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Entry
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- *608206 - SH3 DOMAIN AND TETRATRICOPEPTIDE REPEAT DOMAIN 2; SH3TC2
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*608206</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/608206">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<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=ENSG00000169247;t=ENST00000515425" 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=79628" 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=608206" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000169247;t=ENST00000515425" 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_024577" 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_024577" 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=608206" 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=10496&isoform_id=10496_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/SH3TC2" 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/10435659,18916898,34534079,37790790,38488692,46396469,109730317,109731642,193784954,193785278,193785309,193785863,221043206,1700449591" 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/Q8TF17" 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=79628" 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=ENSG00000169247;t=ENST00000515425" 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=SH3TC2" 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=SH3TC2" 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+79628" 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/SH3TC2" 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:79628" 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/79628" 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=chr5&hgg_gene=ENST00000515425.6&hgg_start=148982150&hgg_end=149063062&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/gene-dosage/HGNC:29427" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:29427" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608206[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=608206[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/SH3TC2/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/ENSG00000169247" 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=SH3TC2" 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=SH3TC2" 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=SH3TC2" 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="http://www.molgen.ua.ac.be/CMTMutations/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=SH3TC2&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/PA134951912" 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:29427" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2444417" 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/SH3TC2#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:2444417" 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/79628/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://omia.org/OMIA002740/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=79628" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-081104-347" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=SH3TC2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715797002<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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608206
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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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SH3 DOMAIN AND TETRATRICOPEPTIDE REPEAT DOMAIN 2; SH3TC2
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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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KIAA1985
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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=SH3TC2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SH3TC2</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/5/646?start=-3&limit=10&highlight=646">5q32</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr5:148982150-149063062&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'})">5:148,982,150-149,063,062</a> </span>
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</em>
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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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>
|
|
Location
|
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</th>
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<th>
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Phenotype
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=601596,613353" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
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</th>
|
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
|
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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</tr>
|
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</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/5/646?start=-3&limit=10&highlight=646">
|
|
5q32
|
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</a>
|
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</span>
|
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</td>
|
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|
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<td>
|
|
<span class="mim-font">
|
|
Charcot-Marie-Tooth disease, type 4C
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/601596"> 601596 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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Mononeuropathy of the median nerve, mild
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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/613353"> 613353 </a>
|
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</span>
|
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</td>
|
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<td>
|
|
<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>
|
|
<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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<p>The SH3TC2 gene encodes a protein expressed in Schwann cells of peripheral nerves, and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions (<a href="#1" class="mim-tip-reference" title="Arnaud, E., Zenker, J., de Preux Charles, A.-S., Stendel, C., Roos, A., Medard, J.-J., Tricaud, N., Kleine, H., Luscher, B., Weis, J., Suter, U., Senderek, J., Chrast, R. <strong>SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.</strong> Proc. Nat. Acad. Sci. 106: 17528-17533, 2009. Note: Erratum: Proc. Nat. Acad. Sci. 107: 15305 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805030</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19805030[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.0905523106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19805030">Arnaud et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19805030" 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 sequencing clones derived from a human adult hippocampus cDNA library, <a href="#10" class="mim-tip-reference" title="Nagase, T., Kikuno, R., Ohara, O. <strong>Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.</strong> DNA Res. 8: 319-327, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11853319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11853319</a>] [<a href="https://doi.org/10.1093/dnares/8.6.319" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11853319">Nagase et al. (2001)</a> cloned the full-length SH3TC2 gene, which they called KIAA1985. The transcript contains multiple SINEs in the 5-prime and 3-prime untranslated regions. The longest ORF predicted a 955-amino acid protein. RT-PCR ELISA detected expression in adult heart, testis, spinal cord, and brain as well as in fetal brain and liver. Expression was found in all specific regions of the brain examined. Little or no expression was detected in adult lung, liver, skeletal muscle, kidney, pancreas, spleen, or ovary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11853319" 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="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> determined that the KIAA1985 sequence predicts a 1,288-amino acid protein with a calculated molecular mass of 144.7 kD. The human protein shares 81% amino acid homology with the murine ortholog. Using Northern blot analysis, <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> showed expression of a 7.5-kb KIAA1985 transcript to be strong in brain and spinal cord, and weak in striated muscle. RT-PCR showed expression in sciatic nerve and spinal cord. A smaller transcript of 4.5 kb was also detected, suggesting alternative splicing. Further analysis of the protein indicated the presence of 2 N-terminal Src homology-3 (SH3) domains and 10 tetratricopeptide repeat (TPR) motifs arranged in tandem arrays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" 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="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> determined that the SH3TC2 gene contains 18 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" 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="Roberts, R. C., Peden, A. A., Buss, F., Bright, N. A., Latouche, M., Reilly, M. M., Kendrick-Jones, J., Luzio, J. P. <strong>Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C.</strong> Hum. Molec. Genet. 19: 1009-1018, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20028792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20028792</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20028792[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/10.1093/hmg/ddp565" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20028792">Roberts et al. (2010)</a> showed that wildtype SH3TC2 localizes to the intracellular recycling endosome by associating with the small GTPase Rab11 (<a href="/entry/605570">605570</a>), which regulates the recycling of internalized membrane and receptors back to the plasma membrane. SH3TC2 interacted preferentially with the GTP-bound form of Rab11, suggesting that SH3TC2 may be a novel Rab11 effector. All SH3TC2 constructs harboring disease-causing mutations were unable to associate with Rab11, with consequent loss of recycling endosome localization. Wildtype, but not mutant, SH3TC2 influenced transferrin receptor (<a href="/entry/190010">190010</a>) dynamics, consistent with a functional role on the endocytic recycling pathway. The authors hypothesized that mistargeting of SH3TC2 away from the recycling endosome may be the fundamental molecular defect in Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20028792" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using computational and functional analyses, <a href="#3" class="mim-tip-reference" title="Brewer, M. H., Ma, K. H., Beecham, G. W., Gopinath, C., the Inherited Neuropathy Consortium (INC), Baas, F., Choi, B.-O., Reilly, M. M., Shy, M. E., Zuchner, S., Svaren, J., Antonellis, A. <strong>Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4c locus SH3TC2.</strong> Hum. Molec. Genet. 23: 5171-5187, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24833716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24833716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24833716[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/10.1093/hmg/ddu240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24833716">Brewer et al. (2014)</a> identified regulatory elements in the SH3TC2 gene that are conserved across several mammalian species. A head-to-head SOX10 (<a href="/entry/602229">602229</a>)-binding site in the proximal promoter region induced expression of an SH3TC2 reporter in both transfected S16 immortalized rat Schwann cells and MN-1 mouse motor neurons. Approximately 150 kb downstream of the transcription start site, <a href="#3" class="mim-tip-reference" title="Brewer, M. H., Ma, K. H., Beecham, G. W., Gopinath, C., the Inherited Neuropathy Consortium (INC), Baas, F., Choi, B.-O., Reilly, M. M., Shy, M. E., Zuchner, S., Svaren, J., Antonellis, A. <strong>Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4c locus SH3TC2.</strong> Hum. Molec. Genet. 23: 5171-5187, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24833716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24833716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24833716[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/10.1093/hmg/ddu240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24833716">Brewer et al. (2014)</a> identified a monomeric SOX10 consensus sequence separated by 7 bp from a CREB (see <a href="/entry/123810">123810</a>)-binding site. This SOX10-CREB element functioned as an enhancer, and SOX10 and CREB activated SH3TC2 expression from this site in a synergistic manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24833716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#13" class="mim-tip-reference" title="Stumpf, A. M. <strong>Personal Communication.</strong> Baltimore, Md. 08/12/2020."None>Stumpf (2020)</a> mapped the SH3TC2 gene to chromosome 5q32 based on an alignment of the SH3TC2 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=BC113879" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">BC113879</a>) with the genomic sequence (GRCh38).</p>
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In affected members of 11 families and 1 sporadic patient with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified 11 different mutations in the SH3TC2 gene (see <a href="#0001">608206.0001</a>-<a href="#0005">608206.0005</a>), 7 of which occurred in exon 11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" 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="#5" class="mim-tip-reference" title="Gooding, R., Colomer, J., King, R., Angelicheva, D., Marns, L., Parman, Y., Chandler, D., Bertranpetit, J., Kalaydjieva, L. <strong>A novel Gypsy founder mutation, pArg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes.</strong> J. Med. Genet. 42: e69, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16326826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16326826</a>] [<a href="https://doi.org/10.1136/jmg.2005.034132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16326826">Gooding et al. (2005)</a> identified a homozygous mutation in the SH3TC2 gene (R1109X; <a href="#0006">608206.0006</a>) in 12 patients with CMT4C from European Gypsy families, of whom 8 were from a large Spanish Gypsy kindred. Haplotype analysis indicated a founder effect with a conserved ancestral segment of approximately 0.6 cM. Among Spanish Gypsies, the carrier rate of R1109X was estimated at 1 in 26. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16326826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 10 families with CMT4C, <a href="#2" class="mim-tip-reference" title="Azzedine, H., Ravise, N., Verny, C., Gabreels-Festen, A., Lammens, M., Grid, D., Vallat, J. M., Durosier, G., Senderek, J., Nouioua, S., Hamadouche, T., Bouhouche, A., Guilbot, A., Stendel, C., Ruberg, M., Brice, A., Birouk, N., Dubourg, O., Tazir, M., LeGuern, E. <strong>Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.</strong> Neurology 67: 602-606, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16924012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16924012</a>] [<a href="https://doi.org/10.1212/01.wnl.0000230225.19797.93" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16924012">Azzedine et al. (2006)</a> identified compound heterozygous or homozygous mutations in the SH3TC2 gene. The authors identified a total of 10 different mutations, including 8 novel ones. R954X (<a href="#0005">608206.0005</a>) was a recurrent mutation, occurring in 4 Dutch families and 1 Algerian family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16924012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Lupo, V., Galindo, M. I., Martinez-Rubio, D., Sevilla, T., Vilchez, J. J., Palau, F., Espinos, C. <strong>Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type 4C affect its localization in the plasma membrane and endocytic pathway.</strong> Hum. Molec. Genet. 18: 4603-4614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744956</a>] [<a href="https://doi.org/10.1093/hmg/ddp427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19744956">Lupo et al. (2009)</a> demonstrated that the SH3TC2 protein was present in several components of the endocytic pathway including early endosomes, late endosomes, and clathrin-coated vesicles close to the trans-Golgi network and in the plasma membrane of COS-7 cells. Myristoylation of SH3TC2 at residue gly2 was necessary but not sufficient for the proper location of the protein in cell membranes. In addition to myristoylation, correct anchoring also required the presence of either SH3 or TPR domains in combination with myristoylation. Mutations, such as R954X and R1109X, that caused a stop codon and produced premature terminations removing most of the C-terminal TPR domains resulted in an expression pattern that was the same as wildtype protein. In contrast, missense mutations, such as R529Q (<a href="#0001">608206.0001</a>) and E657K (<a href="/entry/602806#0007">602806.0007</a>), in or around the region of the first TPR domain were absent from early endosomes, reduced in plasma membrane and late endosomes, and were variably present in clathrin-coated vesicles. <a href="#8" class="mim-tip-reference" title="Lupo, V., Galindo, M. I., Martinez-Rubio, D., Sevilla, T., Vilchez, J. J., Palau, F., Espinos, C. <strong>Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type 4C affect its localization in the plasma membrane and endocytic pathway.</strong> Hum. Molec. Genet. 18: 4603-4614, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744956</a>] [<a href="https://doi.org/10.1093/hmg/ddp427" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19744956">Lupo et al. (2009)</a> suggested that the endocytic and membrane trafficking pathway may be involved in the pathogenesis of CMT4C disease, and that missense mutations of SH3TC2 could impair communication between the Schwann cell and the axon causing abnormal myelin formation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19744956" 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>Mild Mononeuropathy of the Median Nerve</em></strong></p><p>
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<a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> reported a 3-generation family with variable severity of a peripheral neuropathy. The family was ascertained through 4 sibs with phenotype consistent with autosomal recessive CMT4C caused by compound heterozygous mutations in the SH3TC2 gene: R954X (<a href="#0005">608206.0005</a>) and Y169H (<a href="#0008">608206.0008</a>). Three additional family members who were heterozygous for the R954X mutation, resulting in loss of function, had a subtle mild mononeuropathy of the median nerve (MNMN; <a href="/entry/613353">613353</a>) consistent with carpal tunnel syndrome. This involvement of the median nerve was also seen in the patients with CMT4C. <a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. Two additional family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal polyneuropathy, as shown by electrophysiologic studies, with definite median-nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal neuropathy. The phenotype was similar to that of hereditary neuropathy with liability to pressure palsies (HNPP; <a href="/entry/162500">162500</a>). The authors postulated a toxic gain of function for the Y169H-mutant protein. <a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> commented on the subtle apparently autosomal dominant phenotypes segregating independently with the respective SH3TC2 mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20220177" 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>Regulatory Polymorphisms</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Brewer, M. H., Ma, K. H., Beecham, G. W., Gopinath, C., the Inherited Neuropathy Consortium (INC), Baas, F., Choi, B.-O., Reilly, M. M., Shy, M. E., Zuchner, S., Svaren, J., Antonellis, A. <strong>Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4c locus SH3TC2.</strong> Hum. Molec. Genet. 23: 5171-5187, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24833716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24833716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24833716[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/10.1093/hmg/ddu240" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24833716">Brewer et al. (2014)</a> identified a C-T SNP, <a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1759452;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1759452</a>, within a distal enhancer approximately 150 kb downstream of the transcription start site of SH3TC2. The minor allele (T) of the SNP reduced SH3TC2 reporter activity by approximately 80% due to disruption of a CREB-binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24833716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Arnaud, E., Zenker, J., de Preux Charles, A.-S., Stendel, C., Roos, A., Medard, J.-J., Tricaud, N., Kleine, H., Luscher, B., Weis, J., Suter, U., Senderek, J., Chrast, R. <strong>SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.</strong> Proc. Nat. Acad. Sci. 106: 17528-17533, 2009. Note: Erratum: Proc. Nat. Acad. Sci. 107: 15305 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805030</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19805030[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.0905523106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19805030">Arnaud et al. (2009)</a> found that Sh3tc2-null mice developed a progressive peripheral neuropathy manifest by decreased motor and sensory nerve conduction velocity and hypomyelination. Murine Sh3tc2 was specifically expressed in Schwann cells and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions. Analysis of myelin in the peripheral nerve of mutant mice showed abnormal organization of the node of Ranvier, a phenotype that was confirmed in CMT4C patient nerve biopsies. The findings suggested a role for the SH3TC2 gene product in myelination and in the integrity of the node of Ranvier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19805030" 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 2 unrelated Turkish patients with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), both from consanguineous families, <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified a homozygous 1586G-A transition in exon 11 of the SH3TC2 gene, resulting in an arg529-to-gln (R529Q) substitution. The R529Q mutation was also detected in heterozygous state in 1 of 320 Turkish control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80338924 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338924;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338924" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002583" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002583" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002583</a>
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<p>In 2 unrelated Turkish patients with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), both from consanguineous families, <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified a homozygous 2-bp deletion in exon 11 of the SH3TC2 gene, 1747delAG, resulting in a frameshift and premature stop codon at residue 586. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs80338920 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338920;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338920" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002584 OR RCV000790209" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002584, RCV000790209" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002584...</a>
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<p>In 4 affected individuals from a consanguineous Italian family with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified homozygosity for an A-to-G transition in a splice site (IVS5-2A-G), predicted to result in exon skipping. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338932 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338932;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338932?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338932" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002585 OR RCV001223054 OR RCV001310527" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002585, RCV001223054, RCV001310527" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002585...</a>
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<p>In 3 affected sibs from a German family with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified compound heterozygosity for 2 nonsense mutations in exon 11 of the SH3TC2 gene: a 2829T-G transversion, resulting in a tyr943-to-ter (Y943X) mutation, and the R954X mutation (<a href="#0005">608206.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338933 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338933;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338933?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002586 OR RCV000002587 OR RCV000144877 OR RCV000168436 OR RCV000255213 OR RCV000282937 OR RCV000515338 OR RCV000622836 OR RCV001851586" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002586, RCV000002587, RCV000144877, RCV000168436, RCV000255213, RCV000282937, RCV000515338, RCV000622836, RCV001851586" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002586...</a>
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<p>In 3 affected sibs from a German family with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), <a href="#12" class="mim-tip-reference" title="Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others. <strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong> Am. J. Hum. Genet. 73: 1106-1119, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/379525" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14574644">Senderek et al. (2003)</a> identified compound heterozygosity for 2 nonsense mutations in exon 11 of the SH3TC2 gene: a 2860C-T transition, resulting in an arg954-to-ter mutation (R954X; <a href="#0005">608206.0005</a>), and the Y943X mutation (<a href="#0004">608206.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Azzedine, H., Ravise, N., Verny, C., Gabreels-Festen, A., Lammens, M., Grid, D., Vallat, J. M., Durosier, G., Senderek, J., Nouioua, S., Hamadouche, T., Bouhouche, A., Guilbot, A., Stendel, C., Ruberg, M., Brice, A., Birouk, N., Dubourg, O., Tazir, M., LeGuern, E. <strong>Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.</strong> Neurology 67: 602-606, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16924012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16924012</a>] [<a href="https://doi.org/10.1212/01.wnl.0000230225.19797.93" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16924012">Azzedine et al. (2006)</a> reported that the R954X mutation was recurrent in their patient series, identified in 4 Dutch families and 1 Algerian family with CMT4C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16924012" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a French Canadian cluster of 17 CMT4C patients from Quebec, Canada, <a href="#6" class="mim-tip-reference" title="Gosselin, I., Thiffault, I., Tetreault, M., Chau, V., Dicaire, M.-J., Loisel, L., Emond, M., Senderek, J., Mathieu, J., Dupre, N., Vanasse, M., Puymirat, J., Brais, B. <strong>Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster.</strong> Neuromusc. Disord. 18: 483-492, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18511281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18511281</a>] [<a href="https://doi.org/10.1016/j.nmd.2008.04.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18511281">Gosselin et al. (2008)</a> identified the R954X mutation in homozygosity in 12 patients from 7 families and in compound heterozygosity with an unidentified mutation in 2 patients from 1 family. In total, the R954X mutation was identified in 26 (76%) of 34 alleles from 10 families. Thirteen patients, including 10 homozygous for R954X, originated from a series of coastal villages in the Gaspesie, a sparsely populated peninsular region of Quebec, near the Maine/U.S. border. The villages are distributed along a 150-km stretch of the western shore of Chaleur Bay. Haplotype analysis demonstrated that at least 2 distinct CMT4C mutations are present in the French Canadian population and indicated a founder effect for the R954X mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18511281" 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="Houlden, H., Laura, M., Ginsberg, L., Jungbluth, H., Robb, S. A., Blake, J., Robinson, S., King, R. H. M., Reilly, M. M. <strong>The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy.</strong> Neuromusc. Disord. 19: 264-269, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19272779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19272779</a>] [<a href="https://doi.org/10.1016/j.nmd.2009.01.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19272779">Houlden et al. (2009)</a> identified a homozygous R954X mutation in affected members of 4 English families with CMT4C. A fifth English family was compound heterozygous for R954X and a 1969G-A transition, resulting in a gly657-to-lys substitution (E657K; <a href="#0007">608206.0007</a>). There was significant phenotypic variability between these families: some presented with severe childhood onset, respiratory and cranial nerve involvement, and became wheelchair-bound, whereas others had only mild scoliosis and foot deformity. One patient homozygous for the R954X mutation had a superimposed inflammatory neuropathy associated with steroid treatment for ulcerative colitis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19272779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 sibs with CMT4C, <a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> identified compound heterozygosity for 2 mutations in the SH3TC2 gene: R954X and Y169H (<a href="#0008">608206.0008</a>). Three additional family members who were heterozygous for the R954X mutation had a mild mononeuropathy of the median nerve (MNMN; <a href="/entry/613353">613353</a>) consistent with carpal tunnel syndrome. <a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20220177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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SH3TC2, ARG1109TER
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338934 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338934;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338934?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338934" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002588 OR RCV000218266 OR RCV000654100 OR RCV000857137 OR RCV002496231" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002588, RCV000218266, RCV000654100, RCV000857137, RCV002496231" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002588...</a>
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<p>In 12 patients with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>) from European Gypsy families, <a href="#5" class="mim-tip-reference" title="Gooding, R., Colomer, J., King, R., Angelicheva, D., Marns, L., Parman, Y., Chandler, D., Bertranpetit, J., Kalaydjieva, L. <strong>A novel Gypsy founder mutation, pArg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes.</strong> J. Med. Genet. 42: e69, 2005. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16326826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16326826</a>] [<a href="https://doi.org/10.1136/jmg.2005.034132" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16326826">Gooding et al. (2005)</a> identified a homozygous 3325C-T (genomic position 52751) transition in exon 14 of the SH3TC2 gene, resulting in an arg1109-to-ter (R1109X) substitution near the C-terminal domain of the protein. Eight of the patients came from a large Spanish Gypsy kindred. Haplotype analysis indicated a founder effect with a conserved ancestral segment of approximately 0.6 cM. Among Spanish Gypsies, the carrier rate of R1109X was estimated at 1 in 26. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16326826" 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="Claramunt, R., Sevilla, T., Lupo, V., Cuesta, A., Millan, J.M., Vilchez, J. J., Palau, F., Espinos, C. <strong>The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4.</strong> Clin. Genet. 71: 343-349, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17470135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17470135</a>] [<a href="https://doi.org/10.1111/j.1399-0004.2007.00774.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17470135">Claramunt et al. (2007)</a> found that 10 of 20 Spanish Gypsy families with autosomal recessive demyelinating neuropathy had CMT4C. The most common mutation was R1109X, which was identified in 20 of 21 mutation-carrying chromosomes. Haplotype analysis indicated a founder effect that likely arose about 225 years ago, probably as a result of a bottleneck. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17470135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80338925 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80338925;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80338925?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80338925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80338925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000020887 OR RCV000206757 OR RCV000857147 OR RCV002496432 OR RCV004786278" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020887, RCV000206757, RCV000857147, RCV002496432, RCV004786278" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020887...</a>
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<p>For discussion of the glu657-to-lys (E657K) mutation in the SH3TC2 gene that was found in compound heterozygous state in patients with Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>) by <a href="#7" class="mim-tip-reference" title="Houlden, H., Laura, M., Ginsberg, L., Jungbluth, H., Robb, S. A., Blake, J., Robinson, S., King, R. H. M., Reilly, M. M. <strong>The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy.</strong> Neuromusc. Disord. 19: 264-269, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19272779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19272779</a>] [<a href="https://doi.org/10.1016/j.nmd.2009.01.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19272779">Houlden et al. (2009)</a>, see <a href="#0005">608206.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19272779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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MONONEUROPATHY OF THE MEDIAN NERVE, MILD, INCLUDED
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs80359890 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80359890;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs80359890?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs80359890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs80359890" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000002590 OR RCV000002591 OR RCV000415264 OR RCV000656975 OR RCV001079620 OR RCV001172848 OR RCV001293355 OR RCV001705579 OR RCV002345223" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000002590, RCV000002591, RCV000415264, RCV000656975, RCV001079620, RCV001172848, RCV001293355, RCV001705579, RCV002345223" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000002590...</a>
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<p>In sibs with autosomal recessive Charcot-Marie-Tooth disease type 4C (CMT4C; <a href="/entry/601596">601596</a>), <a href="#9" class="mim-tip-reference" title="Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others. <strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong> New Eng. J. Med. 362: 1181-1191, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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/10.1056/NEJMoa0908094" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20220177">Lupski et al. (2010)</a> identified compound heterozygosity for 2 mutations in the SH3TC2 gene: an A-to-G transition, resulting in a tyr169-to-his (Y169H) substitution and R954X (<a href="#0005">608206.0005</a>). Two other family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal neuropathy with median nerve mononeuropathy at the wrist (MNMN; <a href="/entry/613353">613353</a>), as shown by electrophysiologic studies. These findings suggested a toxic gain of function for the mutant protein, and indicated that heterozygous SH3TC2 mutation carriers may also have a phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20220177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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Arnaud, E., Zenker, J., de Preux Charles, A.-S., Stendel, C., Roos, A., Medard, J.-J., Tricaud, N., Kleine, H., Luscher, B., Weis, J., Suter, U., Senderek, J., Chrast, R.
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<strong>SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.</strong>
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Proc. Nat. Acad. Sci. 106: 17528-17533, 2009. Note: Erratum: Proc. Nat. Acad. Sci. 107: 15305 only, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19805030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19805030</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19805030[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=19805030" 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.0905523106" target="_blank">Full Text</a>]
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Azzedine, H., Ravise, N., Verny, C., Gabreels-Festen, A., Lammens, M., Grid, D., Vallat, J. M., Durosier, G., Senderek, J., Nouioua, S., Hamadouche, T., Bouhouche, A., Guilbot, A., Stendel, C., Ruberg, M., Brice, A., Birouk, N., Dubourg, O., Tazir, M., LeGuern, E.
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<strong>Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.</strong>
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Neurology 67: 602-606, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16924012/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16924012</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16924012" 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/10.1212/01.wnl.0000230225.19797.93" target="_blank">Full Text</a>]
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<a id="Brewer2014" class="mim-anchor"></a>
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Brewer, M. H., Ma, K. H., Beecham, G. W., Gopinath, C., the Inherited Neuropathy Consortium (INC), Baas, F., Choi, B.-O., Reilly, M. M., Shy, M. E., Zuchner, S., Svaren, J., Antonellis, A.
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<strong>Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4c locus SH3TC2.</strong>
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Hum. Molec. Genet. 23: 5171-5187, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24833716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24833716</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24833716[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=24833716" 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/10.1093/hmg/ddu240" target="_blank">Full Text</a>]
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<a id="Claramunt2007" class="mim-anchor"></a>
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<div class="">
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Claramunt, R., Sevilla, T., Lupo, V., Cuesta, A., Millan, J.M., Vilchez, J. J., Palau, F., Espinos, C.
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<strong>The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4.</strong>
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Clin. Genet. 71: 343-349, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17470135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17470135</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17470135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.2007.00774.x" target="_blank">Full Text</a>]
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<a id="Gooding2005" class="mim-anchor"></a>
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Gooding, R., Colomer, J., King, R., Angelicheva, D., Marns, L., Parman, Y., Chandler, D., Bertranpetit, J., Kalaydjieva, L.
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<strong>A novel Gypsy founder mutation, pArg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes.</strong>
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J. Med. Genet. 42: e69, 2005. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16326826/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16326826</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16326826" 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/10.1136/jmg.2005.034132" target="_blank">Full Text</a>]
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<a id="Gosselin2008" class="mim-anchor"></a>
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Gosselin, I., Thiffault, I., Tetreault, M., Chau, V., Dicaire, M.-J., Loisel, L., Emond, M., Senderek, J., Mathieu, J., Dupre, N., Vanasse, M., Puymirat, J., Brais, B.
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<strong>Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster.</strong>
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Neuromusc. Disord. 18: 483-492, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18511281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18511281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18511281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2008.04.001" target="_blank">Full Text</a>]
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<a id="Houlden2009" class="mim-anchor"></a>
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Houlden, H., Laura, M., Ginsberg, L., Jungbluth, H., Robb, S. A., Blake, J., Robinson, S., King, R. H. M., Reilly, M. M.
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<strong>The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy.</strong>
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Neuromusc. Disord. 19: 264-269, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19272779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19272779</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19272779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2009.01.006" target="_blank">Full Text</a>]
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<a id="Lupo2009" class="mim-anchor"></a>
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Lupo, V., Galindo, M. I., Martinez-Rubio, D., Sevilla, T., Vilchez, J. J., Palau, F., Espinos, C.
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<strong>Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type 4C affect its localization in the plasma membrane and endocytic pathway.</strong>
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Hum. Molec. Genet. 18: 4603-4614, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744956/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744956</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19744956" 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/10.1093/hmg/ddp427" target="_blank">Full Text</a>]
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<a id="Lupski2010" class="mim-anchor"></a>
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Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others.
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<strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong>
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New Eng. J. Med. 362: 1181-1191, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20220177/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20220177</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20220177[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=20220177" 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/10.1056/NEJMoa0908094" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Nagase2001" class="mim-anchor"></a>
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Nagase, T., Kikuno, R., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.</strong>
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DNA Res. 8: 319-327, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11853319/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11853319</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11853319" 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/10.1093/dnares/8.6.319" target="_blank">Full Text</a>]
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<a id="Roberts2010" class="mim-anchor"></a>
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Roberts, R. C., Peden, A. A., Buss, F., Bright, N. A., Latouche, M., Reilly, M. M., Kendrick-Jones, J., Luzio, J. P.
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<strong>Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C.</strong>
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Hum. Molec. Genet. 19: 1009-1018, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20028792/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20028792</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20028792[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=20028792" 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/10.1093/hmg/ddp565" target="_blank">Full Text</a>]
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<a id="Senderek2003" class="mim-anchor"></a>
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Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others.
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<strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong>
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Am. J. Hum. Genet. 73: 1106-1119, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14574644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14574644</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14574644[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=14574644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/379525" target="_blank">Full Text</a>]
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Stumpf, A. M.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 08/12/2020.
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Anne M. Stumpf - updated : 08/12/2020
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Patricia A. Hartz - updated : 11/5/2014<br>George E. Tiller - updated : 11/10/2011<br>George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 4/13/2010<br>Cassandra L. Kniffin - updated : 11/3/2009<br>Cassandra L. Kniffin - updated : 8/2/2007<br>Cassandra L. Kniffin - updated : 7/6/2007<br>Cassandra L. Kniffin - updated : 5/4/2007<br>Cassandra L. Kniffin - updated : 11/5/2003
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Patricia A. Hartz : 10/27/2003
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<strong>*</strong> 608206
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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SH3 DOMAIN AND TETRATRICOPEPTIDE REPEAT DOMAIN 2; SH3TC2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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KIAA1985
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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: SH3TC2</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>SNOMEDCT:</strong> 715797002;
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</span>
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</p>
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<div>
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<br />
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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: 5q32
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Genomic coordinates <span class="small">(GRCh38)</span> : 5:148,982,150-149,063,062 </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="2">
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<span class="mim-font">
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5q32
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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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Charcot-Marie-Tooth disease, type 4C
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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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601596
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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 recessive
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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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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Mononeuropathy of the median nerve, mild
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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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613353
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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">
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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">
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<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">
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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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<span class="mim-text-font">
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<p>The SH3TC2 gene encodes a protein expressed in Schwann cells of peripheral nerves, and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions (Arnaud et al., 2009). </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>By sequencing clones derived from a human adult hippocampus cDNA library, Nagase et al. (2001) cloned the full-length SH3TC2 gene, which they called KIAA1985. The transcript contains multiple SINEs in the 5-prime and 3-prime untranslated regions. The longest ORF predicted a 955-amino acid protein. RT-PCR ELISA detected expression in adult heart, testis, spinal cord, and brain as well as in fetal brain and liver. Expression was found in all specific regions of the brain examined. Little or no expression was detected in adult lung, liver, skeletal muscle, kidney, pancreas, spleen, or ovary. </p><p>Senderek et al. (2003) determined that the KIAA1985 sequence predicts a 1,288-amino acid protein with a calculated molecular mass of 144.7 kD. The human protein shares 81% amino acid homology with the murine ortholog. Using Northern blot analysis, Senderek et al. (2003) showed expression of a 7.5-kb KIAA1985 transcript to be strong in brain and spinal cord, and weak in striated muscle. RT-PCR showed expression in sciatic nerve and spinal cord. A smaller transcript of 4.5 kb was also detected, suggesting alternative splicing. Further analysis of the protein indicated the presence of 2 N-terminal Src homology-3 (SH3) domains and 10 tetratricopeptide repeat (TPR) motifs arranged in tandem arrays. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Senderek et al. (2003) determined that the SH3TC2 gene contains 18 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Roberts et al. (2010) showed that wildtype SH3TC2 localizes to the intracellular recycling endosome by associating with the small GTPase Rab11 (605570), which regulates the recycling of internalized membrane and receptors back to the plasma membrane. SH3TC2 interacted preferentially with the GTP-bound form of Rab11, suggesting that SH3TC2 may be a novel Rab11 effector. All SH3TC2 constructs harboring disease-causing mutations were unable to associate with Rab11, with consequent loss of recycling endosome localization. Wildtype, but not mutant, SH3TC2 influenced transferrin receptor (190010) dynamics, consistent with a functional role on the endocytic recycling pathway. The authors hypothesized that mistargeting of SH3TC2 away from the recycling endosome may be the fundamental molecular defect in Charcot-Marie-Tooth disease type 4C (CMT4C; 601596). </p><p>Using computational and functional analyses, Brewer et al. (2014) identified regulatory elements in the SH3TC2 gene that are conserved across several mammalian species. A head-to-head SOX10 (602229)-binding site in the proximal promoter region induced expression of an SH3TC2 reporter in both transfected S16 immortalized rat Schwann cells and MN-1 mouse motor neurons. Approximately 150 kb downstream of the transcription start site, Brewer et al. (2014) identified a monomeric SOX10 consensus sequence separated by 7 bp from a CREB (see 123810)-binding site. This SOX10-CREB element functioned as an enhancer, and SOX10 and CREB activated SH3TC2 expression from this site in a synergistic manner. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Stumpf (2020) mapped the SH3TC2 gene to chromosome 5q32 based on an alignment of the SH3TC2 sequence (GenBank BC113879) with the genomic sequence (GRCh38).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Charcot-Marie-Tooth Disease Type 4C</em></strong></p><p>
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In affected members of 11 families and 1 sporadic patient with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), Senderek et al. (2003) identified 11 different mutations in the SH3TC2 gene (see 608206.0001-608206.0005), 7 of which occurred in exon 11. </p><p>Gooding et al. (2005) identified a homozygous mutation in the SH3TC2 gene (R1109X; 608206.0006) in 12 patients with CMT4C from European Gypsy families, of whom 8 were from a large Spanish Gypsy kindred. Haplotype analysis indicated a founder effect with a conserved ancestral segment of approximately 0.6 cM. Among Spanish Gypsies, the carrier rate of R1109X was estimated at 1 in 26. </p><p>In affected members of 10 families with CMT4C, Azzedine et al. (2006) identified compound heterozygous or homozygous mutations in the SH3TC2 gene. The authors identified a total of 10 different mutations, including 8 novel ones. R954X (608206.0005) was a recurrent mutation, occurring in 4 Dutch families and 1 Algerian family. </p><p>Lupo et al. (2009) demonstrated that the SH3TC2 protein was present in several components of the endocytic pathway including early endosomes, late endosomes, and clathrin-coated vesicles close to the trans-Golgi network and in the plasma membrane of COS-7 cells. Myristoylation of SH3TC2 at residue gly2 was necessary but not sufficient for the proper location of the protein in cell membranes. In addition to myristoylation, correct anchoring also required the presence of either SH3 or TPR domains in combination with myristoylation. Mutations, such as R954X and R1109X, that caused a stop codon and produced premature terminations removing most of the C-terminal TPR domains resulted in an expression pattern that was the same as wildtype protein. In contrast, missense mutations, such as R529Q (608206.0001) and E657K (602806.0007), in or around the region of the first TPR domain were absent from early endosomes, reduced in plasma membrane and late endosomes, and were variably present in clathrin-coated vesicles. Lupo et al. (2009) suggested that the endocytic and membrane trafficking pathway may be involved in the pathogenesis of CMT4C disease, and that missense mutations of SH3TC2 could impair communication between the Schwann cell and the axon causing abnormal myelin formation. </p><p><strong><em>Mild Mononeuropathy of the Median Nerve</em></strong></p><p>
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Lupski et al. (2010) reported a 3-generation family with variable severity of a peripheral neuropathy. The family was ascertained through 4 sibs with phenotype consistent with autosomal recessive CMT4C caused by compound heterozygous mutations in the SH3TC2 gene: R954X (608206.0005) and Y169H (608206.0008). Three additional family members who were heterozygous for the R954X mutation, resulting in loss of function, had a subtle mild mononeuropathy of the median nerve (MNMN; 613353) consistent with carpal tunnel syndrome. This involvement of the median nerve was also seen in the patients with CMT4C. Lupski et al. (2010) concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. Two additional family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal polyneuropathy, as shown by electrophysiologic studies, with definite median-nerve mononeuropathy at the wrist associated with evidence of a more widespread axonal neuropathy. The phenotype was similar to that of hereditary neuropathy with liability to pressure palsies (HNPP; 162500). The authors postulated a toxic gain of function for the Y169H-mutant protein. Lupski et al. (2010) commented on the subtle apparently autosomal dominant phenotypes segregating independently with the respective SH3TC2 mutations. </p><p><strong><em>Regulatory Polymorphisms</em></strong></p><p>
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Brewer et al. (2014) identified a C-T SNP, rs1759452, within a distal enhancer approximately 150 kb downstream of the transcription start site of SH3TC2. The minor allele (T) of the SNP reduced SH3TC2 reporter activity by approximately 80% due to disruption of a CREB-binding site. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Arnaud et al. (2009) found that Sh3tc2-null mice developed a progressive peripheral neuropathy manifest by decreased motor and sensory nerve conduction velocity and hypomyelination. Murine Sh3tc2 was specifically expressed in Schwann cells and localized to the plasma membrane and to the perinuclear endocytic recycling compartment, suggesting a possible function in myelination and/or in regions of axoglial interactions. Analysis of myelin in the peripheral nerve of mutant mice showed abnormal organization of the node of Ranvier, a phenotype that was confirmed in CMT4C patient nerve biopsies. The findings suggested a role for the SH3TC2 gene product in myelination and in the integrity of the node of Ranvier. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>8 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, ARG529GLN
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<br />
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SNP: rs80338923,
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gnomAD: rs80338923,
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ClinVar: RCV000002582, RCV000857152, RCV000998463
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated Turkish patients with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), both from consanguineous families, Senderek et al. (2003) identified a homozygous 1586G-A transition in exon 11 of the SH3TC2 gene, resulting in an arg529-to-gln (R529Q) substitution. The R529Q mutation was also detected in heterozygous state in 1 of 320 Turkish control chromosomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, 2-BP DEL, 1747AG
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<br />
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SNP: rs80338924,
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ClinVar: RCV000002583
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated Turkish patients with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), both from consanguineous families, Senderek et al. (2003) identified a homozygous 2-bp deletion in exon 11 of the SH3TC2 gene, 1747delAG, resulting in a frameshift and premature stop codon at residue 586. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, IVS5AS, A-G, -2
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<br />
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SNP: rs80338920,
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ClinVar: RCV000002584, RCV000790209
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 4 affected individuals from a consanguineous Italian family with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), Senderek et al. (2003) identified homozygosity for an A-to-G transition in a splice site (IVS5-2A-G), predicted to result in exon skipping. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, TYR943TER
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<br />
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SNP: rs80338932,
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gnomAD: rs80338932,
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ClinVar: RCV000002585, RCV001223054, RCV001310527
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected sibs from a German family with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), Senderek et al. (2003) identified compound heterozygosity for 2 nonsense mutations in exon 11 of the SH3TC2 gene: a 2829T-G transversion, resulting in a tyr943-to-ter (Y943X) mutation, and the R954X mutation (608206.0005). </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MONONEUROPATHY OF THE MEDIAN NERVE, MILD, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, ARG954TER
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<br />
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SNP: rs80338933,
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gnomAD: rs80338933,
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ClinVar: RCV000002586, RCV000002587, RCV000144877, RCV000168436, RCV000255213, RCV000282937, RCV000515338, RCV000622836, RCV001851586
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 affected sibs from a German family with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), Senderek et al. (2003) identified compound heterozygosity for 2 nonsense mutations in exon 11 of the SH3TC2 gene: a 2860C-T transition, resulting in an arg954-to-ter mutation (R954X; 608206.0005), and the Y943X mutation (608206.0004). </p><p>Azzedine et al. (2006) reported that the R954X mutation was recurrent in their patient series, identified in 4 Dutch families and 1 Algerian family with CMT4C. </p><p>In a French Canadian cluster of 17 CMT4C patients from Quebec, Canada, Gosselin et al. (2008) identified the R954X mutation in homozygosity in 12 patients from 7 families and in compound heterozygosity with an unidentified mutation in 2 patients from 1 family. In total, the R954X mutation was identified in 26 (76%) of 34 alleles from 10 families. Thirteen patients, including 10 homozygous for R954X, originated from a series of coastal villages in the Gaspesie, a sparsely populated peninsular region of Quebec, near the Maine/U.S. border. The villages are distributed along a 150-km stretch of the western shore of Chaleur Bay. Haplotype analysis demonstrated that at least 2 distinct CMT4C mutations are present in the French Canadian population and indicated a founder effect for the R954X mutation. </p><p>Houlden et al. (2009) identified a homozygous R954X mutation in affected members of 4 English families with CMT4C. A fifth English family was compound heterozygous for R954X and a 1969G-A transition, resulting in a gly657-to-lys substitution (E657K; 608206.0007). There was significant phenotypic variability between these families: some presented with severe childhood onset, respiratory and cranial nerve involvement, and became wheelchair-bound, whereas others had only mild scoliosis and foot deformity. One patient homozygous for the R954X mutation had a superimposed inflammatory neuropathy associated with steroid treatment for ulcerative colitis. </p><p>In 4 sibs with CMT4C, Lupski et al. (2010) identified compound heterozygosity for 2 mutations in the SH3TC2 gene: R954X and Y169H (608206.0008). Three additional family members who were heterozygous for the R954X mutation had a mild mononeuropathy of the median nerve (MNMN; 613353) consistent with carpal tunnel syndrome. Lupski et al. (2010) concluded that haploinsufficiency of SH3TC2 may confer susceptibility to carpal tunnel syndrome. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, ARG1109TER
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<br />
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SNP: rs80338934,
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gnomAD: rs80338934,
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ClinVar: RCV000002588, RCV000218266, RCV000654100, RCV000857137, RCV002496231
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 12 patients with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596) from European Gypsy families, Gooding et al. (2005) identified a homozygous 3325C-T (genomic position 52751) transition in exon 14 of the SH3TC2 gene, resulting in an arg1109-to-ter (R1109X) substitution near the C-terminal domain of the protein. Eight of the patients came from a large Spanish Gypsy kindred. Haplotype analysis indicated a founder effect with a conserved ancestral segment of approximately 0.6 cM. Among Spanish Gypsies, the carrier rate of R1109X was estimated at 1 in 26. </p><p>Claramunt et al. (2007) found that 10 of 20 Spanish Gypsy families with autosomal recessive demyelinating neuropathy had CMT4C. The most common mutation was R1109X, which was identified in 20 of 21 mutation-carrying chromosomes. Haplotype analysis indicated a founder effect that likely arose about 225 years ago, probably as a result of a bottleneck. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, GLU657LYS
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<br />
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SNP: rs80338925,
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gnomAD: rs80338925,
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ClinVar: RCV000020887, RCV000206757, RCV000857147, RCV002496432, RCV004786278
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the glu657-to-lys (E657K) mutation in the SH3TC2 gene that was found in compound heterozygous state in patients with Charcot-Marie-Tooth disease type 4C (CMT4C; 601596) by Houlden et al. (2009), see 608206.0005. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0008 CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, TYPE 4C</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
|
|
MONONEUROPATHY OF THE MEDIAN NERVE, MILD, INCLUDED
|
|
</span>
|
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</div>
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<div>
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<span class="mim-text-font">
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SH3TC2, TYR169HIS
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<br />
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SNP: rs80359890,
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gnomAD: rs80359890,
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ClinVar: RCV000002590, RCV000002591, RCV000415264, RCV000656975, RCV001079620, RCV001172848, RCV001293355, RCV001705579, RCV002345223
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In sibs with autosomal recessive Charcot-Marie-Tooth disease type 4C (CMT4C; 601596), Lupski et al. (2010) identified compound heterozygosity for 2 mutations in the SH3TC2 gene: an A-to-G transition, resulting in a tyr169-to-his (Y169H) substitution and R954X (608206.0005). Two other family members who were heterozygous for the Y169H mutation had an apparently autosomal dominant patchy axonal neuropathy with median nerve mononeuropathy at the wrist (MNMN; 613353), as shown by electrophysiologic studies. These findings suggested a toxic gain of function for the mutant protein, and indicated that heterozygous SH3TC2 mutation carriers may also have a phenotype. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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|
<strong>REFERENCES</strong>
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|
</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Arnaud, E., Zenker, J., de Preux Charles, A.-S., Stendel, C., Roos, A., Medard, J.-J., Tricaud, N., Kleine, H., Luscher, B., Weis, J., Suter, U., Senderek, J., Chrast, R.
|
|
<strong>SH3TC2/KIAA1985 protein is required for proper myelination and the integrity of the node of Ranvier in the peripheral nervous system.</strong>
|
|
Proc. Nat. Acad. Sci. 106: 17528-17533, 2009. Note: Erratum: Proc. Nat. Acad. Sci. 107: 15305 only, 2010.
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[PubMed: 19805030]
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[Full Text: https://doi.org/10.1073/pnas.0905523106]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Azzedine, H., Ravise, N., Verny, C., Gabreels-Festen, A., Lammens, M., Grid, D., Vallat, J. M., Durosier, G., Senderek, J., Nouioua, S., Hamadouche, T., Bouhouche, A., Guilbot, A., Stendel, C., Ruberg, M., Brice, A., Birouk, N., Dubourg, O., Tazir, M., LeGuern, E.
|
|
<strong>Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations.</strong>
|
|
Neurology 67: 602-606, 2006.
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[PubMed: 16924012]
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[Full Text: https://doi.org/10.1212/01.wnl.0000230225.19797.93]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Brewer, M. H., Ma, K. H., Beecham, G. W., Gopinath, C., the Inherited Neuropathy Consortium (INC), Baas, F., Choi, B.-O., Reilly, M. M., Shy, M. E., Zuchner, S., Svaren, J., Antonellis, A.
|
|
<strong>Haplotype-specific modulation of a SOX10/CREB response element at the Charcot-Marie-Tooth disease type 4c locus SH3TC2.</strong>
|
|
Hum. Molec. Genet. 23: 5171-5187, 2014.
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[PubMed: 24833716]
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[Full Text: https://doi.org/10.1093/hmg/ddu240]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Claramunt, R., Sevilla, T., Lupo, V., Cuesta, A., Millan, J.M., Vilchez, J. J., Palau, F., Espinos, C.
|
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<strong>The p.R1109X mutation in SH3TC2 gene is predominant in Spanish Gypsies with Charcot-Marie-Tooth disease type 4.</strong>
|
|
Clin. Genet. 71: 343-349, 2007.
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[PubMed: 17470135]
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[Full Text: https://doi.org/10.1111/j.1399-0004.2007.00774.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Gooding, R., Colomer, J., King, R., Angelicheva, D., Marns, L., Parman, Y., Chandler, D., Bertranpetit, J., Kalaydjieva, L.
|
|
<strong>A novel Gypsy founder mutation, pArg1109X in the CMT4C gene, causes variable peripheral neuropathy phenotypes.</strong>
|
|
J. Med. Genet. 42: e69, 2005. Note: Electronic Article.
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[PubMed: 16326826]
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[Full Text: https://doi.org/10.1136/jmg.2005.034132]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gosselin, I., Thiffault, I., Tetreault, M., Chau, V., Dicaire, M.-J., Loisel, L., Emond, M., Senderek, J., Mathieu, J., Dupre, N., Vanasse, M., Puymirat, J., Brais, B.
|
|
<strong>Founder SH3TC2 mutations are responsible for a CMT4C French-Canadians cluster.</strong>
|
|
Neuromusc. Disord. 18: 483-492, 2008.
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|
|
[PubMed: 18511281]
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[Full Text: https://doi.org/10.1016/j.nmd.2008.04.001]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Houlden, H., Laura, M., Ginsberg, L., Jungbluth, H., Robb, S. A., Blake, J., Robinson, S., King, R. H. M., Reilly, M. M.
|
|
<strong>The phenotype of Charcot-Marie-Tooth disease type 4C due to SH3TC2 mutations and possible predisposition to an inflammatory neuropathy.</strong>
|
|
Neuromusc. Disord. 19: 264-269, 2009.
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[PubMed: 19272779]
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[Full Text: https://doi.org/10.1016/j.nmd.2009.01.006]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lupo, V., Galindo, M. I., Martinez-Rubio, D., Sevilla, T., Vilchez, J. J., Palau, F., Espinos, C.
|
|
<strong>Missense mutations in the SH3TC2 protein causing Charcot-Marie-Tooth disease type 4C affect its localization in the plasma membrane and endocytic pathway.</strong>
|
|
Hum. Molec. Genet. 18: 4603-4614, 2009.
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[PubMed: 19744956]
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[Full Text: https://doi.org/10.1093/hmg/ddp427]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Lupski, J. R., Reid, J. G., Gonzaga-Jauregui, C., Rio Deiros, D., Chen, D. C. Y., Nazareth, L., Bainbridge, M., Dinh, H., Jing, C., Wheeler, D. A., McGuire, A. L., Zhang, F., and 10 others.
|
|
<strong>Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy.</strong>
|
|
New Eng. J. Med. 362: 1181-1191, 2010.
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[PubMed: 20220177]
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[Full Text: https://doi.org/10.1056/NEJMoa0908094]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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|
Nagase, T., Kikuno, R., Ohara, O.
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<strong>Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins.</strong>
|
|
DNA Res. 8: 319-327, 2001.
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[PubMed: 11853319]
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[Full Text: https://doi.org/10.1093/dnares/8.6.319]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Roberts, R. C., Peden, A. A., Buss, F., Bright, N. A., Latouche, M., Reilly, M. M., Kendrick-Jones, J., Luzio, J. P.
|
|
<strong>Mistargeting of SH3TC2 away from the recycling endosome causes Charcot-Marie-Tooth disease type 4C.</strong>
|
|
Hum. Molec. Genet. 19: 1009-1018, 2010.
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[PubMed: 20028792]
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[Full Text: https://doi.org/10.1093/hmg/ddp565]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Senderek, J., Bergmann, C., Stendel, C., Kirfel, J., Verpoorten, N., De Jonghe, P., Timmerman, V., Chrast, R., Verheijen, M. H. G., Lemke, G., Battaloglu, E., Parman, Y., and 19 others.
|
|
<strong>Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.</strong>
|
|
Am. J. Hum. Genet. 73: 1106-1119, 2003.
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[PubMed: 14574644]
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[Full Text: https://doi.org/10.1086/379525]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Stumpf, A. M.
|
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<strong>Personal Communication.</strong>
|
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Baltimore, Md. 08/12/2020.
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
|
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Contributors:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Anne M. Stumpf - updated : 08/12/2020<br>Patricia A. Hartz - updated : 11/5/2014<br>George E. Tiller - updated : 11/10/2011<br>George E. Tiller - updated : 10/28/2010<br>Cassandra L. Kniffin - updated : 4/13/2010<br>Cassandra L. Kniffin - updated : 11/3/2009<br>Cassandra L. Kniffin - updated : 8/2/2007<br>Cassandra L. Kniffin - updated : 7/6/2007<br>Cassandra L. Kniffin - updated : 5/4/2007<br>Cassandra L. Kniffin - updated : 11/5/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 10/27/2003
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</span>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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