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- *604427 - SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 10; SCN10A
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- OMIM
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<p>
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<span class="h4">*604427</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/604427">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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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<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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<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=ENSG00000185313;t=ENST00000449082" 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=6336" 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=604427" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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<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=ENSG00000185313;t=ENST00000449082" 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_001293306,NM_001293307,NM_006514,XM_005265371,XM_011533993,XM_011533994" 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_006514" 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=604427" 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=09188&isoform_id=09188_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/SCN10A" 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/4838145,55163977,55163979,119584947,205371821,530372954,693064350,693072646,767923975,767923977,1884731817,2462591808,2462591810,2462591812" 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/Q9Y5Y9" 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=6336" 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=ENSG00000185313;t=ENST00000449082" 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=SCN10A" 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=SCN10A" 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+6336" 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/SCN10A" 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:6336" 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/6336" 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=chr3&hgg_gene=ENST00000449082.3&hgg_start=38696807&hgg_end=38816217&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:10582" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/scn10a" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=604427[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 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=604427[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/SCN10A/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/ENSG00000185313" 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=SCN10A" 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=SCN10A" 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=SCN10A" 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=SCN10A&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/PA35000" 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:10582" 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:108029" 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/SCN10A#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:108029" 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/6336/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=6336" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SCN10A&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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604427
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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 10; SCN10A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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SODIUM CHANNEL, VOLTAGE-GATED, TYPE X, ALPHA SUBUNIT<br />
|
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NAV1.8<br />
|
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PN3<br />
|
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SENSORY NEURON-SPECIFIC SODIUM CHANNEL; SNS
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SCN10A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SCN10A</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/3/182?start=-3&limit=10&highlight=182">3p22.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:38696807-38816217&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'})">3:38,696,807-38,816,217</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/3/182?start=-3&limit=10&highlight=182">
|
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3p22.2
|
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Episodic pain syndrome, familial, 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615551"> 615551 </a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/604427" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/604427" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
|
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</h4>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The SCN10A gene encodes the alpha subunit of a voltage-gated sodium channel. Voltage-gated sodium channels are integral membrane glycoproteins that are responsible for the initial rising phase of action in most excitable cells. They are composed of a large alpha subunit that may be associated with one or more smaller beta subunits. Sodium channels can be differentiated by their primary structure, kinetics, and relative sensitivity to the neurotoxin tetrodotoxin (TTX). Sodium channels, particularly those with TTX-resistant currents, have been found to accumulate in the region of peripheral nerve injury and may be important in chronic pain. SCN10A encodes a TTX-resistant channel that is restricted to the peripheral sensory nervous system (<a href="#9" class="mim-tip-reference" title="Rabert, D. K., Koch, B. D., Ilnicka, M., Obernolte, R. A., Naylor, S. L., Herman, R. C., Eglen, R. M., Hunter, J. C., Sangameswaran, L. <strong>A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.</strong> Pain 78: 107-114, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9839820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9839820</a>] [<a href="https://doi.org/10.1016/S0304-3959(98)00120-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9839820">Rabert et al., 1998</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9839820" 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="#11" class="mim-tip-reference" title="Sangameswaran, L., Delgado, S. G., Fish, L. M., Koch, B. D., Jakeman, L. B., Stewart, G. R., Sze, P., Hunter, J. C., Eglen, R. M., Herman, R. C. <strong>Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons.</strong> J. Biol. Chem. 271: 5953-5956, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626372</a>] [<a href="https://doi.org/10.1074/jbc.271.11.5953" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8626372">Sangameswaran et al. (1996)</a> and <a href="#2" class="mim-tip-reference" title="Akopian, A. N., Sivilotti, L., Wood, J. N. <strong>A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.</strong> Nature 379: 257-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8538791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8538791</a>] [<a href="https://doi.org/10.1038/379257a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8538791">Akopian et al. (1996)</a> independently identified a sodium channel that produced TTX-resistant currents in rat dorsal root ganglion (DRG). <a href="#11" class="mim-tip-reference" title="Sangameswaran, L., Delgado, S. G., Fish, L. M., Koch, B. D., Jakeman, L. B., Stewart, G. R., Sze, P., Hunter, J. C., Eglen, R. M., Herman, R. C. <strong>Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons.</strong> J. Biol. Chem. 271: 5953-5956, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626372</a>] [<a href="https://doi.org/10.1074/jbc.271.11.5953" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8626372">Sangameswaran et al. (1996)</a> called the channel Pn3, and <a href="#2" class="mim-tip-reference" title="Akopian, A. N., Sivilotti, L., Wood, J. N. <strong>A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.</strong> Nature 379: 257-262, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8538791/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8538791</a>] [<a href="https://doi.org/10.1038/379257a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8538791">Akopian et al. (1996)</a> called the channel Sns. <a href="#9" class="mim-tip-reference" title="Rabert, D. K., Koch, B. D., Ilnicka, M., Obernolte, R. A., Naylor, S. L., Herman, R. C., Eglen, R. M., Hunter, J. C., Sangameswaran, L. <strong>A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.</strong> Pain 78: 107-114, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9839820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9839820</a>] [<a href="https://doi.org/10.1016/S0304-3959(98)00120-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9839820">Rabert et al. (1998)</a> obtained the full-length coding sequence for human PN3, symbolized SCN10A, from a human DRG cDNA library. The predicted 1,956-amino acid SCN10A protein contains all the features of a voltage-gated sodium channel: 4 homologous domains consisting of 6 putative alpha-helical transmembrane segments, positively charged residues in the voltage-sensor transmembrane segments, and the ile-phe-met sequence within the highly conserved interdomain region. The amino acid sequence is 90.2% similar to rat PN3 and 70.4% similar to the human cardiac channel, SCN5A (<a href="/entry/600163">600163</a>). By RT-PCR analysis, PN3 is expressed in the peripheral sensory nervous system (i.e., DRG and sciatic nerve) but not in spinal cord, brain, skeletal muscle, or heart. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9839820+8626372+8538791" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By analysis of a panel of somatic cell hybrids, <a href="#9" class="mim-tip-reference" title="Rabert, D. K., Koch, B. D., Ilnicka, M., Obernolte, R. A., Naylor, S. L., Herman, R. C., Eglen, R. M., Hunter, J. C., Sangameswaran, L. <strong>A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.</strong> Pain 78: 107-114, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9839820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9839820</a>] [<a href="https://doi.org/10.1016/S0304-3959(98)00120-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9839820">Rabert et al. (1998)</a> mapped the SCN10A gene to chromosome 3p24.2-p22. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9839820" 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="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 12/3/2013."None>Gross (2013)</a> mapped the SCN10A gene to chromosome 3p22.2 based on an alignment of the SCN10A sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AF117907" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AF117907</a>) with the genomic sequence (GRCh37).</p>
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<p><a href="#8" class="mim-tip-reference" title="Okuse, K., Malik-Hall, M., Baker, M. D., Poon, W.-Y. L., Kong, H., Chao, M. V., Wood, J. N. <strong>Annexin II light chain regulates sensory neuron-specific sodium channel expression.</strong> Nature 417: 653-656, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050667</a>] [<a href="https://doi.org/10.1038/nature00781" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12050667">Okuse et al. (2002)</a> noted earlier work with rats indicating that SCN10A, which they called NAV1.8/SNS, is restricted to small-diameter C-fiber-associated rat sensory neurons and appears to have a role in pain pathways. By a yeast 2-hybrid screen of a rat sensory neuron cDNA library, they found that the annexin II light chain, p11 (S100A10; <a href="/entry/114085">114085</a>), interacts with the N-terminal intracellular domain of rat Nav1.8. Transfection of p11 into Chinese hamster ovary (CHO) cells stably expressing rat Nav1.8 demonstrated that p11 can behave as an accessory beta subunit, promoting the translocation of Nav1.8 to the plasma membrane and generating functional sodium channels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Zimmermann, K., Leffler, A., Babes, A., Cendan, C. M., Carr, R. W., Kobayashi, J., Nau, C., Wood, J. N., Reeh, P. W. <strong>Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures.</strong> Nature 447: 855-858, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17568746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17568746</a>] [<a href="https://doi.org/10.1038/nature05880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17568746">Zimmermann et al. (2007)</a> showed the continuation of nociceptors to function at low temperatures is achieved by endowing superficial endings of slowly conducting nociceptive fibers with the tetrodotoxin-resistant voltage-gated sodium channel NAV1.8. This channel is essential for sustained excitability of nociceptors when the skin is cooled. <a href="#12" class="mim-tip-reference" title="Zimmermann, K., Leffler, A., Babes, A., Cendan, C. M., Carr, R. W., Kobayashi, J., Nau, C., Wood, J. N., Reeh, P. W. <strong>Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures.</strong> Nature 447: 855-858, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17568746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17568746</a>] [<a href="https://doi.org/10.1038/nature05880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17568746">Zimmermann et al. (2007)</a> showed that cooling excitable membranes progressively enhanced the voltage-dependent slow inactivation of tetrodotoxin-sensitive voltage-gated sodium channels. In contrast, the inactivation properties of NAV1.8 were entirely cold-resistant. Moreover, low temperatures decreased the activation threshold of the sodium currents and increased the membrane resistance, augmenting the voltage change caused by any membrane current. Thus, in the cold, NAV1.8 remains available as the sole electrical impulse generator in nociceptors that transmits nociceptive information to the central nervous system. Consistent with this concept was the observation that Nav1.8-null mutant mice (developed by <a href="#3" class="mim-tip-reference" title="Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., Wood, J. N. <strong>The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.</strong> Nature Neurosci. 2: 541-548, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448219</a>] [<a href="https://doi.org/10.1038/9195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448219">Akopian et al., 1999</a>) showed negligible responses to noxious cold and mechanical stimulation at low temperatures. <a href="#12" class="mim-tip-reference" title="Zimmermann, K., Leffler, A., Babes, A., Cendan, C. M., Carr, R. W., Kobayashi, J., Nau, C., Wood, J. N., Reeh, P. W. <strong>Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures.</strong> Nature 447: 855-858, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17568746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17568746</a>] [<a href="https://doi.org/10.1038/nature05880" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17568746">Zimmermann et al. (2007)</a> concluded that their data provided strong evidence for a specialized role of NAV1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17568746+10448219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which generate an inward current, I-h, after hyperpolarization of the membrane. <a href="#5" class="mim-tip-reference" title="Emery, E. C., Young, G. T., Berrocoso, E. M., Chen, L., McNaughton, P. A. <strong>HCN2 ion channels play a central role in inflammatory and neuropathic pain.</strong> Science 333: 1462-1466, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21903816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21903816</a>] [<a href="https://doi.org/10.1126/science.1206243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21903816">Emery et al. (2011)</a> found that genetic deletion of HCN2 (<a href="/entry/602781">602781</a>) removed the cAMP-sensitive component of I-h and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Nav1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. <a href="#5" class="mim-tip-reference" title="Emery, E. C., Young, G. T., Berrocoso, E. M., Chen, L., McNaughton, P. A. <strong>HCN2 ion channels play a central role in inflammatory and neuropathic pain.</strong> Science 333: 1462-1466, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21903816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21903816</a>] [<a href="https://doi.org/10.1126/science.1206243" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21903816">Emery et al. (2011)</a> concluded that neuropathic pain is therefore initiated by HCN2-driven action potential firing in NAV1.8-expressing nociceptors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21903816" 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="#4" class="mim-tip-reference" title="Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., Wainger, B., Strominger, A., Muralidharan, S., Horswill, A. R., Wardenburg, J. B., Hwang, S. W., Carroll, M. C., Woolf, C. J. <strong>Bacteria activate sensory neurons that modulate pain and inflammation.</strong> Nature 501: 52-57, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23965627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23965627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23965627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23965627">Chiu et al. (2013)</a> demonstrated that bacteria directly activate nociceptors and that the immune response mediated through TLR2 (<a href="/entry/603028">603028</a>), MYD88 (<a href="/entry/602170">602170</a>), T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin alpha-hemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. <a href="#4" class="mim-tip-reference" title="Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., Wainger, B., Strominger, A., Muralidharan, S., Horswill, A. R., Wardenburg, J. B., Hwang, S. W., Carroll, M. C., Woolf, C. J. <strong>Bacteria activate sensory neurons that modulate pain and inflammation.</strong> Nature 501: 52-57, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23965627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23965627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23965627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature12479" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23965627">Chiu et al. (2013)</a> concluded that bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23965627" 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="#10" class="mim-tip-reference" title="Riol-Blanco, L., Ordovas-Montanes, J., Perro, M., Naval, E., Thiriot, A., Alvarez, D., Paust, S., Wood, J. N., von Andrian, U. H. <strong>Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.</strong> Nature 510: 157-161, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24759321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24759321</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24759321[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24759321">Riol-Blanco et al. (2014)</a> exposed the skin of mice to imiquimod, which induces IL23 (see <a href="/entry/605580">605580</a>)-dependent psoriasis-like inflammation, and showed that a subset of sensory neurons expressing the ion channels TRPV1 (<a href="/entry/602076">602076</a>) and NAV1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of dermal dendritic cells (DDCs), the principal source of IL23, is in close contact with these nociceptors. Upon selective pharmacologic or genetic ablation of nociceptors, DDCs failed to produce IL23 in imiquimod-exposed skin. Consequently, the local production of IL23-dependent inflammatory cytokines by dermal gamma-delta-T17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response. <a href="#10" class="mim-tip-reference" title="Riol-Blanco, L., Ordovas-Montanes, J., Perro, M., Naval, E., Thiriot, A., Alvarez, D., Paust, S., Wood, J. N., von Andrian, U. H. <strong>Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.</strong> Nature 510: 157-161, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24759321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24759321</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24759321[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature13199" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24759321">Riol-Blanco et al. (2014)</a> concluded that TRPV1-positive/NAV1.8-positive nociceptors, by interacting with DDCs, regulate the IL23/IL17 (<a href="/entry/603149">603149</a>) pathway and control cutaneous immune responses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24759321" 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 father and son with adult-onset familial episodic pain syndrome-2 (FEPS2; <a href="/entry/615551">615551</a>), <a href="#6" class="mim-tip-reference" title="Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G. <strong>Gain-of-function Nav1.8 mutations in painful neuropathy.</strong> Proc. Nat. Acad. Sci. 109: 19444-19449, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23115331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23115331</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23115331[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1216080109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23115331">Faber et al. (2012)</a> identified a heterozygous missense mutation in the SCN10A gene (L554P; <a href="#0001">604427.0001</a>). An unrelated woman with a similar disorder carried a different heterozygous mutation (A1304T; <a href="#0002">604427.0002</a>). In vitro functional expression studies in mouse dorsal root ganglia neurons showed that both mutations caused enhanced channel electrical activities and induced hyperexcitability of DRG neurons. The findings indicated that gain-of-function mutations in SCN10A can cause an episodic pain disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23115331" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between variants in the SCN5A (<a href="/entry/600163">600163</a>), SCN10A, and HEY2 (<a href="/entry/604674">604674</a>) genes and Brugada syndrome, see <a href="/entry/601144">601144</a>.</p>
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<p><a href="#3" class="mim-tip-reference" title="Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., Wood, J. N. <strong>The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.</strong> Nature Neurosci. 2: 541-548, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448219</a>] [<a href="https://doi.org/10.1038/9195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448219">Akopian et al. (1999)</a> found that Sns-null mice were viable, fertile, and apparently normal. However, they showed lowered thresholds of electrical activation of C fibers and increased current densities of TTX-sensitive channels, indicating compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small defects in noxious thermoreception, and delayed development of inflammatory hyperalgesia. <a href="#3" class="mim-tip-reference" title="Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., Wood, J. N. <strong>The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.</strong> Nature Neurosci. 2: 541-548, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448219</a>] [<a href="https://doi.org/10.1038/9195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10448219">Akopian et al. (1999)</a> concluded that SNS is involved in pain perception. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10448219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Abrahamsen, B., Zhao, J., Asante, C. O., Cendan, C. M., Marsh, S., Martinez-Barbera, J. P., Nassar, M. A., Dickenson, A. H., Wood, J. N. <strong>The cell and molecular basis of mechanical, cold, and inflammatory pain.</strong> Science 321: 702-705, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18669863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18669863</a>] [<a href="https://doi.org/10.1126/science.1156916" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18669863">Abrahamsen et al. (2008)</a> tested pain responses in mice treated with diphtheria toxin to kill all postmitotic sensory neurons expressing the Nav1.8 sodium channel. They found that Nav1.8-expressing neurons were essential for mechanical, cold, and inflammatory pain sensitivity, but not for neuropathic pain or heat sensing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18669863" 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 father and son with familial episodic pain syndrome-2 (FEPS2; <a href="/entry/615551">615551</a>), <a href="#6" class="mim-tip-reference" title="Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G. <strong>Gain-of-function Nav1.8 mutations in painful neuropathy.</strong> Proc. Nat. Acad. Sci. 109: 19444-19449, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23115331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23115331</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23115331[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1216080109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23115331">Faber et al. (2012)</a> identified a heterozygous c.1661T-C transition in exon 11 of the SCN10A gene, resulting in a leu554-to-pro (L554P) substitution at a highly conserved residue in loop 1. The mutation was not found in 650 control chromosomes, but was present in 1 of 4,552 chromosomes in the dbSNP database (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138404783;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs138404783</a>). In vitro function expression assays in mouse dorsal root ganglia neurons showed that the mutation caused hyperexcitability with an increased response to slow ramp stimuli, reduced current threshold, and increased frequency of spontaneous firing compared to wildtype. Inactivation kinetics were similar to wildtype. The findings indicated a gain-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23115331" 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 Dutch woman with familial episodic pain syndrome (FEPS2; <a href="/entry/615551">615551</a>), <a href="#6" class="mim-tip-reference" title="Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G. <strong>Gain-of-function Nav1.8 mutations in painful neuropathy.</strong> Proc. Nat. Acad. Sci. 109: 19444-19449, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23115331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23115331</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23115331[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.1216080109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23115331">Faber et al. (2012)</a> identified a heterozygous c.3910G-A transition in the SCN10A gene, resulting in an ala1304-to-thr (A1304T) substitution at a highly conserved residue in transmembrane domain DIII/S5. The mutation was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases or in 600 controls. In vitro functional expression assays in mouse dorsal root ganglia neurons showed that the mutation caused a depolarization in the resting potential, hyperpolarization of the potential of peak ramp current, reduced current threshold, and increased firing frequency compared to wildtype, consistent with hyperactivity. Inactivation kinetics were similar to wildtype. The findings indicated a gain-of-function effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23115331" 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="">
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Abrahamsen, B., Zhao, J., Asante, C. O., Cendan, C. M., Marsh, S., Martinez-Barbera, J. P., Nassar, M. A., Dickenson, A. H., Wood, J. N.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18669863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18669863</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18669863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1156916" target="_blank">Full Text</a>]
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<a id="Akopian1996" class="mim-anchor"></a>
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<p class="mim-text-font">
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Akopian, A. N., Sivilotti, L., Wood, J. N.
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<strong>A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.</strong>
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[<a href="https://doi.org/10.1038/379257a0" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., Wood, J. N.
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<strong>The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.</strong>
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Nature Neurosci. 2: 541-548, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448219/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448219</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10448219" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/9195" target="_blank">Full Text</a>]
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<a id="Chiu2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., Wainger, B., Strominger, A., Muralidharan, S., Horswill, A. R., Wardenburg, J. B., Hwang, S. W., Carroll, M. C., Woolf, C. J.
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<strong>Bacteria activate sensory neurons that modulate pain and inflammation.</strong>
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Nature 501: 52-57, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23965627/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23965627</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23965627[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23965627" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature12479" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Emery2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Emery, E. C., Young, G. T., Berrocoso, E. M., Chen, L., McNaughton, P. A.
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<strong>HCN2 ion channels play a central role in inflammatory and neuropathic pain.</strong>
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Science 333: 1462-1466, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21903816/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21903816</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21903816" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1206243" target="_blank">Full Text</a>]
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<a id="Faber2012" class="mim-anchor"></a>
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Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G.
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<strong>Gain-of-function Nav1.8 mutations in painful neuropathy.</strong>
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Proc. Nat. Acad. Sci. 109: 19444-19449, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23115331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23115331</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23115331[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23115331" 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.1216080109" target="_blank">Full Text</a>]
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<a id="Gross2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 12/3/2013.
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<a id="8" class="mim-anchor"></a>
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<a id="Okuse2002" class="mim-anchor"></a>
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Okuse, K., Malik-Hall, M., Baker, M. D., Poon, W.-Y. L., Kong, H., Chao, M. V., Wood, J. N.
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<strong>Annexin II light chain regulates sensory neuron-specific sodium channel expression.</strong>
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Nature 417: 653-656, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12050667/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12050667</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12050667" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature00781" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Rabert1998" class="mim-anchor"></a>
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<div class="">
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Rabert, D. K., Koch, B. D., Ilnicka, M., Obernolte, R. A., Naylor, S. L., Herman, R. C., Eglen, R. M., Hunter, J. C., Sangameswaran, L.
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<strong>A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A.</strong>
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Pain 78: 107-114, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9839820/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9839820</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9839820" 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/S0304-3959(98)00120-1" target="_blank">Full Text</a>]
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<a id="Riol-Blanco2014" class="mim-anchor"></a>
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<div class="">
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Riol-Blanco, L., Ordovas-Montanes, J., Perro, M., Naval, E., Thiriot, A., Alvarez, D., Paust, S., Wood, J. N., von Andrian, U. H.
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<strong>Nociceptive sensory neurons drive interleukin-23-mediated psoriasiform skin inflammation.</strong>
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Nature 510: 157-161, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24759321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24759321</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24759321[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24759321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature13199" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Sangameswaran1996" class="mim-anchor"></a>
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<div class="">
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Sangameswaran, L., Delgado, S. G., Fish, L. M., Koch, B. D., Jakeman, L. B., Stewart, G. R., Sze, P., Hunter, J. C., Eglen, R. M., Herman, R. C.
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<strong>Structure and function of a novel voltage-gated, tetrodotoxin-resistant sodium channel specific to sensory neurons.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8626372/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8626372</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8626372" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.271.11.5953" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Zimmermann2007" class="mim-anchor"></a>
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Zimmermann, K., Leffler, A., Babes, A., Cendan, C. M., Carr, R. W., Kobayashi, J., Nau, C., Wood, J. N., Reeh, P. W.
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<strong>Sensory neuron sodium channel NaV1.8 is essential for pain at low temperatures.</strong>
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Nature 447: 855-858, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17568746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17568746</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17568746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature05880" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Ada Hamosh - updated : 6/26/2014
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<span class="mim-text-font">
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Matthew B. Gross - updated : 12/3/2013<br>Cassandra L. Kniffin - updated : 12/2/2013<br>Ada Hamosh - updated : 10/16/2013<br>Ada Hamosh - updated : 11/22/2011<br>Paul J. Converse - updated : 8/28/2008<br>Patricia A. Hartz - updated : 7/8/2008<br>Ada Hamosh - updated : 6/29/2007<br>Patricia A. Hartz - updated : 10/20/2005<br>Patricia A. Hartz - updated : 6/5/2002
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Paul J. Converse : 1/13/2000
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carol : 09/01/2020
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carol : 06/29/2018<br>carol : 08/07/2017<br>alopez : 11/12/2014<br>carol : 11/10/2014<br>alopez : 6/26/2014<br>joanna : 12/9/2013<br>carol : 12/4/2013<br>mcolton : 12/4/2013<br>mgross : 12/3/2013<br>ckniffin : 12/2/2013<br>alopez : 10/16/2013<br>alopez : 11/29/2011<br>terry : 11/22/2011<br>alopez : 6/29/2010<br>alopez : 6/29/2010<br>terry : 6/18/2010<br>mgross : 8/28/2008<br>terry : 8/28/2008<br>mgross : 7/8/2008<br>alopez : 7/3/2007<br>terry : 6/29/2007<br>carol : 10/4/2006<br>carol : 6/9/2006<br>mgross : 10/26/2005<br>terry : 10/20/2005<br>alopez : 6/5/2002<br>alopez : 6/5/2002<br>carol : 1/18/2000
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SODIUM VOLTAGE-GATED CHANNEL, ALPHA SUBUNIT 10; SCN10A
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SODIUM CHANNEL, VOLTAGE-GATED, TYPE X, ALPHA SUBUNIT<br />
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NAV1.8<br />
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PN3<br />
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SENSORY NEURON-SPECIFIC SODIUM CHANNEL; SNS
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SCN10A</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>
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Cytogenetic location: 3p22.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:38,696,807-38,816,217 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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3p22.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Episodic pain syndrome, familial, 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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615551
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Description</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>The SCN10A gene encodes the alpha subunit of a voltage-gated sodium channel. Voltage-gated sodium channels are integral membrane glycoproteins that are responsible for the initial rising phase of action in most excitable cells. They are composed of a large alpha subunit that may be associated with one or more smaller beta subunits. Sodium channels can be differentiated by their primary structure, kinetics, and relative sensitivity to the neurotoxin tetrodotoxin (TTX). Sodium channels, particularly those with TTX-resistant currents, have been found to accumulate in the region of peripheral nerve injury and may be important in chronic pain. SCN10A encodes a TTX-resistant channel that is restricted to the peripheral sensory nervous system (Rabert et al., 1998). </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>Sangameswaran et al. (1996) and Akopian et al. (1996) independently identified a sodium channel that produced TTX-resistant currents in rat dorsal root ganglion (DRG). Sangameswaran et al. (1996) called the channel Pn3, and Akopian et al. (1996) called the channel Sns. Rabert et al. (1998) obtained the full-length coding sequence for human PN3, symbolized SCN10A, from a human DRG cDNA library. The predicted 1,956-amino acid SCN10A protein contains all the features of a voltage-gated sodium channel: 4 homologous domains consisting of 6 putative alpha-helical transmembrane segments, positively charged residues in the voltage-sensor transmembrane segments, and the ile-phe-met sequence within the highly conserved interdomain region. The amino acid sequence is 90.2% similar to rat PN3 and 70.4% similar to the human cardiac channel, SCN5A (600163). By RT-PCR analysis, PN3 is expressed in the peripheral sensory nervous system (i.e., DRG and sciatic nerve) but not in spinal cord, brain, skeletal muscle, or heart. </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">
|
|
<strong>Mapping</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>By analysis of a panel of somatic cell hybrids, Rabert et al. (1998) mapped the SCN10A gene to chromosome 3p24.2-p22. </p><p>Gross (2013) mapped the SCN10A gene to chromosome 3p22.2 based on an alignment of the SCN10A sequence (GenBank AF117907) with the genomic sequence (GRCh37).</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">
|
|
<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">
|
|
<p>Okuse et al. (2002) noted earlier work with rats indicating that SCN10A, which they called NAV1.8/SNS, is restricted to small-diameter C-fiber-associated rat sensory neurons and appears to have a role in pain pathways. By a yeast 2-hybrid screen of a rat sensory neuron cDNA library, they found that the annexin II light chain, p11 (S100A10; 114085), interacts with the N-terminal intracellular domain of rat Nav1.8. Transfection of p11 into Chinese hamster ovary (CHO) cells stably expressing rat Nav1.8 demonstrated that p11 can behave as an accessory beta subunit, promoting the translocation of Nav1.8 to the plasma membrane and generating functional sodium channels. </p><p>Zimmermann et al. (2007) showed the continuation of nociceptors to function at low temperatures is achieved by endowing superficial endings of slowly conducting nociceptive fibers with the tetrodotoxin-resistant voltage-gated sodium channel NAV1.8. This channel is essential for sustained excitability of nociceptors when the skin is cooled. Zimmermann et al. (2007) showed that cooling excitable membranes progressively enhanced the voltage-dependent slow inactivation of tetrodotoxin-sensitive voltage-gated sodium channels. In contrast, the inactivation properties of NAV1.8 were entirely cold-resistant. Moreover, low temperatures decreased the activation threshold of the sodium currents and increased the membrane resistance, augmenting the voltage change caused by any membrane current. Thus, in the cold, NAV1.8 remains available as the sole electrical impulse generator in nociceptors that transmits nociceptive information to the central nervous system. Consistent with this concept was the observation that Nav1.8-null mutant mice (developed by Akopian et al., 1999) showed negligible responses to noxious cold and mechanical stimulation at low temperatures. Zimmermann et al. (2007) concluded that their data provided strong evidence for a specialized role of NAV1.8 in nociceptors as the critical molecule for the perception of cold pain and pain in the cold. </p><p>The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, which generate an inward current, I-h, after hyperpolarization of the membrane. Emery et al. (2011) found that genetic deletion of HCN2 (602781) removed the cAMP-sensitive component of I-h and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Nav1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Emery et al. (2011) concluded that neuropathic pain is therefore initiated by HCN2-driven action potential firing in NAV1.8-expressing nociceptors. </p><p>Chiu et al. (2013) demonstrated that bacteria directly activate nociceptors and that the immune response mediated through TLR2 (603028), MYD88 (602170), T cells, B cells, and neutrophils and monocytes is not necessary for Staphylococcus aureus-induced pain in mice. Mechanical and thermal hyperalgesia in mice is correlated with live bacterial load rather than tissue swelling or immune activation. Bacteria induce calcium flux and action potentials in nociceptor neurons, in part via bacterial N-formylated peptides and the pore-forming toxin alpha-hemolysin, through distinct mechanisms. Specific ablation of Nav1.8-lineage neurons, which include nociceptors, abrogated pain during bacterial infection, but concurrently increased local immune infiltration and lymphadenopathy of the draining lymph node. Chiu et al. (2013) concluded that bacterial pathogens produce pain by directly activating sensory neurons that modulate inflammation. </p><p>Riol-Blanco et al. (2014) exposed the skin of mice to imiquimod, which induces IL23 (see 605580)-dependent psoriasis-like inflammation, and showed that a subset of sensory neurons expressing the ion channels TRPV1 (602076) and NAV1.8 is essential to drive this inflammatory response. Imaging of intact skin revealed that a large fraction of dermal dendritic cells (DDCs), the principal source of IL23, is in close contact with these nociceptors. Upon selective pharmacologic or genetic ablation of nociceptors, DDCs failed to produce IL23 in imiquimod-exposed skin. Consequently, the local production of IL23-dependent inflammatory cytokines by dermal gamma-delta-T17 cells and the subsequent recruitment of inflammatory cells to the skin were markedly reduced. Intradermal injection of IL23 bypassed the requirement for nociceptor communication with DDCs and restored the inflammatory response. Riol-Blanco et al. (2014) concluded that TRPV1-positive/NAV1.8-positive nociceptors, by interacting with DDCs, regulate the IL23/IL17 (603149) pathway and control cutaneous immune responses. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a father and son with adult-onset familial episodic pain syndrome-2 (FEPS2; 615551), Faber et al. (2012) identified a heterozygous missense mutation in the SCN10A gene (L554P; 604427.0001). An unrelated woman with a similar disorder carried a different heterozygous mutation (A1304T; 604427.0002). In vitro functional expression studies in mouse dorsal root ganglia neurons showed that both mutations caused enhanced channel electrical activities and induced hyperexcitability of DRG neurons. The findings indicated that gain-of-function mutations in SCN10A can cause an episodic pain disorder. </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variants in the SCN5A (600163), SCN10A, and HEY2 (604674) genes and Brugada syndrome, see 601144.</p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Akopian et al. (1999) found that Sns-null mice were viable, fertile, and apparently normal. However, they showed lowered thresholds of electrical activation of C fibers and increased current densities of TTX-sensitive channels, indicating compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small defects in noxious thermoreception, and delayed development of inflammatory hyperalgesia. Akopian et al. (1999) concluded that SNS is involved in pain perception. </p><p>Abrahamsen et al. (2008) tested pain responses in mice treated with diphtheria toxin to kill all postmitotic sensory neurons expressing the Nav1.8 sodium channel. They found that Nav1.8-expressing neurons were essential for mechanical, cold, and inflammatory pain sensitivity, but not for neuropathic pain or heat sensing. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>2 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 EPISODIC PAIN SYNDROME, FAMILIAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN10A, LEU554PRO ({dbSNP rs138404783})
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs138404783,
|
|
|
|
|
|
gnomAD: rs138404783,
|
|
|
|
|
|
ClinVar: RCV000074497, RCV000805966, RCV000998049, RCV002222378, RCV002399426
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a father and son with familial episodic pain syndrome-2 (FEPS2; 615551), Faber et al. (2012) identified a heterozygous c.1661T-C transition in exon 11 of the SCN10A gene, resulting in a leu554-to-pro (L554P) substitution at a highly conserved residue in loop 1. The mutation was not found in 650 control chromosomes, but was present in 1 of 4,552 chromosomes in the dbSNP database (rs138404783). In vitro function expression assays in mouse dorsal root ganglia neurons showed that the mutation caused hyperexcitability with an increased response to slow ramp stimuli, reduced current threshold, and increased frequency of spontaneous firing compared to wildtype. Inactivation kinetics were similar to wildtype. The findings indicated a gain-of-function effect. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
</div>
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|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 EPISODIC PAIN SYNDROME, FAMILIAL, 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
SCN10A, ALA1304THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs142173735,
|
|
|
|
|
|
gnomAD: rs142173735,
|
|
|
|
|
|
ClinVar: RCV000074498, RCV001318345, RCV004019091
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Dutch woman with familial episodic pain syndrome (FEPS2; 615551), Faber et al. (2012) identified a heterozygous c.3910G-A transition in the SCN10A gene, resulting in an ala1304-to-thr (A1304T) substitution at a highly conserved residue in transmembrane domain DIII/S5. The mutation was not present in the dbSNP, 1000 Genomes Project, or Exome Variant Server databases or in 600 controls. In vitro functional expression assays in mouse dorsal root ganglia neurons showed that the mutation caused a depolarization in the resting potential, hyperpolarization of the potential of peak ramp current, reduced current threshold, and increased firing frequency compared to wildtype, consistent with hyperactivity. Inactivation kinetics were similar to wildtype. The findings indicated a gain-of-function effect. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Abrahamsen, B., Zhao, J., Asante, C. O., Cendan, C. M., Marsh, S., Martinez-Barbera, J. P., Nassar, M. A., Dickenson, A. H., Wood, J. N.
|
|
<strong>The cell and molecular basis of mechanical, cold, and inflammatory pain.</strong>
|
|
Science 321: 702-705, 2008.
|
|
|
|
|
|
[PubMed: 18669863]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1126/science.1156916]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Akopian, A. N., Sivilotti, L., Wood, J. N.
|
|
<strong>A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons.</strong>
|
|
Nature 379: 257-262, 1996.
|
|
|
|
|
|
[PubMed: 8538791]
|
|
|
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|
|
[Full Text: https://doi.org/10.1038/379257a0]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., Wood, J. N.
|
|
<strong>The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways.</strong>
|
|
Nature Neurosci. 2: 541-548, 1999.
|
|
|
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|
|
[PubMed: 10448219]
|
|
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|
|
[Full Text: https://doi.org/10.1038/9195]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Chiu, I. M., Heesters, B. A., Ghasemlou, N., Von Hehn, C. A., Zhao, F., Tran, J., Wainger, B., Strominger, A., Muralidharan, S., Horswill, A. R., Wardenburg, J. B., Hwang, S. W., Carroll, M. C., Woolf, C. J.
|
|
<strong>Bacteria activate sensory neurons that modulate pain and inflammation.</strong>
|
|
Nature 501: 52-57, 2013.
|
|
|
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|
|
[PubMed: 23965627]
|
|
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|
|
[Full Text: https://doi.org/10.1038/nature12479]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Emery, E. C., Young, G. T., Berrocoso, E. M., Chen, L., McNaughton, P. A.
|
|
<strong>HCN2 ion channels play a central role in inflammatory and neuropathic pain.</strong>
|
|
Science 333: 1462-1466, 2011.
|
|
|
|
|
|
[PubMed: 21903816]
|
|
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|
|
[Full Text: https://doi.org/10.1126/science.1206243]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Faber, C. G., Lauria, G., Merkies, I. S. J., Cheng, X., Han, C., Ahn, H.-S., Persson, A.-K., Hoeijmakers, J. G. J., Gerrits, M. M., Pierro, T., Lombardi, R., Kapetis, D., Dib-Hajj, S. D., Waxman, S. G.
|
|
<strong>Gain-of-function Nav1.8 mutations in painful neuropathy.</strong>
|
|
Proc. Nat. Acad. Sci. 109: 19444-19449, 2012.
|
|
|
|
|
|
[PubMed: 23115331]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.1216080109]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gross, M. B.
|
|
<strong>Personal Communication.</strong>
|
|
Baltimore, Md. 12/3/2013.
|
|
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