve conduction. The intrinsic passive properties of CA3 pyramidal cells in hippocampal slices from homozygous Kcna1-null mice were normal; however, antidromic action potentials were recruited at lower thresholds. In a subset of slices, mossy fiber stimulation triggered long-latency epileptiform burst discharges. Axonal action potential conduction was also altered in the sciatic nerve. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9581771" 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 homologous recombination, <a href="#18" class="mim-tip-reference" title="Herson, P. S., Virk, M., Rustay, N. R., Bond, C. T., Crabbe, J. C., Adelman, J. P., Maylie, J. <strong>A mouse model of episodic ataxia type-1.</strong> Nature Neurosci. 6: 378-383, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12612586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12612586</a>] [<a href="https://doi.org/10.1038/nn1025" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12612586">Herson et al. (2003)</a> introduced the Kcna1 val408-to-ala mutation (V408A; <a href="#0001">176260.0001</a>) into mice. In contrast to Kcna1-null mice, homozygous V408A mice died after embryonic day 3, consistent with V408A being a homozygous lethal allele. V408A heterozygous mice showed stress-induced loss of motor coordination that was ameliorated by acetazolamide, similar to patients with EA1. Cerebellar Purkinje cells from V408A heterozygous mice showed a greater frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents than did wildtype. The authors noted that Kcna1 is localized to GABAergic interneurons in the cerebellum, suggesting that it may be important for regulating GABA release, and that mutations in the gene may alter excitability in the cerebellum, leading to clinical symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12612586" 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>Sleep in fruit flies shares many similarities with mammalian sleep; flies sleep for many hours (9 to 15 hours) and, when sleep deprived, show sleep rebound and performance impairments. To determine which genes underlie short sleeping, <a href="#10" class="mim-tip-reference" title="Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G. <strong>Reduced sleep in Drosophila Shaker mutants.</strong> Nature 434: 1087-1092, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15858564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15858564</a>] [<a href="https://doi.org/10.1038/nature03486" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15858564">Cirelli et al. (2005)</a> performed mutagenesis in Drosophila melanogaster. By screening 9,000 mutant lines, <a href="#10" class="mim-tip-reference" title="Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G. <strong>Reduced sleep in Drosophila Shaker mutants.</strong> Nature 434: 1087-1092, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15858564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15858564</a>] [<a href="https://doi.org/10.1038/nature03486" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15858564">Cirelli et al. (2005)</a> found 'minisleep' (mns), a line that sleeps for one-third of the wildtype amount. Mns flies perform normally in a number of tasks, have preserved sleep homeostasis, and are not impaired by sleep deprivation. <a href="#10" class="mim-tip-reference" title="Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G. <strong>Reduced sleep in Drosophila Shaker mutants.</strong> Nature 434: 1087-1092, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15858564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15858564</a>] [<a href="https://doi.org/10.1038/nature03486" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15858564">Cirelli et al. (2005)</a> showed that mns flies carry a point mutation in Shaker, a C-to-T transition in exon 9 resulting in a threonine-to-isoleucine substitution. This substitution of a polar amino acid with a highly hydrophobic one occurs at the extracellular end of S1. The mutated threonine residue is extremely well conserved from Aplysia to human. After crossing out genetic modifiers accumulated over many generations, other Shaker null alleles also caused a short-sleeping phenotype and failed to complement the mns phenotype. <a href="#10" class="mim-tip-reference" title="Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G. <strong>Reduced sleep in Drosophila Shaker mutants.</strong> Nature 434: 1087-1092, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15858564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15858564</a>] [<a href="https://doi.org/10.1038/nature03486" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15858564">Cirelli et al. (2005)</a> found that short-sleeping Shaker flies have a reduced life span. <a href="#10" class="mim-tip-reference" title="Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G. <strong>Reduced sleep in Drosophila Shaker mutants.</strong> Nature 434: 1087-1092, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15858564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15858564</a>] [<a href="https://doi.org/10.1038/nature03486" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15858564">Cirelli et al. (2005)</a> concluded that Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15858564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Beraud, E., Viola, A., Regaya, I., Confort-Gouny, S., Siaud, P., Ibarrola, D., Le Fur, Y., Barbaria, J., Pellissier, J.-F., Sabatier, J.-M., Medina, I., Cozzone, P. J. <strong>Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.</strong> Ann. Neurol. 60: 586-596, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044011</a>] [<a href="https://doi.org/10.1002/ana.21007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17044011">Beraud et al. (2006)</a> demonstrated that intracerebroventricular infusion of a specific Kcna1 blocker, BgK-F6A, greatly reduced neurologic deficits in rats with experimental autoimmune encephalitis, an animal model of multiple sclerosis (MS; <a href="/entry/126200">126200</a>). BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in cultured rat hippocampal cells without affecting T-cell activation. Treated rats showed decreased ventriculomegaly, decreased cerebral injury, and preservation of brain bioenergetics compared to control rats. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17044011" 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">rs104894352 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894352;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894352" 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=rs104894352" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; <a href="/entry/160120">160120</a>), <a href="#7" class="mim-tip-reference" title="Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M. <strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong> Nature Genet. 8: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842011</a>] [<a href="https://doi.org/10.1038/ng1094-136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842011">Browne et al. (1994)</a> demonstrated heterozygosity for a val408-to-ala mutation in the KCNA1 gene. Valine-408 resides in the C-terminal domain of the sixth transmembrane region of KCNA1, which compromises the inner portion of the pore. By recording from Xenopus oocytes injected with the mutant transcript, <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> demonstrated that V408A channels have voltage dependence similar to that of wildtype channels but with faster kinetics and increased C-type inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7842011+8845167" 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 affected members of a family with the episodic ataxia/myokymia syndrome (EA1; <a href="/entry/160120">160120</a>), <a href="#7" class="mim-tip-reference" title="Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M. <strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong> Nature Genet. 8: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842011</a>] [<a href="https://doi.org/10.1038/ng1094-136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842011">Browne et al. (1994)</a> demonstrated heterozygosity for an arg239-to-ser mutation in the KCNA1 gene. Residue 239 is in the intracytoplasmic loop between the putative first and second transmembrane domains. <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> made voltage recordings of Xenopus oocytes microinjected with the mutated transcript and found that homomeric channels with a serine substitution at this site are not functional. Unlike other residues that are conserved among the KV1 family members but vary in other delayed rectifier families, all rectifier potassium subunits contain arginine at a position analogous to 239, suggesting to the authors a crucial role for this position. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7842011+8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, VAL174PHE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894349 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894349;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894349" 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=rs104894349" 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=RCV000014426 OR RCV001265691" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014426, RCV001265691" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014426...</a>
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; <a href="/entry/160120">160120</a>), <a href="#7" class="mim-tip-reference" title="Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M. <strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong> Nature Genet. 8: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842011</a>] [<a href="https://doi.org/10.1038/ng1094-136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842011">Browne et al. (1994)</a> demonstrated heterozygosity for a val174-to-phe mutation in the KCNA1 gene. Residue 174 lies within the first putative transmembrane domain. <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> recorded from Xenopus oocytes microinjected with the mutant transcript and found that subunits with a phenylalanine substitution at this residue do not produce a functional homomeric channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7842011+8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0004" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0004 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, PHE249ILE
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894356 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894356;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894356" 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=rs104894356" 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=RCV000014427" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014427" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014427</a>
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<span class="mim-text-font">
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; <a href="/entry/160120">160120</a>), <a href="#7" class="mim-tip-reference" title="Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M. <strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong> Nature Genet. 8: 136-140, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7842011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7842011</a>] [<a href="https://doi.org/10.1038/ng1094-136" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7842011">Browne et al. (1994)</a> demonstrated heterozygosity for a phe249-to-ile mutation in the KCNA1 gene. Residue 249 lies in the cytoplasmic loop between the first and second putative transmembrane domain, a region conserved in all delayed rectifier potassium channels. <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> recorded from Xenopus oocytes microinjected with the mutated transcript and found that subunits with an isoleucine substitution at residue 249 did not produce a functional homomeric channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7842011+8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0005 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, PHE184CYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894357 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894357;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894357" 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=rs104894357" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014428" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014428" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014428</a>
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<span class="mim-text-font">
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<p><a href="#6" class="mim-tip-reference" title="Browne, D. L., Brunt, E. R. P., Griggs, R. C., Nutt, J. G., Gancher, S. T., Smith, E. A., Litt, M. <strong>Identification of two new KCNA1 mutations in episodic ataxia/myokymia families.</strong> Hum. Molec. Genet. 4: 1671-1672, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541859</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541859">Browne et al. (1995)</a> reported mutation analysis in a family with type 1 episodic ataxia (EA1; <a href="/entry/160120">160120</a>). Affected individuals were found to be heterozygous for a T-to-G transversion at position 551 of the KCNA1 gene, resulting in a substitution of cysteine for phenylalanine at codon 184. Residue 184 is in the C-terminal domain of the first transmembrane region of KCNA1 close to the extracellular border of the membrane. It is a conserved residue in all Shaker family members. By recording from Xenopus oocytes microinjected with the mutant transcript <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> demonstrated that substitution of cysteine at this residue alters voltage dependence and kinetics of activation though not of C-type inactivation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8541859+8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0006 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, GLU325ASP
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894353;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894353" 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=rs104894353" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014429" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014429" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014429</a>
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<p><a href="#6" class="mim-tip-reference" title="Browne, D. L., Brunt, E. R. P., Griggs, R. C., Nutt, J. G., Gancher, S. T., Smith, E. A., Litt, M. <strong>Identification of two new KCNA1 mutations in episodic ataxia/myokymia families.</strong> Hum. Molec. Genet. 4: 1671-1672, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541859/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541859</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541859">Browne et al. (1995)</a> reported mutation analysis in a family with type 1 episodic ataxia (EA1; <a href="/entry/160120">160120</a>). Affected individuals were found to be heterozygous for a G-to-C transversion at position 975 of the KCNA1 gene, resulting in a substitution of aspartic acid for glutamic acid at codon 325. This residue is conserved throughout evolution, from Drosophila to Homo sapiens. Residue 325 is at the interface of the fifth transmembrane region in KCNA1 in the cytoplasm, a region that forms part of the internal lining of the pore. This residue is completely conserved among delayed rectifier subunits. By recording from Xenopus oocytes microinjected with cDNA from a human gene with a conservative asparagine substitution at this residue, <a href="#1" class="mim-tip-reference" title="Adelman, J. P., Bond, C. T., Pessia, M., Maylie, J. <strong>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong> Neuron 15: 1449-1454, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>] [<a href="https://doi.org/10.1016/0896-6273(95)90022-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8845167">Adelman et al. (1995)</a> found that this mutation results in nonfunctional homomeric channels, even though the same alteration in the Shaker channel from Drosophila results in functional channels with reduced unit conductance and open probability. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8541859+8845167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0007 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, THR226ALA
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs104894354 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894354;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894354" 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=rs104894354" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014430 OR RCV003221784" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014430, RCV003221784" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014430...</a>
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<p><a href="#28" class="mim-tip-reference" title="Scheffer, H., Brunt, E. R. P., Mol, G. J. J., van der Vlies, P., Stulp, R. P., Verlind, E., Mantel, G., Averyanov, Y. N., Hofstra, R. M. W., Buys, C. H. C. M. <strong>Three novel KCNA1 mutations in episodic ataxia type 1 families.</strong> Hum. Genet. 102: 464-466, 1998. Note: Erratum: Hum. Genet. 102: 713 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600245</a>] [<a href="https://doi.org/10.1007/s004390050722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600245">Scheffer et al. (1998)</a> described a family with multiple affected individuals clinically diagnosed as having episodic ataxia (EA1; <a href="/entry/160120">160120</a>). Those affected had an A-to-G transversion at position 676 of the KCNA1 gene, resulting in a thr-to-ala substitution at codon 226. Clinical details of the family were not presented. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600245" 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>.0008 EPISODIC ATAXIA, TYPE 1</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">rs104894355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894355;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs104894355" 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=rs104894355" 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=RCV000014431 OR RCV002509157" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014431, RCV002509157" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014431...</a>
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<p>In affected members of a family with episodic ataxia (EA1; <a href="/entry/160120">160120</a>), <a href="#28" class="mim-tip-reference" title="Scheffer, H., Brunt, E. R. P., Mol, G. J. J., van der Vlies, P., Stulp, R. P., Verlind, E., Mantel, G., Averyanov, Y. N., Hofstra, R. M. W., Buys, C. H. C. M. <strong>Three novel KCNA1 mutations in episodic ataxia type 1 families.</strong> Hum. Genet. 102: 464-466, 1998. Note: Erratum: Hum. Genet. 102: 713 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600245</a>] [<a href="https://doi.org/10.1007/s004390050722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600245">Scheffer et al. (1998)</a> identified a G-to-A transition at position 1210 of the KCNA1 gene, leading to a val-to-ile substitution at codon 404. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a large British family with 16 members over 4 generations affected with type 1 episodic ataxia, <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> identified the V404I mutation in the KCNA1 gene. Functional expression studies of the mutation in Xenopus oocytes yielded current amplitudes that were not different from wildtype. Coexpression with wildtype partially corrected the alterations in activation parameters. The authors noted that the phenotype was relatively typical and responded well to treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11026449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0009" class="mim-anchor"></a>
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<strong>.0009 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, ILE177ASN
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs267607195 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267607195;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs267607195" 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=rs267607195" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014432</a>
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<span class="mim-text-font">
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<p>In affected members of a family with episodic ataxia (EA1; <a href="/entry/160120">160120</a>), <a href="#28" class="mim-tip-reference" title="Scheffer, H., Brunt, E. R. P., Mol, G. J. J., van der Vlies, P., Stulp, R. P., Verlind, E., Mantel, G., Averyanov, Y. N., Hofstra, R. M. W., Buys, C. H. C. M. <strong>Three novel KCNA1 mutations in episodic ataxia type 1 families.</strong> Hum. Genet. 102: 464-466, 1998. Note: Erratum: Hum. Genet. 102: 713 only, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9600245/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9600245</a>] [<a href="https://doi.org/10.1007/s004390050722" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9600245">Scheffer et al. (1998)</a> identified heterozygosity for a T-to-A transversion at position 530 of the KCNA1 gene, leading to an ile-to-asn substitution at codon 177 (I177N). The original description of the mutation, ILE176ARG (527T-A), was corrected in an erratum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9600245" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0010" class="mim-anchor"></a>
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<h4>
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<strong>.0010 MYOKYMIA 1</strong>
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</h4>
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KCNA1, ALA242PRO
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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> rs28933381 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933381;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/rs28933381?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=rs28933381" 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=rs28933381" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014433 OR RCV000441803" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014433, RCV000441803" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014433...</a>
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<p>In a mother and son with myokymia (see <a href="/entry/160120">160120</a>) and seizures, but not ataxic episodes, <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> identified a heterozygous 724G-C point mutation in the KCNA1 gene, resulting in an ala242-to-pro substitution (A242P) in the second transmembrane segment of the channel. The proband's deceased father was reported to have had seizures and myokymia. Functional studies of the mutation expressed in Xenopus oocytes showed significantly reduced mean peak current amplitudes compared to wildtype (10%). Mutant and wildtype expression together was consistent with a loss-of-function effect of the mutation. Importantly, the A242P mutation still resulted in a correctly translated and functional potassium channel. <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> stressed that the observations in this family are the first demonstration that a defect in this potassium channel may associate with epilepsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11026449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<strong>.0011 MYOKYMIA 1</strong>
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KCNA1, PRO244HIS
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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> rs28933382 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933382;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/rs28933382?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=rs28933382" 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=rs28933382" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000014434" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014434" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014434</a>
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<p>In a boy and his father with isolated myokymia (see <a href="/entry/160120">160120</a>) and leg muscle hypertrophy, but without ataxic episodes, <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> identified a heterozygous 731C-A point mutation in the KCNA1 gene, resulting in a pro244-to-his substitution (P244H) in the intracellular loop between transmembrane segments 2 and 3. Functional studies of current amplitudes in Xenopus oocytes showed no difference between the mutation compared to wildtype. Although coexpression experiments with wildtype RNA yielded a peak current amplitude that was 200% of wildtype alone, coexpression of the mutant and wildtype genes had only a small effect on current activation parameters, which the authors suggested may be reflected in the relatively simple phenotype of myokymia without ataxia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11026449" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0012" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>.0012 EPISODIC ATAXIA, TYPE 1</strong>
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KCNA1, ARG417TER
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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> rs104894358 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs104894358;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/rs104894358?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=rs104894358" 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=rs104894358" 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=RCV000014435" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014435" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014435</a>
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<p>In a patient with drug-resistant type 1 episodic ataxia (EA1; <a href="/entry/160120">160120</a>), <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> identified a 1249C-T mutation in the KCNA1 gene, resulting in a premature stop codon at amino acid 417 (R417X). This was predicted to result in the loss of nearly 80 amino acids at the intracellular C terminus. Family studies were consistent with the mutation being a de novo event. Functional expression studies of the mutation in Xenopus oocytes showed a significantly reduced current amplitude compared to wildtype (2%). Coexpression with wildtype showed a dominant-negative effect of the R417X mutation as well as a profound alteration in kinetic parameters. <a href="#14" class="mim-tip-reference" title="Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A. <strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong> Ann. Neurol. 48: 647-656, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11026449/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11026449</a>]" pmid="11026449">Eunson et al. (2000)</a> suggested that the severe drug-resistant phenotype may be related to the functional consequences of a truncated protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11026449" 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>.0013 EPISODIC ATAXIA, TYPE 1</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">rs28933383 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933383;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933383" 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=rs28933383" 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=RCV000014436 OR RCV001785451" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014436, RCV001785451" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014436...</a>
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<p><a href="#33" class="mim-tip-reference" title="Zuberi, S. M., Eunson, L. H., Spauschus, A., De Silva, R., Tolmie, J., Wood, N. W., McWilliam, R. C., Stephenson, J. B. P., Kullmann, D. M., Hanna, M. G. <strong>A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy.</strong> Brain 122: 817-825, 1999. Note: Erratum: Brain 130: 879 only, 2007. Erratum: Brain 133: 1569 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10355668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10355668</a>] [<a href="https://doi.org/10.1093/brain/122.5.817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10355668">Zuberi et al. (1999)</a> reported a Scottish family with episodic ataxia type 1 (EA1; <a href="/entry/160120">160120</a>) in which a 677C-G transversion in the KCNA1 gene resulted in a thr226-to-arg amino acid substitution at a highly conserved position in the second transmembrane segment of the channel. Of 5 affected individuals over 3 generations, 2 had partial epilepsy in addition to EA1. A review of previously reported EA1 families showed an overrepresentation of epilepsy in family members with EA1. The initial presentation was postural abnormalities in all except 1 case. The fists are clenched, knees flexed, and feet held in plantar flexion as a result of continual muscle fiber activity. A misdiagnosis of familial arthrogryposis is sometimes made. Inguinal hernias were thought to be secondary to myokymia of the abdominal wall musculature. Functional studies by <a href="#33" class="mim-tip-reference" title="Zuberi, S. M., Eunson, L. H., Spauschus, A., De Silva, R., Tolmie, J., Wood, N. W., McWilliam, R. C., Stephenson, J. B. P., Kullmann, D. M., Hanna, M. G. <strong>A novel mutation in the human voltage-gated potassium channel gene (Kv1.1) associates with episodic ataxia type 1 and sometimes with partial epilepsy.</strong> Brain 122: 817-825, 1999. Note: Erratum: Brain 130: 879 only, 2007. Erratum: Brain 133: 1569 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10355668/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10355668</a>] [<a href="https://doi.org/10.1093/brain/122.5.817" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10355668">Zuberi et al. (1999)</a> showed that mutant subunits exhibited a dominant-negative effect on potassium channel function and would be predicted to impair neuronal repolarization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10355668" 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>.0014 MYOKYMIA 1</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">rs28933383 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs28933383;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs28933383" 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=rs28933383" 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=RCV000014437" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014437" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014437</a>
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<p>In 4 affected members of a family with isolated myokymia (see <a href="/entry/160120">160120</a>) without epilepsy or episodic ataxia, <a href="#9" class="mim-tip-reference" title="Chen, H., von Hehn, C., Kaczmarek, L. K., Ment, L. R., Pober, B. R., Hisama, F. M. <strong>Functional analysis of a novel potassium channel (KCNA1) mutation in hereditary myokymia.</strong> Neurogenetics 8: 131-135, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17136396/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17136396</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17136396[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/10.1007/s10048-006-0071-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17136396">Chen et al. (2007)</a> identified a heterozygous 676C-A transversion in the KCNA1 gene, resulting in a thr226-to-lys (T226K) substitution in the second transmembrane domain. Electrophysiologic studies in transfected Xenopus oocytes showed that the T226K protein resulted in reduced efflux of potassium ions during depolarization, which likely results in increased muscle cell activity. Coexpression studies of the mutant protein with the wildtype protein produced significantly reduced currents, suggesting a severe effect of the mutation. The phenotype in this family was unusual with extensor plantar responses suggestive of corticospinal tract involvement and worsening of symptoms with febrile illness or anesthesia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17136396" 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>.0015 MYOKYMIA 1 WITH HYPOMAGNESEMIA</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">rs121918067 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121918067;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121918067" 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=rs121918067" 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=RCV000014438" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014438" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014438</a>
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<p>In affected members of a large 5-generation Brazilian family segregating autosomal dominant hypomagnesemia and myokymia (see <a href="/entry/160120">160120</a>), <a href="#15" class="mim-tip-reference" title="Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. W., Knoers, N. V., Hoenderop, J. G., Bindels, R. J. <strong>A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia.</strong> J. Clin. Invest. 119: 936-942, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19307729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19307729</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19307729[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI36948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19307729">Glaudemans et al. (2009)</a> identified heterozygosity for a 763A-G transition in the KCNA1 gene, resulting in an asn255-to-asp (N255D) substitution at a highly conserved residue in the third transmembrane segment (S3) close to the voltage sensor. The mutation was not found in 100 control chromosomes. Patch-clamp analysis after overexpression in a human kidney cell line revealed that the N255D mutation results in a nonfunctional channel, with a dominant-negative effect on wildtype Kv1.1 channel function. <a href="#15" class="mim-tip-reference" title="Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. W., Knoers, N. V., Hoenderop, J. G., Bindels, R. J. <strong>A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia.</strong> J. Clin. Invest. 119: 936-942, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19307729/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19307729</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19307729[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI36948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19307729">Glaudemans et al. (2009)</a> found that Dv1.1 colocalizes with the epithelial magnesium channel TRPM6 (<a href="/entry/607009">607009</a>) in the distal convoluted tubule (DCT) of the kidney; they suggested that Kv1.1 is a renal potassium channel that establishes a favorable luminal membrane potential in DCT cells to control TRPM6-mediated magnesium reabsorption. Although the proband reported episodes during which she was 'not able to walk straight,' no objective clinical signs of cerebellar dysfunction were apparent on examination; cerebral MRI showed slight atrophy of the cerebellar vermis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19307729" 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>Episodic ataxia results from voltage-dependent potassium channels with altered functions.</strong>
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Neuron 15: 1449-1454, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8845167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8845167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8845167" 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/10.1016/0896-6273(95)90022-5" target="_blank">Full Text</a>]
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Albrecht, B., Weber, K., Pongs, O.
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<strong>Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13.</strong>
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Receptors Channels 3: 213-220, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8821794/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8821794</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8821794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Beraud, E., Viola, A., Regaya, I., Confort-Gouny, S., Siaud, P., Ibarrola, D., Le Fur, Y., Barbaria, J., Pellissier, J.-F., Sabatier, J.-M., Medina, I., Cozzone, P. J.
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<strong>Block of neural Kv1.1 potassium channels for neuroinflammatory disease therapy.</strong>
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Ann. Neurol. 60: 586-596, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17044011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17044011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17044011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11055439/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11055439</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11055439" 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/10.1126/science.1094113" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.1131693" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/1044-7431(90)90004-n" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.7554/eLife.56058" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390050722" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0896-6273(00)81018-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nature05396" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/35079500" target="_blank">Full Text</a>]
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Zhou, Y., Morais-Cabral, J. H., Kaufman, A., MacKinnon, R.
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[<a href="https://doi.org/10.1038/35102009" target="_blank">Full Text</a>]
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Zuberi, S. M., Eunson, L. H., Spauschus, A., De Silva, R., Tolmie, J., Wood, N. W., McWilliam, R. C., Stephenson, J. B. P., Kullmann, D. M., Hanna, M. G.
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[<a href="https://doi.org/10.1093/brain/122.5.817" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<span class="mim-text-font">
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Bao Lige - updated : 05/18/2021
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 11/15/2010<br>Ada Hamosh - updated : 8/24/2010<br>Marla J. F. O'Neill - updated : 9/11/2009<br>Cassandra L. Kniffin - updated : 11/13/2007<br>Cassandra L. Kniffin - updated : 5/2/2007<br>Ada Hamosh - updated : 4/25/2007<br>Ada Hamosh - updated : 10/24/2006<br>Ada Hamosh - updated : 5/3/2005<br>Ada Hamosh - updated : 4/20/2004<br>Ada Hamosh - updated : 8/12/2003<br>Cassandra L. Kniffin - updated : 3/18/2003<br>Victor A. McKusick - updated : 2/11/2003<br>Cassandra L. Kniffin - updated : 1/31/2003<br>Patricia A. Hartz - updated : 1/6/2003<br>Ada Hamosh - updated : 11/1/2001<br>Ada Hamosh - updated : 10/23/2001<br>Ada Hamosh - updated : 6/7/2001<br>Ada Hamosh - updated : 5/17/2001<br>Joanna S. Amberger - updated : 4/24/2001<br>Rebekah S. Rasooly - updated : 8/10/1999<br>Ada Hamosh - updated : 8/12/1998<br>Clair A. Francomano - updated : 6/25/1998<br>Orest Hurko - updated : 3/9/1996
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Victor A. McKusick : 7/12/1990
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carol : 09/24/2022<br>mgross : 05/18/2021<br>carol : 05/07/2019<br>carol : 10/29/2018<br>joanna : 01/30/2017<br>carol : 12/20/2013<br>alopez : 12/14/2012<br>terry : 6/20/2012<br>carol : 10/6/2011<br>mgross : 11/16/2010<br>terry : 11/15/2010<br>carol : 10/4/2010<br>mgross : 8/31/2010<br>terry : 8/24/2010<br>carol : 9/11/2009<br>wwang : 4/14/2008<br>ckniffin : 4/1/2008<br>wwang : 11/20/2007<br>ckniffin : 11/13/2007<br>wwang : 5/11/2007<br>ckniffin : 5/2/2007<br>alopez : 5/1/2007<br>terry : 4/25/2007<br>alopez : 10/25/2006<br>terry : 10/24/2006<br>terry : 10/12/2005<br>alopez : 5/9/2005<br>terry : 5/3/2005<br>terry : 3/16/2005<br>alopez : 4/20/2004<br>terry : 4/20/2004<br>terry : 4/20/2004<br>mgross : 8/12/2003<br>tkritzer : 4/8/2003<br>tkritzer : 4/7/2003<br>ckniffin : 3/18/2003<br>carol : 2/21/2003<br>ckniffin : 2/21/2003<br>carol : 2/11/2003<br>carol : 2/11/2003<br>ckniffin : 1/31/2003<br>mgross : 1/7/2003<br>terry : 1/6/2003<br>terry : 3/8/2002<br>alopez : 11/1/2001<br>terry : 11/1/2001<br>cwells : 10/24/2001<br>cwells : 10/24/2001<br>terry : 10/23/2001<br>alopez : 6/7/2001<br>terry : 6/7/2001<br>alopez : 5/18/2001<br>terry : 5/17/2001<br>terry : 5/1/2001<br>joanna : 4/24/2001<br>joanna : 4/1/2001<br>mgross : 2/28/2000<br>alopez : 8/10/1999<br>alopez : 8/10/1999<br>alopez : 8/10/1999<br>carol : 3/9/1999<br>carol : 8/12/1998<br>terry : 8/3/1998<br>carol : 6/26/1998<br>dholmes : 6/25/1998<br>terry : 4/15/1996<br>mark : 3/9/1996<br>terry : 2/23/1996<br>mark : 7/2/1995<br>mimadm : 2/25/1995<br>terry : 10/26/1994<br>carol : 2/1/1994<br>carol : 4/1/1992<br>supermim : 3/16/1992
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<span class="mim-font">
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<strong>*</strong> 176260
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<h3>
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<span class="mim-font">
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POTASSIUM CHANNEL, VOLTAGE-GATED, SHAKER-RELATED SUBFAMILY, MEMBER 1; KCNA1
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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MK1, MOUSE, HOMOLOG OF<br />
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KV1.1
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: KCNA1</em></strong>
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<strong>SNOMEDCT:</strong> 421182009;
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Cytogenetic location: 12p13.32
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:4,909,905-4,918,256 </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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<span class="mim-font">
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12p13.32
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Episodic ataxia/myokymia syndrome
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160120
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<strong>Description</strong>
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<p>Potassium channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Present in all eukaryotic cells, their diverse functions include maintaining membrane potential, regulating cell volume, and modulating electrical excitability in neurons. The delayed rectifier function of potassium channels allows nerve cells to efficiently repolarize following an action potential. In Drosophila, 4 sequence-related K+ channel genes--Shaker, Shaw, Shab, and Shal--have been identified. Each has been shown to have a human homolog (Chandy et al., 1990; McPherson et al., 1991). </p>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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<p>By PCR of genomic DNA with primers based on regions conserved between Drosophila Shaker and a mouse voltage-gated potassium channel, Ramaswami et al. (1990) isolated fragments of several related human genes. They used the fragments to screen cDNA libraries and cloned cDNAs encoding several potassium channels that they designated HuKI (KCNA1), HuKII (KCNA4; 176266), HuKIV (KCNA2; 176262), and HuKV (KCNA6; 176257). Like other Shaker-class potassium channels, the predicted 495-amino acid KCNA1 protein contains 6 hydrophobic segments, a positively charged region called S4 between hydrophobic segments 3 and 4, and a leucine zipper. KCNA1 shares 98% amino acid identity with its rat homolog, RCK1. When expressed in Xenopus oocytes, KCNA1, KCNA4, and KCNA2 exhibited different voltage dependence, kinetics, and sensitivity to pharmacologic potassium channel blockers. KCNA1 and KCNA2 were noninactivating channels and resembled delayed rectifiers, while KCNA4 was rapidly inactivating. </p><p>Glaudemans et al. (2009) demonstrated the presence of Kv1.1 channels in the superficial cortex of mouse kidney. Using serial kidney sections, they showed that Kv1.1 channels colocalize with the epithelial magnesium channel TRPM6 (607009) in the distal convoluted tubule. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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<span class="mim-text-font">
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<p>Chandy et al. (1990) demonstrated that 3 closely related potassium channel genes, MK1, MK2, and MK3, are located at separate sites in the genome of the mouse. These genes, encoding subunits of voltage-dependent K+ channels, are homologous to the Drosophila Shaker gene. McPherson et al. (1991) mapped member 1 of the Shaker-related subfamily of K+ channel genes (the homolog of MK1) to human chromosome 12 by study of somatic cell hybrids. Curran et al. (1992) mapped the KCNA1 gene to chromosome 12 by use of human-rodent somatic cell panels and narrowed the localization to the distal short arm by in situ hybridization. Linkage studies had shown a maximum lod score of 2.72 at a recombination fraction of 0.05 between KCNA1 and the von Willebrand locus (VWF; 613160). Using interspecific backcrosses between Mus musculus and Mus spretus, Klocke et al. (1993) mapped the Kcna1, Kcna5 (176267), and Kcna6 genes to mouse chromosome 6, close to the homolog of TPI1 (190450), which is located on 12p13 in the human. Albrecht et al. (1995) determined that a 300-kb cluster on chromosome 12p13 contains the human KCNA6, KCNA1, and KCNA5 genes arranged in tandem. </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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</h4>
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<span class="mim-text-font">
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<p>Adelman et al. (1995) injected Xenopus oocytes with cDNAs corresponding to 6 different mutations associated with autosomal dominant myokymia with episodic ataxia, also known as episodic ataxia type 1 (EA1; 160120). They demonstrated that coassembly of one or more episodic ataxia subunits with a wildtype subunit can alter channel function, giving a dominant-negative effect. </p><p>Larsson and Elinder (2000) investigated the role of conserved glutamate at the extracellular end of segment 5 (S5) in slow inactivation by mutating it to a cysteine (E418C in Shaker). Larsson and Elinder (2000) could lock the channel in 2 different conformations by disulfide-linking 418C to 2 different cysteines, introduced in the Pore-S6 (P-S6) loop. Their results suggested that E418 normally stabilizes the open conformation of the slow inactivation gate by forming hydrogen bonds with the P-S6 loop. Breaking these bonds allows the P-S6 loop to rotate, which closes the slow inactivation gate. </p><p>Zhou et al. (2001) showed that the central cavity and inner pore of the Shaker type potassium channel form the receptor site for both the inactivation gate and small-molecule inhibitors. Zhou et al. (2001) proposed that inactivation occurs by a sequential reaction in which the gate binds initially to the cytoplasmic channel surface and then enters the pore as an extended peptide. This mechanism accounts for the functional properties of potassium channel inactivation and indicates that the cavity may be the site of action for certain drugs that alter cation channel function. </p><p>Gu et al. (2003) found that Kv1 axonal targeting required its T1 tetramerization domain. When fused to unpolarized CD4 (186940) or dendritic transferrin receptor (TFR; 190010), T1 domains from Kv1.1, Kv1.2, and Kv1.4 promoted their axonal surface expression. Moreover, mutations in the T1 domain of Kv1.2 that eliminated association with Kv-beta-2 (601142) compromised axonal targeting, but not surface expression, of CD4-T1 fusion proteins. The authors concluded that proper association of Kv-beta with the Kv1 T1 domain is essential for axonal targeting. </p><p>The combinatorial association between distinct alpha and beta subunits is thought to determine whether Kv channels function as noninactivating delayed rectifiers or as rapidly inactivating A-type channels. Oliver et al. (2004) showed that membrane lipids can convert A-type channels into delayed rectifiers and vice versa. Phosphoinositides, particularly phosphatidylinositol-4,5-bisphosphate (PIP2), remove N-type inactivation from A-type channels by immobilizing the inactivation domains. Conversely, arachidonic acid and its amide anandamide endow delayed rectifiers with rapid voltage-dependent inactivation. Oliver et al. (2004) concluded that the bidirectional control of Kv channel gating by lipids may provide a mechanism for the dynamic regulation of electrical signaling in the nervous system. </p><p>Raab-Graham et al. (2006) found that the mTOR (601231) inhibitor rapamycin increased the Kv1.1 voltage-gated potassium channel protein in hippocampal neurons and promoted Kv1.1 surface expression on dendrites without altering its axonal expression. Moreover, endogenous Kv1.1 mRNA was detected in dendrites. Using Kv1.1 fused to the photoconvertible fluorescence protein Kaede as a reporter for local synthesis, Raab-Graham et al. (2006) observed Kv1.1 synthesis in dendrites upon inhibition of mTOR or the N-methyl-D-aspartate (NMDA) glutamate receptor (see 138251). Thus, Raab-Graham et al. (2006) concluded that synaptic excitation may cause local suppression of dendritic Kv1 channels by reducing their local synthesis. </p><p>Sanders et al. (2020) found that developmental expression profiles of the palmitoyl acyltranserase (PAT) Zdhhc14 (619295) in rat hippocampal neurons were almost identical to those of Kv1-type potassium channels. Zdhhc14 functioned as a major neuronal PAT for Kv1.1, Kv1.2, and Kv1.4 in neurons and was required for axon initial segment (AIS) targeting of these channel subunits. As Zdhhc14 localized predominantly to Golgi, palmitoylation of Kv1 channel subunits took place in Golgi apparatus of hippocampal neurons, rather than directly at the AIS. Additionally, knockout analysis revealed that loss of Zdhhc14 reduced outward currents, which were likely mediated by voltage-dependent potassium channels, and increased action potential firing in rat hippocampal neurons. </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Doyle et al. (1998) determined the atomic structure of the Streptomyces lividans KcsA potassium channel pore by means of x-ray crystallography. However, serious doubts were raised concerning whether the prokaryotic potassium channel pore actually represents those of eukaryotes. Lu et al. (2001) addressed this issue by substituting the prokaryotic potassium channel pore into eukaryotic voltage-gated and inward-rectifier (see 600681) potassium channels. The resulting chimeras retained the respective functional hallmarks of the eukaryotic channels, which indicates that the ion conduction pore is indeed conserved among potassium channels. </p><p>Zhou et al. (2001) determined the chemistry of ion coordination and hydration of the KcsA potassium channel pore at 2-angstrom resolution. Morais-Cabral et al. (2001) further determined the energetic optimization by the potassium selectivity filter. Berneche and Roux (2001) performed molecular dynamics free energy simulations on the basis of the x-ray structure of the KcsA potassium channel. </p><p>Gubitosi-Klug et al. (2005) determined that human Kv1.1 is palmitoylated at cys243. This palmitoylation modulated voltage sensing by Kv1.1 and facilitated its dynamic interactions with surrounding lipids during voltage-induced conformational changes. </p><p>In the Shaker potassium channel, mutation of the first charged residue of the S4 helix to a smaller uncharged residue makes the voltage-sensing domain permeable to ions ('omega current') in the resting conformation ('S4 down'). Tombola et al. (2007) performed a structure-guided perturbation analysis of the omega conductance to map its voltage-sensing domain permeation pathway. Tombola et al. (2007) found that there are 4 omega pores per channel, which is consistent with 1 conduction path per voltage-sensing domain. Permeating ions from the extracellular medium enter the voltage-sensing domain at its peripheral junction with the pore domain, and then plunge into the core of the voltage-sending domain in a curved conduction pathway. Tombola et al. (2007) concluded that their results provided a model of the resting conformation of the voltage-sensing domain. </p><p>Cuello et al. (2010) identified the mechanistic principles by which movements on the inner bundle gate trigger conformational changes at the selectivity filter, leading to the nonconductive C-type inactivated state of the KcsA potassium channel. Analysis of a series of KcsA open structures suggested that, as a consequence of the hinge bending and rotation of the transmembrane-2 helix, the aromatic ring of phe103 tilts toward thr74 and thr75 in the pore-helix and toward ile100 in the neighboring subunit. This allows the network of hydrogen bonds among trp67, glu71, and asp80 to destabilize the selectivity filter, allowing entry to its nonconductive conformation. Mutations at position 103 had a size-dependent effect on gating kinetics: small side-chain substitutions F103A and F103C severely impaired inactivation kinetics, whereas larger side-chain substitutions, such as F103W, had more subtle effects. This finding suggested that the allosteric coupling between the inner helical bundle and the selectivity filter might rely on straightforward mechanical deformation propagated through a network of steric contacts. </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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<p>Browne et al. (1994) performed mutation analysis of the KCNA1 coding region in 4 families with myokymia (rippling of muscles) with episodic ataxia (160120). They found 4 different missense mutations present in heterozygous state (176260.0001-176260.0004). </p><p>For a comprehensive review of episodic ataxia type 1 and its causative mutations, see Brandt and Strupp (1997). </p><p>In a 5-generation Brazilian family segregating autosomal dominant hypomagnesemia and myokymia mapping to chromosome 12q, Glaudemans et al. (2009) identified a heterozygous missense mutation in the KCNA1 gene (N255D; 176250.0015) that segregated with disease and was not found in 100 control chromosomes. </p>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Eunson et al. (2000) identified 4 families with different neurologic phenotypes, including seizures and myokymia, isolated myokymia, severe drug-resistant EA1, and typical drug-responsive EA1, each of which carried a different heterozygous mutation in the KCNA1 gene (176260.0008, 176260.0010-176260.0012). Functional expression studies of the mutations expressed in Xenopus oocytes revealed that the mutations impaired the channel function via different mechanisms, and Eunson et al. (2000) concluded that there may be a genotype/phenotype correlation (see each allelic variant for details). </p>
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<strong>Animal Model</strong>
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<span class="mim-text-font">
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<p>Smart et al. (1998) found that Kcna1-null mice displayed frequent spontaneous seizures and that these seizures correlated on the cellular level with alterations in hippocampal excitability and nerve conduction. The intrinsic passive properties of CA3 pyramidal cells in hippocampal slices from homozygous Kcna1-null mice were normal; however, antidromic action potentials were recruited at lower thresholds. In a subset of slices, mossy fiber stimulation triggered long-latency epileptiform burst discharges. Axonal action potential conduction was also altered in the sciatic nerve. </p><p>Using homologous recombination, Herson et al. (2003) introduced the Kcna1 val408-to-ala mutation (V408A; 176260.0001) into mice. In contrast to Kcna1-null mice, homozygous V408A mice died after embryonic day 3, consistent with V408A being a homozygous lethal allele. V408A heterozygous mice showed stress-induced loss of motor coordination that was ameliorated by acetazolamide, similar to patients with EA1. Cerebellar Purkinje cells from V408A heterozygous mice showed a greater frequency and amplitude of spontaneous GABAergic inhibitory postsynaptic currents than did wildtype. The authors noted that Kcna1 is localized to GABAergic interneurons in the cerebellum, suggesting that it may be important for regulating GABA release, and that mutations in the gene may alter excitability in the cerebellum, leading to clinical symptoms. </p><p>Sleep in fruit flies shares many similarities with mammalian sleep; flies sleep for many hours (9 to 15 hours) and, when sleep deprived, show sleep rebound and performance impairments. To determine which genes underlie short sleeping, Cirelli et al. (2005) performed mutagenesis in Drosophila melanogaster. By screening 9,000 mutant lines, Cirelli et al. (2005) found 'minisleep' (mns), a line that sleeps for one-third of the wildtype amount. Mns flies perform normally in a number of tasks, have preserved sleep homeostasis, and are not impaired by sleep deprivation. Cirelli et al. (2005) showed that mns flies carry a point mutation in Shaker, a C-to-T transition in exon 9 resulting in a threonine-to-isoleucine substitution. This substitution of a polar amino acid with a highly hydrophobic one occurs at the extracellular end of S1. The mutated threonine residue is extremely well conserved from Aplysia to human. After crossing out genetic modifiers accumulated over many generations, other Shaker null alleles also caused a short-sleeping phenotype and failed to complement the mns phenotype. Cirelli et al. (2005) found that short-sleeping Shaker flies have a reduced life span. Cirelli et al. (2005) concluded that Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency. </p><p>Beraud et al. (2006) demonstrated that intracerebroventricular infusion of a specific Kcna1 blocker, BgK-F6A, greatly reduced neurologic deficits in rats with experimental autoimmune encephalitis, an animal model of multiple sclerosis (MS; 126200). BgK-F6A increased the frequency of miniature excitatory postsynaptic currents in cultured rat hippocampal cells without affecting T-cell activation. Treated rats showed decreased ventriculomegaly, decreased cerebral injury, and preservation of brain bioenergetics compared to control rats. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>15 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 EPISODIC ATAXIA, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, VAL408ALA
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<br />
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SNP: rs104894352,
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ClinVar: RCV000014424
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; 160120), Browne et al. (1994) demonstrated heterozygosity for a val408-to-ala mutation in the KCNA1 gene. Valine-408 resides in the C-terminal domain of the sixth transmembrane region of KCNA1, which compromises the inner portion of the pore. By recording from Xenopus oocytes injected with the mutant transcript, Adelman et al. (1995) demonstrated that V408A channels have voltage dependence similar to that of wildtype channels but with faster kinetics and increased C-type inactivation. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 EPISODIC ATAXIA, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, ARG239SER
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<br />
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SNP: rs104894348,
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ClinVar: RCV000014425
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; 160120), Browne et al. (1994) demonstrated heterozygosity for an arg239-to-ser mutation in the KCNA1 gene. Residue 239 is in the intracytoplasmic loop between the putative first and second transmembrane domains. Adelman et al. (1995) made voltage recordings of Xenopus oocytes microinjected with the mutated transcript and found that homomeric channels with a serine substitution at this site are not functional. Unlike other residues that are conserved among the KV1 family members but vary in other delayed rectifier families, all rectifier potassium subunits contain arginine at a position analogous to 239, suggesting to the authors a crucial role for this position. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 EPISODIC ATAXIA, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, VAL174PHE
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<br />
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SNP: rs104894349,
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ClinVar: RCV000014426, RCV001265691
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; 160120), Browne et al. (1994) demonstrated heterozygosity for a val174-to-phe mutation in the KCNA1 gene. Residue 174 lies within the first putative transmembrane domain. Adelman et al. (1995) recorded from Xenopus oocytes microinjected with the mutant transcript and found that subunits with a phenylalanine substitution at this residue do not produce a functional homomeric channel. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 EPISODIC ATAXIA, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, PHE249ILE
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<br />
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SNP: rs104894356,
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ClinVar: RCV000014427
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a family with the episodic ataxia/myokymia syndrome (EA1; 160120), Browne et al. (1994) demonstrated heterozygosity for a phe249-to-ile mutation in the KCNA1 gene. Residue 249 lies in the cytoplasmic loop between the first and second putative transmembrane domain, a region conserved in all delayed rectifier potassium channels. Adelman et al. (1995) recorded from Xenopus oocytes microinjected with the mutated transcript and found that subunits with an isoleucine substitution at residue 249 did not produce a functional homomeric channel. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 EPISODIC ATAXIA, TYPE 1</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, PHE184CYS
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<br />
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SNP: rs104894357,
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ClinVar: RCV000014428
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Browne et al. (1995) reported mutation analysis in a family with type 1 episodic ataxia (EA1; 160120). Affected individuals were found to be heterozygous for a T-to-G transversion at position 551 of the KCNA1 gene, resulting in a substitution of cysteine for phenylalanine at codon 184. Residue 184 is in the C-terminal domain of the first transmembrane region of KCNA1 close to the extracellular border of the membrane. It is a conserved residue in all Shaker family members. By recording from Xenopus oocytes microinjected with the mutant transcript Adelman et al. (1995) demonstrated that substitution of cysteine at this residue alters voltage dependence and kinetics of activation though not of C-type inactivation. </p>
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</span>
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 EPISODIC ATAXIA, TYPE 1</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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|
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KCNA1, GLU325ASP
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|
|
<br />
|
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|
|
SNP: rs104894353,
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|
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ClinVar: RCV000014429
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Browne et al. (1995) reported mutation analysis in a family with type 1 episodic ataxia (EA1; 160120). Affected individuals were found to be heterozygous for a G-to-C transversion at position 975 of the KCNA1 gene, resulting in a substitution of aspartic acid for glutamic acid at codon 325. This residue is conserved throughout evolution, from Drosophila to Homo sapiens. Residue 325 is at the interface of the fifth transmembrane region in KCNA1 in the cytoplasm, a region that forms part of the internal lining of the pore. This residue is completely conserved among delayed rectifier subunits. By recording from Xenopus oocytes microinjected with cDNA from a human gene with a conservative asparagine substitution at this residue, Adelman et al. (1995) found that this mutation results in nonfunctional homomeric channels, even though the same alteration in the Shaker channel from Drosophila results in functional channels with reduced unit conductance and open probability. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 EPISODIC ATAXIA, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNA1, THR226ALA
|
|
|
|
|
|
<br />
|
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|
|
SNP: rs104894354,
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|
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|
|
ClinVar: RCV000014430, RCV003221784
|
|
|
|
|
|
</span>
|
|
</div>
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>Scheffer et al. (1998) described a family with multiple affected individuals clinically diagnosed as having episodic ataxia (EA1; 160120). Those affected had an A-to-G transversion at position 676 of the KCNA1 gene, resulting in a thr-to-ala substitution at codon 226. Clinical details of the family were not presented. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 EPISODIC ATAXIA, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNA1, VAL404ILE
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs104894355,
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|
|
|
|
|
|
|
ClinVar: RCV000014431, RCV002509157
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with episodic ataxia (EA1; 160120), Scheffer et al. (1998) identified a G-to-A transition at position 1210 of the KCNA1 gene, leading to a val-to-ile substitution at codon 404. </p><p>In a large British family with 16 members over 4 generations affected with type 1 episodic ataxia, Eunson et al. (2000) identified the V404I mutation in the KCNA1 gene. Functional expression studies of the mutation in Xenopus oocytes yielded current amplitudes that were not different from wildtype. Coexpression with wildtype partially corrected the alterations in activation parameters. The authors noted that the phenotype was relatively typical and responded well to treatment. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 EPISODIC ATAXIA, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
KCNA1, ILE177ASN
|
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|
|
<br />
|
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|
|
SNP: rs267607195,
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|
|
|
|
|
|
|
ClinVar: RCV000014432
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In affected members of a family with episodic ataxia (EA1; 160120), Scheffer et al. (1998) identified heterozygosity for a T-to-A transversion at position 530 of the KCNA1 gene, leading to an ile-to-asn substitution at codon 177 (I177N). The original description of the mutation, ILE176ARG (527T-A), was corrected in an erratum. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
|
|
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<div>
|
|
<br />
|
|
</div>
|
|
|
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</div>
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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 MYOKYMIA 1</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
|
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|
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KCNA1, ALA242PRO
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|
|
|
|
<br />
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|
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SNP: rs28933381,
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|
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|
|
|
gnomAD: rs28933381,
|
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|
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ClinVar: RCV000014433, RCV000441803
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|
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|
|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a mother and son with myokymia (see 160120) and seizures, but not ataxic episodes, Eunson et al. (2000) identified a heterozygous 724G-C point mutation in the KCNA1 gene, resulting in an ala242-to-pro substitution (A242P) in the second transmembrane segment of the channel. The proband's deceased father was reported to have had seizures and myokymia. Functional studies of the mutation expressed in Xenopus oocytes showed significantly reduced mean peak current amplitudes compared to wildtype (10%). Mutant and wildtype expression together was consistent with a loss-of-function effect of the mutation. Importantly, the A242P mutation still resulted in a correctly translated and functional potassium channel. Eunson et al. (2000) stressed that the observations in this family are the first demonstration that a defect in this potassium channel may associate with epilepsy. </p>
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|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 MYOKYMIA 1</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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KCNA1, PRO244HIS
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<br />
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|
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SNP: rs28933382,
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gnomAD: rs28933382,
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ClinVar: RCV000014434
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy and his father with isolated myokymia (see 160120) and leg muscle hypertrophy, but without ataxic episodes, Eunson et al. (2000) identified a heterozygous 731C-A point mutation in the KCNA1 gene, resulting in a pro244-to-his substitution (P244H) in the intracellular loop between transmembrane segments 2 and 3. Functional studies of current amplitudes in Xenopus oocytes showed no difference between the mutation compared to wildtype. Although coexpression experiments with wildtype RNA yielded a peak current amplitude that was 200% of wildtype alone, coexpression of the mutant and wildtype genes had only a small effect on current activation parameters, which the authors suggested may be reflected in the relatively simple phenotype of myokymia without ataxia. </p>
|
|
</span>
|
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</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 EPISODIC ATAXIA, TYPE 1</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
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|
KCNA1, ARG417TER
|
|
|
|
|
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<br />
|
|
|
|
SNP: rs104894358,
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|
|
gnomAD: rs104894358,
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|
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|
|
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ClinVar: RCV000014435
|
|
|
|
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</span>
|
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</div>
|
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<div>
|
|
<span class="mim-text-font">
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<p>In a patient with drug-resistant type 1 episodic ataxia (EA1; 160120), Eunson et al. (2000) identified a 1249C-T mutation in the KCNA1 gene, resulting in a premature stop codon at amino acid 417 (R417X). This was predicted to result in the loss of nearly 80 amino acids at the intracellular C terminus. Family studies were consistent with the mutation being a de novo event. Functional expression studies of the mutation in Xenopus oocytes showed a significantly reduced current amplitude compared to wildtype (2%). Coexpression with wildtype showed a dominant-negative effect of the R417X mutation as well as a profound alteration in kinetic parameters. Eunson et al. (2000) suggested that the severe drug-resistant phenotype may be related to the functional consequences of a truncated protein. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0013 EPISODIC ATAXIA, TYPE 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, THR226ARG
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<br />
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SNP: rs28933383,
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ClinVar: RCV000014436, RCV001785451
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Zuberi et al. (1999) reported a Scottish family with episodic ataxia type 1 (EA1; 160120) in which a 677C-G transversion in the KCNA1 gene resulted in a thr226-to-arg amino acid substitution at a highly conserved position in the second transmembrane segment of the channel. Of 5 affected individuals over 3 generations, 2 had partial epilepsy in addition to EA1. A review of previously reported EA1 families showed an overrepresentation of epilepsy in family members with EA1. The initial presentation was postural abnormalities in all except 1 case. The fists are clenched, knees flexed, and feet held in plantar flexion as a result of continual muscle fiber activity. A misdiagnosis of familial arthrogryposis is sometimes made. Inguinal hernias were thought to be secondary to myokymia of the abdominal wall musculature. Functional studies by Zuberi et al. (1999) showed that mutant subunits exhibited a dominant-negative effect on potassium channel function and would be predicted to impair neuronal repolarization. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0014 MYOKYMIA 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, THR226LYS
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<br />
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SNP: rs28933383,
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ClinVar: RCV000014437
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 affected members of a family with isolated myokymia (see 160120) without epilepsy or episodic ataxia, Chen et al. (2007) identified a heterozygous 676C-A transversion in the KCNA1 gene, resulting in a thr226-to-lys (T226K) substitution in the second transmembrane domain. Electrophysiologic studies in transfected Xenopus oocytes showed that the T226K protein resulted in reduced efflux of potassium ions during depolarization, which likely results in increased muscle cell activity. Coexpression studies of the mutant protein with the wildtype protein produced significantly reduced currents, suggesting a severe effect of the mutation. The phenotype in this family was unusual with extensor plantar responses suggestive of corticospinal tract involvement and worsening of symptoms with febrile illness or anesthesia. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0015 MYOKYMIA 1 WITH HYPOMAGNESEMIA</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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KCNA1, ASN255ASP
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<br />
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SNP: rs121918067,
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ClinVar: RCV000014438
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In affected members of a large 5-generation Brazilian family segregating autosomal dominant hypomagnesemia and myokymia (see 160120), Glaudemans et al. (2009) identified heterozygosity for a 763A-G transition in the KCNA1 gene, resulting in an asn255-to-asp (N255D) substitution at a highly conserved residue in the third transmembrane segment (S3) close to the voltage sensor. The mutation was not found in 100 control chromosomes. Patch-clamp analysis after overexpression in a human kidney cell line revealed that the N255D mutation results in a nonfunctional channel, with a dominant-negative effect on wildtype Kv1.1 channel function. Glaudemans et al. (2009) found that Dv1.1 colocalizes with the epithelial magnesium channel TRPM6 (607009) in the distal convoluted tubule (DCT) of the kidney; they suggested that Kv1.1 is a renal potassium channel that establishes a favorable luminal membrane potential in DCT cells to control TRPM6-mediated magnesium reabsorption. Although the proband reported episodes during which she was 'not able to walk straight,' no objective clinical signs of cerebellar dysfunction were apparent on examination; cerebral MRI showed slight atrophy of the cerebellar vermis. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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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Albrecht, B., Weber, K., Pongs, O.
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Browne, D. L., Gancher, S. T., Nutt, J. G., Brunt, E. R. P., Smith, E. A., Kramer, P., Litt, M.
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<strong>Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1.</strong>
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Chandy, K. G., Williams, C. B., Spencer, R. H., Aguilar, B. A., Ghanshani, S., Tempel, B. L., Gutman, G. A.
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<strong>A family of three mouse potassium channel genes with intronless coding regions.</strong>
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Science 247: 973-975, 1990.
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[PubMed: 2305265]
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Chen, H., von Hehn, C., Kaczmarek, L. K., Ment, L. R., Pober, B. R., Hisama, F. M.
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Cirelli, C., Bushey, D., Hill, S., Huber, R., Kreber, R., Ganetzky, B., Tononi, G.
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Cuello, L. G., Jogini, V., Cortes, D. M., Pan, A. C., Gagnon, D. G., Dalmas, O., Cordero-Morales, J. F., Chakrapani, S., Roux, B., Perozo, E.
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Doyle, D. A., Morais-Cabral, J., Pfuetzner, R. A., Kuo, A., Gulbis, J. M., Cohen, S. L., Chait, B. T., MacKinnon, R.
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<strong>The structure of the potassium channel: molecular basis of K+ conduction and selectivity.</strong>
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<p class="mim-text-font">
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Eunson, L. H., Rea, R., Zuberi, S. M., Youroukos, S., Panayiotopoulos, C. P., Liguori, R., Avoni, P., McWilliam, R. C., Stephenson, J. B. P., Hanna, M. G., Kullmann, D. M., Spauschus, A.
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<strong>Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.</strong>
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[PubMed: 11026449]
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<p class="mim-text-font">
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Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. W., Knoers, N. V., Hoenderop, J. G., Bindels, R. J.
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<strong>A missense mutation in the Kv1.1 voltage-gated potassium channel-encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia.</strong>
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Gu, C., Jan, Y. N., Jan, L. Y.
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<p class="mim-text-font">
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Gubitosi-Klug, R. A., Mancuso, D. J., Gross, R. W.
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<strong>The human Kv1.1 channel is palmitoylated, modulating voltage sensing: identification of a palmitoylation consensus sequence.</strong>
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<p class="mim-text-font">
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<p class="mim-text-font">
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Klocke, R., Roberds, S. L., Tamkun, M. M., Gronemeier, M., Augustin, A., Albrecht, B., Pongs, O., Jockusch, H.
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<strong>Chromosomal mapping in the mouse of eight K(+)-channel genes representing the four Shaker-like subfamilies Shaker, Shab, Shaw, and Shal.</strong>
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Genomics 18: 568-574, 1993.
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[PubMed: 7905852]
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[Full Text: https://doi.org/10.1016/s0888-7543(05)80358-1]
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</p>
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<li>
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<p class="mim-text-font">
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Larsson, H. P., Elinder, F.
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<strong>A conserved glutamate is important for slow inactivation in K(+) channels.</strong>
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Neuron 27: 573-583, 2000.
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[PubMed: 11055439]
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[Full Text: https://doi.org/10.1016/s0896-6273(00)00067-2]
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<p class="mim-text-font">
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Lu, Z., Klem, A. M., Ramu, Y.
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<strong>Ion conduction pore is conserved among potassium channels.</strong>
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Nature 413: 809-813, 2001.
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[PubMed: 11677598]
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[Full Text: https://doi.org/10.1038/35101535]
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</p>
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<li>
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<p class="mim-text-font">
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McPherson, J. D., Wasmuth, J. J., Chandy, K. G., Swanson, R., Dethlefs, B., Chandy, G., Wymore, R., Ghanshani, S.
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<strong>Chromosomal localization of 7 potassium channel genes. (Abstract)</strong>
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Cytogenet. Cell Genet. 58: 1979, 1991.
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<p class="mim-text-font">
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|
Morais-Cabral, J. H., Zhou, Y., MacKinnon, R.
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<strong>Energetic optimization of ion conduction rate by the K(+) selectivity filter.</strong>
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|
Nature 414: 37-42, 2001.
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[PubMed: 11689935]
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[Full Text: https://doi.org/10.1038/35102000]
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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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Oliver, D., Lien, C.-C., Soom, M., Baukrowitz, T., Jonas, P., Fakler, B.
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|
<strong>Functional conversion between A-type and delayed rectifier K+ channels by membrane lipids.</strong>
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|
Science 304: 265-270, 2004.
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[PubMed: 15031437]
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[Full Text: https://doi.org/10.1126/science.1094113]
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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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