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<title>
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Entry
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- *600922 - MYOSIN LIGHT CHAIN KINASE; MYLK
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- OMIM
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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 style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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<p />
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</div>
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<div id="mimAlertBanner">
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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">*600922</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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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>
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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>
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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/600922">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=ENSG00000065534;t=ENST00000360304" 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=4638" 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=600922" 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=ENSG00000065534;t=ENST00000360304" 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_001321309,NM_053025,NM_053026,NM_053027,NM_053028,NM_053031,NM_053032,XM_011512860,XM_011512861,XM_017006469,XM_017006470,XM_017006471,XM_017006472,XM_017006473,XM_024453532,XM_024453534,XM_024453537,XM_047448182,XM_047448183,XM_047448184,XM_047448185,XM_047448186,XM_047448187,XM_047448188" 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_053025" 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=600922" 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=02952&isoform_id=02952_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/MYLK" 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/1103677,1262345,1834520,4322022,4322024,4322026,5771403,5852346,5852348,5852350,7239696,7239698,12597190,16950623,16950625,33304521,33337970,39636592,39636606,51476454,78070392,109138669,109138671,115583640,115583642,116008188,116008190,116008192,116008194,116283432,119599841,119599842,119599843,119599844,119599845,119599846,119599847,119599848,119599849,119599850,119599851,119599852,133777074,133777252,133777279,133777738,189067323,189069386,194373985,300669714,1008806537,1034633497,1034633499,1034633501,1034633503,1370484208,1370484210,1370484214,1370484216,1370484222,2217344006,2217344008,2217344011,2217344013,2217344016,2217344018,2217344020,2217344024,2462589987,2462589989,2462589991,2462589993,2462589995,2462589997,2462589999,2462590001,2462590003,2462590005,2462590007,2462590009,2462590011,2462590013,2462590015,2462590017,2462590019,2462590021,2462590023" 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/Q15746" 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=4638" 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=ENSG00000065534;t=ENST00000360304" 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=MYLK" 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=MYLK" 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+4638" 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/MYLK" 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:4638" 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/4638" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr3&hgg_gene=ENST00000360304.8&hgg_start=123610049&hgg_end=123884332&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:7590" 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:7590" 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=600922[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=600922[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/MYLK/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000065534" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=MYLK" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=MYLK" 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=MYLK" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MYLK&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/PA31388" 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:7590" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:894806" 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/MYLK#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:894806" 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/4638/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=4638" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-030131-8207" 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">
|
|
<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:4638" 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=MYLK&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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600922
|
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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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MYOSIN LIGHT CHAIN KINASE; MYLK
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</span>
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</h3>
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</div>
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<div>
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
MYOSIN LIGHT POLYPEPTIDE KINASE; MLCK
|
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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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<a id="includedTitles" class="mim-anchor"></a>
|
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<div>
|
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<p>
|
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<span class="mim-font">
|
|
Other entities represented in this entry:
|
|
</span>
|
|
</p>
|
|
</div>
|
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<div>
|
|
<span class="h3 mim-font">
|
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KINASE-RELATED PROTEIN, INCLUDED; KRP, INCLUDED
|
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</span>
|
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</div>
|
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<div>
|
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<span class="h4 mim-font">
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|
TELOKIN, INCLUDED
|
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</span>
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</div>
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</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MYLK" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MYLK</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/3/622?start=-3&limit=10&highlight=622">3q21.1</a>
|
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:123610049-123884332&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">3:123,610,049-123,884,332</a> </span>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<p>The contraction of smooth muscle begins with the phosphorylation of the light chain of myosin (e.g., MYL2; <a href="/entry/160781">160781</a>), a reaction catalyzed by myosin light chain kinase that is itself activated by the binding of calcium-calmodulin (see <a href="/entry/114180">114180</a>). This key enzyme in muscle contraction, which exists in both nonmuscle and smooth muscle isoforms, has been shown by immunohistology to be present in neurons and glia.</p>
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<p><a href="#8" class="mim-tip-reference" title="Potier, M.-C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W. G. <strong>The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3cen-q21.</strong> Genomics 29: 562-570, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575746</a>] [<a href="https://doi.org/10.1006/geno.1995.9965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575746">Potier et al. (1995)</a> cloned the cDNA for human myosin light chain kinase, which they symbolized MLCK, from hippocampus and showed that it encodes a protein sequence 95% similar to smooth muscle MLCKs but less than 60% similar to skeletal muscle MLCKs. The cDNA clone detected 2 RNA transcripts in human frontal and entorhinal cortex, in hippocampus, and in jejunum, one corresponding to MLCK and the other probably to telokin (kinase-related protein), the carboxy-terminal 154 codons of MLCK expressed as an independent protein in smooth muscle. The authors found that levels of expression were lower in brain than in smooth muscle. <a href="#8" class="mim-tip-reference" title="Potier, M.-C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W. G. <strong>The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3cen-q21.</strong> Genomics 29: 562-570, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575746</a>] [<a href="https://doi.org/10.1006/geno.1995.9965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575746">Potier et al. (1995)</a> showed that the protein sequence contains a motif of 28 or 24 residues repeated 5 times, the second repeat ending with the putative methionine start codon. These repeats overlap with the second previously reported module of 12 residues repeated 5 times in the human sequence. In addition, the acidic C terminus of all MLCKs from both brain and smooth muscle resembles the C terminus of tubulins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575746" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Garcia, J. G., Lazar, V., Gilbert-McClain, L. I., Gallagher, P. J., Verin, A. D. <strong>Myosin light chain kinase in endothelium: molecular cloning and regulation.</strong> Am. J. Resp. Cell Molec. Biol. 16: 489-494, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9160829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9160829</a>] [<a href="https://doi.org/10.1165/ajrcmb.16.5.9160829" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9160829">Garcia et al. (1997)</a> cloned a human endothelial nonmuscle MLCK cDNA encoding a deduced 1,914-amino acid protein with a calculated molecular mass of 210 kD. The protein contains 9 C2-type immunoglobulin-like homology domains, an SH2-binding domain, and a single tyrosine phosphorylation site in the CaM-binding region. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9160829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Lazar, V., Garcia, J. G. N. <strong>A single human myosin light chain kinase gene (MLCK; MYLK) transcribes multiple nonmuscle isoforms.</strong> Genomics 57: 256-267, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10198165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10198165</a>] [<a href="https://doi.org/10.1006/geno.1999.5774" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10198165">Lazar and Garcia (1999)</a> reported the cloning of several additional nonmuscle variants of MLCK by RT-PCR from umbilical vein endothelial cell RNA. They noted that the full-length MLCK gene contains at least 2 additional promoters that initiate transcription of 2 shorter isoforms. The shorter isoforms include smooth muscle (SM) MLCK, a 5.8-kb transcript that encodes a deduced 130-kD protein, and a 2.6-kb transcript that encodes the deduced kinase-related protein. KRP contains only the final C2 immunoglobulin-like domain. Northern blot analysis detected the full-length, 8.1-kb nonmuscle MLCK isoform in all tissues examined except skeletal muscle, with highest expression in lung, placenta, liver, and kidney, and intermediate expression in heart, brain, and pancreas. The transcript was also detected in fetal lung and kidney, with lower expression in fetal brain and liver. The 5.8-kb SM-MLCK transcript was detected in all adult tissues except liver, and in fetal lung and kidney, with weaker expression in fetal brain and liver. <a href="#6" class="mim-tip-reference" title="Lazar, V., Garcia, J. G. N. <strong>A single human myosin light chain kinase gene (MLCK; MYLK) transcribes multiple nonmuscle isoforms.</strong> Genomics 57: 256-267, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10198165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10198165</a>] [<a href="https://doi.org/10.1006/geno.1999.5774" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10198165">Lazar and Garcia (1999)</a> also identified several isoforms that resulted from in-frame internal deletions and were widely expressed in adult and fetal tissues. The dominant isoform, which they designated MLCK2, contains a deletion of residues 437-505, causing loss of the tyrosine phosphorylation site and the SH2 binding site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10198165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Watterson, D. M., Schavocky, J. P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V. P., Van Eldik, L. J., Haiech, J. <strong>Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.</strong> J. Cell. Biochem. 75: 481-491, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10536370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10536370</a>]" pmid="10536370">Watterson et al. (1999)</a> cloned kinase-related protein from a genomic DNA library by PCR using primers based on a previously isolated human placenta KRP sequence. They noted that the human and chicken KRP proteins share 80% sequence identity. Northern blot analysis detected a 2.7-kb KRP transcript in all adult and fetal tissues examined, with highest expression in placenta, brain, heart, colon, small intestine, and fetal small intestine. Probing with a sequence common to the 3 main start site variants, <a href="#12" class="mim-tip-reference" title="Watterson, D. M., Schavocky, J. P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V. P., Van Eldik, L. J., Haiech, J. <strong>Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.</strong> J. Cell. Biochem. 75: 481-491, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10536370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10536370</a>]" pmid="10536370">Watterson et al. (1999)</a> identified transcripts of 2.7 and 5.5 kb in heart, and of 2.7, 5.5, and 9.0 kb in placenta. By immunohistochemical analysis of adult and fetal heart sections, they found both full-length MLCK and the shorter KRP in cardiac muscle and in the smooth muscle layer of major blood vessels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10536370" 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 immunohistochemistry in human embryonic specimens of small intestine and bladder, <a href="#4" class="mim-tip-reference" title="Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M. <strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong> Am. J. Hum. Genet. 101: 123-129, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28602422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28602422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28602422[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.ajhg.2017.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28602422">Halim et al. (2017)</a> observed MYLK localized in smooth muscle cells of all muscular layers of the intestine and bladder, from weeks 9 to 22 of development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28602422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Watterson, D. M., Schavocky, J. P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V. P., Van Eldik, L. J., Haiech, J. <strong>Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.</strong> J. Cell. Biochem. 75: 481-491, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10536370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10536370</a>]" pmid="10536370">Watterson et al. (1999)</a> noted that the various isoforms of MLCK are encoded by differential use of 31 coding exons. They also noted that KRP is derived from the last 3 exons spanning approximately 6.0 kb of the MLCK gene, and that the transcription initiation site for KRP lies within the intron preceding exon 29. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10536370" 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 PCR and Southern blotting using 2 somatic cell hybrid panels, <a href="#8" class="mim-tip-reference" title="Potier, M.-C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W. G. <strong>The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3cen-q21.</strong> Genomics 29: 562-570, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575746</a>] [<a href="https://doi.org/10.1006/geno.1995.9965" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8575746">Potier et al. (1995)</a> localized the MLCK gene to chromosome 3cen-q21. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575746" 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 analysis of YAC clones, <a href="#2" class="mim-tip-reference" title="Giorgi, D., Brand-Arpon, V., Rouquier, S. <strong>The functional myosin light chain kinase (MYLK) gene localizes with marker D3S3552 on human chromosome 3q21 in a greater than 5-Mb yeast artificial chromosome region and is not linked to olfactory receptor genes.</strong> Cytogenet. Cell Genet. 92: 85-88, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11306802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11306802</a>] [<a href="https://doi.org/10.1159/000056874" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11306802">Giorgi et al. (2001)</a> colocalized the MYLK gene with D3S3552 in a greater than 5-Mb region of chromosome 3q21. They confirmed the location of a pseudogene, MYLKP, to chromosome 3p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11306802" 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="Walker, L. A., MacDonald, J. A., Liu, X., Nakamoto, R. K., Haystead, T. A. J., Somlyo, A. V., Somlyo, A. P. <strong>Site-specific phosphorylation and point mutations of telokin modulate its Ca(2+)-desensitizing effect in smooth muscle.</strong> J. Biol. Chem. 276: 24519-24524, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11346659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11346659</a>] [<a href="https://doi.org/10.1074/jbc.M103560200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11346659">Walker et al. (2001)</a> studied the KRP variant in the rabbit and demonstrated that recombinant rabbit telokin could relax telokin-depleted rabbit ileal smooth muscle in a dose-dependent manner. Mutation analysis revealed that ser13 is the phosphorylation site associated with cyclic nucleotide-induced Ca(2+)-independent relaxation of smooth muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11346659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Goeckeler, Z. M., Masaracchia, R. A., Zeng, Q., Chew, T.-L., Gallagher, P., Wysolmerski, R. B. <strong>Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2.</strong> J. Biol. Chem. 275: 18366-18374, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748018</a>] [<a href="https://doi.org/10.1074/jbc.M001339200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10748018">Goeckeler et al. (2000)</a> found that human PAK2 (<a href="/entry/605022">605022</a>) phosphorylated MLCK on ser439 and ser991, which downregulated MLCK activity and inhibited MLCK-catalyzed phosphorylation of MYL2. Only ser439 of MLCK was phosphorylated by PAK2 in the presence of Ca(2+)/calmodulin. PAK2-catalyzed MLCK phosphorylation limited development of isometric tension in endothelial cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10748018" 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><strong><em>Familial Thoracic Aortic Aneurysm 7</em></strong></p><p>
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<a href="#11" class="mim-tip-reference" title="Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M. <strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong> Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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.ajhg.2010.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21055718">Wang et al. (2010)</a> analyzed the MYLK gene in 193 probands from unrelated families in which 2 or more members had thoracic aortic aneurysms or dissections. They identified 2 heterozygous variants (<a href="#0001">600922.0001</a> and <a href="#0002">600922.0002</a>) that segregated with aortic dissections (AAT7; <a href="/entry/613780">613780</a>) in 2 families, respectively, and were not found in 188 ethnically matched controls. Incomplete penetrance was observed in 1 of the families. Three additional MYLK variants were identified in 3 unrelated probands that were not detected in controls, but family members were not available for segregation analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21055718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a large Swedish family segregating autosomal dominant aortic dissection, <a href="#5" class="mim-tip-reference" title="Hannuksela, M., Stattin, E.-L., Klar, J., Ameur, A., Johansson, B., Sorensen, K., Carlberg, B. <strong>A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description.</strong> BMC Med. Genet. 17: 61, 2016. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27586135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27586135</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27586135[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/s12881-016-0326-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27586135">Hannuksela et al. (2016)</a> identified a 2-bp deletion in the MYLK gene causing a premature termination codon (S1091X) that was present in all 5 affected individuals as well as 9 unaffected family members. In addition, a family member with an intramural hematoma of the descending aorta did not carry the mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27586135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Luyckx, I., Proost, D., Hendriks, J. M. H., Saenen, J., Van Craenenbroeck, E. M., Vermeulen, T., Peeters, N., Wuyts, W., Rodrigus, I., Verstraeten, A., Van Laer, L., Loeys, B. L. <strong>Two novel MYLK nonsense mutations causing thoracic aortic aneurysms/dissections in patients without apparent family history.</strong> Clin. Genet. 92: 444-446, 2017. Note: Erratum: Clin. Genet. 93: 938 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28401540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28401540</a>] [<a href="https://doi.org/10.1111/cge.13000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28401540">Luyckx et al. (2017)</a> screened a cohort of 358 cases of aortic aneurysmal disease for mutations in thoracic aortic aneurysm-associated genes and identified 2 probands who were heterozygous for nonsense mutations in the MYLK gene (Q1458X and R1487X). In the first family, the Q1458X mutation was also identified in the patient's unaffected father, and in the second family, the R1487X mutation was also present in the proband's unaffected half brother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28401540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a large consanguineous Arab family with thoracic aortic aneurysm and dissection, <a href="#9" class="mim-tip-reference" title="Shalata, A., Mahroom, M., Milewicz, D. M., Limin, G., Kassum, F., Badarna, K., Tarabeih, N., Assy, N., Fell, R., Cohen, H., Nashashibi, M., Livoff, A., Azab, M., Habib, G., Geiger, D., Weissbrod, O., Nseir, W. <strong>Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.</strong> Orphanet J. Rare Dis. 13: 41, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29544503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29544503</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29544503[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/s13023-018-0769-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29544503">Shalata et al. (2018)</a> identified a missense mutation in the MYLK gene (A1491S; <a href="#0005">600922.0005</a>) that was not found in ethnically matched controls or public variant databases. The mutation was present in homozygosity in 6 severely affected family members and in heterozygosity in 3 patients with a later age of onset; the mutation was also present in heterozygosity in 16 asymptomatic family members. The authors stated that the most appropriate designation for the mode of inheritance in this family was autosomal dominant with incomplete penetrance. Comprehensive medical history and clinical data analysis of homozygous individuals excluded congenital bladder or intestine involvement; there was thus no evidence for megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS; see below) in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29544503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome 1</em></strong></p><p>
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In 2 unrelated consanguineous families in which 5 children had died with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; <a href="/entry/249210">249210</a>), <a href="#4" class="mim-tip-reference" title="Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M. <strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong> Am. J. Hum. Genet. 101: 123-129, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28602422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28602422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28602422[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.ajhg.2017.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28602422">Halim et al. (2017)</a> identified homozygosity for mutations in the MYLK gene: a 7-bp duplication (<a href="#0003">600922.0003</a>) and a splicing variant (<a href="#0004">600922.0004</a>), respectively. The unaffected parents in each family were heterozygous for the mutation. Noting that heterozygous mutations in MYLK had previously been associated with aortic aneurysm, the authors stated that they were not aware of any cardiac problems in the unaffected parents and suggested that other kinases might salvage smooth muscle contraction of extravisceral organs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28602422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M. <strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong> Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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.ajhg.2010.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21055718">Wang et al. (2010)</a> studied mice with smooth muscle cell-specific knockdown of Mylk and observed increased pools of proteoglycans in the aortic media compared to controls, along with increased expression of lumican (<a href="/entry/600616">600616</a>) and decorin (<a href="/entry/125255">125255</a>). Increased collagen staining in the adventitial layer and increased type III collagen (COL3A1; <a href="/entry/120180">120180</a>) expression were also identified. In addition, expression of the elastin-degrading metalloproteinase MMP2 (<a href="/entry/120360">120360</a>) was also increased in the aortas of the mice, although elastic fibers were not degraded in the aortic media. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21055718" 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 3 affected members of a family (family TAA026) with aortic aneurysm and dissection (AAT7; <a href="/entry/613780">613780</a>), <a href="#11" class="mim-tip-reference" title="Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M. <strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong> Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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.ajhg.2010.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21055718">Wang et al. (2010)</a> identified heterozygosity for a 5275T-C transition in the MYLK gene, resulting in a ser1759-to-pro (S1759P) substitution in the alpha-helix of the calmodulin-binding sequence that was predicted to cause loss of MLCK function by altering calmodulin binding. The mutation segregated with disease in the family and was not found in 188 ethnically matched controls. Transfection studies in COS-7 cells showed minimal endogenous expression of MLCK, and immunoprecipitation studies revealed that binding to calmodulin was abolished with the S1759P mutant. Analysis of kinase activity showed a 6-fold reduction for S1759P compared to wildtype. <a href="#11" class="mim-tip-reference" title="Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M. <strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong> Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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.ajhg.2010.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21055718">Wang et al. (2010)</a> noted that affected individuals had acute aortic dissections with little to no aortic enlargement. Examination of ascending aortic tissue from 2 family members showed medial degeneration of the aorta and a significant increase in small arteries in the medial layer. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21055718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs387906782 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387906782;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs387906782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs387906782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000023045 OR RCV001798012" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023045, RCV001798012" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023045...</a>
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<p>In a 51-year-old father and his 18-year-old son (family TAA400) with aortic aneurysm and dissection (AAT7; <a href="/entry/613780">613780</a>), <a href="#11" class="mim-tip-reference" title="Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M. <strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong> Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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.ajhg.2010.10.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21055718">Wang et al. (2010)</a> identified heterozygosity for a 4438C-T transition in the MYLK gene, resulting in an arg1480-to-ter (R1480X) substitution that would lead to either nonsense-mediated decay or a truncated protein missing the kinase and calmodulin-binding domains, and was therefore predicted to disrupt kinase activity but not to disturb telokin expression. The father had undergone a type A dissection at 37 years of age, and the son had a type B dissection at 16 years of age. The R1480X mutation was also detected in 5 asymptomatic family members, with ages ranging from 59 years to 76 years. The mutation was not found in 188 ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21055718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553787823 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553787823;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1553787823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1553787823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000508615 OR RCV001804175" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000508615, RCV001804175" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000508615...</a>
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<p>In a deceased sister and brother of North African origin (family 1) with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; <a href="/entry/249210">249210</a>), <a href="#4" class="mim-tip-reference" title="Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M. <strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong> Am. J. Hum. Genet. 101: 123-129, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28602422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28602422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28602422[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.ajhg.2017.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28602422">Halim et al. (2017)</a> identified homozygosity for a 7-bp duplication (c.3838_3844dupGAAAGCG, NM_053025.3) in exon 23 of the MYLK gene,, causing a frameshift predicted to result in a premature termination codon (Glu1282GlyfsTer51). The unaffected consanguineous parents were heterozygous for the mutation, whereas an unaffected younger sister did not carry the mutation; DNA was unavailable from an older sister, who died in utero with a distended bladder. Immunostained specimens of patient small intestine and bladder showed no MYLK signal. The structure and cellular constituents of the bladder and intestine showed no apparent pathologic abnormalities compared to age-matched control samples, suggesting that although MYLK is instrumental for proper functioning of smooth muscle cells, its presence is not required for maintaining the structural architecture of those organs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28602422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1553787619 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1553787619;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1553787619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1553787619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000508669 OR RCV001804176" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000508669, RCV001804176" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000508669...</a>
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<p>In a girl of Indian origin (family 2) who died with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; <a href="/entry/249210">249210</a>), <a href="#4" class="mim-tip-reference" title="Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M. <strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong> Am. J. Hum. Genet. 101: 123-129, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28602422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28602422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28602422[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.ajhg.2017.05.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28602422">Halim et al. (2017)</a> identified homozygosity for a splicing mutation (c.3985+5C-A, NM_053025.3) in intron 23 of the MYLK gene, for which her unaffected consanguineous parents were heterozygous. DNA was not available from a younger sister who also died with MMIHS, or from a younger brother who was unaffected. Splicing assays revealed that the mutant construct eliminated all transcription products observed with wildtype MYLK and produced a band with the same size as empty vector, indicating likely skipping of exon 23 with an early stop codon at the beginning of exon 24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28602422" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1576422965 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1576422965;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1576422965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1576422965" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a large consanguineous Arab family with thoracic aortic aneurysm and dissection (AAT7; <a href="/entry/613780">613780</a>), <a href="#9" class="mim-tip-reference" title="Shalata, A., Mahroom, M., Milewicz, D. M., Limin, G., Kassum, F., Badarna, K., Tarabeih, N., Assy, N., Fell, R., Cohen, H., Nashashibi, M., Livoff, A., Azab, M., Habib, G., Geiger, D., Weissbrod, O., Nseir, W. <strong>Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.</strong> Orphanet J. Rare Dis. 13: 41, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29544503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29544503</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29544503[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/s13023-018-0769-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29544503">Shalata et al. (2018)</a> identified a c.4471G-T transversion in exon 27 of the MYLK gene, resulting in an ala1491-to-ser (A1491S) substitution at a conserved residue within the kinase domain. Functional analysis in transfected HeLa cells showed a significant reduction in kinase activity with the A1491S mutant compared to wildtype MYLK. The mutation was not found in 100 ethnically matched controls or in the ExAC or 1000 Genomes Project databases. The mutation was present in homozygosity in 6 severely affected family members with early-onset disease, 5 of whom were deceased, and was found in heterozygosity in 3 individuals with a later age of onset, 1 of whom was deceased; the mutation was also present in heterozygosity in 16 asymptomatic family members. The authors stated that the most appropriate designation for the mode of inheritance in this family was autosomal dominant with incomplete penetrance. In addition, the authors noted that comprehensive medical history and clinical data analysis of homozygotes excluded congenital bladder or intestine involvement in this family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29544503" 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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Garcia, J. G., Lazar, V., Gilbert-McClain, L. I., Gallagher, P. J., Verin, A. D.
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[<a href="https://doi.org/10.1165/ajrcmb.16.5.9160829" target="_blank">Full Text</a>]
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<a id="Giorgi2001" class="mim-anchor"></a>
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Giorgi, D., Brand-Arpon, V., Rouquier, S.
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<strong>The functional myosin light chain kinase (MYLK) gene localizes with marker D3S3552 on human chromosome 3q21 in a greater than 5-Mb yeast artificial chromosome region and is not linked to olfactory receptor genes.</strong>
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Cytogenet. Cell Genet. 92: 85-88, 2001.
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[<a href="https://doi.org/10.1159/000056874" target="_blank">Full Text</a>]
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Goeckeler, Z. M., Masaracchia, R. A., Zeng, Q., Chew, T.-L., Gallagher, P., Wysolmerski, R. B.
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<strong>Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10748018/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10748018</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10748018" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M001339200" target="_blank">Full Text</a>]
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<a id="Halim2017" class="mim-anchor"></a>
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Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M.
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<strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong>
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Am. J. Hum. Genet. 101: 123-129, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28602422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28602422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28602422[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=28602422" 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.ajhg.2017.05.011" target="_blank">Full Text</a>]
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<a id="Hannuksela2016" class="mim-anchor"></a>
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Hannuksela, M., Stattin, E.-L., Klar, J., Ameur, A., Johansson, B., Sorensen, K., Carlberg, B.
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<strong>A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description.</strong>
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BMC Med. Genet. 17: 61, 2016. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27586135/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27586135</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27586135[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=27586135" 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/s12881-016-0326-y" target="_blank">Full Text</a>]
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Lazar, V., Garcia, J. G. N.
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<strong>A single human myosin light chain kinase gene (MLCK; MYLK) transcribes multiple nonmuscle isoforms.</strong>
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Genomics 57: 256-267, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10198165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10198165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10198165" 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/10.1006/geno.1999.5774" target="_blank">Full Text</a>]
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<a id="Luyckx2017" class="mim-anchor"></a>
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Luyckx, I., Proost, D., Hendriks, J. M. H., Saenen, J., Van Craenenbroeck, E. M., Vermeulen, T., Peeters, N., Wuyts, W., Rodrigus, I., Verstraeten, A., Van Laer, L., Loeys, B. L.
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<strong>Two novel MYLK nonsense mutations causing thoracic aortic aneurysms/dissections in patients without apparent family history.</strong>
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Clin. Genet. 92: 444-446, 2017. Note: Erratum: Clin. Genet. 93: 938 only, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28401540/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28401540</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28401540" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.13000" target="_blank">Full Text</a>]
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<a id="Potier1995" class="mim-anchor"></a>
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Potier, M.-C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W. G.
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<strong>The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3cen-q21.</strong>
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Genomics 29: 562-570, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8575746/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8575746</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8575746" 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/10.1006/geno.1995.9965" target="_blank">Full Text</a>]
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<a id="Shalata2018" class="mim-anchor"></a>
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Shalata, A., Mahroom, M., Milewicz, D. M., Limin, G., Kassum, F., Badarna, K., Tarabeih, N., Assy, N., Fell, R., Cohen, H., Nashashibi, M., Livoff, A., Azab, M., Habib, G., Geiger, D., Weissbrod, O., Nseir, W.
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<strong>Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.</strong>
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Orphanet J. Rare Dis. 13: 41, 2018. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29544503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29544503</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29544503[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=29544503" 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/s13023-018-0769-7" target="_blank">Full Text</a>]
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Walker, L. A., MacDonald, J. A., Liu, X., Nakamoto, R. K., Haystead, T. A. J., Somlyo, A. V., Somlyo, A. P.
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<strong>Site-specific phosphorylation and point mutations of telokin modulate its Ca(2+)-desensitizing effect in smooth muscle.</strong>
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J. Biol. Chem. 276: 24519-24524, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11346659/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11346659</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11346659" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.M103560200" target="_blank">Full Text</a>]
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Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M.
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<strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong>
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Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21055718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21055718</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21055718[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=21055718" 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.ajhg.2010.10.006" target="_blank">Full Text</a>]
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Watterson, D. M., Schavocky, J. P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V. P., Van Eldik, L. J., Haiech, J.
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<strong>Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.</strong>
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J. Cell. Biochem. 75: 481-491, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10536370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10536370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10536370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Marla J. F. O'Neill - updated : 11/07/2019
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Bao Lige - updated : 04/18/2019<br>Marla J. F. O'Neill - updated : 2/24/2011<br>Patricia A. Hartz - updated : 5/24/2002<br>Joanna S. Amberger - updated : 6/22/2001
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<span class="mim-text-font">
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Victor A. McKusick : 11/7/1995
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carol : 05/27/2021<br>carol : 03/17/2020<br>carol : 12/23/2019<br>alopez : 11/07/2019<br>mgross : 04/18/2019<br>carol : 12/19/2013<br>wwang : 4/28/2011<br>wwang : 2/28/2011<br>terry : 2/24/2011<br>wwang : 12/20/2005<br>carol : 5/30/2002<br>carol : 5/29/2002<br>carol : 5/29/2002<br>terry : 5/24/2002<br>mcapotos : 6/25/2001<br>joanna : 6/22/2001<br>alopez : 4/30/1999<br>alopez : 3/26/1999<br>jenny : 4/4/1997<br>mark : 11/9/1995<br>terry : 11/7/1995
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 600922
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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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MYOSIN LIGHT CHAIN KINASE; MYLK
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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MYOSIN LIGHT POLYPEPTIDE KINASE; MLCK
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div>
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<p>
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<span class="mim-font">
|
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Other entities represented in this entry:
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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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KINASE-RELATED PROTEIN, INCLUDED; KRP, INCLUDED
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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TELOKIN, INCLUDED
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</span>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: MYLK</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: 3q21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:123,610,049-123,884,332 </span>
|
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</em>
|
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</strong>
|
|
<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>
|
|
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>
|
|
Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
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</th>
|
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<th>
|
|
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>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
3q21.1
|
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</span>
|
|
</td>
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<td>
|
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<span class="mim-font">
|
|
Aortic aneurysm, familial thoracic 7
|
|
</span>
|
|
</td>
|
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<td>
|
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<span class="mim-font">
|
|
613780
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Megacystis-microcolon-intestinal hypoperistalsis syndrome 1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
249210
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</h4>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>The contraction of smooth muscle begins with the phosphorylation of the light chain of myosin (e.g., MYL2; 160781), a reaction catalyzed by myosin light chain kinase that is itself activated by the binding of calcium-calmodulin (see 114180). This key enzyme in muscle contraction, which exists in both nonmuscle and smooth muscle isoforms, has been shown by immunohistology to be present in neurons and glia.</p>
|
|
</span>
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<div>
|
|
<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>Cloning and Expression</strong>
|
|
</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>Potier et al. (1995) cloned the cDNA for human myosin light chain kinase, which they symbolized MLCK, from hippocampus and showed that it encodes a protein sequence 95% similar to smooth muscle MLCKs but less than 60% similar to skeletal muscle MLCKs. The cDNA clone detected 2 RNA transcripts in human frontal and entorhinal cortex, in hippocampus, and in jejunum, one corresponding to MLCK and the other probably to telokin (kinase-related protein), the carboxy-terminal 154 codons of MLCK expressed as an independent protein in smooth muscle. The authors found that levels of expression were lower in brain than in smooth muscle. Potier et al. (1995) showed that the protein sequence contains a motif of 28 or 24 residues repeated 5 times, the second repeat ending with the putative methionine start codon. These repeats overlap with the second previously reported module of 12 residues repeated 5 times in the human sequence. In addition, the acidic C terminus of all MLCKs from both brain and smooth muscle resembles the C terminus of tubulins. </p><p>Garcia et al. (1997) cloned a human endothelial nonmuscle MLCK cDNA encoding a deduced 1,914-amino acid protein with a calculated molecular mass of 210 kD. The protein contains 9 C2-type immunoglobulin-like homology domains, an SH2-binding domain, and a single tyrosine phosphorylation site in the CaM-binding region. </p><p>Lazar and Garcia (1999) reported the cloning of several additional nonmuscle variants of MLCK by RT-PCR from umbilical vein endothelial cell RNA. They noted that the full-length MLCK gene contains at least 2 additional promoters that initiate transcription of 2 shorter isoforms. The shorter isoforms include smooth muscle (SM) MLCK, a 5.8-kb transcript that encodes a deduced 130-kD protein, and a 2.6-kb transcript that encodes the deduced kinase-related protein. KRP contains only the final C2 immunoglobulin-like domain. Northern blot analysis detected the full-length, 8.1-kb nonmuscle MLCK isoform in all tissues examined except skeletal muscle, with highest expression in lung, placenta, liver, and kidney, and intermediate expression in heart, brain, and pancreas. The transcript was also detected in fetal lung and kidney, with lower expression in fetal brain and liver. The 5.8-kb SM-MLCK transcript was detected in all adult tissues except liver, and in fetal lung and kidney, with weaker expression in fetal brain and liver. Lazar and Garcia (1999) also identified several isoforms that resulted from in-frame internal deletions and were widely expressed in adult and fetal tissues. The dominant isoform, which they designated MLCK2, contains a deletion of residues 437-505, causing loss of the tyrosine phosphorylation site and the SH2 binding site. </p><p>Watterson et al. (1999) cloned kinase-related protein from a genomic DNA library by PCR using primers based on a previously isolated human placenta KRP sequence. They noted that the human and chicken KRP proteins share 80% sequence identity. Northern blot analysis detected a 2.7-kb KRP transcript in all adult and fetal tissues examined, with highest expression in placenta, brain, heart, colon, small intestine, and fetal small intestine. Probing with a sequence common to the 3 main start site variants, Watterson et al. (1999) identified transcripts of 2.7 and 5.5 kb in heart, and of 2.7, 5.5, and 9.0 kb in placenta. By immunohistochemical analysis of adult and fetal heart sections, they found both full-length MLCK and the shorter KRP in cardiac muscle and in the smooth muscle layer of major blood vessels. </p><p>By immunohistochemistry in human embryonic specimens of small intestine and bladder, Halim et al. (2017) observed MYLK localized in smooth muscle cells of all muscular layers of the intestine and bladder, from weeks 9 to 22 of development. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Watterson et al. (1999) noted that the various isoforms of MLCK are encoded by differential use of 31 coding exons. They also noted that KRP is derived from the last 3 exons spanning approximately 6.0 kb of the MLCK gene, and that the transcription initiation site for KRP lies within the intron preceding exon 29. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>By PCR and Southern blotting using 2 somatic cell hybrid panels, Potier et al. (1995) localized the MLCK gene to chromosome 3cen-q21. </p><p>By analysis of YAC clones, Giorgi et al. (2001) colocalized the MYLK gene with D3S3552 in a greater than 5-Mb region of chromosome 3q21. They confirmed the location of a pseudogene, MYLKP, to chromosome 3p13. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Walker et al. (2001) studied the KRP variant in the rabbit and demonstrated that recombinant rabbit telokin could relax telokin-depleted rabbit ileal smooth muscle in a dose-dependent manner. Mutation analysis revealed that ser13 is the phosphorylation site associated with cyclic nucleotide-induced Ca(2+)-independent relaxation of smooth muscle. </p><p>Goeckeler et al. (2000) found that human PAK2 (605022) phosphorylated MLCK on ser439 and ser991, which downregulated MLCK activity and inhibited MLCK-catalyzed phosphorylation of MYL2. Only ser439 of MLCK was phosphorylated by PAK2 in the presence of Ca(2+)/calmodulin. PAK2-catalyzed MLCK phosphorylation limited development of isometric tension in endothelial cells. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Familial Thoracic Aortic Aneurysm 7</em></strong></p><p>
|
|
Wang et al. (2010) analyzed the MYLK gene in 193 probands from unrelated families in which 2 or more members had thoracic aortic aneurysms or dissections. They identified 2 heterozygous variants (600922.0001 and 600922.0002) that segregated with aortic dissections (AAT7; 613780) in 2 families, respectively, and were not found in 188 ethnically matched controls. Incomplete penetrance was observed in 1 of the families. Three additional MYLK variants were identified in 3 unrelated probands that were not detected in controls, but family members were not available for segregation analysis. </p><p>In a large Swedish family segregating autosomal dominant aortic dissection, Hannuksela et al. (2016) identified a 2-bp deletion in the MYLK gene causing a premature termination codon (S1091X) that was present in all 5 affected individuals as well as 9 unaffected family members. In addition, a family member with an intramural hematoma of the descending aorta did not carry the mutation. </p><p>Luyckx et al. (2017) screened a cohort of 358 cases of aortic aneurysmal disease for mutations in thoracic aortic aneurysm-associated genes and identified 2 probands who were heterozygous for nonsense mutations in the MYLK gene (Q1458X and R1487X). In the first family, the Q1458X mutation was also identified in the patient's unaffected father, and in the second family, the R1487X mutation was also present in the proband's unaffected half brother. </p><p>In a large consanguineous Arab family with thoracic aortic aneurysm and dissection, Shalata et al. (2018) identified a missense mutation in the MYLK gene (A1491S; 600922.0005) that was not found in ethnically matched controls or public variant databases. The mutation was present in homozygosity in 6 severely affected family members and in heterozygosity in 3 patients with a later age of onset; the mutation was also present in heterozygosity in 16 asymptomatic family members. The authors stated that the most appropriate designation for the mode of inheritance in this family was autosomal dominant with incomplete penetrance. Comprehensive medical history and clinical data analysis of homozygous individuals excluded congenital bladder or intestine involvement; there was thus no evidence for megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS; see below) in this family. </p><p><strong><em>Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome 1</em></strong></p><p>
|
|
In 2 unrelated consanguineous families in which 5 children had died with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; 249210), Halim et al. (2017) identified homozygosity for mutations in the MYLK gene: a 7-bp duplication (600922.0003) and a splicing variant (600922.0004), respectively. The unaffected parents in each family were heterozygous for the mutation. Noting that heterozygous mutations in MYLK had previously been associated with aortic aneurysm, the authors stated that they were not aware of any cardiac problems in the unaffected parents and suggested that other kinases might salvage smooth muscle contraction of extravisceral organs. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Wang et al. (2010) studied mice with smooth muscle cell-specific knockdown of Mylk and observed increased pools of proteoglycans in the aortic media compared to controls, along with increased expression of lumican (600616) and decorin (125255). Increased collagen staining in the adventitial layer and increased type III collagen (COL3A1; 120180) expression were also identified. In addition, expression of the elastin-degrading metalloproteinase MMP2 (120360) was also increased in the aortas of the mice, although elastic fibers were not degraded in the aortic media. </p>
|
|
</span>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>5 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 AORTIC ANEURYSM, FAMILIAL THORACIC 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MYLK, SER1759PRO
|
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|
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<br />
|
|
|
|
SNP: rs387906781,
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|
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ClinVar: RCV000023044, RCV000603875
|
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|
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</span>
|
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</div>
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|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 affected members of a family (family TAA026) with aortic aneurysm and dissection (AAT7; 613780), Wang et al. (2010) identified heterozygosity for a 5275T-C transition in the MYLK gene, resulting in a ser1759-to-pro (S1759P) substitution in the alpha-helix of the calmodulin-binding sequence that was predicted to cause loss of MLCK function by altering calmodulin binding. The mutation segregated with disease in the family and was not found in 188 ethnically matched controls. Transfection studies in COS-7 cells showed minimal endogenous expression of MLCK, and immunoprecipitation studies revealed that binding to calmodulin was abolished with the S1759P mutant. Analysis of kinase activity showed a 6-fold reduction for S1759P compared to wildtype. Wang et al. (2010) noted that affected individuals had acute aortic dissections with little to no aortic enlargement. Examination of ascending aortic tissue from 2 family members showed medial degeneration of the aorta and a significant increase in small arteries in the medial layer. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 AORTIC ANEURYSM, FAMILIAL THORACIC 7</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
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<span class="mim-text-font">
|
|
|
|
MYLK, ARG1480TER
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|
|
<br />
|
|
|
|
SNP: rs387906782,
|
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|
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ClinVar: RCV000023045, RCV001798012
|
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|
|
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 51-year-old father and his 18-year-old son (family TAA400) with aortic aneurysm and dissection (AAT7; 613780), Wang et al. (2010) identified heterozygosity for a 4438C-T transition in the MYLK gene, resulting in an arg1480-to-ter (R1480X) substitution that would lead to either nonsense-mediated decay or a truncated protein missing the kinase and calmodulin-binding domains, and was therefore predicted to disrupt kinase activity but not to disturb telokin expression. The father had undergone a type A dissection at 37 years of age, and the son had a type B dissection at 16 years of age. The R1480X mutation was also detected in 5 asymptomatic family members, with ages ranging from 59 years to 76 years. The mutation was not found in 188 ethnically matched controls. </p>
|
|
</span>
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</div>
|
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|
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<div>
|
|
<br />
|
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</div>
|
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|
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</div>
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<div>
|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 1</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
MYLK, 7-BP DUP, 3838GAAAGCG
|
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|
|
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<br />
|
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|
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SNP: rs1553787823,
|
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|
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ClinVar: RCV000508615, RCV001804175
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|
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</span>
|
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</div>
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<p>In a deceased sister and brother of North African origin (family 1) with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; 249210), Halim et al. (2017) identified homozygosity for a 7-bp duplication (c.3838_3844dupGAAAGCG, NM_053025.3) in exon 23 of the MYLK gene,, causing a frameshift predicted to result in a premature termination codon (Glu1282GlyfsTer51). The unaffected consanguineous parents were heterozygous for the mutation, whereas an unaffected younger sister did not carry the mutation; DNA was unavailable from an older sister, who died in utero with a distended bladder. Immunostained specimens of patient small intestine and bladder showed no MYLK signal. The structure and cellular constituents of the bladder and intestine showed no apparent pathologic abnormalities compared to age-matched control samples, suggesting that although MYLK is instrumental for proper functioning of smooth muscle cells, its presence is not required for maintaining the structural architecture of those organs. </p>
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<strong>.0004 MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME 1</strong>
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MYLK, IVS23, C-A, +5
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SNP: rs1553787619,
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ClinVar: RCV000508669, RCV001804176
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<p>In a girl of Indian origin (family 2) who died with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS1; 249210), Halim et al. (2017) identified homozygosity for a splicing mutation (c.3985+5C-A, NM_053025.3) in intron 23 of the MYLK gene, for which her unaffected consanguineous parents were heterozygous. DNA was not available from a younger sister who also died with MMIHS, or from a younger brother who was unaffected. Splicing assays revealed that the mutant construct eliminated all transcription products observed with wildtype MYLK and produced a band with the same size as empty vector, indicating likely skipping of exon 23 with an early stop codon at the beginning of exon 24. </p>
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<span class="mim-font">
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<strong>.0005 AORTIC ANEURYSM, FAMILIAL THORACIC 7</strong>
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MYLK, ALA1491SER
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<br />
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SNP: rs1576422965,
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ClinVar: RCV000855690
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<p>In affected members of a large consanguineous Arab family with thoracic aortic aneurysm and dissection (AAT7; 613780), Shalata et al. (2018) identified a c.4471G-T transversion in exon 27 of the MYLK gene, resulting in an ala1491-to-ser (A1491S) substitution at a conserved residue within the kinase domain. Functional analysis in transfected HeLa cells showed a significant reduction in kinase activity with the A1491S mutant compared to wildtype MYLK. The mutation was not found in 100 ethnically matched controls or in the ExAC or 1000 Genomes Project databases. The mutation was present in homozygosity in 6 severely affected family members with early-onset disease, 5 of whom were deceased, and was found in heterozygosity in 3 individuals with a later age of onset, 1 of whom was deceased; the mutation was also present in heterozygosity in 16 asymptomatic family members. The authors stated that the most appropriate designation for the mode of inheritance in this family was autosomal dominant with incomplete penetrance. In addition, the authors noted that comprehensive medical history and clinical data analysis of homozygotes excluded congenital bladder or intestine involvement in this family. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Garcia, J. G., Lazar, V., Gilbert-McClain, L. I., Gallagher, P. J., Verin, A. D.
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<strong>Myosin light chain kinase in endothelium: molecular cloning and regulation.</strong>
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Am. J. Resp. Cell Molec. Biol. 16: 489-494, 1997.
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[PubMed: 9160829]
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[Full Text: https://doi.org/10.1165/ajrcmb.16.5.9160829]
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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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Giorgi, D., Brand-Arpon, V., Rouquier, S.
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<strong>The functional myosin light chain kinase (MYLK) gene localizes with marker D3S3552 on human chromosome 3q21 in a greater than 5-Mb yeast artificial chromosome region and is not linked to olfactory receptor genes.</strong>
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Cytogenet. Cell Genet. 92: 85-88, 2001.
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[PubMed: 11306802]
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[Full Text: https://doi.org/10.1159/000056874]
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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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Goeckeler, Z. M., Masaracchia, R. A., Zeng, Q., Chew, T.-L., Gallagher, P., Wysolmerski, R. B.
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<strong>Phosphorylation of myosin light chain kinase by p21-activated kinase PAK2.</strong>
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J. Biol. Chem. 275: 18366-18374, 2000.
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[PubMed: 10748018]
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[Full Text: https://doi.org/10.1074/jbc.M001339200]
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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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Halim, D., Brosens, E., Muller, F., Wangler, M. F., Beaudet, A. L., Lupski, J. R., Akdemir, Z. H. C., Doukas, M., Stoop, H. J., de Graaf, B. M., Brouwer, R. W. W., van Ijcken, W. F. J., Oury, J.-F., Rosenblatt, J., Burns, A. J., Tibboel, D., Hofstra, R. M. W., Alves, M. M.
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<strong>Loss-of-function variants in MYLK cause recessive megacystis microcolon intestinal hypoperistalsis syndrome.</strong>
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Am. J. Hum. Genet. 101: 123-129, 2017.
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[PubMed: 28602422]
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[Full Text: https://doi.org/10.1016/j.ajhg.2017.05.011]
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Hannuksela, M., Stattin, E.-L., Klar, J., Ameur, A., Johansson, B., Sorensen, K., Carlberg, B.
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<strong>A novel variant in MYLK causes thoracic aortic dissections: genotypic and phenotypic description.</strong>
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BMC Med. Genet. 17: 61, 2016. Note: Electronic Article.
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[PubMed: 27586135]
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[Full Text: https://doi.org/10.1186/s12881-016-0326-y]
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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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Lazar, V., Garcia, J. G. N.
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<strong>A single human myosin light chain kinase gene (MLCK; MYLK) transcribes multiple nonmuscle isoforms.</strong>
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Genomics 57: 256-267, 1999.
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[PubMed: 10198165]
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[Full Text: https://doi.org/10.1006/geno.1999.5774]
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<p class="mim-text-font">
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Luyckx, I., Proost, D., Hendriks, J. M. H., Saenen, J., Van Craenenbroeck, E. M., Vermeulen, T., Peeters, N., Wuyts, W., Rodrigus, I., Verstraeten, A., Van Laer, L., Loeys, B. L.
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<strong>Two novel MYLK nonsense mutations causing thoracic aortic aneurysms/dissections in patients without apparent family history.</strong>
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Clin. Genet. 92: 444-446, 2017. Note: Erratum: Clin. Genet. 93: 938 only, 2018.
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[PubMed: 28401540]
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[Full Text: https://doi.org/10.1111/cge.13000]
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Potier, M.-C., Chelot, E., Pekarsky, Y., Gardiner, K., Rossier, J., Turnell, W. G.
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<strong>The human myosin light chain kinase (MLCK) from hippocampus: cloning, sequencing, expression, and localization to 3cen-q21.</strong>
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Genomics 29: 562-570, 1995.
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[PubMed: 8575746]
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[Full Text: https://doi.org/10.1006/geno.1995.9965]
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Shalata, A., Mahroom, M., Milewicz, D. M., Limin, G., Kassum, F., Badarna, K., Tarabeih, N., Assy, N., Fell, R., Cohen, H., Nashashibi, M., Livoff, A., Azab, M., Habib, G., Geiger, D., Weissbrod, O., Nseir, W.
|
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<strong>Fatal thoracic aortic aneurysm and dissection in a large family with a novel MYLK gene mutation: delineation of the clinical phenotype.</strong>
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Orphanet J. Rare Dis. 13: 41, 2018. Note: Electronic Article.
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[PubMed: 29544503]
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[Full Text: https://doi.org/10.1186/s13023-018-0769-7]
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Walker, L. A., MacDonald, J. A., Liu, X., Nakamoto, R. K., Haystead, T. A. J., Somlyo, A. V., Somlyo, A. P.
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<strong>Site-specific phosphorylation and point mutations of telokin modulate its Ca(2+)-desensitizing effect in smooth muscle.</strong>
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J. Biol. Chem. 276: 24519-24524, 2001.
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[PubMed: 11346659]
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[Full Text: https://doi.org/10.1074/jbc.M103560200]
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<p class="mim-text-font">
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Wang, L., Guo, D., Cao, J., Gong, L., Kamm, K. E., Regalado, E., Li, L., Shete, S., He, W.-Q., Zhu, M.-S., Offermanns, S., Gilchrist, D., Elefteriades, J., Stull, J. T., Milewicz, D. M.
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<strong>Mutations in myosin light chain kinase cause familial aortic dissections.</strong>
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Am. J. Hum. Genet. 87: 701-707, 2010. Note: Erratum: Am. J. Hum. Genet. 88: 516 only, 2011.
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[PubMed: 21055718]
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[Full Text: https://doi.org/10.1016/j.ajhg.2010.10.006]
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Watterson, D. M., Schavocky, J. P., Guo, L., Weiss, C., Chlenski, A., Shirinsky, V. P., Van Eldik, L. J., Haiech, J.
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<strong>Analysis of the kinase-related protein gene found at human chromosome 3q21 in a multi-gene cluster: organization, expression, alternative splicing, and polymorphic marker.</strong>
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J. Cell. Biochem. 75: 481-491, 1999.
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[PubMed: 10536370]
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Marla J. F. O'Neill - updated : 11/07/2019<br>Bao Lige - updated : 04/18/2019<br>Marla J. F. O'Neill - updated : 2/24/2011<br>Patricia A. Hartz - updated : 5/24/2002<br>Joanna S. Amberger - updated : 6/22/2001
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Victor A. McKusick : 11/7/1995
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</p>
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</div>
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</div>
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</div>
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<div class="modal-footer">
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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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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</body>
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</html>
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