3323 lines
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- *609512 - CHARGED MULTIVESICULAR BODY PROTEIN 2B; CHMP2B
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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">*609512</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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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/609512">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000083937;t=ENST00000263780" 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=25978" 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=609512" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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<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=ENSG00000083937;t=ENST00000263780" 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_001244644,NM_001410777,NM_014043,XM_011533576" 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_014043" 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=609512" 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=13174&isoform_id=13174_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/CHMP2B" 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/4929637,5262501,16306739,40254866,49065338,62896867,73917746,119589274,189067568,193785587,193785590,194382150,347582619,767922905,2286439389,2462588976" 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/Q9UQN3" 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=25978" 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=ENSG00000083937;t=ENST00000263780" 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=CHMP2B" 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=CHMP2B" 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+25978" 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/CHMP2B" 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:25978" 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/25978" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr3&hgg_gene=ENST00000263780.9&hgg_start=87227309&hgg_end=87255556&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:24537" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/chmp2b" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=609512[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=609512[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://gnomad.broadinstitute.org/gene/ENSG00000083937" 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=CHMP2B" 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=CHMP2B" 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=CHMP2B" 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/ADMutations/" 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=CHMP2B&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/PA142672112" 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:24537" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0035589.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1916192" 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/CHMP2B#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:1916192" 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/25978/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=25978" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00007216;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-2539" 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://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:25978" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=CHMP2B&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> 702393003<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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609512
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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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CHARGED MULTIVESICULAR BODY PROTEIN 2B; CHMP2B
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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>
|
|
<span class="mim-font">
|
|
CHMP FAMILY, MEMBER 2B<br />
|
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CHROMATIN-MODIFYING PROTEIN 2B<br />
|
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VACUOLAR PROTEIN SORTING 2, YEAST, HOMOLOG OF, B; VPS2B
|
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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=CHMP2B" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CHMP2B</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: <a href="/geneMap/3/475?start=-3&limit=10&highlight=475">3p11.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:87227309-87255556&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">3:87,227,309-87,255,556</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
|
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</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/475?start=-3&limit=10&highlight=475">
|
|
3p11.2
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7
|
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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/600795"> 600795 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/609512" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/609512" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<p>CHMP2B belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (<a href="/entry/164010">164010</a>), is required for both MVB formation and regulation of cell cycle progression (summary by <a href="#9" class="mim-tip-reference" title="Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M. <strong>A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.</strong> Genomics 88: 333-346, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16730941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16730941</a>] [<a href="https://doi.org/10.1016/j.ygeno.2006.04.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16730941">Tsang et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16730941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> identified the human CHMP2B gene by positional cloning of a candidate gene region identified for frontotemporal dementia linked to a 15.5-Mb region on chromosome 3 (FTD3; <a href="/entry/600795">600795</a>). The deduced 213-amino acid protein contains coiled-coil, Snf-7, and acidic C-terminal domains. Northern blot analysis identified a major 2.4-kb mRNA transcript in multiple human tissues and all major regions of the brain. Two minor transcripts of approximately 1.9 and 1.35 kb were also identified, suggestive of alternative 5-prime and 3-prime untranslated regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> determined that the CHMP2B gene contains 6 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" 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 in situ hybridization of mouse brain, <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> found widespread Chmp2b expression in all neuronal populations, especially in the hippocampus, frontal and temporal lobes, and cerebellum. No astrocytes or oligodendrocytes were labeled. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The yeast ortholog of CHMP2B, Vps2, was initially identified in a mutagenesis screen for unusual vacuolar protein sorting (vps) phenotypes in S. cerevisiae, and was found to be part of the ESCRTIII complex (endosomal secretory complex required for transport), which participates in endosomal trafficking (<a href="#1" class="mim-tip-reference" title="Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T., Emr, S. D. <strong>ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting.</strong> Dev. Cell 3: 271-282, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12194857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12194857</a>] [<a href="https://doi.org/10.1016/s1534-5807(02)00220-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12194857">Babst et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12194857" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Urwin, H., Authier, A., Nielsen, J. E., Metcalf, D., Powell, C., Froud, K., Malcolm, D. S., Holm, I., Johannsen, P., Brown, J., Fisher, E. M. C., van der Zee, J., Bruyland, M., the FReJA Consortium, Collinge, J., Brandner, S., Futter, C., Isaacs, A. M. <strong>Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations.</strong> Hum. Molec. Genet. 19: 2228-2238, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223751[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/ddq100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20223751">Urwin et al. (2010)</a> described endosomal pathology in CHMP2B mutation-positive patient brains and also identified and characterized abnormal endosomes in patient fibroblasts. Functional studies demonstrated a specific disruption of endosome-lysosome fusion but not protein sorting by the multivesicular body (MVB). The authors proposed a mechanism for impaired endosome-lysosome fusion whereby mutant CHMP2B constitutively binds to MVBs and prevents recruitment of proteins, such as Rab7 (<a href="/entry/602298">602298</a>), that are necessary for fusion to occur. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20223751" 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 11 affected members of a large Danish family with frontotemporal dementia linked to chromosome 3 (FTDALS7; <a href="/entry/600795">600795</a>) reported by <a href="#2" class="mim-tip-reference" title="Brown, J., Ashworth, A., Gydesen, S., Sorensen, A., Rossor, M., Hardy, J., Collinge, J. <strong>Familial non-specific dementia maps to chromosome 3.</strong> Hum. Molec. Genet. 4: 1625-1628, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541850</a>] [<a href="https://doi.org/10.1093/hmg/4.9.1625" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8541850">Brown et al. (1995)</a> and <a href="#5" class="mim-tip-reference" title="Gydesen, S., Brown, J. M., Brun, A., Chakrabarti, L., Gade, A., Johannsen, P., Rossor, M., Thusgaard, T., Grove, A., Yancopoulou, D., Spillantini, M. G., Fisher, E. M. C., Collinge, J., Sorensen, S. A. <strong>Chromosome 3 linked frontotemporal dementia (FTD-3).</strong> Neurology 59: 1585-1594, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451202</a>] [<a href="https://doi.org/10.1212/01.wnl.0000034763.54161.1f" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12451202">Gydesen et al. (2002)</a>, <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> identified a heterozygous mutation in the CHMPB2 gene (<a href="#0001">609512.0001</a>). The authors identified a different CHMPB2 mutation (<a href="#0002">609512.0002</a>) in a single unrelated patient with nonspecific dementia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8541850+16041373+12451202" 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="Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. <strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong> Neurology 67: 1074-1077, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231510.89311.8b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16807408">Parkinson et al. (2006)</a> identified a heterozygous CHMPB2 mutation (<a href="#0003">609512.0003</a>) in a patient with rapidly progressive motor deterioration consistent with a diagnosis of amyotrophic lateral sclerosis. No dementia was present in this patient. A second unrelated man with FTD and ALS had a different heterozygous mutation (I29V; <a href="#0005">609512.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16807408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#11" class="mim-tip-reference" title="van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., Fisher, E. M., Collinge, J., Isaacs, A. M., Van Broeckhoven, C. <strong>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro.</strong> Hum. Molec. Genet. 17: 313-322, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17956895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17956895</a>] [<a href="https://doi.org/10.1093/hmg/ddm309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17956895">Van der Zee et al. (2008)</a> identified a truncating mutation in the CHMPB2 gene (<a href="#0004">609512.0004</a>) in a Belgian patient with autosomal dominant frontotemporal lobar degeneration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17956895" 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="Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. <strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong> PLoS One 5: e9872, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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/10.1371/journal.pone.0009872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20352044">Cox et al. (2010)</a> identified heterozygous mutations in the CHMP2B gene (see, e.g., <a href="#0003">609512.0003</a>, <a href="#0005">609512.0005</a>, and <a href="#0006">609512.0006</a>) in 4 (1%) of 433 patients with ALS17. However, CHMP2B mutations were found in 10% of those with the specific lower motor neuron variant of ALS. Microarray analysis of motor neurons with CHMP2B mutations showed downregulation of genes involved in axonal transport, autophagy induction, protein translation, and certain signaling pathways, such as MAPK-related pathways (see, e.g., <a href="/entry/600289">600289</a>). Transfection of mutant CHMP2B into HEK293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localization, and impaired autophagy. <a href="#4" class="mim-tip-reference" title="Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. <strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong> PLoS One 5: e9872, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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/10.1371/journal.pone.0009872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20352044">Cox et al. (2010)</a> hypothesized that CHMP2B mutations may contribute to motor neuron injury through dysfunction of the autophagic clearance of cellular proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20352044" 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>Exclusion Studies</em></strong></p><p>
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<a href="#6" class="mim-tip-reference" title="Momeni, P., Rogaeva, E., Van Deerlin, V., Yuan, W., Grafman, J., Tierney, M., Huey, E., Bell, J., Morris, C. M., Kalaria, R. N., van Rensburg, S. J., Niehaus, D., Potocnik, F., Kawarai, T., Salehi-Rad, S., Sato, C., St. George-Hyslop, P., Hardy, J. <strong>Genetic variability in CHMP2B and frontotemporal dementia.</strong> Neurodegener. Dis. 3: 129-133, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16954699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16954699</a>] [<a href="https://doi.org/10.1159/000094771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16954699">Momeni et al. (2006)</a> did not identify pathogenic mutations in the CHMPB2 gene in 128 probands with frontotemporal dementia in whom MAPT mutations had been excluded. A truncating mutation in the CHMPB2 gene was identified in 2 middle-aged unaffected Afrikaner individuals from a large affected family; however, their affected father and 5 affected paternal relatives did not have the mutation. The maternal side of the family had no reported dementia. <a href="#6" class="mim-tip-reference" title="Momeni, P., Rogaeva, E., Van Deerlin, V., Yuan, W., Grafman, J., Tierney, M., Huey, E., Bell, J., Morris, C. M., Kalaria, R. N., van Rensburg, S. J., Niehaus, D., Potocnik, F., Kawarai, T., Salehi-Rad, S., Sato, C., St. George-Hyslop, P., Hardy, J. <strong>Genetic variability in CHMP2B and frontotemporal dementia.</strong> Neurodegener. Dis. 3: 129-133, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16954699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16954699</a>] [<a href="https://doi.org/10.1159/000094771" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16954699">Momeni et al. (2006)</a> noted that the large Danish family reported by <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> had a similar truncating mutation in the CHMPB2 gene, which resulted from a different nucleotide change. The findings raised questions about the pathogenicity of the CHMPB2 mutation identified by <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> and suggested that CHMPB2 mutations are not a common cause of frontotemporal dementia. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16041373+16954699" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Cannon, A., Baker, M., Boeve, B., Josephs, K., Knopman, D., Petersen, R., Parisi, J., Dickison, D., Adamson, J., Snowden, J., Neary, D., Mann, D., Hutton, M., Pickering-Brown, S. M. <strong>CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.</strong> Neurosci. Lett. 398: 83-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16431024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16431024</a>] [<a href="https://doi.org/10.1016/j.neulet.2005.12.056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16431024">Cannon et al. (2006)</a> did not identify pathogenic CHMPB2 mutations in 141 familial frontotemporal probands from the U.S. and U.K. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16431024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=609512[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs63750652 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs63750652;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=rs63750652" 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=rs63750652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 11 affected members from a large Danish family with frontotemporal dementia (FTDALS7; <a href="/entry/600795">600795</a>), <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> identified a heterozygous G-to-C transversion in the acceptor splice site of exon 6 of the CHMP2B gene. RT-PCR analysis showed that the mutation resulted in either inclusion of the 201-bp intronic sequence spanning exons 5 and 6 or a short deletion resulting from the use of a cryptic splice site mapping 10 bp from the 5-prime end of exon 6. Evidence suggested the presence of a third abnormal product which may have resulted from a heteroduplex formed between wildtype and mutant CHMP2B. The G-to-C transversion was not identified in 14 unaffected family members or 220 control DNA samples. In vitro functional expression studies in rat PC12 cells showed that the mutant proteins accumulated on the outer membrane of large aberrant cytoplasmic bodies, consistent with the formation of dysmorphic organelles of the late endosomal pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Cannon, A., Baker, M., Boeve, B., Josephs, K., Knopman, D., Petersen, R., Parisi, J., Dickison, D., Adamson, J., Snowden, J., Neary, D., Mann, D., Hutton, M., Pickering-Brown, S. M. <strong>CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.</strong> Neurosci. Lett. 398: 83-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16431024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16431024</a>] [<a href="https://doi.org/10.1016/j.neulet.2005.12.056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16431024">Cannon et al. (2006)</a> did not identify the splice site mutation reported by <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> in 450 control individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16041373+16431024" 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">rs63750653 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs63750653;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=rs63750653" 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=rs63750653" 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=RCV000001720 OR RCV000084275" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000001720, RCV000084275" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000001720...</a>
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<p>In a patient with frontotemporal dementia (FTDALS7; <a href="/entry/600795">600795</a>), <a href="#8" class="mim-tip-reference" title="Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J. <strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong> Nature Genet. 37: 806-808, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>] [<a href="https://doi.org/10.1038/ng1609" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16041373">Skibinski et al. (2005)</a> identified a 442G-T transversion in exon 5 of the CHMP2B gene, resulting in an asp148-to-tyr (D148Y) substitution in the conserved Snf-7 domain. The patient was 1 of 400 unrelated European patients studied. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" 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 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</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> rs63751126 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs63751126;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/rs63751126?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=rs63751126" 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=rs63751126" 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=RCV000020696 OR RCV000084279" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000020696, RCV000084279" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000020696...</a>
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<p>In a 75-year-old man with rapidly progressive amyotrophic lateral sclerosis (FTDALS7; <a href="/entry/600795">600795</a>), <a href="#7" class="mim-tip-reference" title="Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. <strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong> Neurology 67: 1074-1077, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231510.89311.8b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16807408">Parkinson et al. (2006)</a> identified a heterozygous 694A-C transversion in exon 6 of the CHMP2B gene, resulting in a gln206-to-his (Q206H) substitution in a highly conserved residue. The mutation was not identified in 640 control samples. At age 74 years, the patient developed bulbar-onset weakness with flaccid dysarthria and tongue fasciculations. He later developed weakness and wasting of the intrinsic hand muscles and respiratory weakness. Although he had a previous right leg amputation from trauma, neurophysiologic testing showed neurogenic changes in all 4 limbs. He had depressed reflexes and flexor plantar responses, consistent with lower motor neuron involvement. He died of respiratory failure 15 months after symptom onset. There was no evidence of dementia or extramotor neurologic involvement. A cousin reportedly had died of ALS. Neuropathologic examination showed a predominantly lower motor neuron disease with intraneuronal inclusions immunopositive for ubiquitin (UBB; <a href="/entry/191339">191339</a>) and p62/sequestosome (SQSTM1; <a href="/entry/601530">601530</a>). SQSTM1-reactive inclusions were also detected within oligodendroglia in the cerebral motor cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16807408" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro functional studies in HEK293 and COS-7 cells, <a href="#4" class="mim-tip-reference" title="Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. <strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong> PLoS One 5: e9872, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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/10.1371/journal.pone.0009872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20352044">Cox et al. (2010)</a> showed that cells expressing the Q206H mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (<a href="/entry/155740">155740</a>) and an increase in LC3-II (<a href="/entry/601242">601242</a>), overall indicating a defect in the autophagic pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20352044" 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">rs63750355 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs63750355;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=rs63750355" 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=rs63750355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Belgian woman with onset of frontotemporal dementia (FTDALS7; <a href="/entry/600795">600795</a>) at age 58, <a href="#11" class="mim-tip-reference" title="van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., Fisher, E. M., Collinge, J., Isaacs, A. M., Van Broeckhoven, C. <strong>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro.</strong> Hum. Molec. Genet. 17: 313-322, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17956895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17956895</a>] [<a href="https://doi.org/10.1093/hmg/ddm309" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17956895">van der Zee et al. (2008)</a> identified a heterozygous 493C-T transition in exon 5 of the CHMP2B gene, resulting in a gln165-to-ter (Q165X) substitution. Her mother and maternal aunt were reportedly similarly affected. RT-PCR studies confirmed the presence of a mutant transcript in patient cells. The mutation was not found in 459 Belgian control individuals. Overexpression of the Q165X mutant in human neuroblastoma cells resulted in accumulation of truncated protein in enlarged vesicular structures. Normally, the C terminal of CHMP2B functions as an autoinhibitor, allowing the protein to shuttle between the inactive and active states. The truncation eliminates this inhibitory effect, resulting in constitutive activation and involvement in the endosomal complex and accumulation on the endosomal membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17956895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a man with onset of progressive frontotemporal dementia (FTDALS7; <a href="/entry/600795">600795</a>) in his late sixties followed by amyotrophic lateral sclerosis, <a href="#7" class="mim-tip-reference" title="Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. <strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong> Neurology 67: 1074-1077, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231510.89311.8b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16807408">Parkinson et al. (2006)</a> identified a heterozygous 161A-G transition in the CHMP3B gene, resulting in an ile29-to-val (I29V) substitution located between 2 conserved regions of the protein. The mutation was not found in 640 controls or in 400 FTD samples. However, <a href="#7" class="mim-tip-reference" title="Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. <strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong> Neurology 67: 1074-1077, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231510.89311.8b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16807408">Parkinson et al. (2006)</a> noted that <a href="#3" class="mim-tip-reference" title="Cannon, A., Baker, M., Boeve, B., Josephs, K., Knopman, D., Petersen, R., Parisi, J., Dickison, D., Adamson, J., Snowden, J., Neary, D., Mann, D., Hutton, M., Pickering-Brown, S. M. <strong>CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.</strong> Neurosci. Lett. 398: 83-84, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16431024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16431024</a>] [<a href="https://doi.org/10.1016/j.neulet.2005.12.056" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16431024">Cannon et al. (2006)</a> found the I29V variant in 1 of 141 probands with frontotemporal dementia and at a frequency of 0.5% among 200 control chromosomes, thus suggesting that it may be a benign variant. The patient reported by <a href="#7" class="mim-tip-reference" title="Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium. <strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong> Neurology 67: 1074-1077, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>] [<a href="https://doi.org/10.1212/01.wnl.0000231510.89311.8b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16807408">Parkinson et al. (2006)</a> had brisk tendon reflexes and extensor plantar responses. His father reportedly had motor disturbances and frontal lobe dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16431024+16807408" 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="Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. <strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong> PLoS One 5: e9872, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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/10.1371/journal.pone.0009872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20352044">Cox et al. (2010)</a> identified a heterozygous I29V substitution, which they stated resulted from an 85A-G transition, in 2 unrelated patients with onset of amyotrophic lateral sclerosis at ages 64 and 49 years, respectively. The mutation was not found in 1,000 control chromosomes. Both patients had involvement of the upper and lower limbs, as well as bulbar symptoms, but no signs of upper motor neuron involvement. In vitro functional studies in HEK293 and COS-7 cells showed that cells expressing the mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (<a href="/entry/155740">155740</a>) and an increase in LC3-II (<a href="/entry/601242">601242</a>), overall indicating a defect in the autophagic pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20352044" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 54-year-old man with amyotrophic lateral sclerosis (FTDALS7; <a href="/entry/600795">600795</a>), <a href="#4" class="mim-tip-reference" title="Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J. <strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong> PLoS One 5: e9872, 2010. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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/10.1371/journal.pone.0009872" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20352044">Cox et al. (2010)</a> identified a heterozygous 311C-A transversion in exon 3 of the CHMP2B gene, resulting in a thr104-to-asn (T104N) substitution at a highly conserved residue. The mutation was not found in 1,000 control chromosomes. The patient presented with bulbar and respiratory dysfunction and later developed wasting and fasciculation in the upper and lower limbs. Reflexes were normal, suggesting only lower motor neuron involvement. In vitro functional studies in HEK293 and COS-7 cells showed that cells expressing the mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (<a href="/entry/155740">155740</a>) and an increase in LC3-II (<a href="/entry/601242">601242</a>), overall indicating a defect in the autophagic pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20352044" 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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<a id="Babst2002" class="mim-anchor"></a>
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Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T., Emr, S. D.
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<strong>ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting.</strong>
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Dev. Cell 3: 271-282, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12194857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12194857</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12194857" 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/s1534-5807(02)00220-4" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Brown1995" class="mim-anchor"></a>
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Brown, J., Ashworth, A., Gydesen, S., Sorensen, A., Rossor, M., Hardy, J., Collinge, J.
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<strong>Familial non-specific dementia maps to chromosome 3.</strong>
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Hum. Molec. Genet. 4: 1625-1628, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8541850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8541850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8541850" 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/4.9.1625" target="_blank">Full Text</a>]
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<a id="Cannon2006" class="mim-anchor"></a>
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Cannon, A., Baker, M., Boeve, B., Josephs, K., Knopman, D., Petersen, R., Parisi, J., Dickison, D., Adamson, J., Snowden, J., Neary, D., Mann, D., Hutton, M., Pickering-Brown, S. M.
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<strong>CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.</strong>
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Neurosci. Lett. 398: 83-84, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16431024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16431024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16431024" 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.neulet.2005.12.056" target="_blank">Full Text</a>]
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<a id="Cox2010" class="mim-anchor"></a>
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Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J.
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<strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong>
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PLoS One 5: e9872, 2010. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20352044/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20352044</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20352044[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=20352044" 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/10.1371/journal.pone.0009872" target="_blank">Full Text</a>]
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<a id="Gydesen2002" class="mim-anchor"></a>
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Gydesen, S., Brown, J. M., Brun, A., Chakrabarti, L., Gade, A., Johannsen, P., Rossor, M., Thusgaard, T., Grove, A., Yancopoulou, D., Spillantini, M. G., Fisher, E. M. C., Collinge, J., Sorensen, S. A.
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<strong>Chromosome 3 linked frontotemporal dementia (FTD-3).</strong>
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Neurology 59: 1585-1594, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12451202/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12451202</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12451202" 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.0000034763.54161.1f" target="_blank">Full Text</a>]
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<a id="Momeni2006" class="mim-anchor"></a>
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Momeni, P., Rogaeva, E., Van Deerlin, V., Yuan, W., Grafman, J., Tierney, M., Huey, E., Bell, J., Morris, C. M., Kalaria, R. N., van Rensburg, S. J., Niehaus, D., Potocnik, F., Kawarai, T., Salehi-Rad, S., Sato, C., St. George-Hyslop, P., Hardy, J.
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<strong>Genetic variability in CHMP2B and frontotemporal dementia.</strong>
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Neurodegener. Dis. 3: 129-133, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16954699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16954699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16954699" 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/10.1159/000094771" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Parkinson2006" class="mim-anchor"></a>
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<div class="">
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Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium.
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<strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong>
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Neurology 67: 1074-1077, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16807408/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16807408</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16807408" 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.0000231510.89311.8b" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Skibinski2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J.
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<strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong>
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Nature Genet. 37: 806-808, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16041373/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16041373</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16041373" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1609" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Tsang2006" class="mim-anchor"></a>
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<div class="">
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Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M.
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<strong>A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.</strong>
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Genomics 88: 333-346, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16730941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16730941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16730941" 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.ygeno.2006.04.003" target="_blank">Full Text</a>]
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<a id="Urwin2010" class="mim-anchor"></a>
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Urwin, H., Authier, A., Nielsen, J. E., Metcalf, D., Powell, C., Froud, K., Malcolm, D. S., Holm, I., Johannsen, P., Brown, J., Fisher, E. M. C., van der Zee, J., Bruyland, M., the FReJA Consortium, Collinge, J., Brandner, S., Futter, C., Isaacs, A. M.
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<strong>Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations.</strong>
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Hum. Molec. Genet. 19: 2228-2238, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20223751/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20223751</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=20223751[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=20223751" 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/ddq100" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="van der Zee2008" class="mim-anchor"></a>
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van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., Fisher, E. M., Collinge, J., Isaacs, A. M., Van Broeckhoven, C.
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<strong>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro.</strong>
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Hum. Molec. Genet. 17: 313-322, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17956895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17956895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17956895" 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/ddm309" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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George E. Tiller - updated : 8/19/2013
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 7/2/2012<br>Cassandra L. Kniffin - updated : 4/29/2009<br>Cassandra L. Kniffin - updated : 11/8/2006
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Cassandra L. Kniffin : 8/3/2005
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carol : 01/07/2021
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carol : 01/06/2021<br>carol : 11/11/2020<br>carol : 08/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>carol : 7/10/2012<br>terry : 7/10/2012<br>ckniffin : 7/2/2012<br>carol : 6/22/2012<br>wwang : 5/20/2009<br>ckniffin : 4/29/2009<br>mgross : 4/2/2007<br>mgross : 3/28/2007<br>mgross : 3/28/2007<br>wwang : 11/29/2006<br>wwang : 11/28/2006<br>ckniffin : 11/8/2006<br>terry : 9/27/2005<br>alopez : 8/3/2005<br>ckniffin : 8/3/2005
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<strong>*</strong> 609512
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CHARGED MULTIVESICULAR BODY PROTEIN 2B; CHMP2B
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</h3>
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<div >
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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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CHMP FAMILY, MEMBER 2B<br />
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CHROMATIN-MODIFYING PROTEIN 2B<br />
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VACUOLAR PROTEIN SORTING 2, YEAST, HOMOLOG OF, B; VPS2B
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</span>
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</h4>
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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: CHMP2B</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> 702393003;
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</span>
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</p>
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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: 3p11.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:87,227,309-87,255,556 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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3p11.2
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</span>
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</td>
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<td>
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<span class="mim-font">
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Frontotemporal dementia and/or amyotrophic lateral sclerosis 7
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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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600795
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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>CHMP2B belongs to the chromatin-modifying protein/charged multivesicular body protein (CHMP) family. These proteins are components of ESCRT-III (endosomal sorting complex required for transport III), a complex involved in degradation of surface receptor proteins and formation of endocytic multivesicular bodies (MVBs). Some CHMPs have both nuclear and cytoplasmic/vesicular distributions, and one such CHMP, CHMP1A (164010), is required for both MVB formation and regulation of cell cycle progression (summary by Tsang et al., 2006). </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>Skibinski et al. (2005) identified the human CHMP2B gene by positional cloning of a candidate gene region identified for frontotemporal dementia linked to a 15.5-Mb region on chromosome 3 (FTD3; 600795). The deduced 213-amino acid protein contains coiled-coil, Snf-7, and acidic C-terminal domains. Northern blot analysis identified a major 2.4-kb mRNA transcript in multiple human tissues and all major regions of the brain. Two minor transcripts of approximately 1.9 and 1.35 kb were also identified, suggestive of alternative 5-prime and 3-prime untranslated regions. </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>Skibinski et al. (2005) determined that the CHMP2B gene contains 6 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>By in situ hybridization of mouse brain, Skibinski et al. (2005) found widespread Chmp2b expression in all neuronal populations, especially in the hippocampus, frontal and temporal lobes, and cerebellum. No astrocytes or oligodendrocytes were labeled. </p><p>The yeast ortholog of CHMP2B, Vps2, was initially identified in a mutagenesis screen for unusual vacuolar protein sorting (vps) phenotypes in S. cerevisiae, and was found to be part of the ESCRTIII complex (endosomal secretory complex required for transport), which participates in endosomal trafficking (Babst et al., 2002). </p><p>Urwin et al. (2010) described endosomal pathology in CHMP2B mutation-positive patient brains and also identified and characterized abnormal endosomes in patient fibroblasts. Functional studies demonstrated a specific disruption of endosome-lysosome fusion but not protein sorting by the multivesicular body (MVB). The authors proposed a mechanism for impaired endosome-lysosome fusion whereby mutant CHMP2B constitutively binds to MVBs and prevents recruitment of proteins, such as Rab7 (602298), that are necessary for fusion to occur. </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>In 11 affected members of a large Danish family with frontotemporal dementia linked to chromosome 3 (FTDALS7; 600795) reported by Brown et al. (1995) and Gydesen et al. (2002), Skibinski et al. (2005) identified a heterozygous mutation in the CHMPB2 gene (609512.0001). The authors identified a different CHMPB2 mutation (609512.0002) in a single unrelated patient with nonspecific dementia. </p><p>Parkinson et al. (2006) identified a heterozygous CHMPB2 mutation (609512.0003) in a patient with rapidly progressive motor deterioration consistent with a diagnosis of amyotrophic lateral sclerosis. No dementia was present in this patient. A second unrelated man with FTD and ALS had a different heterozygous mutation (I29V; 609512.0005). </p><p>Van der Zee et al. (2008) identified a truncating mutation in the CHMPB2 gene (609512.0004) in a Belgian patient with autosomal dominant frontotemporal lobar degeneration. </p><p>Cox et al. (2010) identified heterozygous mutations in the CHMP2B gene (see, e.g., 609512.0003, 609512.0005, and 609512.0006) in 4 (1%) of 433 patients with ALS17. However, CHMP2B mutations were found in 10% of those with the specific lower motor neuron variant of ALS. Microarray analysis of motor neurons with CHMP2B mutations showed downregulation of genes involved in axonal transport, autophagy induction, protein translation, and certain signaling pathways, such as MAPK-related pathways (see, e.g., 600289). Transfection of mutant CHMP2B into HEK293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localization, and impaired autophagy. Cox et al. (2010) hypothesized that CHMP2B mutations may contribute to motor neuron injury through dysfunction of the autophagic clearance of cellular proteins. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
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|
Momeni et al. (2006) did not identify pathogenic mutations in the CHMPB2 gene in 128 probands with frontotemporal dementia in whom MAPT mutations had been excluded. A truncating mutation in the CHMPB2 gene was identified in 2 middle-aged unaffected Afrikaner individuals from a large affected family; however, their affected father and 5 affected paternal relatives did not have the mutation. The maternal side of the family had no reported dementia. Momeni et al. (2006) noted that the large Danish family reported by Skibinski et al. (2005) had a similar truncating mutation in the CHMPB2 gene, which resulted from a different nucleotide change. The findings raised questions about the pathogenicity of the CHMPB2 mutation identified by Skibinski et al. (2005) and suggested that CHMPB2 mutations are not a common cause of frontotemporal dementia. </p><p>Cannon et al. (2006) did not identify pathogenic CHMPB2 mutations in 141 familial frontotemporal probands from the U.S. and U.K. </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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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
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CHMP2B, IVS5AS, G-C
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|
<br />
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|
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SNP: rs63750652,
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|
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ClinVar: RCV000084277, RCV002055246
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 11 affected members from a large Danish family with frontotemporal dementia (FTDALS7; 600795), Skibinski et al. (2005) identified a heterozygous G-to-C transversion in the acceptor splice site of exon 6 of the CHMP2B gene. RT-PCR analysis showed that the mutation resulted in either inclusion of the 201-bp intronic sequence spanning exons 5 and 6 or a short deletion resulting from the use of a cryptic splice site mapping 10 bp from the 5-prime end of exon 6. Evidence suggested the presence of a third abnormal product which may have resulted from a heteroduplex formed between wildtype and mutant CHMP2B. The G-to-C transversion was not identified in 14 unaffected family members or 220 control DNA samples. In vitro functional expression studies in rat PC12 cells showed that the mutant proteins accumulated on the outer membrane of large aberrant cytoplasmic bodies, consistent with the formation of dysmorphic organelles of the late endosomal pathway. </p><p>Cannon et al. (2006) did not identify the splice site mutation reported by Skibinski et al. (2005) in 450 control individuals. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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|
|
CHMP2B, ASP148TYR
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<br />
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|
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SNP: rs63750653,
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ClinVar: RCV000001720, RCV000084275
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with frontotemporal dementia (FTDALS7; 600795), Skibinski et al. (2005) identified a 442G-T transversion in exon 5 of the CHMP2B gene, resulting in an asp148-to-tyr (D148Y) substitution in the conserved Snf-7 domain. The patient was 1 of 400 unrelated European patients studied. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</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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CHMP2B, GLN206HIS
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<br />
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SNP: rs63751126,
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gnomAD: rs63751126,
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ClinVar: RCV000020696, RCV000084279
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 75-year-old man with rapidly progressive amyotrophic lateral sclerosis (FTDALS7; 600795), Parkinson et al. (2006) identified a heterozygous 694A-C transversion in exon 6 of the CHMP2B gene, resulting in a gln206-to-his (Q206H) substitution in a highly conserved residue. The mutation was not identified in 640 control samples. At age 74 years, the patient developed bulbar-onset weakness with flaccid dysarthria and tongue fasciculations. He later developed weakness and wasting of the intrinsic hand muscles and respiratory weakness. Although he had a previous right leg amputation from trauma, neurophysiologic testing showed neurogenic changes in all 4 limbs. He had depressed reflexes and flexor plantar responses, consistent with lower motor neuron involvement. He died of respiratory failure 15 months after symptom onset. There was no evidence of dementia or extramotor neurologic involvement. A cousin reportedly had died of ALS. Neuropathologic examination showed a predominantly lower motor neuron disease with intraneuronal inclusions immunopositive for ubiquitin (UBB; 191339) and p62/sequestosome (SQSTM1; 601530). SQSTM1-reactive inclusions were also detected within oligodendroglia in the cerebral motor cortex. </p><p>By in vitro functional studies in HEK293 and COS-7 cells, Cox et al. (2010) showed that cells expressing the Q206H mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (155740) and an increase in LC3-II (601242), overall indicating a defect in the autophagic pathway. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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CHMP2B, GLN165TER
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<br />
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SNP: rs63750355,
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ClinVar: RCV000001722, RCV000084276
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a Belgian woman with onset of frontotemporal dementia (FTDALS7; 600795) at age 58, van der Zee et al. (2008) identified a heterozygous 493C-T transition in exon 5 of the CHMP2B gene, resulting in a gln165-to-ter (Q165X) substitution. Her mother and maternal aunt were reportedly similarly affected. RT-PCR studies confirmed the presence of a mutant transcript in patient cells. The mutation was not found in 459 Belgian control individuals. Overexpression of the Q165X mutant in human neuroblastoma cells resulted in accumulation of truncated protein in enlarged vesicular structures. Normally, the C terminal of CHMP2B functions as an autoinhibitor, allowing the protein to shuttle between the inactive and active states. The truncation eliminates this inhibitory effect, resulting in constitutive activation and involvement in the endosomal complex and accumulation on the endosomal membrane. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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CHMP2B, ILE29VAL
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<br />
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SNP: rs63750818,
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gnomAD: rs63750818,
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ClinVar: RCV000020697, RCV000084271
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
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<p>In a man with onset of progressive frontotemporal dementia (FTDALS7; 600795) in his late sixties followed by amyotrophic lateral sclerosis, Parkinson et al. (2006) identified a heterozygous 161A-G transition in the CHMP3B gene, resulting in an ile29-to-val (I29V) substitution located between 2 conserved regions of the protein. The mutation was not found in 640 controls or in 400 FTD samples. However, Parkinson et al. (2006) noted that Cannon et al. (2006) found the I29V variant in 1 of 141 probands with frontotemporal dementia and at a frequency of 0.5% among 200 control chromosomes, thus suggesting that it may be a benign variant. The patient reported by Parkinson et al. (2006) had brisk tendon reflexes and extensor plantar responses. His father reportedly had motor disturbances and frontal lobe dysfunction. </p><p>Cox et al. (2010) identified a heterozygous I29V substitution, which they stated resulted from an 85A-G transition, in 2 unrelated patients with onset of amyotrophic lateral sclerosis at ages 64 and 49 years, respectively. The mutation was not found in 1,000 control chromosomes. Both patients had involvement of the upper and lower limbs, as well as bulbar symptoms, but no signs of upper motor neuron involvement. In vitro functional studies in HEK293 and COS-7 cells showed that cells expressing the mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (155740) and an increase in LC3-II (601242), overall indicating a defect in the autophagic pathway. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
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<strong>.0006 FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 7</strong>
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CHMP2B, THR104ASN
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<br />
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SNP: rs281864934,
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gnomAD: rs281864934,
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ClinVar: RCV000055937
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<p>In a 54-year-old man with amyotrophic lateral sclerosis (FTDALS7; 600795), Cox et al. (2010) identified a heterozygous 311C-A transversion in exon 3 of the CHMP2B gene, resulting in a thr104-to-asn (T104N) substitution at a highly conserved residue. The mutation was not found in 1,000 control chromosomes. The patient presented with bulbar and respiratory dysfunction and later developed wasting and fasciculation in the upper and lower limbs. Reflexes were normal, suggesting only lower motor neuron involvement. In vitro functional studies in HEK293 and COS-7 cells showed that cells expressing the mutant protein had large cytoplasmic vacuoles with an accumulation of mutant CHMP2B on the outer membrane, termed halos. Cells with the mutant protein also had aberrant localization of CD63 (155740) and an increase in LC3-II (601242), overall indicating a defect in the autophagic pathway. </p>
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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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<ol>
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Babst, M., Katzmann, D. J., Estepa-Sabal, E. J., Meerloo, T., Emr, S. D.
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<strong>ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting.</strong>
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Dev. Cell 3: 271-282, 2002.
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[PubMed: 12194857]
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[Full Text: https://doi.org/10.1016/s1534-5807(02)00220-4]
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<li>
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<p class="mim-text-font">
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Brown, J., Ashworth, A., Gydesen, S., Sorensen, A., Rossor, M., Hardy, J., Collinge, J.
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<strong>Familial non-specific dementia maps to chromosome 3.</strong>
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Hum. Molec. Genet. 4: 1625-1628, 1995.
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[PubMed: 8541850]
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[Full Text: https://doi.org/10.1093/hmg/4.9.1625]
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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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Cannon, A., Baker, M., Boeve, B., Josephs, K., Knopman, D., Petersen, R., Parisi, J., Dickison, D., Adamson, J., Snowden, J., Neary, D., Mann, D., Hutton, M., Pickering-Brown, S. M.
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<strong>CHMP2B mutations are not a common cause of frontotemporal lobar degeneration.</strong>
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Neurosci. Lett. 398: 83-84, 2006.
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[PubMed: 16431024]
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[Full Text: https://doi.org/10.1016/j.neulet.2005.12.056]
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</p>
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<li>
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<p class="mim-text-font">
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Cox, L. E., Ferraiuolo, L., Goodall, E. F., Heath, P. R., Higginbottom, A., Mortiboys, H., Hollinger, H. C., Hartley, J. A., Brockington, A., Burness, C. E., Morrison, K. E., Wharton, S. B., Grierson, A. J., Ince, P. G., Kirby, J., Shaw, P. J.
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<strong>Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS).</strong>
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PLoS One 5: e9872, 2010. Note: Electronic Article.
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[PubMed: 20352044]
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[Full Text: https://doi.org/10.1371/journal.pone.0009872]
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<p class="mim-text-font">
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Gydesen, S., Brown, J. M., Brun, A., Chakrabarti, L., Gade, A., Johannsen, P., Rossor, M., Thusgaard, T., Grove, A., Yancopoulou, D., Spillantini, M. G., Fisher, E. M. C., Collinge, J., Sorensen, S. A.
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<strong>Chromosome 3 linked frontotemporal dementia (FTD-3).</strong>
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Neurology 59: 1585-1594, 2002.
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[PubMed: 12451202]
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[Full Text: https://doi.org/10.1212/01.wnl.0000034763.54161.1f]
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<p class="mim-text-font">
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Momeni, P., Rogaeva, E., Van Deerlin, V., Yuan, W., Grafman, J., Tierney, M., Huey, E., Bell, J., Morris, C. M., Kalaria, R. N., van Rensburg, S. J., Niehaus, D., Potocnik, F., Kawarai, T., Salehi-Rad, S., Sato, C., St. George-Hyslop, P., Hardy, J.
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<strong>Genetic variability in CHMP2B and frontotemporal dementia.</strong>
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Neurodegener. Dis. 3: 129-133, 2006.
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[PubMed: 16954699]
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[Full Text: https://doi.org/10.1159/000094771]
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<li>
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<p class="mim-text-font">
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Parkinson, N., Ince, P. G., Smith, M. O., Highley, R., Skibinski, G., Andersen, P. M., Morrison, K. E., Pall, H. S., Hardiman, O., Collinge, J., Shaw, P. J., Disher, E. M. C., MRC Proteomics in ALS Study and the FReJA Consortium.
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<strong>ALS phenotypes with mutations in CHMP2B (charged multivesicular body protein 2B).</strong>
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Neurology 67: 1074-1077, 2006.
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[PubMed: 16807408]
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[Full Text: https://doi.org/10.1212/01.wnl.0000231510.89311.8b]
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<p class="mim-text-font">
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Skibinski, G., Parkinson, N. J., Brown, J. M., Chakrabarti, L., Lloyd, S. L., Hummerich, H., Nielsen, J. E., Hodges, J. R., Spillantini, M. G., Thusgaard, T., Brandner, S., Brun, A., Rossor, M. N., Gade, A., Johannsen, P., Sorensen, S. A., Gydesen, S., Fisher, E. M. C., Collinge, J.
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<strong>Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia.</strong>
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Nature Genet. 37: 806-808, 2005.
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[PubMed: 16041373]
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[Full Text: https://doi.org/10.1038/ng1609]
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<p class="mim-text-font">
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Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M.
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<strong>A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex.</strong>
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Genomics 88: 333-346, 2006.
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[PubMed: 16730941]
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[Full Text: https://doi.org/10.1016/j.ygeno.2006.04.003]
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</p>
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<li>
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<p class="mim-text-font">
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Urwin, H., Authier, A., Nielsen, J. E., Metcalf, D., Powell, C., Froud, K., Malcolm, D. S., Holm, I., Johannsen, P., Brown, J., Fisher, E. M. C., van der Zee, J., Bruyland, M., the FReJA Consortium, Collinge, J., Brandner, S., Futter, C., Isaacs, A. M.
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<strong>Disruption of endocytic trafficking in frontotemporal dementia with CHMP2B mutations.</strong>
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Hum. Molec. Genet. 19: 2228-2238, 2010.
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[PubMed: 20223751]
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[Full Text: https://doi.org/10.1093/hmg/ddq100]
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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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van der Zee, J., Urwin, H., Engelborghs, S., Bruyland, M., Vandenberghe, R., Dermaut, B., De Pooter, T., Peeters, K., Santens, P., De Deyn, P. P., Fisher, E. M., Collinge, J., Isaacs, A. M., Van Broeckhoven, C.
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<strong>CHMP2B C-truncating mutations in frontotemporal lobar degeneration are associated with an aberrant endosomal phenotype in vitro.</strong>
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Hum. Molec. Genet. 17: 313-322, 2008.
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[PubMed: 17956895]
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[Full Text: https://doi.org/10.1093/hmg/ddm309]
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</ol>
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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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George E. Tiller - updated : 8/19/2013<br>Cassandra L. Kniffin - updated : 7/2/2012<br>Cassandra L. Kniffin - updated : 4/29/2009<br>Cassandra L. Kniffin - updated : 11/8/2006
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<span class="mim-text-font">
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Cassandra L. Kniffin : 8/3/2005
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carol : 01/07/2021<br>carol : 01/06/2021<br>carol : 11/11/2020<br>carol : 08/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/20/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>tpirozzi : 8/19/2013<br>carol : 7/10/2012<br>terry : 7/10/2012<br>ckniffin : 7/2/2012<br>carol : 6/22/2012<br>wwang : 5/20/2009<br>ckniffin : 4/29/2009<br>mgross : 4/2/2007<br>mgross : 3/28/2007<br>mgross : 3/28/2007<br>wwang : 11/29/2006<br>wwang : 11/28/2006<br>ckniffin : 11/8/2006<br>terry : 9/27/2005<br>alopez : 8/3/2005<br>ckniffin : 8/3/2005
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