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<title>
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Entry
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- *601443 - COFILIN 2; CFL2
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- OMIM
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</ul>
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</nav>
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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="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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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>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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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 class="col-lg-2 col-md-2 col-sm-2 hidden-sm hidden-xs">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*601443</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 role="presentation">
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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>
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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>
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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 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/601443">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=ENSG00000165410;t=ENST00000298159" 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=1073" 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=601443" 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=ENSG00000165410;t=ENST00000298159" 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_001243645,NM_021914,NM_138638,NR_028130,NR_028131" 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_138638" 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=601443" 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=03262&isoform_id=03262_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/CFL2" 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/4868363,4868364,6831517,7595916,9739169,14719392,15030332,18490213,18606108,20086423,33946278,119586312,119586314,119586315,119586316,189054322,343887344" 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/Q9Y281" 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=1073" 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=ENSG00000165410;t=ENST00000298159" 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=CFL2" 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=CFL2" 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+1073" 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/CFL2" 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:1073" 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/1073" 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=chr14&hgg_gene=ENST00000298159.11&hgg_start=34709113&hgg_end=34714593&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:1875" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:1875" 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=601443[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=601443[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/ENSG00000165410" 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.gwascentral.org/search?q=CFL2" 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=CFL2" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="http://www.LOVD.nl/CFL2" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=CFL2&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/PA26424" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/gene/HGNC:1875" 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/FBgn0030951.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:101763" 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/CFL2#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:101763" 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/1073/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=1073" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00006794;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00006794 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00302980;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00302980 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1815" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:1073" 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=CFL2&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
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601443
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
|
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<span class="mim-font">
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COFILIN 2; CFL2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
|
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
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COFILIN, MUSCLE<br />
|
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COFILIN, M-TYPE
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=CFL2" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">CFL2</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/14/164?start=-3&limit=10&highlight=164">14q13.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr14:34709113-34714593&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'})">14:34,709,113-34,714,593</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
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Nemaline myopathy 7, autosomal recessive
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/601443" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </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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<strong>TEXT</strong>
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<p>Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. (<a href="#4" class="mim-tip-reference" title="Gillett, G. T., Fox, M. F., Rowe, P. S. N., Casimir, C. M., Povey, S. <strong>Mapping of human non-muscle type cofilin (CFL1) to chromosome 11q13 and muscle-type cofilin (CFL2) to chromosome 14.</strong> Ann. Hum. Genet. 60: 201-211, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8800436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8800436</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1996.tb00423.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8800436">Gillett et al., 1996</a>). Cofilin-2 is a member of the AC group of proteins that also includes cofilin-1 (CFL1; <a href="/entry/601442">601442</a>) and destrin (DSTN; <a href="/entry/609114">609114</a>), all of which regulate actin-filament dynamics (<a href="#3" class="mim-tip-reference" title="Bamburg, J. R., McGough, A., Ono, S. <strong>Putting a new twist on actin: ADF/cofilins modulate actin dynamics.</strong> Trends Cell Biol. 9: 364-370, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10461190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10461190</a>] [<a href="https://doi.org/10.1016/s0962-8924(99)01619-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10461190">Bamburg et al., 1999</a>; <a href="#5" class="mim-tip-reference" title="Maciver, S. K., Hussey, P. J. <strong>The ADF/cofilin family: actin-remodeling proteins.</strong> Genome Biol. 3: reviews3007, 2002. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12049672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12049672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12049672[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/10.1186/gb-2002-3-5-reviews3007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12049672">Maciver and Hussey, 2002</a>). The CFL2 gene encodes a skeletal muscle-specific isoform (<a href="#11" class="mim-tip-reference" title="Vartiainen, M. K., Mustonen, T., Mattila, P. K., Ojala, P. J., Thesleff, I., Partanen, J., Lappalainen, P. <strong>The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.</strong> Molec. Biol. Cell 13: 183-194, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11809832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11809832</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11809832[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/10.1091/mbc.01-07-0331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11809832">Vartiainen et al., 2002</a>) localized to the thin filaments, where it exerts its effect on actin, in part through interactions with tropomyosins (<a href="#8" class="mim-tip-reference" title="Ono, S., Ono, K. <strong>Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics.</strong> J. Cell Biol. 156: 1065-1076, 2002. Note: Erratum: J. Cell Biol. 157: 727 only, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11901171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11901171</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11901171[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/10.1083/jcb.200110013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11901171">Ono and Ono, 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8800436+11809832+10461190+12049672+11901171" 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>Cloning and Expression</strong>
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<p><a href="#7" class="mim-tip-reference" title="Ono, S., Minami, N., Abe, H., Obinata, T. <strong>Characterization of a novel cofilin isoform that is predominantly expressed in mammalian skeletal muscle.</strong> J. Biol. Chem. 269: 15280-15286, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8195165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8195165</a>]" pmid="8195165">Ono et al. (1994)</a> cloned mouse Cfl2, which they called M-type cofilin. The deduced protein contains 166 amino acids and has a calculated molecular mass of 18.7 kD. It shares 81.3% amino acid identity with mouse brain cofilin (CFL1). Cfl2 has an N-terminal nuclear localization signal, followed by an actin- and phosphoinositide-binding site and a region homologous to the N-terminal sequence of tropomyosin (see <a href="/entry/191010">191010</a>). Northern blot analysis of mouse tissues detected Cfl2 transcripts of 1.8 and 3.0 kb in heart, skeletal muscle, and testis. Among mouse cell lines, high expression was detected in 3Y1 fibroblasts, C2 myogenic cells, and A10 smooth muscle cells. The amount of Cfl2 expressed in C2 cells increased during differentiation from myoblasts to myotubes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8195165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR using primers based on murine Cfl2, <a href="#10" class="mim-tip-reference" title="Thirion, C., Stucka, R., Mendel, B., Gruhler, A., Jaksch, M., Nowak, K. J., Binz, N., Laing, N. G., Lochmuller, H. <strong>Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle.</strong> Europ. J. Biochem. 268: 3473-3482, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11422377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11422377</a>] [<a href="https://doi.org/10.1046/j.1432-1327.2001.02247.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11422377">Thirion et al. (2001)</a> cloned 4 CFL2 variants from human fetal and adult myoblasts. The transcripts differ in their 5-prime and 3-prime ends, but have identical coding regions, due to alternative splicing of the first exon and the use of alternative polyadenylation signals. The deduced 166-amino acid CFL2 protein has a calculated molecular mass of 19 kD and shares 99% and 81% identity with mouse Cfl2 and human CFL1, respectively. Northern blot analysis detected 2 major CLF2 transcripts that were highly expressed in heart and skeletal muscle, with weaker expression in all other tissues examined. Primary human myoblasts and myotubes expressed transcripts of 1.55, 1.65, and 3.2 kb. Immunohistochemical analysis of murine and human skeletal muscle localized CFL2 in a uniform cytoplasmic distribution characteristic of sarcomeric proteins. Western blot analysis of healthy mouse muscle showed that 30 to 50% of Cfl2 was phosphorylated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11422377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H. <strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong> Hum. Molec. Genet. 21: 2341-2356, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22343409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22343409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22343409[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22343409">Agrawal et al. (2012)</a> stated that mouse Cfl2 is expressed as 1.8- and 3.0-kb transcripts that differ in their 3-prime UTRs only and are alternately expressed during striated muscle development. The 1.8-kb transcript is expressed at embryonic day 13, peaks in skeletal and cardiac muscle at birth, and decreases thereafter. The 3.0-kb transcript is expressed in skeletal muscle only, and its expression increases as expression of the 1.8-kb transcript decreases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22343409" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By RT-PCR analysis, <a href="#9" class="mim-tip-reference" title="Rosen, S. M., Joshi, M., Hitt, T., Beggs, A. H., Agrawal, P. B. <strong>Knockin mouse model of the human CFL2 p.A35T mutation results in a unique splicing defect and severe myopathy phenotype.</strong> Hum. Molec. Genet. 29: 1996-2003, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddaa035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32160286">Rosen et al. (2020)</a> identified 3 Cfl2 splice variants in mouse: a predominantly expressed full-length transcript, and 2 shorter transcripts that were expressed at low levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32160286" 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="#10" class="mim-tip-reference" title="Thirion, C., Stucka, R., Mendel, B., Gruhler, A., Jaksch, M., Nowak, K. J., Binz, N., Laing, N. G., Lochmuller, H. <strong>Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle.</strong> Europ. J. Biochem. 268: 3473-3482, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11422377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11422377</a>] [<a href="https://doi.org/10.1046/j.1432-1327.2001.02247.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11422377">Thirion et al. (2001)</a> determined that the CFL2 gene contains 5 exons, including alternative first exons (exons 1a and 1b) that encode the initiating methionine only. Identification of transcription factor-binding sites upstream of exons 1a and 1b suggested the presence of 2 promoters. CFL2 has 2 polyadenylation signals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11422377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Gillett, G. T., Fox, M. F., Rowe, P. S. N., Casimir, C. M., Povey, S. <strong>Mapping of human non-muscle type cofilin (CFL1) to chromosome 11q13 and muscle-type cofilin (CFL2) to chromosome 14.</strong> Ann. Hum. Genet. 60: 201-211, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8800436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8800436</a>] [<a href="https://doi.org/10.1111/j.1469-1809.1996.tb00423.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8800436">Gillett et al. (1996)</a> mapped CFL2, the human muscle-type (M-type) cofilin, to chromosome 14 by analysis of a somatic cell hybrid panel using an expressed sequence tag (EST) with homology to the mouse muscle-type cofilin and chicken cofilin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8800436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H. <strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong> Hum. Molec. Genet. 21: 2341-2356, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22343409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22343409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22343409[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22343409">Agrawal et al. (2012)</a> stated that the CFL2 gene maps to chromosome 14q12. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22343409" 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 Western blot analysis of 2-dimensional gels, <a href="#10" class="mim-tip-reference" title="Thirion, C., Stucka, R., Mendel, B., Gruhler, A., Jaksch, M., Nowak, K. J., Binz, N., Laing, N. G., Lochmuller, H. <strong>Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle.</strong> Europ. J. Biochem. 268: 3473-3482, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11422377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11422377</a>] [<a href="https://doi.org/10.1046/j.1432-1327.2001.02247.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11422377">Thirion et al. (2001)</a> found that expression of Clf2 decreased sharply and that phosphorylated Cfl2 became undetectable following acute muscle damage in mice. Skeletal muscle of Duchenne muscular dystrophy (<a href="/entry/310200">310200</a>) patients and dystrophin (DMD; <a href="/entry/300377">300377</a>)-deficient mdx mice, where continuous muscle degeneration and regeneration occurs, showed a similar phenomenon. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11422377" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V.-L., Wallgren-Pettersson, C., Wallefeld, W., Laing, N. G., Darras, B. T., Maciver, S. K., Dormitzer, P. R., Beggs, A. H. <strong>Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.</strong> Am. J. Hum. Genet. 80: 162-167, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160903</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160903[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/510402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17160903">Agrawal et al. (2007)</a> used genomic PCR and DNA sequencing to screen the CFL2 gene in 113 unrelated patients with nemaline myopathy and 58 patients with clinical pathologic diagnoses of other congenital myopathies. None of the patients had known mutations in previously identified genes. In 2 sibs with nemaline myopathy (NEM7; <a href="/entry/610687">610687</a>) in a large family of Middle Eastern origin, <a href="#1" class="mim-tip-reference" title="Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V.-L., Wallgren-Pettersson, C., Wallefeld, W., Laing, N. G., Darras, B. T., Maciver, S. K., Dormitzer, P. R., Beggs, A. H. <strong>Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.</strong> Am. J. Hum. Genet. 80: 162-167, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160903</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160903[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/510402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17160903">Agrawal et al. (2007)</a> identified a homozygous mutation in the CFL2 gene (A35T; <a href="#0001">601443.0001</a>). The proband's muscle contained characteristic nemaline bodies, as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. Cofilin-2 levels were significantly lower in the proband's muscle, and the mutant protein was less soluble when expressed in Escherichia coli, suggesting that deficiency of cofilin-2 may result in reduced depolymerization of actin filaments, causing their accumulation in nemaline bodies, minicores, and, possibly concentric laminated bodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17160903" 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 2 Iraqi sisters, born of consanguineous parents, with nemaline myopathy-7, <a href="#6" class="mim-tip-reference" title="Ockeloen, C. W., Gilhuis, H. J., Pfundt, R., Kamsteeg, E. J., Agrawal, P. B., Beggs, A. H., Dara Hama-Amin, A., Diekstra, A., Knoers, N. V. A. M., Lammens, M., van Alfen, N. <strong>Congenital myopathy caused by a novel missense mutation in the CFL2 gene.</strong> Neuromusc. Disord. 22: 632-639, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22560515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22560515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22560515[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/10.1016/j.nmd.2012.03.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22560515">Ockeloen et al. (2012)</a> identified a homozygous missense mutation in the CFL2 gene (V7M; <a href="#0002">601443.0002</a>). The mutation was found by homozygosity mapping followed by candidate gene sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22560515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H. <strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong> Hum. Molec. Genet. 21: 2341-2356, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22343409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22343409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22343409[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22343409">Agrawal et al. (2012)</a> found that Cfl2 -/- mice were indistinguishable from wildtype at birth. However, by postnatal day 3, Cfl2 -/- mice showed reduced size and activity, followed by rapid deterioration and death by postnatal day 8. Presence of milk in stomachs of Cfl2 -/- mice at postnatal day 3, but not at postnatal day 7, suggested that the older animals had lost the ability to suckle. Targeted disruption of Cfl2 to skeletal or cardiac muscle resulted in a phenotype that was only modestly less severe. Electron microscopic analysis revealed ballooning degeneration of skeletal muscle fibers, core-like lesions, extensive sarcomeric disruption, nemaline bodies, and actin accumulation. Cardiac muscle fibers did not show evidence of degeneration. Muscle degeneration and weakness in Cfl2 -/- mice coincided with normal developmental depletion of Cfl1 in myofibers. <a href="#2" class="mim-tip-reference" title="Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H. <strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong> Hum. Molec. Genet. 21: 2341-2356, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22343409/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22343409</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22343409[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/dds053" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22343409">Agrawal et al. (2012)</a> hypothesized that Cfl1 may initiate myofibrillogenesis, whereas Cfl2 is required for myofiber maintenance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22343409" 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="#9" class="mim-tip-reference" title="Rosen, S. M., Joshi, M., Hitt, T., Beggs, A. H., Agrawal, P. B. <strong>Knockin mouse model of the human CFL2 p.A35T mutation results in a unique splicing defect and severe myopathy phenotype.</strong> Hum. Molec. Genet. 29: 1996-2003, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160286[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddaa035" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32160286">Rosen et al. (2020)</a> found that knockin mice homozygous for the A35T mutation in Cfl2 associated with congenital myopathy in human were born at the expected mendelian ratio and were indistinguishable from wildtype. However, mutant mice began to display growth defects by postnatal day-3 (P3), and all died by P9. Mutant mice had lower body weight and shorter average length than controls and displayed disrupted early postnatal muscle maintenance and abnormal muscle structure. Western blot analysis revealed that Cfl2 protein was absent in several organs of mutant mice, including skeletal muscle, heart, brain, lung, and kidney, whereas skeletal actin (see <a href="/entry/102610">102610</a>) was increased in skeletal muscle and heart. Further analysis demonstrated that a splicing defect in mutant mice resulted in significant upregulation of the short Cfl2 splice variant with concomitant and marked reduction of the full-length transcript. Similar alternative splicing was observed in human, with patients with the A35T mutation displaying marked reduction of the full-length CFL2 transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32160286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sisters in a family of Middle Eastern origin, <a href="#1" class="mim-tip-reference" title="Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V.-L., Wallgren-Pettersson, C., Wallefeld, W., Laing, N. G., Darras, B. T., Maciver, S. K., Dormitzer, P. R., Beggs, A. H. <strong>Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.</strong> Am. J. Hum. Genet. 80: 162-167, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17160903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17160903</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17160903[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/510402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17160903">Agrawal et al. (2007)</a> found that nemaline myopathy with some unusual histopathologic and clinical features (NEM7; <a href="/entry/610687">610687</a>) was related to homozygous mutation of the CFL2 gene, 103G-A, predicted to result in an alanine-to-threonine substitution at residue 35 (A35T). An unaffected sib, both unaffected parents, and a number of other members of the extended family were heterozygous for this change. Extensive intermarriage, with multiple consanguinity loops, strongly suggested identity by descent for the 2 mutant alleles, a supposition that was supported by linkage studies using flanking markers. The mutation was ruled out in 282 unaffected control individuals, including 91 originating from the same geographic region and ethnic group as the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17160903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 Iraqi sisters, born of consanguineous parents, with nemaline myopathy-7 (NEM7; <a href="/entry/610687">610687</a>), <a href="#6" class="mim-tip-reference" title="Ockeloen, C. W., Gilhuis, H. J., Pfundt, R., Kamsteeg, E. J., Agrawal, P. B., Beggs, A. H., Dara Hama-Amin, A., Diekstra, A., Knoers, N. V. A. M., Lammens, M., van Alfen, N. <strong>Congenital myopathy caused by a novel missense mutation in the CFL2 gene.</strong> Neuromusc. Disord. 22: 632-639, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22560515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22560515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22560515[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/10.1016/j.nmd.2012.03.008" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22560515">Ockeloen et al. (2012)</a> identified a homozygous c.19G-A transition in exon 2 of the CFL2 gene, resulting in a val7-to-met (V7M) substitution at a highly conserved residue. The mutation was found by homozygosity mapping followed by candidate gene sequencing. The unaffected parents were heterozygous for the mutation, which was not found in 250 controls or in dbSNP. Functional studies were not performed. The girls had delayed walking and proximal and axial muscle weakness; muscle biopsy showed nemaline rods and abnormal protein aggregates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22560515" 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="https://doi.org/10.1086/510402" target="_blank">Full Text</a>]
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Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H.
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<strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong>
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[<a href="https://doi.org/10.1093/hmg/dds053" target="_blank">Full Text</a>]
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Bamburg, J. R., McGough, A., Ono, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10461190/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10461190</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10461190" 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/s0962-8924(99)01619-0" target="_blank">Full Text</a>]
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Gillett, G. T., Fox, M. F., Rowe, P. S. N., Casimir, C. M., Povey, S.
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[<a href="https://doi.org/10.1111/j.1469-1809.1996.tb00423.x" target="_blank">Full Text</a>]
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<strong>The ADF/cofilin family: actin-remodeling proteins.</strong>
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Genome Biol. 3: reviews3007, 2002. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12049672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12049672</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12049672[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=12049672" 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/10.1186/gb-2002-3-5-reviews3007" target="_blank">Full Text</a>]
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Ockeloen, C. W., Gilhuis, H. J., Pfundt, R., Kamsteeg, E. J., Agrawal, P. B., Beggs, A. H., Dara Hama-Amin, A., Diekstra, A., Knoers, N. V. A. M., Lammens, M., van Alfen, N.
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<strong>Congenital myopathy caused by a novel missense mutation in the CFL2 gene.</strong>
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Neuromusc. Disord. 22: 632-639, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22560515/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22560515</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22560515[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=22560515" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2012.03.008" target="_blank">Full Text</a>]
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Ono, S., Minami, N., Abe, H., Obinata, T.
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<strong>Characterization of a novel cofilin isoform that is predominantly expressed in mammalian skeletal muscle.</strong>
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J. Biol. Chem. 269: 15280-15286, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8195165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8195165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8195165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Ono, S., Ono, K.
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<strong>Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics.</strong>
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J. Cell Biol. 156: 1065-1076, 2002. Note: Erratum: J. Cell Biol. 157: 727 only, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11901171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11901171</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11901171[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=11901171" 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/10.1083/jcb.200110013" target="_blank">Full Text</a>]
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Rosen, S. M., Joshi, M., Hitt, T., Beggs, A. H., Agrawal, P. B.
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<strong>Knockin mouse model of the human CFL2 p.A35T mutation results in a unique splicing defect and severe myopathy phenotype.</strong>
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Hum. Molec. Genet. 29: 1996-2003, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32160286/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32160286</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32160286[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=32160286" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddaa035" target="_blank">Full Text</a>]
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Thirion, C., Stucka, R., Mendel, B., Gruhler, A., Jaksch, M., Nowak, K. J., Binz, N., Laing, N. G., Lochmuller, H.
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<strong>Characterization of human muscle type cofilin (CFL2) in normal and regenerating muscle.</strong>
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Europ. J. Biochem. 268: 3473-3482, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11422377/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11422377</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11422377" 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/10.1046/j.1432-1327.2001.02247.x" target="_blank">Full Text</a>]
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Vartiainen, M. K., Mustonen, T., Mattila, P. K., Ojala, P. J., Thesleff, I., Partanen, J., Lappalainen, P.
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<strong>The three mouse actin-depolymerizing factor/cofilins evolved to fulfill cell-type-specific requirements for actin dynamics.</strong>
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Molec. Biol. Cell 13: 183-194, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11809832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11809832</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11809832[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=11809832" 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/10.1091/mbc.01-07-0331" target="_blank">Full Text</a>]
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Bao Lige - updated : 05/02/2024
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Bao Lige - updated : 01/06/2022<br>Cassandra L. Kniffin - updated : 8/5/2013<br>Patricia A. Hartz - updated : 7/10/2013<br>Victor A. McKusick - updated : 1/3/2007
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Lori M. Kelman : 9/23/1996
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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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mgross : 01/11/2022<br>mgross : 01/06/2022<br>carol : 09/14/2017<br>carol : 06/24/2016<br>tpirozzi : 8/7/2013<br>tpirozzi : 8/7/2013<br>tpirozzi : 8/7/2013<br>ckniffin : 8/5/2013<br>mgross : 7/10/2013<br>mgross : 7/10/2013<br>terry : 12/19/2012<br>alopez : 1/5/2007<br>terry : 1/3/2007<br>mark : 4/10/1997<br>mark : 9/24/1996<br>mark : 9/23/1996<br>mark : 9/23/1996
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</span>
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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="col-md-8 col-md-offset-1">
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 601443
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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COFILIN 2; CFL2
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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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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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COFILIN, MUSCLE<br />
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COFILIN, M-TYPE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: CFL2</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: 14q13.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 14:34,709,113-34,714,593 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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14q13.1
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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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Nemaline myopathy 7, autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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610687
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. (Gillett et al., 1996). Cofilin-2 is a member of the AC group of proteins that also includes cofilin-1 (CFL1; 601442) and destrin (DSTN; 609114), all of which regulate actin-filament dynamics (Bamburg et al., 1999; Maciver and Hussey, 2002). The CFL2 gene encodes a skeletal muscle-specific isoform (Vartiainen et al., 2002) localized to the thin filaments, where it exerts its effect on actin, in part through interactions with tropomyosins (Ono and Ono, 2002). </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>Ono et al. (1994) cloned mouse Cfl2, which they called M-type cofilin. The deduced protein contains 166 amino acids and has a calculated molecular mass of 18.7 kD. It shares 81.3% amino acid identity with mouse brain cofilin (CFL1). Cfl2 has an N-terminal nuclear localization signal, followed by an actin- and phosphoinositide-binding site and a region homologous to the N-terminal sequence of tropomyosin (see 191010). Northern blot analysis of mouse tissues detected Cfl2 transcripts of 1.8 and 3.0 kb in heart, skeletal muscle, and testis. Among mouse cell lines, high expression was detected in 3Y1 fibroblasts, C2 myogenic cells, and A10 smooth muscle cells. The amount of Cfl2 expressed in C2 cells increased during differentiation from myoblasts to myotubes. </p><p>By RT-PCR using primers based on murine Cfl2, Thirion et al. (2001) cloned 4 CFL2 variants from human fetal and adult myoblasts. The transcripts differ in their 5-prime and 3-prime ends, but have identical coding regions, due to alternative splicing of the first exon and the use of alternative polyadenylation signals. The deduced 166-amino acid CFL2 protein has a calculated molecular mass of 19 kD and shares 99% and 81% identity with mouse Cfl2 and human CFL1, respectively. Northern blot analysis detected 2 major CLF2 transcripts that were highly expressed in heart and skeletal muscle, with weaker expression in all other tissues examined. Primary human myoblasts and myotubes expressed transcripts of 1.55, 1.65, and 3.2 kb. Immunohistochemical analysis of murine and human skeletal muscle localized CFL2 in a uniform cytoplasmic distribution characteristic of sarcomeric proteins. Western blot analysis of healthy mouse muscle showed that 30 to 50% of Cfl2 was phosphorylated. </p><p>Agrawal et al. (2012) stated that mouse Cfl2 is expressed as 1.8- and 3.0-kb transcripts that differ in their 3-prime UTRs only and are alternately expressed during striated muscle development. The 1.8-kb transcript is expressed at embryonic day 13, peaks in skeletal and cardiac muscle at birth, and decreases thereafter. The 3.0-kb transcript is expressed in skeletal muscle only, and its expression increases as expression of the 1.8-kb transcript decreases. </p><p>By RT-PCR analysis, Rosen et al. (2020) identified 3 Cfl2 splice variants in mouse: a predominantly expressed full-length transcript, and 2 shorter transcripts that were expressed at low levels. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Thirion et al. (2001) determined that the CFL2 gene contains 5 exons, including alternative first exons (exons 1a and 1b) that encode the initiating methionine only. Identification of transcription factor-binding sites upstream of exons 1a and 1b suggested the presence of 2 promoters. CFL2 has 2 polyadenylation signals. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Gillett et al. (1996) mapped CFL2, the human muscle-type (M-type) cofilin, to chromosome 14 by analysis of a somatic cell hybrid panel using an expressed sequence tag (EST) with homology to the mouse muscle-type cofilin and chicken cofilin. </p><p>Agrawal et al. (2012) stated that the CFL2 gene maps to chromosome 14q12. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>By Western blot analysis of 2-dimensional gels, Thirion et al. (2001) found that expression of Clf2 decreased sharply and that phosphorylated Cfl2 became undetectable following acute muscle damage in mice. Skeletal muscle of Duchenne muscular dystrophy (310200) patients and dystrophin (DMD; 300377)-deficient mdx mice, where continuous muscle degeneration and regeneration occurs, showed a similar phenomenon. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Agrawal et al. (2007) used genomic PCR and DNA sequencing to screen the CFL2 gene in 113 unrelated patients with nemaline myopathy and 58 patients with clinical pathologic diagnoses of other congenital myopathies. None of the patients had known mutations in previously identified genes. In 2 sibs with nemaline myopathy (NEM7; 610687) in a large family of Middle Eastern origin, Agrawal et al. (2007) identified a homozygous mutation in the CFL2 gene (A35T; 601443.0001). The proband's muscle contained characteristic nemaline bodies, as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. Cofilin-2 levels were significantly lower in the proband's muscle, and the mutant protein was less soluble when expressed in Escherichia coli, suggesting that deficiency of cofilin-2 may result in reduced depolymerization of actin filaments, causing their accumulation in nemaline bodies, minicores, and, possibly concentric laminated bodies. </p><p>In 2 Iraqi sisters, born of consanguineous parents, with nemaline myopathy-7, Ockeloen et al. (2012) identified a homozygous missense mutation in the CFL2 gene (V7M; 601443.0002). The mutation was found by homozygosity mapping followed by candidate gene sequencing. </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>Animal Model</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Agrawal et al. (2012) found that Cfl2 -/- mice were indistinguishable from wildtype at birth. However, by postnatal day 3, Cfl2 -/- mice showed reduced size and activity, followed by rapid deterioration and death by postnatal day 8. Presence of milk in stomachs of Cfl2 -/- mice at postnatal day 3, but not at postnatal day 7, suggested that the older animals had lost the ability to suckle. Targeted disruption of Cfl2 to skeletal or cardiac muscle resulted in a phenotype that was only modestly less severe. Electron microscopic analysis revealed ballooning degeneration of skeletal muscle fibers, core-like lesions, extensive sarcomeric disruption, nemaline bodies, and actin accumulation. Cardiac muscle fibers did not show evidence of degeneration. Muscle degeneration and weakness in Cfl2 -/- mice coincided with normal developmental depletion of Cfl1 in myofibers. Agrawal et al. (2012) hypothesized that Cfl1 may initiate myofibrillogenesis, whereas Cfl2 is required for myofiber maintenance. </p><p>Rosen et al. (2020) found that knockin mice homozygous for the A35T mutation in Cfl2 associated with congenital myopathy in human were born at the expected mendelian ratio and were indistinguishable from wildtype. However, mutant mice began to display growth defects by postnatal day-3 (P3), and all died by P9. Mutant mice had lower body weight and shorter average length than controls and displayed disrupted early postnatal muscle maintenance and abnormal muscle structure. Western blot analysis revealed that Cfl2 protein was absent in several organs of mutant mice, including skeletal muscle, heart, brain, lung, and kidney, whereas skeletal actin (see 102610) was increased in skeletal muscle and heart. Further analysis demonstrated that a splicing defect in mutant mice resulted in significant upregulation of the short Cfl2 splice variant with concomitant and marked reduction of the full-length transcript. Similar alternative splicing was observed in human, with patients with the A35T mutation displaying marked reduction of the full-length CFL2 transcript. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>2 Selected Examples):</strong>
|
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</span>
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</h4>
|
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0001 NEMALINE MYOPATHY 7</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CFL2, ALA35THR
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<br />
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SNP: rs80358250,
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ClinVar: RCV000008638
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 sisters in a family of Middle Eastern origin, Agrawal et al. (2007) found that nemaline myopathy with some unusual histopathologic and clinical features (NEM7; 610687) was related to homozygous mutation of the CFL2 gene, 103G-A, predicted to result in an alanine-to-threonine substitution at residue 35 (A35T). An unaffected sib, both unaffected parents, and a number of other members of the extended family were heterozygous for this change. Extensive intermarriage, with multiple consanguinity loops, strongly suggested identity by descent for the 2 mutant alleles, a supposition that was supported by linkage studies using flanking markers. The mutation was ruled out in 282 unaffected control individuals, including 91 originating from the same geographic region and ethnic group as the family. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 NEMALINE MYOPATHY 7</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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CFL2, VAL7MET
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<br />
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SNP: rs397515451,
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ClinVar: RCV000054442
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In 2 Iraqi sisters, born of consanguineous parents, with nemaline myopathy-7 (NEM7; 610687), Ockeloen et al. (2012) identified a homozygous c.19G-A transition in exon 2 of the CFL2 gene, resulting in a val7-to-met (V7M) substitution at a highly conserved residue. The mutation was found by homozygosity mapping followed by candidate gene sequencing. The unaffected parents were heterozygous for the mutation, which was not found in 250 controls or in dbSNP. Functional studies were not performed. The girls had delayed walking and proximal and axial muscle weakness; muscle biopsy showed nemaline rods and abnormal protein aggregates. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
|
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<p class="mim-text-font">
|
|
Agrawal, P. B., Greenleaf, R. S., Tomczak, K. K., Lehtokari, V.-L., Wallgren-Pettersson, C., Wallefeld, W., Laing, N. G., Darras, B. T., Maciver, S. K., Dormitzer, P. R., Beggs, A. H.
|
|
<strong>Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2.</strong>
|
|
Am. J. Hum. Genet. 80: 162-167, 2007.
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[PubMed: 17160903]
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[Full Text: https://doi.org/10.1086/510402]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Agrawal, P. B., Joshi, M., Savic, T., Chen, Z., Beggs, A. H.
|
|
<strong>Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance.</strong>
|
|
Hum. Molec. Genet. 21: 2341-2356, 2012.
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[PubMed: 22343409]
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[Full Text: https://doi.org/10.1093/hmg/dds053]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Bamburg, J. R., McGough, A., Ono, S.
|
|
<strong>Putting a new twist on actin: ADF/cofilins modulate actin dynamics.</strong>
|
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Trends Cell Biol. 9: 364-370, 1999.
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[PubMed: 10461190]
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[Full Text: https://doi.org/10.1016/s0962-8924(99)01619-0]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Gillett, G. T., Fox, M. F., Rowe, P. S. N., Casimir, C. M., Povey, S.
|
|
<strong>Mapping of human non-muscle type cofilin (CFL1) to chromosome 11q13 and muscle-type cofilin (CFL2) to chromosome 14.</strong>
|
|
Ann. Hum. Genet. 60: 201-211, 1996.
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[PubMed: 8800436]
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