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- *182391 - SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 3; SCN3A
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*182391</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/182391">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000153253;t=ENST00000283254" 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=6328" 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=182391" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000153253;t=ENST00000283254" 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_001081676,NM_001081677,NM_006922,XM_011511610,XM_011511613,XM_017004660,XM_017004661,XM_017004662,XM_017004664,XM_017004665,XM_017004666,XM_047445394,XM_047445395" 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_006922" 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=182391" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=01671&isoform_id=01671_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/SCN3A" 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/546368,2665782,2665784,7243093,7271918,7414320,9801812,9801814,9801826,12382857,12382858,12642272,12642274,25014054,62822524,119631736,119631737,119631738,119631739,119631740,126362947,126362949,126362955,194377864,194389370,444738631,767919193,767919199,1034615737,1034615739,1034615741,1034615746,1034615748,1034615750,2217330074,2217330078,2462575879,2462575881,2462575883,2462575885,2462575887,2462575889,2462575891,2462575893,2462575895,2462575897" 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/Q9NY46" 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=6328" 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=ENSG00000153253;t=ENST00000283254" 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=SCN3A" 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=SCN3A" 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+6328" 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/SCN3A" 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:6328" 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/6328" 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=chr2&hgg_gene=ENST00000283254.12&hgg_start=165087526&hgg_end=165204050&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:10590" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=182391[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=182391[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/SCN3A/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/ENSG00000153253" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=SCN3A" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=SCN3A" 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=SCN3A" 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=SCN3A&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/PA35005" 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:10590" 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/FBgn0285944.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:98249" 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/SCN3A#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:98249" 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/6328/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=6328" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:6328" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=SCN3A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
|
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
182391
|
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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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SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 3; SCN3A
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</span>
|
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</h3>
|
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE III, ALPHA SUBUNIT<br />
|
|
SODIUM CHANNEL, NEURONAL TYPE III, ALPHA SUBUNIT<br />
|
|
SODIUM CHANNEL, BRAIN TYPE III, ALPHA SUBUNIT; NAC3<br />
|
|
NAV1.3
|
|
</span>
|
|
</h4>
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SCN3A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SCN3A</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/735?start=-3&limit=10&highlight=735">2q24.3</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:165087526-165204050&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'})">2:165,087,526-165,204,050</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
|
|
|
|
</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=617938,617935" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/735?start=-3&limit=10&highlight=735">
|
|
2q24.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Developmental and epileptic encephalopathy 62
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617938"> 617938 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
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|
|
|
|
|
|
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|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epilepsy, familial focal, with variable foci 4
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617935"> 617935 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
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|
|
|
|
|
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|
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</tbody>
|
|
</table>
|
|
</div>
|
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</div>
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<div>
|
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<p>The SCN3A gene encodes the alpha subunit of the voltage-gated sodium channel Na(v)1.3, which shows rapid activation and inactivation (summary by <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24157691" 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>Voltage-gated sodium channels from the central nervous system consist of a large pore-forming alpha subunit, such as SCN3A, associated with smaller auxiliary subunits (see SCN1B, <a href="/entry/600235">600235</a>) (<a href="#2" class="mim-tip-reference" title="Chen, Y. H., Dale, T. J., Romanos, M. A., Whitaker, W. R. J., Xie, X. M., Clare, J. J. <strong>Cloning, distribution and functional analysis of the type III sodium channel from human brain.</strong> Europ. J. Neurosci. 12: 4281-4289, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11122339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11122339</a>]" pmid="11122339">Chen et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11122339" 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="Ahmed, C. M. I., Ware, D. H., Lee, S. C., Patten, C. D., Ferrer-Montiel, A. V., Schinder, A. F., McPherson, J. D., Wagner-McPherson, C. B., Wasmuth, J. J., Evans, G. A., Montal, M. <strong>Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain.</strong> Proc. Nat. Acad. Sci. 89: 8220-8224, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1325650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1325650</a>] [<a href="https://doi.org/10.1073/pnas.89.17.8220" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1325650">Ahmed et al. (1992)</a> isolated 2 cDNAs from a human cerebral cortex library by screening for the presence of sodium channel alpha-subunit-specific clones. One of the clones showed greatest homology to rat brain sodium channel II. The second clone encoded a different subtype sodium channel, probably a type III channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1325650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR of frontal pole mRNA using primers based on rat sodium channel cDNAs, followed by screening a human cerebellum cDNA library, <a href="#2" class="mim-tip-reference" title="Chen, Y. H., Dale, T. J., Romanos, M. A., Whitaker, W. R. J., Xie, X. M., Clare, J. J. <strong>Cloning, distribution and functional analysis of the type III sodium channel from human brain.</strong> Europ. J. Neurosci. 12: 4281-4289, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11122339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11122339</a>]" pmid="11122339">Chen et al. (2000)</a> cloned SCN3A. The deduced 1,951-amino acid protein contains 24 transmembrane domains. Northern blot analysis detected a transcript of about 9.5 kb with strong expression in brain, weak expression in heart, and no expression in placenta, lung, liver, kidney, or pancreas. A strong band of about 7.5 kb was also found in skeletal muscle. Within specific brain regions, highest SCN3A expression was detected in cerebellum and frontal lobe, with moderate expression in amygdala, caudate nucleus, hippocampus, substantia nigra, medulla, and occipital pole, weak expression in subthalamic nucleus, thalamus, cerebral cortex, temporal lobe, and putamen, and no expression in corpus callosum and spinal cord. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11122339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By EST database analysis, 3-prime RACE, and long-range PCR of human cDNA libraries, <a href="#3" class="mim-tip-reference" title="Kasai, N., Fukushima, K., Ueki, Y., Prasad, S., Nosakowski, J., Sugata, K., Sugata, A., Nishizaki, K., Meyer, N. C., Smith, R. J. H. <strong>Genomic structures of SCN2A and SCN3A--candidate genes for deafness at the DFNA16 locus.</strong> Gene 264: 113-122, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11245985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11245985</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00594-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11245985">Kasai et al. (2001)</a> cloned splice variants of SCN3A that differed in inclusion or exclusion of a 5-prime noncoding exon, selection of exon 6A or 6N, which are identical in size, and inclusion or exclusion of coding exon 12b. Transcripts with and without exon 12b encode proteins of 1,983 and 1,951 amino acids, respectively. Transcripts containing exon 6N were detected in lymphocyte and fetal brain cDNA libraries, and transcripts containing 6A were found in adult human brain. Transcripts containing exon 12b were detected in lymphocyte, fetal brain, and adult brain libraries, but no SCN3A expression was detected in human fetal cochlea. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11245985" 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="#2" class="mim-tip-reference" title="Chen, Y. H., Dale, T. J., Romanos, M. A., Whitaker, W. R. J., Xie, X. M., Clare, J. J. <strong>Cloning, distribution and functional analysis of the type III sodium channel from human brain.</strong> Europ. J. Neurosci. 12: 4281-4289, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11122339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11122339</a>]" pmid="11122339">Chen et al. (2000)</a> found that stable expression of SCN3A in Chinese hamster ovary cells resulted in a robust inward sodium current. The voltage dependence and kinetics of activation/inactivation of SCN3A were similar to that of SCN2A (<a href="/entry/182390">182390</a>). However, SCN3A inactivated at more hyperpolarized potentials and was slower to recover from inactivation than SCN2A. When expressed in human embryonic kidney cells, SCN3A produced currents with a prominent persistent component, similar to that reported for rat type II channels; however, unlike type II channels, the persistent component was prominent even in the absence of coexpressed G proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11122339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> did not observe large persistent sodium currents in cells expressing wildtype SCN3A using an exon 5A splice variant with an aspartic acid at position 208, rather than exon 5N, which has a serine at position 208. Additional in vitro comparisons of both variants indicated that they had similar persistent currents, suggesting that large persistent current is not an intrinsic property of the Na(v)1.3 channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24157691" 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="#3" class="mim-tip-reference" title="Kasai, N., Fukushima, K., Ueki, Y., Prasad, S., Nosakowski, J., Sugata, K., Sugata, A., Nishizaki, K., Meyer, N. C., Smith, R. J. H. <strong>Genomic structures of SCN2A and SCN3A--candidate genes for deafness at the DFNA16 locus.</strong> Gene 264: 113-122, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11245985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11245985</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00594-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11245985">Kasai et al. (2001)</a> determined that the SCN3A gene spans approximately 120 kb and has 30 exons, including a noncoding alternative first exon, alternative exons 6, and alternative exon 12b. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11245985" 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>On physical mapping by pulsed field gel electrophoresis in the mouse, <a href="#5" class="mim-tip-reference" title="Malo, D., Schurr, E., Dorfman, J., Canfield, V., Levenson, R., Gros, P. <strong>Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2.</strong> Genomics 10: 666-672, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679748</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90450-s" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1679748">Malo et al. (1991)</a> demonstrated that the Scn2a and Scn3a genes encoding type II and type III sodium channel alpha-subunit isoforms, respectively, are physically linked and are separated by a maximum distance of 600 kb. The gene for type II maps to chromosome 2 in both mouse and man; hence, SCN3A in the human must be located on chromosome 2. Both of the genes were mapped to human chromosome 2 by study of human-hamster somatic cell hybrids; PCR with primers derived from the second cDNA was used for localizing the gene, which presumably was SCN3A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1679748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in situ hybridization, both of the genes mapped to 2q23-q24.3. <a href="#6" class="mim-tip-reference" title="Malo, M. S., Srivastava, K., Andresen, J. M., Chen, X.-N., Korenberg, J. R., Ingram, V. M. <strong>Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.</strong> Proc. Nat. Acad. Sci. 91: 2975-2979, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8159690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8159690</a>] [<a href="https://doi.org/10.1073/pnas.91.8.2975" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8159690">Malo et al. (1994)</a> mapped the SCN3A gene to chromosome 2 with 100% concordance using PCR on human/rodent somatic cell hybrid panels. By fluorescence in situ hybridization, they mapped the SCN3A gene to chromosome 2q24-q31. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8159690" 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="Kasai, N., Fukushima, K., Ueki, Y., Prasad, S., Nosakowski, J., Sugata, K., Sugata, A., Nishizaki, K., Meyer, N. C., Smith, R. J. H. <strong>Genomic structures of SCN2A and SCN3A--candidate genes for deafness at the DFNA16 locus.</strong> Gene 264: 113-122, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11245985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11245985</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00594-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11245985">Kasai et al. (2001)</a> reported that the human SCN3A gene maps to chromosome 2q24. The SCN2A and SCN3A genes are oriented head-to-head, separated by 40 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11245985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Familial Focal Epilepsy with Variable Foci 4</em></strong></p><p>
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In 4 unrelated patients with familial focal epilepsy with variable foci-4 (FFEVF4; <a href="/entry/617935">617935</a>), <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> identified 4 different heterozygous missense mutations in the SCN3A gene (see, e.g., <a href="#0001">182391.0001</a>-<a href="#0003">182391.0003</a>). The mutations were found by genetic screening of the SCN3A gene in 179 pediatric patients with focal epilepsy who were negative for mutations in the SCN1A (<a href="/entry/182389">182389</a>) gene. No family members were available for study, so analysis of inheritance pattern and/or segregation was not possible. In vitro functional expression studies showed that the mutations caused variable defects of channel function, with only some of the mutations altering the activation and/or inactivation kinetics. However, all the mutations resulted in increased inward currents during a slow depolarizing voltage ramp, indicating channel dysfunction capable of enhancing the response to subthreshold depolarizing inputs and promoting hyperexcitable networks. <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> noted that all the variants identified by <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> were found at a low frequency in the ExAC database and may either result in subtle changes in channel function or may act as risk alleles. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24157691+29466837" 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 an 2-year-old girl with FFEVF4, <a href="#4" class="mim-tip-reference" title="Lamar, T., Vanoye, C. G., Calhoun, J., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M., Escayg, A., Kearney, J. A. <strong>SCN3A deficiency associated with increased seizure susceptibility.</strong> Neurobiol. Dis. 102: 38-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28235671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28235671</a>] [<a href="https://doi.org/10.1016/j.nbd.2017.02.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28235671">Lamar et al. (2017)</a> identified a de novo heterozygous missense mutation in the SCN3A gene (L247P; <a href="#0004">182391.0004</a>). The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies showed that the mutant channel had no detectable sodium current resulting from a significant reduction of mutant SCN3A at the cell surface, suggesting that the mutation caused a trafficking defect. Fewer channels at the cell surface would be predicted to reduce the magnitude of the inward current, which may contribute to disease pathogenesis. The findings were consistent with a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28235671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Developmental and Epileptic Encephalopathy 62</em></strong></p><p>
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In 4 unrelated patients with developmental and epileptic encephalopathy-62 (DEE62; <a href="/entry/617938">617938</a>), <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> identified 3 different de novo heterozygous missense mutations in the SCN3A gene (<a href="#0005">182391.0005</a>-<a href="#0007">182391.0007</a>). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Whole-cell voltage clamp electrophysiologic recordings showed that the mutant channels had an increase of a slowly inactivating/noninactivating persistent current compared to controls, consistent with a gain-of-function effect. In addition, 2 variants (I875T, <a href="#0005">182391.0005</a> and P1333L, <a href="#0006">182391.0006</a>) caused a leftward shift in the voltage dependence of activation to a hyperpolarized potential. Both mechanisms were predicted to increase neuronal excitability. Both patients with the I875T variant had polymicrogyria. In vitro studies showed that the antiseizure medications lacosamide and phenytoin selectively blocked the abnormal currents. <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> noted that SCN3A is highly expressed in embryonic brain, with low or undetectable postnatal expression in rodents, which may explain why this encephalopathy presents in the early infantile period. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29466837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Lamar, T., Vanoye, C. G., Calhoun, J., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M., Escayg, A., Kearney, J. A. <strong>SCN3A deficiency associated with increased seizure susceptibility.</strong> Neurobiol. Dis. 102: 38-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28235671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28235671</a>] [<a href="https://doi.org/10.1016/j.nbd.2017.02.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28235671">Lamar et al. (2017)</a> found that heterozygous Scn3a +/- mice had decreased Scn3a mRNA and protein levels in the brain compared to wildtype. Mutant mice had increased susceptibility to induced seizures, but did not exhibit spontaneous seizures. Heterozygous mice also showed deficits in locomotor activity and motor learning. Some of the mutant mice showed focal cortical abnormalities, including disruptions in cortical lamination and invaginations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28235671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs774195502 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs774195502;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/rs774195502?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=rs774195502" 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=rs774195502" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a boy with familial focal epilepsy with variable foci-4 (FFEVF4; <a href="/entry/617935">617935</a>), <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> identified a heterozygous mutation in the SCN3A gene that resulted in an arg357-to-gln (R357Q) substitution at a highly conserved residue in the pore region of domain 1. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the R357Q substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> noted that the R357Q mutation was found at a low frequency in the ExAC database. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24157691+29466837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a boy with familial focal epilepsy with variable foci-4 (FFEVF4; <a href="/entry/617935">617935</a>), <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> identified a heterozygous mutation in the SCN3A gene that resulted in an asp766-to-asn (D766N) substitution at a highly conserved residue at the intracellular face of a transmembrane alpha helix. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the D766N substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> noted that this variant, which they referred to as D815N, was found at a low frequency in the ExAC database. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24157691+29466837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs758906955 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs758906955;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/rs758906955?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=rs758906955" 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=rs758906955" 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=RCV000625710 OR RCV001239906" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000625710, RCV001239906" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000625710...</a>
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<p>In an individual with familial focal epilepsy with variable foci-4 (FFEVF4; <a href="/entry/617935">617935</a>), <a href="#7" class="mim-tip-reference" title="Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A. <strong>Novel SCN3A variants associated with focal epilepsy in children.</strong> Neurobiol. Dis. 62: 313-322, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>] [<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24157691">Vanoye et al. (2014)</a> identified a heterozygous mutation in the SCN3A gene, resulting in a met1323-to-val (M1323V) substitution at a conserved residue in the extracellular linker between transmembrane segment 5 and the pore region of domain 2. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the M1323V substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> noted that this variant, which they referred to as M1372V, was found at a low frequency in the ExAC database. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24157691+29466837" 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">rs2105890565 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2105890565;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=rs2105890565" 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=rs2105890565" 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=RCV000625711" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000625711" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000625711</a>
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<p>In a 2-year-old girl with familial focal epilepsy with variable foci-4 (FFEVF4; <a href="/entry/617935">617935</a>), <a href="#4" class="mim-tip-reference" title="Lamar, T., Vanoye, C. G., Calhoun, J., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M., Escayg, A., Kearney, J. A. <strong>SCN3A deficiency associated with increased seizure susceptibility.</strong> Neurobiol. Dis. 102: 38-48, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28235671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28235671</a>] [<a href="https://doi.org/10.1016/j.nbd.2017.02.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28235671">Lamar et al. (2017)</a> identified a de novo heterozygous mutation in the SCN3A gene that resulted in a leu247-to-pro (L247P) substitution at a highly conserved residue at the cytoplasmic face of the S5 transmembrane segment in domain 1. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or ExAC databases. In vitro functional expression studies showed that the mutant channel had no detectable sodium current resulting from a significant reduction of mutant SCN3A at the cell surface, suggesting that the mutation caused a trafficking defect. Fewer channels at the cell surface would be predicted to reduce the magnitude of the inward current, which may contribute to disease pathogenesis. The findings were consistent with a loss-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28235671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</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">rs1057518801 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057518801;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=rs1057518801" 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=rs1057518801" 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=RCV000415038 OR RCV000494116 OR RCV000625712 OR RCV001199328 OR RCV003243119 OR RCV004798831" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000415038, RCV000494116, RCV000625712, RCV001199328, RCV003243119, RCV004798831" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000415038...</a>
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<p>In 2 unrelated patients with developmental and epileptic encephalopathy-62 (DEE62; <a href="/entry/617938">617938</a>), <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> identified a de novo heterozygous c.2624T-C transition in the SCN3A gene, resulting in an ile875-to-thr (I875T) substitution at a highly conserved residue in the S4-S5 linker of D2. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patients had onset of multifocal seizures at 2 weeks of age. In addition to seizures, both patients had polymicrogyria on brain imaging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29466837" 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>.0006 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</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">rs1057520753 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1057520753;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=rs1057520753" 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=rs1057520753" 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=RCV000420271 OR RCV000625713 OR RCV003992291" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000420271, RCV000625713, RCV003992291" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000420271...</a>
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<p>In a patient with developmental and epileptic encephalopathy-62 (DEE62; <a href="/entry/617938">617938</a>), <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> identified a de novo heterozygous c.3998C-T transition in the SCN3A gene, resulting in pro1333-to-leu (P1333L) substitution at a highly conserved residue in the S4-S5 linker of D3. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patient had onset of seizures on the first day of life. EEG showed multifocal discharges and hypsarrhythmia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29466837" 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>.0007 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</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">rs1553517274 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553517274;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=rs1553517274" 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=rs1553517274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with developmental and epileptic encephalopathy-62 (DEE62; <a href="/entry/617938">617938</a>), <a href="#8" class="mim-tip-reference" title="Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M. <strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong> Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>] [<a href="https://doi.org/10.1002/ana.25188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29466837">Zaman et al. (2018)</a> identified a de novo heterozygous c.5306T-C transition in the SCN3A gene, resulting in a val1769-to-ala (V1769A) substitution at a highly conserved residue in the S6 segment of D4. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patient had onset of seizures associated with multifocal discharges in the first year of life. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29466837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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</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 id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<ol>
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<li>
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<a id="1" class="mim-anchor"></a>
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<a id="Ahmed1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ahmed, C. M. I., Ware, D. H., Lee, S. C., Patten, C. D., Ferrer-Montiel, A. V., Schinder, A. F., McPherson, J. D., Wagner-McPherson, C. B., Wasmuth, J. J., Evans, G. A., Montal, M.
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|
<strong>Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain.</strong>
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|
Proc. Nat. Acad. Sci. 89: 8220-8224, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1325650/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1325650</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1325650" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.89.17.8220" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="2" class="mim-anchor"></a>
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<a id="Chen2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Chen, Y. H., Dale, T. J., Romanos, M. A., Whitaker, W. R. J., Xie, X. M., Clare, J. J.
|
|
<strong>Cloning, distribution and functional analysis of the type III sodium channel from human brain.</strong>
|
|
Europ. J. Neurosci. 12: 4281-4289, 2000.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11122339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11122339</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11122339" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="3" class="mim-anchor"></a>
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<a id="Kasai2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kasai, N., Fukushima, K., Ueki, Y., Prasad, S., Nosakowski, J., Sugata, K., Sugata, A., Nishizaki, K., Meyer, N. C., Smith, R. J. H.
|
|
<strong>Genomic structures of SCN2A and SCN3A--candidate genes for deafness at the DFNA16 locus.</strong>
|
|
Gene 264: 113-122, 2001.
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|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11245985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11245985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11245985" 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/s0378-1119(00)00594-1" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Lamar2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lamar, T., Vanoye, C. G., Calhoun, J., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M., Escayg, A., Kearney, J. A.
|
|
<strong>SCN3A deficiency associated with increased seizure susceptibility.</strong>
|
|
Neurobiol. Dis. 102: 38-48, 2017.
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|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28235671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28235671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28235671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nbd.2017.02.006" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Malo1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Malo, D., Schurr, E., Dorfman, J., Canfield, V., Levenson, R., Gros, P.
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|
<strong>Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2.</strong>
|
|
Genomics 10: 666-672, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1679748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1679748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1679748" 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/10.1016/0888-7543(91)90450-s" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Malo1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Malo, M. S., Srivastava, K., Andresen, J. M., Chen, X.-N., Korenberg, J. R., Ingram, V. M.
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<strong>Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.</strong>
|
|
Proc. Nat. Acad. Sci. 91: 2975-2979, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8159690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8159690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8159690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.91.8.2975" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Vanoye2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A.
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<strong>Novel SCN3A variants associated with focal epilepsy in children.</strong>
|
|
Neurobiol. Dis. 62: 313-322, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24157691/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24157691</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24157691" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nbd.2013.10.015" target="_blank">Full Text</a>]
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</p>
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</li>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Zaman2018" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M.
|
|
<strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong>
|
|
Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29466837/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29466837</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29466837" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.25188" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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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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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 04/17/2018
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 03/08/2016<br>Patricia A. Hartz - updated : 11/10/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/20/1991
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 11/17/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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joanna : 11/04/2020<br>carol : 09/01/2020<br>carol : 10/14/2019<br>carol : 10/08/2019<br>alopez : 06/05/2018<br>alopez : 04/18/2018<br>ckniffin : 04/17/2018<br>alopez : 09/02/2016<br>alopez : 03/08/2016<br>wwang : 11/16/2006<br>terry : 11/10/2006<br>carol : 10/4/2006<br>mgross : 10/30/2003<br>kayiaros : 7/8/1999<br>mark : 9/11/1997<br>carol : 6/7/1994<br>carol : 9/29/1992<br>supermim : 3/16/1992<br>carol : 6/20/1991
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 182391
|
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</span>
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</h3>
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</div>
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<div>
|
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<h3>
|
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<span class="mim-font">
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SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 3; SCN3A
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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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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
SODIUM CHANNEL, VOLTAGE-GATED, TYPE III, ALPHA SUBUNIT<br />
|
|
SODIUM CHANNEL, NEURONAL TYPE III, ALPHA SUBUNIT<br />
|
|
SODIUM CHANNEL, BRAIN TYPE III, ALPHA SUBUNIT; NAC3<br />
|
|
NAV1.3
|
|
</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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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: SCN3A</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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<p>
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: 2q24.3
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 2:165,087,526-165,204,050 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
2q24.3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Developmental and epileptic encephalopathy 62
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617938
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Epilepsy, familial focal, with variable foci 4
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
617935
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
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</tbody>
|
|
</table>
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</div>
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</div>
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<div>
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<br />
|
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</div>
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<div>
|
|
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
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</div>
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<span class="mim-text-font">
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<p>The SCN3A gene encodes the alpha subunit of the voltage-gated sodium channel Na(v)1.3, which shows rapid activation and inactivation (summary by Vanoye et al., 2014). </p><p>Voltage-gated sodium channels from the central nervous system consist of a large pore-forming alpha subunit, such as SCN3A, associated with smaller auxiliary subunits (see SCN1B, 600235) (Chen et al., 2000). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ahmed et al. (1992) isolated 2 cDNAs from a human cerebral cortex library by screening for the presence of sodium channel alpha-subunit-specific clones. One of the clones showed greatest homology to rat brain sodium channel II. The second clone encoded a different subtype sodium channel, probably a type III channel. </p><p>By RT-PCR of frontal pole mRNA using primers based on rat sodium channel cDNAs, followed by screening a human cerebellum cDNA library, Chen et al. (2000) cloned SCN3A. The deduced 1,951-amino acid protein contains 24 transmembrane domains. Northern blot analysis detected a transcript of about 9.5 kb with strong expression in brain, weak expression in heart, and no expression in placenta, lung, liver, kidney, or pancreas. A strong band of about 7.5 kb was also found in skeletal muscle. Within specific brain regions, highest SCN3A expression was detected in cerebellum and frontal lobe, with moderate expression in amygdala, caudate nucleus, hippocampus, substantia nigra, medulla, and occipital pole, weak expression in subthalamic nucleus, thalamus, cerebral cortex, temporal lobe, and putamen, and no expression in corpus callosum and spinal cord. </p><p>By EST database analysis, 3-prime RACE, and long-range PCR of human cDNA libraries, Kasai et al. (2001) cloned splice variants of SCN3A that differed in inclusion or exclusion of a 5-prime noncoding exon, selection of exon 6A or 6N, which are identical in size, and inclusion or exclusion of coding exon 12b. Transcripts with and without exon 12b encode proteins of 1,983 and 1,951 amino acids, respectively. Transcripts containing exon 6N were detected in lymphocyte and fetal brain cDNA libraries, and transcripts containing 6A were found in adult human brain. Transcripts containing exon 12b were detected in lymphocyte, fetal brain, and adult brain libraries, but no SCN3A expression was detected in human fetal cochlea. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Chen et al. (2000) found that stable expression of SCN3A in Chinese hamster ovary cells resulted in a robust inward sodium current. The voltage dependence and kinetics of activation/inactivation of SCN3A were similar to that of SCN2A (182390). However, SCN3A inactivated at more hyperpolarized potentials and was slower to recover from inactivation than SCN2A. When expressed in human embryonic kidney cells, SCN3A produced currents with a prominent persistent component, similar to that reported for rat type II channels; however, unlike type II channels, the persistent component was prominent even in the absence of coexpressed G proteins. </p><p>Vanoye et al. (2014) did not observe large persistent sodium currents in cells expressing wildtype SCN3A using an exon 5A splice variant with an aspartic acid at position 208, rather than exon 5N, which has a serine at position 208. Additional in vitro comparisons of both variants indicated that they had similar persistent currents, suggesting that large persistent current is not an intrinsic property of the Na(v)1.3 channel. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</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>Kasai et al. (2001) determined that the SCN3A gene spans approximately 120 kb and has 30 exons, including a noncoding alternative first exon, alternative exons 6, and alternative exon 12b. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>On physical mapping by pulsed field gel electrophoresis in the mouse, Malo et al. (1991) demonstrated that the Scn2a and Scn3a genes encoding type II and type III sodium channel alpha-subunit isoforms, respectively, are physically linked and are separated by a maximum distance of 600 kb. The gene for type II maps to chromosome 2 in both mouse and man; hence, SCN3A in the human must be located on chromosome 2. Both of the genes were mapped to human chromosome 2 by study of human-hamster somatic cell hybrids; PCR with primers derived from the second cDNA was used for localizing the gene, which presumably was SCN3A. </p><p>By in situ hybridization, both of the genes mapped to 2q23-q24.3. Malo et al. (1994) mapped the SCN3A gene to chromosome 2 with 100% concordance using PCR on human/rodent somatic cell hybrid panels. By fluorescence in situ hybridization, they mapped the SCN3A gene to chromosome 2q24-q31. </p><p>Kasai et al. (2001) reported that the human SCN3A gene maps to chromosome 2q24. The SCN2A and SCN3A genes are oriented head-to-head, separated by 40 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Familial Focal Epilepsy with Variable Foci 4</em></strong></p><p>
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In 4 unrelated patients with familial focal epilepsy with variable foci-4 (FFEVF4; 617935), Vanoye et al. (2014) identified 4 different heterozygous missense mutations in the SCN3A gene (see, e.g., 182391.0001-182391.0003). The mutations were found by genetic screening of the SCN3A gene in 179 pediatric patients with focal epilepsy who were negative for mutations in the SCN1A (182389) gene. No family members were available for study, so analysis of inheritance pattern and/or segregation was not possible. In vitro functional expression studies showed that the mutations caused variable defects of channel function, with only some of the mutations altering the activation and/or inactivation kinetics. However, all the mutations resulted in increased inward currents during a slow depolarizing voltage ramp, indicating channel dysfunction capable of enhancing the response to subthreshold depolarizing inputs and promoting hyperexcitable networks. Zaman et al. (2018) noted that all the variants identified by Vanoye et al. (2014) were found at a low frequency in the ExAC database and may either result in subtle changes in channel function or may act as risk alleles. </p><p>In an 2-year-old girl with FFEVF4, Lamar et al. (2017) identified a de novo heterozygous missense mutation in the SCN3A gene (L247P; 182391.0004). The mutation was found by exome sequencing and confirmed by Sanger sequencing. In vitro functional expression studies showed that the mutant channel had no detectable sodium current resulting from a significant reduction of mutant SCN3A at the cell surface, suggesting that the mutation caused a trafficking defect. Fewer channels at the cell surface would be predicted to reduce the magnitude of the inward current, which may contribute to disease pathogenesis. The findings were consistent with a loss-of-function effect. </p><p><strong><em>Developmental and Epileptic Encephalopathy 62</em></strong></p><p>
|
|
In 4 unrelated patients with developmental and epileptic encephalopathy-62 (DEE62; 617938), Zaman et al. (2018) identified 3 different de novo heterozygous missense mutations in the SCN3A gene (182391.0005-182391.0007). The mutations were found by exome sequencing and confirmed by Sanger sequencing. Whole-cell voltage clamp electrophysiologic recordings showed that the mutant channels had an increase of a slowly inactivating/noninactivating persistent current compared to controls, consistent with a gain-of-function effect. In addition, 2 variants (I875T, 182391.0005 and P1333L, 182391.0006) caused a leftward shift in the voltage dependence of activation to a hyperpolarized potential. Both mechanisms were predicted to increase neuronal excitability. Both patients with the I875T variant had polymicrogyria. In vitro studies showed that the antiseizure medications lacosamide and phenytoin selectively blocked the abnormal currents. Zaman et al. (2018) noted that SCN3A is highly expressed in embryonic brain, with low or undetectable postnatal expression in rodents, which may explain why this encephalopathy presents in the early infantile period. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Lamar et al. (2017) found that heterozygous Scn3a +/- mice had decreased Scn3a mRNA and protein levels in the brain compared to wildtype. Mutant mice had increased susceptibility to induced seizures, but did not exhibit spontaneous seizures. Heterozygous mice also showed deficits in locomotor activity and motor learning. Some of the mutant mice showed focal cortical abnormalities, including disruptions in cortical lamination and invaginations. </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>7 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 EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 4</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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SCN3A, ARG357GLN
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<br />
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SNP: rs774195502,
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gnomAD: rs774195502,
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ClinVar: RCV000625708, RCV000819557
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
<p>In a boy with familial focal epilepsy with variable foci-4 (FFEVF4; 617935), Vanoye et al. (2014) identified a heterozygous mutation in the SCN3A gene that resulted in an arg357-to-gln (R357Q) substitution at a highly conserved residue in the pore region of domain 1. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the R357Q substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. Zaman et al. (2018) noted that the R357Q mutation was found at a low frequency in the ExAC database. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 4</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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|
SCN3A, ASP766ASN
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<br />
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SNP: rs755440336,
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|
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gnomAD: rs755440336,
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|
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ClinVar: RCV000625709, RCV001855321, RCV002252180
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|
|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a boy with familial focal epilepsy with variable foci-4 (FFEVF4; 617935), Vanoye et al. (2014) identified a heterozygous mutation in the SCN3A gene that resulted in an asp766-to-asn (D766N) substitution at a highly conserved residue at the intracellular face of a transmembrane alpha helix. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the D766N substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. Zaman et al. (2018) noted that this variant, which they referred to as D815N, was found at a low frequency in the ExAC database. </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>.0003 EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
|
|
SCN3A, MET1323VAL
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<br />
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|
|
SNP: rs758906955,
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|
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gnomAD: rs758906955,
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|
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ClinVar: RCV000625710, RCV001239906
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|
|
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|
|
</span>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an individual with familial focal epilepsy with variable foci-4 (FFEVF4; 617935), Vanoye et al. (2014) identified a heterozygous mutation in the SCN3A gene, resulting in a met1323-to-val (M1323V) substitution at a conserved residue in the extracellular linker between transmembrane segment 5 and the pore region of domain 2. The authors noted that nucleotide numbering corresponded to the major SCN53A isoform that includes the exon 5 adult (5A) and exon 12v1 (646 bp) splice variants (NM_001081676.1), although they did not include the nucleotide change that resulted in the M1323V substitution. The mutation was found by exome sequencing; parental DNA was not available for study. The mutation was not found in the Exome Variant Server or in 590 control chromosomes. Zaman et al. (2018) noted that this variant, which they referred to as M1372V, was found at a low frequency in the ExAC database. </p>
|
|
</span>
|
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</div>
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<div>
|
|
<br />
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|
</div>
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</div>
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 4</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN3A, LEU247PRO
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|
|
|
|
<br />
|
|
|
|
SNP: rs2105890565,
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|
|
|
|
|
|
|
ClinVar: RCV000625711
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|
|
|
|
|
</span>
|
|
</div>
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 2-year-old girl with familial focal epilepsy with variable foci-4 (FFEVF4; 617935), Lamar et al. (2017) identified a de novo heterozygous mutation in the SCN3A gene that resulted in a leu247-to-pro (L247P) substitution at a highly conserved residue at the cytoplasmic face of the S5 transmembrane segment in domain 1. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or ExAC databases. In vitro functional expression studies showed that the mutant channel had no detectable sodium current resulting from a significant reduction of mutant SCN3A at the cell surface, suggesting that the mutation caused a trafficking defect. Fewer channels at the cell surface would be predicted to reduce the magnitude of the inward current, which may contribute to disease pathogenesis. The findings were consistent with a loss-of-function effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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<div>
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|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN3A, ILE875THR
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|
|
|
|
|
<br />
|
|
|
|
SNP: rs1057518801,
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|
|
|
|
ClinVar: RCV000415038, RCV000494116, RCV000625712, RCV001199328, RCV003243119, RCV004798831
|
|
|
|
|
|
</span>
|
|
</div>
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with developmental and epileptic encephalopathy-62 (DEE62; 617938), Zaman et al. (2018) identified a de novo heterozygous c.2624T-C transition in the SCN3A gene, resulting in an ile875-to-thr (I875T) substitution at a highly conserved residue in the S4-S5 linker of D2. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patients had onset of multifocal seizures at 2 weeks of age. In addition to seizures, both patients had polymicrogyria on brain imaging. </p>
|
|
</span>
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</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</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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|
SCN3A, PRO1333LEU
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<br />
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|
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SNP: rs1057520753,
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|
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|
|
ClinVar: RCV000420271, RCV000625713, RCV003992291
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|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with developmental and epileptic encephalopathy-62 (DEE62; 617938), Zaman et al. (2018) identified a de novo heterozygous c.3998C-T transition in the SCN3A gene, resulting in pro1333-to-leu (P1333L) substitution at a highly conserved residue in the S4-S5 linker of D3. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patient had onset of seizures on the first day of life. EEG showed multifocal discharges and hypsarrhythmia. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 62</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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SCN3A, VAL1769ALA
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<br />
|
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|
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SNP: rs1553517274,
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ClinVar: RCV000622981, RCV000625714, RCV003992349
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a patient with developmental and epileptic encephalopathy-62 (DEE62; 617938), Zaman et al. (2018) identified a de novo heterozygous c.5306T-C transition in the SCN3A gene, resulting in a val1769-to-ala (V1769A) substitution at a highly conserved residue in the S6 segment of D4. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Variant Server or gnomAD databases. The patient had onset of seizures associated with multifocal discharges in the first year of life. </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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<span class="mim-font">
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<strong>REFERENCES</strong>
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Ahmed, C. M. I., Ware, D. H., Lee, S. C., Patten, C. D., Ferrer-Montiel, A. V., Schinder, A. F., McPherson, J. D., Wagner-McPherson, C. B., Wasmuth, J. J., Evans, G. A., Montal, M.
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<strong>Primary structure, chromosomal localization, and functional expression of a voltage-gated sodium channel from human brain.</strong>
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Proc. Nat. Acad. Sci. 89: 8220-8224, 1992.
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[PubMed: 1325650]
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[Full Text: https://doi.org/10.1073/pnas.89.17.8220]
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Chen, Y. H., Dale, T. J., Romanos, M. A., Whitaker, W. R. J., Xie, X. M., Clare, J. J.
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<strong>Cloning, distribution and functional analysis of the type III sodium channel from human brain.</strong>
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Europ. J. Neurosci. 12: 4281-4289, 2000.
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[PubMed: 11122339]
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Kasai, N., Fukushima, K., Ueki, Y., Prasad, S., Nosakowski, J., Sugata, K., Sugata, A., Nishizaki, K., Meyer, N. C., Smith, R. J. H.
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<strong>Genomic structures of SCN2A and SCN3A--candidate genes for deafness at the DFNA16 locus.</strong>
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Gene 264: 113-122, 2001.
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[PubMed: 11245985]
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[Full Text: https://doi.org/10.1016/s0378-1119(00)00594-1]
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Lamar, T., Vanoye, C. G., Calhoun, J., Wong, J. C., Dutton, S. B. B., Jorge, B. S., Velinov, M., Escayg, A., Kearney, J. A.
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<strong>SCN3A deficiency associated with increased seizure susceptibility.</strong>
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Neurobiol. Dis. 102: 38-48, 2017.
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[PubMed: 28235671]
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[Full Text: https://doi.org/10.1016/j.nbd.2017.02.006]
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Malo, D., Schurr, E., Dorfman, J., Canfield, V., Levenson, R., Gros, P.
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<strong>Three brain sodium channel alpha-subunit genes are clustered on the proximal segment of mouse chromosome 2.</strong>
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Genomics 10: 666-672, 1991.
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[PubMed: 1679748]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90450-s]
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Malo, M. S., Srivastava, K., Andresen, J. M., Chen, X.-N., Korenberg, J. R., Ingram, V. M.
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<strong>Targeted gene walking by low stringency polymerase chain reaction: assignment of a putative human brain sodium channel gene (SCN3A) to chromosome 2q24-31.</strong>
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Proc. Nat. Acad. Sci. 91: 2975-2979, 1994.
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[PubMed: 8159690]
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[Full Text: https://doi.org/10.1073/pnas.91.8.2975]
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Vanoye, C. G., Gurnett, C. A., Holland, K. D., George, A. L., Jr., Kearney, J. A.
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<strong>Novel SCN3A variants associated with focal epilepsy in children.</strong>
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Neurobiol. Dis. 62: 313-322, 2014.
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[PubMed: 24157691]
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[Full Text: https://doi.org/10.1016/j.nbd.2013.10.015]
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Zaman, T., Helbig, I., Babic Bozovic, I., DeBrosse, S. D, Bergqvist, A. C., Wallis, K., Medne, L., Maver, A., Peterlin, B., Helbig, K. L., Zhang, X., Goldberg, E. M.
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<strong>Mutations in SCN3A cause early infantile epileptic encephalopathy.</strong>
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Ann. Neurol. 83: 703-717, 2018. Note: Erratum: Ann. Neurol. 85: 948 only, 2019.
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[PubMed: 29466837]
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[Full Text: https://doi.org/10.1002/ana.25188]
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Cassandra L. Kniffin - updated : 04/17/2018<br>Patricia A. Hartz - updated : 03/08/2016<br>Patricia A. Hartz - updated : 11/10/2006
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Victor A. McKusick : 6/20/1991
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alopez : 11/17/2020<br>joanna : 11/04/2020<br>carol : 09/01/2020<br>carol : 10/14/2019<br>carol : 10/08/2019<br>alopez : 06/05/2018<br>alopez : 04/18/2018<br>ckniffin : 04/17/2018<br>alopez : 09/02/2016<br>alopez : 03/08/2016<br>wwang : 11/16/2006<br>terry : 11/10/2006<br>carol : 10/4/2006<br>mgross : 10/30/2003<br>kayiaros : 7/8/1999<br>mark : 9/11/1997<br>carol : 6/7/1994<br>carol : 9/29/1992<br>supermim : 3/16/1992<br>carol : 6/20/1991
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