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<title>
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Entry
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- *193065 - VINCULIN; VCL
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*193065</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/193065">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
|
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
|
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
|
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
|
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</span>
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</span>
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000035403;t=ENST00000211998" 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=7414" 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=193065" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
|
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000035403;t=ENST00000211998" 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_003373,NM_014000" 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_014000" 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=193065" 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=01900&isoform_id=01900_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/VCL" 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/246707,246714,292902,340237,4507877,7669550,21903479,24657579,31874074,119574932,119574933,119574934,119574935,119574936,193785261,194383170,194388374,194390560,211948011,308219118,1471157344,1471853956" 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/P18206" 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=7414" 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=ENSG00000035403;t=ENST00000211998" 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=VCL" 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=VCL" 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+7414" 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/VCL" 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:7414" 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/7414" 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=chr10&hgg_gene=ENST00000211998.10&hgg_start=73998116&hgg_end=74121363&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">
|
|
<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">
|
|
<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:12665" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=193065[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=193065[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/ENSG00000035403" 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=VCL" 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=VCL" 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=VCL" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=VCL&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/PA37288" 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">
|
|
<div style="display: table-row">
|
|
<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:12665" 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/FBgn0004397.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:98927" 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/VCL#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:98927" 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/7414/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=7414" 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=WBGene00000942;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-050506-61" 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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
|
<span class="panel-title">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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|
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<div style="display: table-cell;">Cellular Pathways</div>
|
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</div>
|
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</a>
|
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</span>
|
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</span>
|
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</div>
|
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
|
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:7414" 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=VCL&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>
|
|
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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193065
|
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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>
|
|
<span class="mim-font">
|
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|
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VINCULIN; VCL
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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>
|
|
<a id="includedTitles" class="mim-anchor"></a>
|
|
<div>
|
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<p>
|
|
<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<span class="h3 mim-font">
|
|
METAVINCULIN, INCLUDED
|
|
</span>
|
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</div>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=VCL" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">VCL</a></em></strong>
|
|
</span>
|
|
</p>
|
|
</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/10/312?start=-3&limit=10&highlight=312">10q22.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr10:73998116-74121363&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'})">10:73,998,116-74,121,363</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=611407,613255" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
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|
<tr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/radial/193065" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<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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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>Vinculin is a cytoskeletal protein associated with the cytoplasmic face of both cell-cell and cell-extracellular matrix adherens-type junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane (<a href="#16" class="mim-tip-reference" title="Weller, P. A., Ogryzko, E. P., Corben, E. B., Zhidkova, N. I., Patel, B., Price, G. J., Spurr, N. K., Koteliansky, V. E., Critchley, D. R. <strong>Complete sequence of human vinculin and assignment of the gene to chromosome 10.</strong> Proc. Nat. Acad. Sci. 87: 5667-5671, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2116004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2116004</a>] [<a href="https://doi.org/10.1073/pnas.87.15.5667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2116004">Weller et al., 1990</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2116004" 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="#16" class="mim-tip-reference" title="Weller, P. A., Ogryzko, E. P., Corben, E. B., Zhidkova, N. I., Patel, B., Price, G. J., Spurr, N. K., Koteliansky, V. E., Critchley, D. R. <strong>Complete sequence of human vinculin and assignment of the gene to chromosome 10.</strong> Proc. Nat. Acad. Sci. 87: 5667-5671, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2116004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2116004</a>] [<a href="https://doi.org/10.1073/pnas.87.15.5667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2116004">Weller et al. (1990)</a> determined the complete sequence of the human vinculin gene. They found that both human and chicken embryo sequences of vinculin contain 1,066 amino acids and, furthermore, that the 2 proteins exhibit a high level of sequence identity (greater than 95%). Southern blots of human genomic DNA hybridized with short vinculin cDNA fragments indicated that there is a single vinculin gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2116004" 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="#6" class="mim-tip-reference" title="Koteliansky, V. E., Ogryzko, E. P., Zhidkova, N. I., Weller, P. A., Critchley, D. R., Vancompernolle, K., Vandekerckhove, J., Strasser, P., Way, M., Gimona, M., Small, J. V. <strong>An additional exon in the human vinculin gene specifically encodes meta-vinculin-specific difference peptide: cross-species comparison reveals variable and conserved motifs in the meta-vinculin insert.</strong> Europ. J. Biochem. 204: 767-772, 1992. Note: Erratum: Europ. J. Biochem. 205: 1218 only, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339348</a>] [<a href="https://doi.org/10.1111/j.1432-1033.1992.tb16692.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1339348">Koteliansky et al. (1992)</a> determined that metavinculin is the result of alternative splicing of the VCL gene and contains an additional exon. Across species, the deduced protein differs from vinculin in having an additional insert of 68 to 79 amino acids in the C-terminal half of the molecule. By comparison of metavinculin sequences from pig, man, chicken, and frog, <a href="#11" class="mim-tip-reference" title="Strasser, P., Gimona, M., Herzog, M., Geiger, B., Small, J. V. <strong>Variable and constant regions in the C-terminus of vinculin and metavinculin: cloning and expression of fragments in E. coli.</strong> FEBS Lett. 317: 189-194, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8425604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8425604</a>] [<a href="https://doi.org/10.1016/0014-5793(93)81274-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8425604">Strasser et al. (1993)</a> found a division of the insert into 2 parts: the first variable and the second highly conserved. The longest insert, 79 amino acids, was found in Xenopus laevis. Three different C-terminal constructs of vinculin and metavinculin overexpressed in E. coli could be purified by column chromatography. Using amino acid sequencing methods on the intact molecules and their proteolytic subfragments, together with a polyclonal antibody specific only for metavinculin from porcine stomach, <a href="#3" class="mim-tip-reference" title="Gimona, M., Small, J. V., Moeremans, M., Van Damme, J., Puype, M., Vandekerckhove, J. <strong>Porcine vinculin and metavinculin differ by a 68-residue insert located close to the carboxy-terminal part of the molecule.</strong> EMBO J. 7: 2329-2334, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3142762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3142762</a>] [<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03076.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3142762">Gimona et al. (1988)</a> identified and sequenced the insert in the porcine metavinculin molecule. By alignment with the complete sequence of chick fibroblast vinculin, they determined the exact location of the insert. In porcine metavinculin, this insert lies between the 90-kD protease-resistant N-terminal core and the C terminus of the molecule. It contains 68 amino acids and is flanked by KWSSK sequences, one of which is present in vinculin. The identity of the mapped vinculin and metavinculin sequences outside this different peptide is consistent with 2 proteins arising via alternative splicing at the mRNA level. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8425604+1339348+3142762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Moiseyeva, E. P., Weller, P. A., Zhidkova, N. I., Corben, E. B., Patel, B., Jasinka, I., Koteliansky, V. E., Critchley, D. R. <strong>Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter.</strong> J. Biol. Chem. 268: 4318-4325, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8440716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8440716</a>]" pmid="8440716">Moiseyeva et al. (1993)</a> determined that the VCL gene contains 22 exons spanning greater than 75 kb. Alternative splicing of exon 19 results in the cardiac- and smooth muscle-specific metavinculin isoform, containing an additional 68 amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8440716" 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 use of a panel of human-rodent somatic cell hybrids, <a href="#16" class="mim-tip-reference" title="Weller, P. A., Ogryzko, E. P., Corben, E. B., Zhidkova, N. I., Patel, B., Price, G. J., Spurr, N. K., Koteliansky, V. E., Critchley, D. R. <strong>Complete sequence of human vinculin and assignment of the gene to chromosome 10.</strong> Proc. Nat. Acad. Sci. 87: 5667-5671, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2116004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2116004</a>] [<a href="https://doi.org/10.1073/pnas.87.15.5667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2116004">Weller et al. (1990)</a> mapped the VCL gene to chromosome 10q11.2-qter. By linkage studies in a 3-generation family, <a href="#8" class="mim-tip-reference" title="Mulligan, L. M., Gardner, E., Telenius, H., Ponder, B. A. J. <strong>Complementary physical and genetic techniques map the vinculin (VCL) gene on chromosome 10q.</strong> Genomics 13: 1347-1349, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505973</a>] [<a href="https://doi.org/10.1016/0888-7543(92)90066-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1505973">Mulligan et al. (1992)</a> mapped the VCL gene to chromosome 10q22.1-q23, distal to D10S22. They confirmed the assignment by hybridization of the vinculin cDNA to flow-sorted translocation derivative chromosomes containing that portion of chromosome 10. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1505973+2116004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#1" class="mim-tip-reference" title="Bakolitsa, C., Cohen, D. M., Bankston, L. A., Bobkov, A. A., Cadwell, G. W., Jennings, L., Critchley, D. R., Craig, S. W., Liddington, R. C. <strong>Structural basis for vinculin activation at sites of cell adhesion.</strong> Nature 430: 583-586, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15195105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15195105</a>] [<a href="https://doi.org/10.1038/nature02610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15195105">Bakolitsa et al. (2004)</a> described the crystal structure of the full-length vinculin molecule (1,066 amino acids), which shows a 5-domain autoinhibited conformation in which the carboxy-terminal tail domain is held pincer-like by the vinculin head, and ligand binding is regulated both sterically and allosterically. <a href="#1" class="mim-tip-reference" title="Bakolitsa, C., Cohen, D. M., Bankston, L. A., Bobkov, A. A., Cadwell, G. W., Jennings, L., Critchley, D. R., Craig, S. W., Liddington, R. C. <strong>Structural basis for vinculin activation at sites of cell adhesion.</strong> Nature 430: 583-586, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15195105/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15195105</a>] [<a href="https://doi.org/10.1038/nature02610" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15195105">Bakolitsa et al. (2004)</a> showed that the conformational changes in the head, tail, and proline-rich domains are linked structurally and thermodynamically, and proposed a combinatorial pathway to activation that ensures that vinculin is activated only at sites of cell adhesion when 2 or more of its binding partners are brought into apposition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15195105" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using magnetic tweezers, total internal reflection fluorescence, and atomic force microscopy, <a href="#2" class="mim-tip-reference" title="del Rio, A., Perez-Jimenez, R., Liu, R., Roca-Cusachs, P., Fernandez, J. M., Sheetz, M. P. <strong>Stretching single talin rod molecules activates vinculin binding.</strong> Science 323: 638-641, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179532</a>] [<a href="https://doi.org/10.1126/science.1162912" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19179532">del Rio et al. (2009)</a> investigated the effect of force on the interaction between talin (<a href="/entry/186745">186745</a>), a protein that links liganded membrane integrins to the cytoskeleton, and vinculin, a focal adhesion protein that is activated by talin binding, leading to reorganization of the cytoskeleton. Application of physiologically relevant forces caused stretching of single talin rods that exposed cryptic binding sites for vinculin. Thus in the talin-vinculin system, molecular mechanotransduction can occur by protein binding after exposure of buried binding sites in the talin-vinculin system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Turner, C. E., Burridge, K. <strong>Detection of metavinculin in human platelets using a modified talin overlay assay.</strong> Europ. J. Cell Biol. 49: 202-206, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2503380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2503380</a>]" pmid="2503380">Turner and Burridge (1989)</a> reported experiments indicating that vinculin is the major talin-binding protein in platelets. However, in addition, a less abundant protein of approximately 150 kD also interacted strongly with the talin fragment. <a href="#12" class="mim-tip-reference" title="Turner, C. E., Burridge, K. <strong>Detection of metavinculin in human platelets using a modified talin overlay assay.</strong> Europ. J. Cell Biol. 49: 202-206, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2503380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2503380</a>]" pmid="2503380">Turner and Burridge (1989)</a> confirmed that this protein is metavinculin, a protein previously believed to be confined to cardiac and smooth muscle tissue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2503380" 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="Hu, K., Ji, L., Applegate, K. T., Danuser, G., Waterman-Storer, C. M. <strong>Differential transmission of actin motion within focal adhesions.</strong> Science 315: 111-115, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17204653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17204653</a>] [<a href="https://doi.org/10.1126/science.1135085" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17204653">Hu et al. (2007)</a> developed correlational fluorescent speckle microscopy to measure the coupling of focal adhesion proteins to actin filaments (see <a href="/entry/102610">102610</a>). Different classes of focal adhesion structural and regulatory molecules exhibited varying degrees of correlated motions with actin filaments, indicating hierarchical transmission of actin motion through focal adhesions. Interactions between vinculin, talin, and actin filaments appear to constitute a slippage interface between the cytoskeleton and integrins, generating a molecular clutch that is regulated during the morphodynamic transitions of cell migration. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17204653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using immunohistochemistry, <a href="#13" class="mim-tip-reference" title="Vasile, V. C., Edwards, W. D., Ommen, S. R., Ackerman, M. J. <strong>Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc.</strong> Biochem. Biophys. Res. Commun. 349: 709-715, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949038</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.08.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949038">Vasile et al. (2006)</a> examined the pattern of vinculin/metavinculin expression in the intercalated- and Z discs of cardiomyocytes from patients with various cardiovascular conditions associated with hypertrophy. Tissue specimens derived from patients with obstructive hypertrophic cardiomyopathy (CMH; see CMH15, <a href="/entry/613255">613255</a>) and aortic stenosis (see <a href="/entry/109730">109730</a>) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z disc, whereas tissue specimens from patients with dilated cardiomyopathy (CMD; see CMD1W, <a href="/entry/611407">611407</a>), hypertensive heart disease (see <a href="/entry/145500">145500</a>), or pulmonary hypertension (see <a href="/entry/178600">178600</a>) exhibited normal expression of vinculin/metavinculin in both the Z and the intercalated disc, despite being associated with hypertrophy. <a href="#13" class="mim-tip-reference" title="Vasile, V. C., Edwards, W. D., Ommen, S. R., Ackerman, M. J. <strong>Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc.</strong> Biochem. Biophys. Res. Commun. 349: 709-715, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949038</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.08.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949038">Vasile et al. (2006)</a> suggested that differential expression of vinculin/metavinculin in cardiac hypertrophy might depend on the underlying pathophysiology, with localization unaffected by hemodynamic overload but expression in the intercalated disc substantially reduced by obstructive disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949038" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M. <strong>Nanoscale architecture of integrin-based cell adhesions.</strong> Nature 468: 580-584, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107430">Kanchanawong et al. (2010)</a> used 3-dimensional super-resolution fluorescence microscopy to map nanoscale protein organization in focal adhesions. Their results revealed that integrins and actin are vertically separated by an approximately 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signaling layer containing integrin cytoplasmic tails (see <a href="/entry/193210">193210</a>), focal adhesion kinase (<a href="/entry/600758">600758</a>), and paxillin (<a href="/entry/602505">602505</a>); an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin (<a href="/entry/602002">602002</a>), vasodilator-stimulated phosphoprotein (<a href="/entry/601703">601703</a>), and alpha-actinin (<a href="/entry/102575">102575</a>). By localizing amino- and carboxy-terminally tagged talins, <a href="#5" class="mim-tip-reference" title="Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M. <strong>Nanoscale architecture of integrin-based cell adhesions.</strong> Nature 468: 580-584, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107430">Kanchanawong et al. (2010)</a> revealed talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. <a href="#5" class="mim-tip-reference" title="Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M. <strong>Nanoscale architecture of integrin-based cell adhesions.</strong> Nature 468: 580-584, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107430[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature09621" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21107430">Kanchanawong et al. (2010)</a> concluded that their composite multilaminar protein architecture provided a molecular blueprint for understanding focal adhesion functions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21107430" 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="#9" class="mim-tip-reference" title="Olson, T. M., Illenberger, S., Kishimoto, N. Y., Huttelmaier, S., Keating, M. T., Jockusch, B. M. <strong>Metavinculin mutations alter actin interaction in dilated cardiomyopathy.</strong> Circulation 105: 431-437, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11815424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11815424</a>] [<a href="https://doi.org/10.1161/hc0402.102930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11815424">Olson et al. (2002)</a> used SSCP to analyze the vinculin gene in 350 unrelated patients with sporadic or familial dilated cardiomyopathy (<a href="/entry/611407">611407</a>) who were negative for mutations in the ACTC (<a href="/entry/102540">102540</a>) and TPM1 (<a href="/entry/191010">191010</a>) genes, and identified heterozygosity for a 3-bp in-frame deletion (L954del; <a href="#0001">193065.0001</a>) and a missense mutation (R975W; <a href="#0002">193065.0002</a>) in 2 patients, respectively. Neither mutation was found in 500 controls. A potential risk-conferring polymorphism, A934V, was identified in heterozygosity in a 30-year-old man with dilated cardiomyopathy who died 2 years after diagnosis of progressive heart failure; this variant was also found in 1 of 500 controls, a 67-year-old woman in whom electrocardiography showed abnormal T waves but echocardiogram was nondiagnostic for dilated cardiomyopathy. All variants were located in exon 19, the metavinculin-specific exon of the vinculin gene. Low-shear viscometry studies revealed variable reductions in viscosity associated with the mutations, with greater reductions caused by the L954del and R975W mutants. Fluorescence microscopy confirmed the viscosity findings, with actin organization by the A934V variant similar to wildtype, although the network appeared coarser; more prominent bundles were observed for L954del, and R975W showed the highest bundling activity. Electron microscopy of cardiac myocytes from a patient with the R975W mutation showed irregular and fragmented intercalated discs, with intact sarcomeric thin and thick filaments. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11815424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Vasile, V. C., Will, M. L., Ommen, S. R., Edwards, W. D., Olson, T. M., Ackerman, M. J. <strong>Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy.</strong> Molec. Genet. Metab. 87: 169-174, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236538</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236538">Vasile et al. (2006)</a> analyzed the metavinculin-specific exon 19 of the VCL gene in 389 unrelated patients with hypertrophic cardiomyopathy (CMH), who were negative for mutation in 8 known CMH-associated sarcomere/myofilament-encoding genes, and identified heterozygosity for the R975W mutation in a patient with CMH15 (<a href="/entry/613255">613255</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236538" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a cohort of 228 CMH patients who were negative for mutation in 12 known CMH-associated sarcomere/myofilament-encoding genes, <a href="#14" class="mim-tip-reference" title="Vasile, V. C., Ommen, S. R., Edwards, W. D., Ackerman, M. J. <strong>A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 345: 998-1003, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712796</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.04.151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16712796">Vasile et al. (2006)</a> performed comprehensive analysis of the 22 exons of the VCL gene and identified a heterozygous mutation in 1 patient (L277M; <a href="#0003">193065.0003</a>). The authors noted that despite its ubiquitous expression, the HCM-associated VCL mutation clinically yielded a cardiac-specific phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712796" 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="#17" class="mim-tip-reference" title="Xu, W., Baribault, H., Adamson, E. D. <strong>Vinculin knockout results in heart and brain defects during embryonic development.</strong> Development 125: 327-337, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486805</a>] [<a href="https://doi.org/10.1242/dev.125.2.327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486805">Xu et al. (1998)</a> used a targeting vector to inactivate vinculin in embryonic stem cells, which were then injected into mice. They found that Vcl -/- embryos failed to develop beyond the tenth day of gestation and at best were two-thirds of the normal size range. The most prominent defect was lack of midline fusion of the rostral neural tube, producing a cranial bilobular appearance and attenuation of cranial and spinal nerve development. Heart development was curtailed at E9.5, with severely reduced and akinetic myocardial and endocardial structures. Somites and limbs were retarded, and ectodermal tissues were sparse and fragile. Fibroblasts isolated from mutant embryos showed reduced adhesion to fibronectin, vitronectin, laminin, and collagen compared to wildtype. In addition, migration rates over these substrata were 2-fold higher and the level of focal adhesion kinase (FAK; <a href="/entry/600758">600758</a>) was 3-fold higher. <a href="#17" class="mim-tip-reference" title="Xu, W., Baribault, H., Adamson, E. D. <strong>Vinculin knockout results in heart and brain defects during embryonic development.</strong> Development 125: 327-337, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486805</a>] [<a href="https://doi.org/10.1242/dev.125.2.327" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9486805">Xu et al. (1998)</a> concluded that vinculin is necessary for normal embryonic development, probably because of its role in the regulation of cell adhesion and locomotion, although specific roles in neural and cardiac development could not be ruled out. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9486805" 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="Richards, M., Nikolski, V. P., Green, K. G., Zemljic-Harpf, A. E., Efimov, I. E., Ross, R. S., Saffitz, J. E. <strong>Ventricular arrhythmias in a mouse model of vinculin-related cardiomyopathy.</strong> Heart Rhythm 2: S178 only, 2005."None>Richards et al. (2005)</a> analyzed hearts from Vcl +/- and wildtype mice and found that although decreased vinculin expression enhanced inducibility of ventricular arrhythmias, connexin-43 (GJA1; <a href="/entry/121014">121014</a>) content and distribution, and conduction velocities, were not significantly different between mutant and wildtype mice. <a href="#10" class="mim-tip-reference" title="Richards, M., Nikolski, V. P., Green, K. G., Zemljic-Harpf, A. E., Efimov, I. E., Ross, R. S., Saffitz, J. E. <strong>Ventricular arrhythmias in a mouse model of vinculin-related cardiomyopathy.</strong> Heart Rhythm 2: S178 only, 2005."None>Richards et al. (2005)</a> suggested that other mechanisms, such as altered integrin (see <a href="/entry/192968">192968</a>) signaling, might contribute to arrhythmogenesis.</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">rs397517237 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs397517237;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=rs397517237" 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=rs397517237" 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=RCV000038819 OR RCV000171847 OR RCV000619949 OR RCV000678764 OR RCV000727177 OR RCV000988386 OR RCV003227625" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000038819, RCV000171847, RCV000619949, RCV000678764, RCV000727177, RCV000988386, RCV003227625" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000038819...</a>
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<p>In a 39-year-old man with dilated cardiomyopathy (CMD1W; <a href="/entry/611407">611407</a>), <a href="#9" class="mim-tip-reference" title="Olson, T. M., Illenberger, S., Kishimoto, N. Y., Huttelmaier, S., Keating, M. T., Jockusch, B. M. <strong>Metavinculin mutations alter actin interaction in dilated cardiomyopathy.</strong> Circulation 105: 431-437, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11815424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11815424</a>] [<a href="https://doi.org/10.1161/hc0402.102930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11815424">Olson et al. (2002)</a> identified heterozygosity for a 3-bp deletion (2862delGTT) in exon 19 of the vinculin gene, resulting in the in-frame deletion of a leucine residue (leu954del). The patient's father died of heart failure at 59 years of age, and a 70-year-old paternal uncle had heart failure, but the patient's relatives declined clinical and genetic evaluation. The mutation was not found in 500 unrelated controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11815424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121917776 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917776;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/rs121917776?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=rs121917776" 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=rs121917776" 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=RCV000012980 OR RCV000012981 OR RCV000620759 OR RCV002482857" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012980, RCV000012981, RCV000620759, RCV002482857" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012980...</a>
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<p>In a 57-year-old woman with dilated cardiomyopathy (CMD1W; <a href="/entry/611407">611407</a>) who had undergone cardiac transplantation, <a href="#9" class="mim-tip-reference" title="Olson, T. M., Illenberger, S., Kishimoto, N. Y., Huttelmaier, S., Keating, M. T., Jockusch, B. M. <strong>Metavinculin mutations alter actin interaction in dilated cardiomyopathy.</strong> Circulation 105: 431-437, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11815424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11815424</a>] [<a href="https://doi.org/10.1161/hc0402.102930" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11815424">Olson et al. (2002)</a> identified heterozygosity for a 2923C-T transition in exon 19 of the vinculin gene, resulting in an arg975-to-trp (R975W) substitution in the metavinculin isoform. The mutation was also found in heterozygosity in 3 asymptomatic relatives, 2 of whom were found to have disease on screening echocardiogram: a 70-year-old maternal aunt had dilated cardiomyopathy, and a 38-year-old daughter had mild left ventricular dilation. The patient's 55-year-old sister carried the mutation but had normal left ventricular dimensions and shortening/ejection fractions. The mutation was not found in 500 unrelated controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11815424" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy (CMH15; <a href="/entry/613255">613255</a>), <a href="#15" class="mim-tip-reference" title="Vasile, V. C., Will, M. L., Ommen, S. R., Edwards, W. D., Olson, T. M., Ackerman, M. J. <strong>Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy.</strong> Molec. Genet. Metab. 87: 169-174, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236538</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236538">Vasile et al. (2006)</a> identified heterozygosity for the R975W substitution in the VCL gene, located in a highly conserved residue in the tail region of metavinculin and predicted to cause significant alterations in the secondary structure and helical organization of the protein. The mutation was not found in 1,400 reference allele. Immunohistochemical analysis of the patient's myocardium demonstrated a marked reduction of both vinculin and metavinculin in the intercalated discs. Noting that the patient was homozygous for wildtype vinculin and heterozygous for R975W metavinculin, <a href="#15" class="mim-tip-reference" title="Vasile, V. C., Will, M. L., Ommen, S. R., Edwards, W. D., Olson, T. M., Ackerman, M. J. <strong>Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy.</strong> Molec. Genet. Metab. 87: 169-174, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236538</a>] [<a href="https://doi.org/10.1016/j.ymgme.2005.08.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16236538">Vasile et al. (2006)</a> suggested that the marked reduction of proteins in the intercalated discs might be due to a dominant-negative effect. However, after analyzing immunohistochemically stained tissue specimens from patients with various cardiovascular conditions associated with hypertrophy, <a href="#13" class="mim-tip-reference" title="Vasile, V. C., Edwards, W. D., Ommen, S. R., Ackerman, M. J. <strong>Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc.</strong> Biochem. Biophys. Res. Commun. 349: 709-715, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949038</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.08.106" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949038">Vasile et al. (2006)</a> suggested that differential expression of vinculin/metavinculin in cardiac hypertrophy might depend on the underlying pathophysiology, with localization unaffected by hemodynamic overload but expression in the intercalated disc substantially reduced by obstructive disease (see GENE FUNCTION). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16236538+16949038" 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 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 15</strong>
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VCL, LEU277MET
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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> rs71579353 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs71579353;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/rs71579353?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=rs71579353" 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=rs71579353" 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=RCV000012982 OR RCV000617420 OR RCV000645321 OR RCV000768535 OR RCV000845477 OR RCV000994445 OR RCV002298443 OR RCV002496333 OR RCV003149568" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000012982, RCV000617420, RCV000645321, RCV000768535, RCV000845477, RCV000994445, RCV002298443, RCV002496333, RCV003149568" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000012982...</a>
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<p>In a 76-year-old Caucasian woman with severely obstructive hypertrophic cardiomyopathy (CMH15; <a href="/entry/613255">613255</a>), <a href="#14" class="mim-tip-reference" title="Vasile, V. C., Ommen, S. R., Edwards, W. D., Ackerman, M. J. <strong>A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 345: 998-1003, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712796</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.04.151" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16712796">Vasile et al. (2006)</a> identified a heterozygous 829C-A transversion in exon 8 of the VCL gene, resulting in a leu277-to-met (L277M) substitution at a conserved residue in a key functional domain. The mutation was not detected in 400 reference alleles. Immunostaining of myomectomy tissue from the patient showed normal Z line staining but markedly reduced vinculin/metavinculin staining in the intercalated discs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712796" 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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Bakolitsa, C., Cohen, D. M., Bankston, L. A., Bobkov, A. A., Cadwell, G. W., Jennings, L., Critchley, D. R., Craig, S. W., Liddington, R. C.
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[<a href="https://doi.org/10.1038/nature02610" target="_blank">Full Text</a>]
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del Rio, A., Perez-Jimenez, R., Liu, R., Roca-Cusachs, P., Fernandez, J. M., Sheetz, M. P.
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<strong>Stretching single talin rod molecules activates vinculin binding.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19179532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19179532</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19179532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1162912" target="_blank">Full Text</a>]
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Gimona, M., Small, J. V., Moeremans, M., Van Damme, J., Puype, M., Vandekerckhove, J.
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<strong>Porcine vinculin and metavinculin differ by a 68-residue insert located close to the carboxy-terminal part of the molecule.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3142762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3142762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3142762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/j.1460-2075.1988.tb03076.x" target="_blank">Full Text</a>]
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<strong>Differential transmission of actin motion within focal adhesions.</strong>
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Science 315: 111-115, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17204653/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17204653</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17204653" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Kanchanawong, P., Shtengel, G., Pasapera, A. M., Ramko, E. B., Davidson, M. W., Hess, H. F., Waterman, C. M.
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<strong>Nanoscale architecture of integrin-based cell adhesions.</strong>
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Nature 468: 580-584, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21107430/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21107430</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21107430[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=21107430" 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/nature09621" target="_blank">Full Text</a>]
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Koteliansky, V. E., Ogryzko, E. P., Zhidkova, N. I., Weller, P. A., Critchley, D. R., Vancompernolle, K., Vandekerckhove, J., Strasser, P., Way, M., Gimona, M., Small, J. V.
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<strong>An additional exon in the human vinculin gene specifically encodes meta-vinculin-specific difference peptide: cross-species comparison reveals variable and conserved motifs in the meta-vinculin insert.</strong>
|
|
Europ. J. Biochem. 204: 767-772, 1992. Note: Erratum: Europ. J. Biochem. 205: 1218 only, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1339348/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1339348</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1339348" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1432-1033.1992.tb16692.x" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Moiseyeva1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Moiseyeva, E. P., Weller, P. A., Zhidkova, N. I., Corben, E. B., Patel, B., Jasinka, I., Koteliansky, V. E., Critchley, D. R.
|
|
<strong>Organization of the human gene encoding the cytoskeletal protein vinculin and the sequence of the vinculin promoter.</strong>
|
|
J. Biol. Chem. 268: 4318-4325, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8440716/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8440716</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8440716" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Mulligan1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mulligan, L. M., Gardner, E., Telenius, H., Ponder, B. A. J.
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<strong>Complementary physical and genetic techniques map the vinculin (VCL) gene on chromosome 10q.</strong>
|
|
Genomics 13: 1347-1349, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1505973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1505973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1505973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(92)90066-2" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Olson2002" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Olson, T. M., Illenberger, S., Kishimoto, N. Y., Huttelmaier, S., Keating, M. T., Jockusch, B. M.
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<strong>Metavinculin mutations alter actin interaction in dilated cardiomyopathy.</strong>
|
|
Circulation 105: 431-437, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11815424/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11815424</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11815424" 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/10.1161/hc0402.102930" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Richards2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Richards, M., Nikolski, V. P., Green, K. G., Zemljic-Harpf, A. E., Efimov, I. E., Ross, R. S., Saffitz, J. E.
|
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<strong>Ventricular arrhythmias in a mouse model of vinculin-related cardiomyopathy.</strong>
|
|
Heart Rhythm 2: S178 only, 2005.
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Strasser1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Strasser, P., Gimona, M., Herzog, M., Geiger, B., Small, J. V.
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<strong>Variable and constant regions in the C-terminus of vinculin and metavinculin: cloning and expression of fragments in E. coli.</strong>
|
|
FEBS Lett. 317: 189-194, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8425604/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8425604</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8425604" 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/10.1016/0014-5793(93)81274-4" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Turner1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Turner, C. E., Burridge, K.
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<strong>Detection of metavinculin in human platelets using a modified talin overlay assay.</strong>
|
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Europ. J. Cell Biol. 49: 202-206, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2503380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2503380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2503380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Vasile2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vasile, V. C., Edwards, W. D., Ommen, S. R., Ackerman, M. J.
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<strong>Obstructive hypertrophic cardiomyopathy is associated with reduced expression of vinculin in the intercalated disc.</strong>
|
|
Biochem. Biophys. Res. Commun. 349: 709-715, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949038/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949038</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949038" 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.bbrc.2006.08.106" target="_blank">Full Text</a>]
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Vasile2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vasile, V. C., Ommen, S. R., Edwards, W. D., Ackerman, M. J.
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<strong>A missense mutation in a ubiquitously expressed protein, vinculin, confers susceptibility to hypertrophic cardiomyopathy.</strong>
|
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Biochem. Biophys. Res. Commun. 345: 998-1003, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16712796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16712796</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16712796" 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.bbrc.2006.04.151" target="_blank">Full Text</a>]
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Vasile2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vasile, V. C., Will, M. L., Ommen, S. R., Edwards, W. D., Olson, T. M., Ackerman, M. J.
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<strong>Identification of a metavinculin missense mutation, R975W, associated with both hypertrophic and dilated cardiomyopathy.</strong>
|
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Molec. Genet. Metab. 87: 169-174, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16236538/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16236538</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16236538" 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.ymgme.2005.08.006" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Weller1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Weller, P. A., Ogryzko, E. P., Corben, E. B., Zhidkova, N. I., Patel, B., Price, G. J., Spurr, N. K., Koteliansky, V. E., Critchley, D. R.
|
|
<strong>Complete sequence of human vinculin and assignment of the gene to chromosome 10.</strong>
|
|
Proc. Nat. Acad. Sci. 87: 5667-5671, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2116004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2116004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2116004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.87.15.5667" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Xu1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Xu, W., Baribault, H., Adamson, E. D.
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<strong>Vinculin knockout results in heart and brain defects during embryonic development.</strong>
|
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Development 125: 327-337, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9486805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9486805</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9486805" 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/10.1242/dev.125.2.327" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 2/2/2011
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 2/17/2010<br>Ada Hamosh - updated : 3/10/2009<br>Marla J. F. O'Neill - updated : 8/31/2007<br>Ada Hamosh - updated : 2/20/2007<br>Ada Hamosh - updated : 9/13/2004<br>Victor A. McKusick - updated : 4/9/2001<br>Victor A. McKusick - updated : 12/13/1999
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 8/23/1990
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 04/17/2013
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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terry : 11/13/2012<br>carol : 2/15/2012<br>alopez : 2/3/2012<br>alopez : 2/7/2011<br>alopez : 2/7/2011<br>terry : 2/2/2011<br>wwang : 2/17/2010<br>alopez : 3/12/2009<br>terry : 3/10/2009<br>carol : 9/4/2007<br>terry : 8/31/2007<br>alopez : 2/21/2007<br>terry : 2/20/2007<br>alopez : 9/16/2004<br>terry : 9/13/2004<br>mcapotos : 4/11/2001<br>terry : 4/9/2001<br>mcapotos : 12/17/1999<br>mcapotos : 12/17/1999<br>mcapotos : 12/14/1999<br>mcapotos : 12/14/1999<br>terry : 12/13/1999<br>carol : 5/13/1993<br>carol : 8/17/1992<br>supermim : 3/16/1992<br>carol : 8/23/1990
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 193065
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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VINCULIN; VCL
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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METAVINCULIN, INCLUDED
|
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: VCL</em></strong>
|
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
|
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<em>
|
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Cytogenetic location: 10q22.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 10:73,998,116-74,121,363 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
|
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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|
Phenotype <br /> mapping key
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</th>
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</tr>
|
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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
|
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10q22.2
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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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Cardiomyopathy, dilated, 1W
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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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611407
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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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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
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|
</span>
|
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
Cardiomyopathy, hypertrophic, 15
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
613255
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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>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
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<p>Vinculin is a cytoskeletal protein associated with the cytoplasmic face of both cell-cell and cell-extracellular matrix adherens-type junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane (Weller et al., 1990). </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>Weller et al. (1990) determined the complete sequence of the human vinculin gene. They found that both human and chicken embryo sequences of vinculin contain 1,066 amino acids and, furthermore, that the 2 proteins exhibit a high level of sequence identity (greater than 95%). Southern blots of human genomic DNA hybridized with short vinculin cDNA fragments indicated that there is a single vinculin gene. </p><p>Koteliansky et al. (1992) determined that metavinculin is the result of alternative splicing of the VCL gene and contains an additional exon. Across species, the deduced protein differs from vinculin in having an additional insert of 68 to 79 amino acids in the C-terminal half of the molecule. By comparison of metavinculin sequences from pig, man, chicken, and frog, Strasser et al. (1993) found a division of the insert into 2 parts: the first variable and the second highly conserved. The longest insert, 79 amino acids, was found in Xenopus laevis. Three different C-terminal constructs of vinculin and metavinculin overexpressed in E. coli could be purified by column chromatography. Using amino acid sequencing methods on the intact molecules and their proteolytic subfragments, together with a polyclonal antibody specific only for metavinculin from porcine stomach, Gimona et al. (1988) identified and sequenced the insert in the porcine metavinculin molecule. By alignment with the complete sequence of chick fibroblast vinculin, they determined the exact location of the insert. In porcine metavinculin, this insert lies between the 90-kD protease-resistant N-terminal core and the C terminus of the molecule. It contains 68 amino acids and is flanked by KWSSK sequences, one of which is present in vinculin. The identity of the mapped vinculin and metavinculin sequences outside this different peptide is consistent with 2 proteins arising via alternative splicing at the mRNA level. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene 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>Moiseyeva et al. (1993) determined that the VCL gene contains 22 exons spanning greater than 75 kb. Alternative splicing of exon 19 results in the cardiac- and smooth muscle-specific metavinculin isoform, containing an additional 68 amino acids. </p>
|
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</span>
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<div>
|
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<br />
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Mapping</strong>
|
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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 use of a panel of human-rodent somatic cell hybrids, Weller et al. (1990) mapped the VCL gene to chromosome 10q11.2-qter. By linkage studies in a 3-generation family, Mulligan et al. (1992) mapped the VCL gene to chromosome 10q22.1-q23, distal to D10S22. They confirmed the assignment by hybridization of the vinculin cDNA to flow-sorted translocation derivative chromosomes containing that portion of chromosome 10. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
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</span>
|
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</h4>
|
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</div>
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|
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<span class="mim-text-font">
|
|
<p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Bakolitsa et al. (2004) described the crystal structure of the full-length vinculin molecule (1,066 amino acids), which shows a 5-domain autoinhibited conformation in which the carboxy-terminal tail domain is held pincer-like by the vinculin head, and ligand binding is regulated both sterically and allosterically. Bakolitsa et al. (2004) showed that the conformational changes in the head, tail, and proline-rich domains are linked structurally and thermodynamically, and proposed a combinatorial pathway to activation that ensures that vinculin is activated only at sites of cell adhesion when 2 or more of its binding partners are brought into apposition. </p><p>Using magnetic tweezers, total internal reflection fluorescence, and atomic force microscopy, del Rio et al. (2009) investigated the effect of force on the interaction between talin (186745), a protein that links liganded membrane integrins to the cytoskeleton, and vinculin, a focal adhesion protein that is activated by talin binding, leading to reorganization of the cytoskeleton. Application of physiologically relevant forces caused stretching of single talin rods that exposed cryptic binding sites for vinculin. Thus in the talin-vinculin system, molecular mechanotransduction can occur by protein binding after exposure of buried binding sites in the talin-vinculin system. </p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
|
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
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|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Turner and Burridge (1989) reported experiments indicating that vinculin is the major talin-binding protein in platelets. However, in addition, a less abundant protein of approximately 150 kD also interacted strongly with the talin fragment. Turner and Burridge (1989) confirmed that this protein is metavinculin, a protein previously believed to be confined to cardiac and smooth muscle tissue. </p><p>Hu et al. (2007) developed correlational fluorescent speckle microscopy to measure the coupling of focal adhesion proteins to actin filaments (see 102610). Different classes of focal adhesion structural and regulatory molecules exhibited varying degrees of correlated motions with actin filaments, indicating hierarchical transmission of actin motion through focal adhesions. Interactions between vinculin, talin, and actin filaments appear to constitute a slippage interface between the cytoskeleton and integrins, generating a molecular clutch that is regulated during the morphodynamic transitions of cell migration. </p><p>Using immunohistochemistry, Vasile et al. (2006) examined the pattern of vinculin/metavinculin expression in the intercalated- and Z discs of cardiomyocytes from patients with various cardiovascular conditions associated with hypertrophy. Tissue specimens derived from patients with obstructive hypertrophic cardiomyopathy (CMH; see CMH15, 613255) and aortic stenosis (see 109730) showed a universal defect of vinculin/metavinculin expression in the intercalated disc but preserved expression in the cardiac Z disc, whereas tissue specimens from patients with dilated cardiomyopathy (CMD; see CMD1W, 611407), hypertensive heart disease (see 145500), or pulmonary hypertension (see 178600) exhibited normal expression of vinculin/metavinculin in both the Z and the intercalated disc, despite being associated with hypertrophy. Vasile et al. (2006) suggested that differential expression of vinculin/metavinculin in cardiac hypertrophy might depend on the underlying pathophysiology, with localization unaffected by hemodynamic overload but expression in the intercalated disc substantially reduced by obstructive disease. </p><p>Kanchanawong et al. (2010) used 3-dimensional super-resolution fluorescence microscopy to map nanoscale protein organization in focal adhesions. Their results revealed that integrins and actin are vertically separated by an approximately 40-nm focal adhesion core region consisting of multiple protein-specific strata: a membrane-apposed integrin signaling layer containing integrin cytoplasmic tails (see 193210), focal adhesion kinase (600758), and paxillin (602505); an intermediate force-transduction layer containing talin and vinculin; and an uppermost actin-regulatory layer containing zyxin (602002), vasodilator-stimulated phosphoprotein (601703), and alpha-actinin (102575). By localizing amino- and carboxy-terminally tagged talins, Kanchanawong et al. (2010) revealed talin's polarized orientation, indicative of a role in organizing the focal adhesion strata. Kanchanawong et al. (2010) concluded that their composite multilaminar protein architecture provided a molecular blueprint for understanding focal adhesion functions. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Olson et al. (2002) used SSCP to analyze the vinculin gene in 350 unrelated patients with sporadic or familial dilated cardiomyopathy (611407) who were negative for mutations in the ACTC (102540) and TPM1 (191010) genes, and identified heterozygosity for a 3-bp in-frame deletion (L954del; 193065.0001) and a missense mutation (R975W; 193065.0002) in 2 patients, respectively. Neither mutation was found in 500 controls. A potential risk-conferring polymorphism, A934V, was identified in heterozygosity in a 30-year-old man with dilated cardiomyopathy who died 2 years after diagnosis of progressive heart failure; this variant was also found in 1 of 500 controls, a 67-year-old woman in whom electrocardiography showed abnormal T waves but echocardiogram was nondiagnostic for dilated cardiomyopathy. All variants were located in exon 19, the metavinculin-specific exon of the vinculin gene. Low-shear viscometry studies revealed variable reductions in viscosity associated with the mutations, with greater reductions caused by the L954del and R975W mutants. Fluorescence microscopy confirmed the viscosity findings, with actin organization by the A934V variant similar to wildtype, although the network appeared coarser; more prominent bundles were observed for L954del, and R975W showed the highest bundling activity. Electron microscopy of cardiac myocytes from a patient with the R975W mutation showed irregular and fragmented intercalated discs, with intact sarcomeric thin and thick filaments. </p><p>Vasile et al. (2006) analyzed the metavinculin-specific exon 19 of the VCL gene in 389 unrelated patients with hypertrophic cardiomyopathy (CMH), who were negative for mutation in 8 known CMH-associated sarcomere/myofilament-encoding genes, and identified heterozygosity for the R975W mutation in a patient with CMH15 (613255). </p><p>In a cohort of 228 CMH patients who were negative for mutation in 12 known CMH-associated sarcomere/myofilament-encoding genes, Vasile et al. (2006) performed comprehensive analysis of the 22 exons of the VCL gene and identified a heterozygous mutation in 1 patient (L277M; 193065.0003). The authors noted that despite its ubiquitous expression, the HCM-associated VCL mutation clinically yielded a cardiac-specific phenotype. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<span class="mim-text-font">
|
|
<p>Xu et al. (1998) used a targeting vector to inactivate vinculin in embryonic stem cells, which were then injected into mice. They found that Vcl -/- embryos failed to develop beyond the tenth day of gestation and at best were two-thirds of the normal size range. The most prominent defect was lack of midline fusion of the rostral neural tube, producing a cranial bilobular appearance and attenuation of cranial and spinal nerve development. Heart development was curtailed at E9.5, with severely reduced and akinetic myocardial and endocardial structures. Somites and limbs were retarded, and ectodermal tissues were sparse and fragile. Fibroblasts isolated from mutant embryos showed reduced adhesion to fibronectin, vitronectin, laminin, and collagen compared to wildtype. In addition, migration rates over these substrata were 2-fold higher and the level of focal adhesion kinase (FAK; 600758) was 3-fold higher. Xu et al. (1998) concluded that vinculin is necessary for normal embryonic development, probably because of its role in the regulation of cell adhesion and locomotion, although specific roles in neural and cardiac development could not be ruled out. </p><p>Richards et al. (2005) analyzed hearts from Vcl +/- and wildtype mice and found that although decreased vinculin expression enhanced inducibility of ventricular arrhythmias, connexin-43 (GJA1; 121014) content and distribution, and conduction velocities, were not significantly different between mutant and wildtype mice. Richards et al. (2005) suggested that other mechanisms, such as altered integrin (see 192968) signaling, might contribute to arrhythmogenesis.</p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>3 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 CARDIOMYOPATHY, DILATED, 1W</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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|
|
VCL, 3-BP DEL, 2862GTT
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|
|
<br />
|
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|
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SNP: rs397517237,
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|
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ClinVar: RCV000038819, RCV000171847, RCV000619949, RCV000678764, RCV000727177, RCV000988386, RCV003227625
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 39-year-old man with dilated cardiomyopathy (CMD1W; 611407), Olson et al. (2002) identified heterozygosity for a 3-bp deletion (2862delGTT) in exon 19 of the vinculin gene, resulting in the in-frame deletion of a leucine residue (leu954del). The patient's father died of heart failure at 59 years of age, and a 70-year-old paternal uncle had heart failure, but the patient's relatives declined clinical and genetic evaluation. The mutation was not found in 500 unrelated controls. </p>
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</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 CARDIOMYOPATHY, DILATED, 1W</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 15
|
|
</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
VCL, ARG975TRP
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|
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<br />
|
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|
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SNP: rs121917776,
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|
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gnomAD: rs121917776,
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ClinVar: RCV000012980, RCV000012981, RCV000620759, RCV002482857
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</span>
|
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</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 57-year-old woman with dilated cardiomyopathy (CMD1W; 611407) who had undergone cardiac transplantation, Olson et al. (2002) identified heterozygosity for a 2923C-T transition in exon 19 of the vinculin gene, resulting in an arg975-to-trp (R975W) substitution in the metavinculin isoform. The mutation was also found in heterozygosity in 3 asymptomatic relatives, 2 of whom were found to have disease on screening echocardiogram: a 70-year-old maternal aunt had dilated cardiomyopathy, and a 38-year-old daughter had mild left ventricular dilation. The patient's 55-year-old sister carried the mutation but had normal left ventricular dimensions and shortening/ejection fractions. The mutation was not found in 500 unrelated controls. </p><p>In a 43-year-old woman with severe apical variant hypertrophic cardiomyopathy (CMH15; 613255), Vasile et al. (2006) identified heterozygosity for the R975W substitution in the VCL gene, located in a highly conserved residue in the tail region of metavinculin and predicted to cause significant alterations in the secondary structure and helical organization of the protein. The mutation was not found in 1,400 reference allele. Immunohistochemical analysis of the patient's myocardium demonstrated a marked reduction of both vinculin and metavinculin in the intercalated discs. Noting that the patient was homozygous for wildtype vinculin and heterozygous for R975W metavinculin, Vasile et al. (2006) suggested that the marked reduction of proteins in the intercalated discs might be due to a dominant-negative effect. However, after analyzing immunohistochemically stained tissue specimens from patients with various cardiovascular conditions associated with hypertrophy, Vasile et al. (2006) suggested that differential expression of vinculin/metavinculin in cardiac hypertrophy might depend on the underlying pathophysiology, with localization unaffected by hemodynamic overload but expression in the intercalated disc substantially reduced by obstructive disease (see GENE FUNCTION). </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">
|
|
<strong>.0003 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 15</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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VCL, LEU277MET
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<br />
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|
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SNP: rs71579353,
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gnomAD: rs71579353,
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ClinVar: RCV000012982, RCV000617420, RCV000645321, RCV000768535, RCV000845477, RCV000994445, RCV002298443, RCV002496333, RCV003149568
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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 76-year-old Caucasian woman with severely obstructive hypertrophic cardiomyopathy (CMH15; 613255), Vasile et al. (2006) identified a heterozygous 829C-A transversion in exon 8 of the VCL gene, resulting in a leu277-to-met (L277M) substitution at a conserved residue in a key functional domain. The mutation was not detected in 400 reference alleles. Immunostaining of myomectomy tissue from the patient showed normal Z line staining but markedly reduced vinculin/metavinculin staining in the intercalated discs. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
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<p />
|
|
</div>
|
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<div>
|
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<ol>
|
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|
|
<li>
|
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<p class="mim-text-font">
|
|
Bakolitsa, C., Cohen, D. M., Bankston, L. A., Bobkov, A. A., Cadwell, G. W., Jennings, L., Critchley, D. R., Craig, S. W., Liddington, R. C.
|
|
<strong>Structural basis for vinculin activation at sites of cell adhesion.</strong>
|
|
Nature 430: 583-586, 2004.
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Weller, P. A., Ogryzko, E. P., Corben, E. B., Zhidkova, N. I., Patel, B., Price, G. J., Spurr, N. K., Koteliansky, V. E., Critchley, D. R.
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<strong>Vinculin knockout results in heart and brain defects during embryonic development.</strong>
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