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<title>
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Entry
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- *600970 - MYOSIN VI; MYO6
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- OMIM
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</ul>
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</nav>
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</div>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="row">
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="form-group">
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<li>
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<a href="/history"> Search History </a>
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</ul>
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</div>
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</div>
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<div class="autocomplete" id="mimEntrySearchAutocomplete"></div>
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<span class="small">
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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 id="mimSearch"> -->
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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">*600970</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li 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>
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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="#biochemicalFeatures">Biochemical Features</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#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/600970">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">
|
|
<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>
|
|
<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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|
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000196586;t=ENST00000369977" 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=4646" 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=600970" 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=ENSG00000196586;t=ENST00000369977" 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_001300899,NM_001368136,NM_001368137,NM_001368138,NM_001368139,NM_001368140,NM_001368865,NM_001368866,NM_004999,NR_160538,NR_160539,XM_005248721,XM_005248722,XM_005248724,XM_017010899,XM_024446447,XM_047418836" 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_004999" 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=600970" 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=02985&isoform_id=02985_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/MYO6" 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/531138,9280816,12642366,92859701,119569113,119569114,119569115,119569116,122065628,148922278,530383146,530383148,530383152,665505983,929653900,1034650382,1197407020,1197407022,1370508113,1559191229,1559191235,1559191252,1559191261,1559191266,1585644943,1585644945,2217361613,2462608663,2462608665,2462608667,2462608669,2462608671,2462608673" 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/Q9UM54" 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=4646" 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=ENSG00000196586;t=ENST00000369977" 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=MYO6" 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=MYO6" 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+4646" 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/MYO6" 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:4646" 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/4646" 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=chr6&hgg_gene=ENST00000369977.8&hgg_start=75749239&hgg_end=75919537&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7605" 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=600970[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=600970[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/MYO6/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/ENSG00000196586" 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=MYO6" 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=MYO6" 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=MYO6" 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="#mimLocusSpecificDBsFold" id="mimLocusSpecificDBsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A gene-specific database of variation."><span id="mimLocusSpecificDBsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Locus Specific DBs</div>
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<div id="mimLocusSpecificDBsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="http://hereditaryhearingloss.org/" title="Hereditary Hearing Loss Homepage" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Hereditary Hearing Loss Ho…</a></div><div style="margin-left: 0.5em;"><a href="https://research.cchmc.org/LOVD2/home.php?select_db=MYO6" title="CCHMC-BMI & UC Hearing Loss Mutation Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">CCHMC-BMI & UC Hearing…</a></div>
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</div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=MYO6&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/PA31410" 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:7605" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0011225.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:104785" 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/MYO6#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:104785" 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/4646/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=4646" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00002041;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00002041 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00004969;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00004969 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-030318-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4646" 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=MYO6&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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600970
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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 VI; MYO6
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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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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=MYO6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">MYO6</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/6/658?start=-3&limit=10&highlight=658">6q14.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:75749239-75919537&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'})">6:75,749,239-75,919,537</a> </span>
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</em>
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</strong>
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Deafness, autosomal dominant 22
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy
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Deafness, autosomal recessive 37
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<a href="/entry/607821"> 607821 </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/600970" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/600970" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>Myosin VI, one of the so-called unconventional myosins, is an actin-based molecular motor involved in intracellular vesicle and organelle transport (<a href="#17" class="mim-tip-reference" title="Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A., Sweeney, H. L. <strong>Myosin VI is a processive motor with a large step size.</strong> Proc. Nat. Acad. Sci. 98: 13655-13659, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11707568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11707568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11707568[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.191512398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11707568">Rock et al., 2001</a>; <a href="#7" class="mim-tip-reference" title="Hasson, T., Mooseker, M. S. <strong>Porcine myosin-VI: characterization of a new mammalian unconventional myosin.</strong> J. Cell. Biol. 127: 425-440, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7929586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7929586</a>] [<a href="https://doi.org/10.1083/jcb.127.2.425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7929586">Hasson and Mooseker, 1994</a>). Myosin VI participates in 2 steps of endocytic trafficking; it is recruited to both clathrin (see CLTC; <a href="/entry/118955">118955</a>)-coated pits and to ensuing uncoated endocytic vesicles (<a href="#15" class="mim-tip-reference" title="Naccache, S. N., Hasson, T., Horowitz, A. <strong>Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.</strong> Proc. Nat. Acad. Sci. 103: 12735-12740, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 15272 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16908842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16908842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16908842[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0605317103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16908842">Naccache et al., 2006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16908842+7929586+11707568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Hasson, T., Mooseker, M. S. <strong>Porcine myosin-VI: characterization of a new mammalian unconventional myosin.</strong> J. Cell. Biol. 127: 425-440, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7929586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7929586</a>] [<a href="https://doi.org/10.1083/jcb.127.2.425" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7929586">Hasson and Mooseker (1994)</a> characterized porcine myosin VI. <a href="#5" class="mim-tip-reference" title="Avraham, K. B., Hasson, T., Steel, K. P., Kingsley, D. M., Russell, L. B., Mooseker, M. S., Copeland, N. G., Jenkins, N. A. <strong>The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells.</strong> Nature Genet. 11: 369-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493015</a>] [<a href="https://doi.org/10.1038/ng1295-369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493015">Avraham et al. (1995)</a> showed that the sequence of the mouse Myo6 gene is 87% identical to that of the pig. The mouse cDNA predicted a protein of 1,266 amino acids with a relative molecular mass of 142 kD. In the pig, rat, and mouse, myosin VI is widely expressed. In the mouse, within the cochlea of the inner ear, myosin VI is expressed specifically within the sensory hair cells. <a href="#5" class="mim-tip-reference" title="Avraham, K. B., Hasson, T., Steel, K. P., Kingsley, D. M., Russell, L. B., Mooseker, M. S., Copeland, N. G., Jenkins, N. A. <strong>The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells.</strong> Nature Genet. 11: 369-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493015</a>] [<a href="https://doi.org/10.1038/ng1295-369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493015">Avraham et al. (1995)</a> found that the Myo6 gene is defective in the Snell's waltzer (sv) mouse mutant, which is associated with deafness. Together with the expression pattern in the sensory hair cells of the cochlea, this suggested to the authors that myosin VI is required for normal hearing and that the human homolog is a candidate for a human recessive deafness gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7929586+7493015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Avraham, K. B., Hasson, T., Sobe, T., Balsara, B., Testa, J. R., Skvorak, A. B., Morton, C. C., Copeland, N. G., Jenkins, N. A. <strong>Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice.</strong> Hum. Molec. Genet. 6: 1225-1231, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259267</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259267">Avraham et al. (1997)</a> cloned and characterized the human MYO6 cDNA. Expression of MYO6 in human fetal cochlea demonstrated the importance of myosin VI in the mammalian inner ear and supported its potential role in human inner ear pathology. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259267" 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="#21" class="mim-tip-reference" title="Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P. C., Crippa, M. P., Bussi, M., Biffo, S. <strong>Nuclear myosin VI enhances RNA polymerase II-dependent transcription.</strong> Molec. Cell 23: 749-755, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949370</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949370">Vreugde et al. (2006)</a> identified 5 putative monopartite nuclear localization signals and 1 putative bipartite nuclear localization signal in MYO6, mainly in the tail region. In the first part of the tail region, they identified a putative protein-protein interaction domain consisting of glutamic acid- and arginine-rich regions. Immunofluorescence and cellular fractionation of human and other mammalian cells revealed a proportion of MYO6 in the nucleus, where it colocalized with RNA polymerase II (see <a href="/entry/180660">180660</a>) and nascent transcripts. MYO6 in the nuclear fraction had an apparent molecular mass of 150 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#1" class="mim-tip-reference" title="Ahituv, N., Sobe, T., Robertson, N. G., Morton, C. C., Taggart, R. T., Avraham, K. B. <strong>Genomic structure of the human unconventional myosin VI gene.</strong> Gene 261: 269-275, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11167014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11167014</a>] [<a href="https://doi.org/10.1016/s0378-1119(00)00535-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11167014">Ahituv et al. (2000)</a> determined that the MYO6 gene contains 32 exons and spans 70 kb. They found that exon 30, which contains a putative casein kinase II (see <a href="/entry/115440">115440</a>) site, is alternatively spliced and appears only in fetal and adult brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11167014" 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="#5" class="mim-tip-reference" title="Avraham, K. B., Hasson, T., Steel, K. P., Kingsley, D. M., Russell, L. B., Mooseker, M. S., Copeland, N. G., Jenkins, N. A. <strong>The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells.</strong> Nature Genet. 11: 369-375, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493015</a>] [<a href="https://doi.org/10.1038/ng1295-369" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7493015">Avraham et al. (1995)</a> suggested that the human MYO6 gene may map to the centromeric region of chromosome 6, a region that shows syntenic homology with the portion of mouse chromosome 9 where the Snell's waltzer (sv) mouse mutation is located. On the basis of location of the Myo6 gene in the mouse, <a href="#8" class="mim-tip-reference" title="Hasson, T., Skowron, J. F., Gilbert, D. J., Avraham, K. B., Perry, W. L., Bement, W. M., Anderson, B. L., Sherr, E. H., Chen, Z.-Y., Greene, L. A., Ward, D. C., Corey, D. P., Mooseker, M. S., Copeland, N. G., Jenkins, N. A. <strong>Mapping of unconventional myosins in mouse and human.</strong> Genomics 36: 431-439, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8884266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8884266</a>] [<a href="https://doi.org/10.1006/geno.1996.0488" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8884266">Hasson et al. (1996)</a> predicted that the homologous human gene is located on 6p12-q16.3. By fluorescence in situ hybridization, <a href="#4" class="mim-tip-reference" title="Avraham, K. B., Hasson, T., Sobe, T., Balsara, B., Testa, J. R., Skvorak, A. B., Morton, C. C., Copeland, N. G., Jenkins, N. A. <strong>Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice.</strong> Hum. Molec. Genet. 6: 1225-1231, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259267</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1225" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259267">Avraham et al. (1997)</a> mapped the MYO6 gene to 6q13. In the mouse, Myo6 maps between Gsta and Htr1b; the human homologs, GSTA2 (<a href="/entry/138360">138360</a>) and HTR1B (<a href="/entry/182131">182131</a>), both map to chromosome 6. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9259267+8884266+7493015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#17" class="mim-tip-reference" title="Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A., Sweeney, H. L. <strong>Myosin VI is a processive motor with a large step size.</strong> Proc. Nat. Acad. Sci. 98: 13655-13659, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11707568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11707568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11707568[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.191512398" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11707568">Rock et al. (2001)</a> noted that myosin VI moves toward the pointed end of actin (see <a href="/entry/102560">102560</a>), whereas all other characterized myosins move toward the barbed end. They found that porcine myosin VI took much larger steps than expected. Unlike other characterized myosins, myosin VI stepping was highly irregular, with a broad distribution of step sizes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11707568" 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="#16" class="mim-tip-reference" title="Rock, R. S., Ramamurthy, B., Dunn, A. R., Beccafico, S., Rami, B. R., Morris, C., Spink, B. J., Franzini-Armstrong, C., Spudich, J. A., Sweeney, H. L. <strong>A flexible domain is essential for the large step size and processivity of myosin VI.</strong> Molec. Cell 17: 603-609, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15721263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15721263</a>] [<a href="https://doi.org/10.1016/j.molcel.2005.01.015" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15721263">Rock et al. (2005)</a> showed that the proximal tail region of porcine myosin VI is a flexible domain that permits the myosin heads to separate and allows the large and variable step size of myosin VI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15721263" 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>MYO6 is thought to function as both a transporter and an anchor. <a href="#3" class="mim-tip-reference" title="Altman, D., Sweeney, H. L., Spudich, J. A. <strong>The mechanism of myosin VI translocation and its load-induced anchoring.</strong> Cell 116: 737-749, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15006355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15006355</a>] [<a href="https://doi.org/10.1016/s0092-8674(04)00211-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15006355">Altman et al. (2004)</a> noted that in vitro studies had suggested possible mechanisms for processive stepping, but a biochemical basis for anchoring had not been demonstrated. Using optical trapping, they observed MYO6 stepping against applied forces. Step size was not strongly affected by such loads. At saturating ATP, MYO6 kinetics showed little dependence on load until, at forces near stall, its stepping slowed dramatically as load increased. At subsaturating ATP or in the presence of ADP, stepping kinetics were significantly inhibited by load. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15006355" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Naccache, S. N., Hasson, T., Horowitz, A. <strong>Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.</strong> Proc. Nat. Acad. Sci. 103: 12735-12740, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 15272 only, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16908842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16908842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16908842[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.0605317103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16908842">Naccache et al. (2006)</a> found that Myo6 recruitment to uncoated endocytic vesicles in cultured mouse kidney epithelial cells was dependent on synectin (GIPC1; <a href="/entry/605072">605072</a>). Myo6 bound a C-terminal domain of synectin, and Myo6 recruitment required the interaction between the PDZ-binding domains of engulfed receptors, such as megalin (LRP2; <a href="/entry/600073">600073</a>), and the PDZ domain of synectin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16908842" 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="#21" class="mim-tip-reference" title="Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P. C., Crippa, M. P., Bussi, M., Biffo, S. <strong>Nuclear myosin VI enhances RNA polymerase II-dependent transcription.</strong> Molec. Cell 23: 749-755, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949370</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949370">Vreugde et al. (2006)</a> found that colocalization and interaction of MYO6 with RNA polymerase II required transcriptional activity. Pharmacologic blockade of transcription resulted in redistribution of nuclear MYO6 to the cytoplasm. Chromatin immunoprecipitation assays showed that MYO6 was recruited to the promoters and intragenic regions of active genes, but not to noncoding, nonregulatory intergenic regions. Downregulation of MYO6 reduced steady-state mRNA levels of the regulated genes in vivo, and antibodies to MYO6 reduced transcription in vitro. <a href="#21" class="mim-tip-reference" title="Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P. C., Crippa, M. P., Bussi, M., Biffo, S. <strong>Nuclear myosin VI enhances RNA polymerase II-dependent transcription.</strong> Molec. Cell 23: 749-755, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949370</a>] [<a href="https://doi.org/10.1016/j.molcel.2006.07.005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16949370">Vreugde et al. (2006)</a> concluded that MYO6 modulates RNA polymerase II-dependent transcription of active genes and suggested that an actin-myosin-based mechanism may be involved in transcription. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949370" 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>Otoferlin (OTOF; <a href="/entry/603681">603681</a>) has been proposed to be the calcium sensor in hair cell exocytosis, compensating for the classic synaptic fusion proteins synaptotagmin-1 (SYT1; <a href="/entry/185605">185605</a>) and synaptotagmin-2 (SYT2; <a href="/entry/600104">600104</a>). <a href="#9" class="mim-tip-reference" title="Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M. <strong>Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell.</strong> Hum. Molec. Genet. 18: 2779-2790, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19417007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19417007</a>] [<a href="https://doi.org/10.1093/hmg/ddp213" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19417007">Heidrych et al. (2009)</a> demonstrated in a yeast 2-hybrid assay that myosin VI is a novel otoferlin-binding partner. Coimmunoprecipitation assay and coexpression suggested an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of Otof- and Myo6-mutant mice indicated noncomplementary and complementary roles of myosin VI and otoferlin for synaptic maturation. IHCs from Otof-mutant mice exhibited a decoupling of Ctbp2 (<a href="/entry/602619">602619</a>) and CaV1.3 (CACNA1D; <a href="/entry/114206">114206</a>) and severe reduction of exocytosis. Myo6-mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature. Otof- and Myo6-mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in Otof-mutant IHCs indicated disturbed transport of endocytotic membranes and linked the above morphologic changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral inner hair cell membrane. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19417007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#22" class="mim-tip-reference" title="Wells, A. L., Lin, A. W., Chen, L.-Q., Safer, D., Cain, S. M., Hasson, T., Carragher, B. O., Milligan, R. A., Sweeney, H. L. <strong>Myosin VI is an actin-based motor that moves backwards.</strong> Nature 401: 505-508, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10519557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10519557</a>] [<a href="https://doi.org/10.1038/46835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10519557">Wells et al. (1999)</a> visualized the myosin VI construct bound to actin (see <a href="/entry/102560">102560</a>) using cryoelectron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. <a href="#22" class="mim-tip-reference" title="Wells, A. L., Lin, A. W., Chen, L.-Q., Safer, D., Cain, S. M., Hasson, T., Carragher, B. O., Milligan, R. A., Sweeney, H. L. <strong>Myosin VI is an actin-based motor that moves backwards.</strong> Nature 401: 505-508, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10519557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10519557</a>] [<a href="https://doi.org/10.1038/46835" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10519557">Wells et al. (1999)</a> concluded that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10519557" 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>Crystal Structure</em></strong></p><p>
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<a href="#13" class="mim-tip-reference" title="Menetrey, J., Bahloul, A., Wells, A. L., Yengo, C. M., Morris, C. A., Sweeney, H. L., Houdusse, A. <strong>The structure of the myosin VI motor reveals the mechanism of directionality reversal.</strong> Nature 435: 779-785, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944696[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature03592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944696">Menetrey et al. (2005)</a> solved the crystal structure of a truncated version of the reverse-direction myosin motor, myosin VI, containing the motor domain and binding sites of 2 calmodulin (<a href="/entry/114180">114180</a>) molecules at a resolution of 2.4 angstroms. The structure revealed only minor differences in the motor domain from that in plus end-directed myosins, with the exception of 2 unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective lever arm of myosin VI, which includes a second calmodulin bound to an IQ motif, towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. <a href="#13" class="mim-tip-reference" title="Menetrey, J., Bahloul, A., Wells, A. L., Yengo, C. M., Morris, C. A., Sweeney, H. L., Houdusse, A. <strong>The structure of the myosin VI motor reveals the mechanism of directionality reversal.</strong> Nature 435: 779-785, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944696[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature03592" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944696">Menetrey et al. (2005)</a> proposed a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944696" 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>Electron Microscopy</em></strong></p><p>
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<a href="#18" class="mim-tip-reference" title="Roux, I., Hosie, S., Johnson, S. L., Bahloul, A., Cayet, N., Nouaille, S., Kros, C. J., Petit, C., Safieddine, S. <strong>Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses.</strong> Hum. Molec. Genet. 18: 4615-4628, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744958</a>] [<a href="https://doi.org/10.1093/hmg/ddp429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19744958">Roux et al. (2009)</a> showed that Myo6 was present at the synaptic active zone of IHCs by immunogold electron microscopy. In Myo6(sv/sv) mice, ionic currents and ribbon synapse maturation of IHCs proceeded normally until at least postnatal day 6. In adult Myo6(sv/sv) mice, however, the IHCs displayed immature potassium currents and still fired action potentials, as normally only observed in immature IHCs. In addition, the number of ribbons per IHC was reduced, and some of the remaining ribbons were morphologically immature. Calcium-dependent exocytosis was markedly reduced despite normal calcium currents and a large proportion of morphologically mature synapses. Yeast 2-hybrid assay, in vitro binding assays, and immunoprecipitation studies of transfected HEK-293 cells and mouse cochlear sensory epithelium showed direct interaction of Myo6 and otoferlin (OTOF; <a href="/entry/603681">603681</a>). Immunogold electron microscopy showed that Myo6 and otoferlin colocalized at the edge of the synaptic active zone in mouse IHCs. <a href="#18" class="mim-tip-reference" title="Roux, I., Hosie, S., Johnson, S. L., Bahloul, A., Cayet, N., Nouaille, S., Kros, C. J., Petit, C., Safieddine, S. <strong>Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses.</strong> Hum. Molec. Genet. 18: 4615-4628, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744958</a>] [<a href="https://doi.org/10.1093/hmg/ddp429" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19744958">Roux et al. (2009)</a> suggested that MYO6/otoferlin interaction may be involved in the recycling of synaptic vesicles. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19744958" 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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In a large family segregating autosomal dominant nonsyndromic sensorineural hearing loss, <a href="#12" class="mim-tip-reference" title="Melchionda, S., Ahituv, N., Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M. L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X., Avraham, K. B., Gasparini, P. <strong>MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.</strong> Am. J. Hum. Genet. 69: 635-640, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11468689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11468689</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11468689[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11468689">Melchionda et al. (2001)</a> demonstrated linkage of the disorder to 6q13 (DFNA22; <a href="/entry/606346">606346</a>) and identified a missense mutation in the MYO6 gene (C442Y; <a href="#0001">600970.0001</a>) in all affected members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11468689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a kindred in which autosomal dominant sensorineural deafness cosegregated with familial hypertrophic cardiomyopathy, <a href="#14" class="mim-tip-reference" title="Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J. <strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong> J. Med. Genet. 41: 309-314, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060111</a>] [<a href="https://doi.org/10.1136/jmg.2003.011973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060111">Mohiddin et al. (2004)</a> identified a his246-to-arg mutation in the MYO6 gene (H246R; <a href="#0005">600970.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060111" 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 Danish family with 18 affected members segregating autosomal dominant nonsyndromic hearing loss (DFNA22; <a href="/entry/606346">606346</a>), <a href="#19" class="mim-tip-reference" title="Sanggaard, K. M., Kjaer, K. W., Eiberg, H., Nurnberg, G., Nurnberg, P., Hoffman, K., Jensen, H., Sorum, C., Rendtorff, N. D., Tranebjaerg, L. <strong>A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.</strong> Am. J. Med. Genet. 146A: 1017-1025, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348273</a>] [<a href="https://doi.org/10.1002/ajmg.a.32174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348273">Sanggaard et al. (2008)</a> detected heterozygosity for a nonsense mutation in the MYO6 gene (R849X; <a href="#0006">600970.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Hilgert, N., Topsakal, V., van Dinther, J., Offeciers, E., Van de Heyning, P., Van Camp. G. <strong>A splice-site mutation and overexpression of MYO6 cause a similar phenotype in two families with autosomal dominant hearing loss.</strong> Europ. J. Hum. Genet. 16: 593-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18212818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18212818</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18212818">Hilgert et al. (2008)</a> analyzed the MYO6 gene in 2 Belgian families with autosomal dominant deafness mapping to the DFNA22 locus and identified a splice site mutation (<a href="#0007">600970.0007</a>) in 'family 2.' No mutation was identified in 'family 1,' although quantitative real-time PCR revealed 1.5- to 1.8-fold overexpression of MYO6 in patients compared to controls. After exclusion of gene duplication, the authors suggested that most likely the overexpression in 'family 1' involved a mutation in an as yet unidentified regulatory region of the MYO6 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18212818" 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>Deafness, Autosomal Dominant 22, with Hypertrophic Cardiomyopathy</em></strong></p><p>
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In affected members of a kindred in which autosomal dominant sensorineural deafness cosegregated with familial hypertrophic cardiomyopathy (see <a href="/entry/606346">606346</a>), <a href="#14" class="mim-tip-reference" title="Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J. <strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong> J. Med. Genet. 41: 309-314, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060111</a>] [<a href="https://doi.org/10.1136/jmg.2003.011973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060111">Mohiddin et al. (2004)</a> identified a heterozygous missense mutation in the MYO6 gene (H246R; <a href="#0005">600970.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060111" 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>Deafness, Autosomal Recessive 37</em></strong></p><p>
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<a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R. <strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong> Am. J. Hum. Genet. 72: 1315-1322, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12687499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12687499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/375122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12687499">Ahmed et al. (2003)</a> identified mutations in the MYO6 gene in 3 families segregating autosomal recessive congenital sensorineural deafness (DFNB37; <a href="/entry/607821">607821</a>); see <a href="#0002">600970.0002</a>-<a href="#0004">600970.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12687499" 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="#6" class="mim-tip-reference" title="Geisbrecht, E. R., Montell, D. J. <strong>Myosin VI is required for E-cadherin-mediated border cell migration.</strong> Nature Cell Biol. 4: 616-620, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12134162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12134162</a>] [<a href="https://doi.org/10.1038/ncb830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12134162">Geisbrecht and Montell (2002)</a> found that depletion of Myo6 from a small group of migratory follicle cells of Drosophila, known as border cells, inhibited their migration. Cells lacking Myo6 also lacked E-cadherin (<a href="/entry/192090">192090</a>) and beta-catenin (<a href="/entry/116806">116806</a>). Conversely, cells lacking E-cadherin or beta-catenin showed reduced levels of Myo6. <a href="#6" class="mim-tip-reference" title="Geisbrecht, E. R., Montell, D. J. <strong>Myosin VI is required for E-cadherin-mediated border cell migration.</strong> Nature Cell Biol. 4: 616-620, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12134162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12134162</a>] [<a href="https://doi.org/10.1038/ncb830" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12134162">Geisbrecht and Montell (2002)</a> concluded that, in Drosophila, Myo6 is required for border cell migration where it stabilizes E-cadherin and beta-catenin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12134162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The MYO15 (<a href="/entry/602666">602666</a>), MYO6, and MYO7A (<a href="/entry/276903">276903</a>) genes are essential for hearing in both humans and mice. Despite widespread expression, homozygosity for mutations in these genes only results in auditory or ocular dysfunction. The pirouette (pi) mouse exhibits deafness and inner ear pathology resembling that of Myo15 mutant mice. <a href="#11" class="mim-tip-reference" title="Karolyi, I. J., Probst, F. J., Beyer, L., Odeh, H., Dootz, G., Cha, K. B., Martin, D. M., Avraham, K. B., Kohrman, D., Dolan, D. F., Raphael, Y., Camper, S. A. <strong>Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.</strong> Hum. Molec. Genet. 12: 2797-2805, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966030</a>] [<a href="https://doi.org/10.1093/hmg/ddg308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12966030">Karolyi et al. (2003)</a> crossed Myo15 mutant mice to Myo6, Myo7a, and pi mutant mouse strains. Viable double-mutant homozygotes were obtained from each cross, and hearing in doubly heterozygous mice was similar to singly heterozygous mice. All critical cell types of the cochlear sensory epithelium were present in double-mutant mice, and cochlear stereocilia exhibited a superimposition of single-mutant phenotypes. <a href="#11" class="mim-tip-reference" title="Karolyi, I. J., Probst, F. J., Beyer, L., Odeh, H., Dootz, G., Cha, K. B., Martin, D. M., Avraham, K. B., Kohrman, D., Dolan, D. F., Raphael, Y., Camper, S. A. <strong>Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.</strong> Hum. Molec. Genet. 12: 2797-2805, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966030</a>] [<a href="https://doi.org/10.1093/hmg/ddg308" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12966030">Karolyi et al. (2003)</a> suggested that the function of Myo15 is distinct from that of Myo6, Myo7a, or pi in development and/or maintenance of stereocilia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966030" 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="Melchionda, S., Ahituv, N., Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M. L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X., Avraham, K. B., Gasparini, P. <strong>MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.</strong> Am. J. Hum. Genet. 69: 635-640, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11468689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11468689</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11468689[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/323156" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11468689">Melchionda et al. (2001)</a> studied a large Italian kindred affected by progressive, postlingual sensorineural deafness linked to chromosome 6q13 (<a href="/entry/606346">606346</a>). Mutation analysis of the MYO6 gene demonstrated that all affected members of the family had a G-to-A transition in exon 12 at position 1325 of the cDNA sequence (relative to the ATG, designated +1), which replaces a cysteine (TGT) with a tyrosine (TAT) at residue 442 of the protein (C442Y). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11468689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By in vitro expression studies, <a href="#20" class="mim-tip-reference" title="Sato, O., White, H. D., Inoue, A., Belknap, B., Ikebe, R., Ikebe, M. <strong>Human deafness mutation of myosin VI (C442Y) accelerates the ADP dissociation rate.</strong> J. Biol. Chem. 279: 28844-28854, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15123708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15123708</a>] [<a href="https://doi.org/10.1074/jbc.M314332200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15123708">Sato et al. (2004)</a> found that the C442Y mutation caused several major changes in myosin VI mechanoenzymatic function. The C442Y mutant protein had an approximately 10-fold increase in the rate of ADP dissociation from myosin VI, and there was an approximately 10-fold increase in the ATPase rate in the absence of actin compared to wildtype. There was a 2-fold increase in the actin gliding velocity of the mutant protein compared to wildtype. The findings suggested that the mutation impedes the processive movement of myosin VI. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15123708" 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">rs1562201376 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562201376;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=rs1562201376" 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=rs1562201376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; <a href="/entry/607821">607821</a>), <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R. <strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong> Am. J. Hum. Genet. 72: 1315-1322, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12687499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12687499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/375122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12687499">Ahmed et al. (2003)</a> identified homozygosity for a 1-bp insertion (36insT) in exon 2 of the MYO6 gene in all 6 affected individuals. The insertion was predicted to cause a frameshift and premature translation termination after the first 12 amino acids of myosin VI. The oldest affected child also had congenital stationary night blindness and retinal pigment epithelial changes; the other 5 affected children with profound deafness were less than 30 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12687499" 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 DEAFNESS, AUTOSOMAL RECESSIVE 37</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">rs121912558 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912558;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=rs121912558" 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=rs121912558" 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=RCV000009110 OR RCV001582472" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009110, RCV001582472" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009110...</a>
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<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; <a href="/entry/607821">607821</a>), <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R. <strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong> Am. J. Hum. Genet. 72: 1315-1322, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12687499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12687499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/375122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12687499">Ahmed et al. (2003)</a> identified homozygosity for a 3496C-T transition in exon 32 of the MYO6 gene, resulting in an arg1166-to-ter (R1166X) substitution, in all affected members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12687499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 DEAFNESS, AUTOSOMAL RECESSIVE 37</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912559 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912559;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912559?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912559" 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=rs121912559" 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=RCV000009111 OR RCV000767071 OR RCV000987740" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009111, RCV000767071, RCV000987740" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009111...</a>
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<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; <a href="/entry/607821">607821</a>), <a href="#2" class="mim-tip-reference" title="Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R. <strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong> Am. J. Hum. Genet. 72: 1315-1322, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12687499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12687499[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/375122" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12687499">Ahmed et al. (2003)</a> identified homozygosity for a 647A-T transversion in the MYO6 gene, resulting in a glu216-to-val (E216V) substitution, in the single affected member. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12687499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 DEAFNESS, AUTOSOMAL DOMINANT 22, WITH HYPERTROPHIC CARDIOMYOPATHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912560 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912560;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912560?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912560" 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=rs121912560" 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=RCV000219073 OR RCV001582473 OR RCV004691086" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000219073, RCV001582473, RCV004691086" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000219073...</a>
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<p>In affected members of a kindred in which autosomal dominant deafness-22 cosegregated with familial hypertrophic cardiomyopathy (see <a href="/entry/606346">606346</a>), <a href="#14" class="mim-tip-reference" title="Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J. <strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong> J. Med. Genet. 41: 309-314, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060111</a>] [<a href="https://doi.org/10.1136/jmg.2003.011973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060111">Mohiddin et al. (2004)</a> identified a 737A-G transition in the MYO6 gene, resulting in a his246-to-arg (H246R) mutation within the highly conserved motor domain of the protein. The sensorineural hearing loss, which was progressive and late in onset, was present in 10 members, 4 of whom also had hypertrophic cardiomyopathy. Six had sensorineural hearing loss without echocardiographic evidence of left ventricular hypertrophy; 4 of these 6 patients, however, had abnormalities on 12-lead ECG, and 3 of the 6 had prolongation of the QT interval. Cardiac symptoms were mild or absent in most affected family members. <a href="#14" class="mim-tip-reference" title="Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J. <strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong> J. Med. Genet. 41: 309-314, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060111</a>] [<a href="https://doi.org/10.1136/jmg.2003.011973" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15060111">Mohiddin et al. (2004)</a> suggested that the cardiac manifestations may have escaped detection in affected members of previously reported pedigrees with MYO6-associated sensorineural hearing loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121912561 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121912561;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs121912561?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121912561" 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=rs121912561" 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=RCV000009113 OR RCV000605133 OR RCV003555982" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009113, RCV000605133, RCV003555982" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009113...</a>
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<p>In a large Danish family with postlingual sensorineural hearing loss mapping to chromosome 6p12.1-q16.1 (<a href="/entry/606346">606346</a>), <a href="#19" class="mim-tip-reference" title="Sanggaard, K. M., Kjaer, K. W., Eiberg, H., Nurnberg, G., Nurnberg, P., Hoffman, K., Jensen, H., Sorum, C., Rendtorff, N. D., Tranebjaerg, L. <strong>A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.</strong> Am. J. Med. Genet. 146A: 1017-1025, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348273</a>] [<a href="https://doi.org/10.1002/ajmg.a.32174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18348273">Sanggaard et al. (2008)</a> identified a heterozygous 2545C-T transition in exon 25 of the MYO6 gene, resulting in an arg849-to-ter (R849X) mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348273" 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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<span class="mim-font">
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<strong>.0007 DEAFNESS, AUTOSOMAL DOMINANT 22</strong>
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MYO6, IVS23, T-G, +2321
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1562283089 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562283089;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=rs1562283089" 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=rs1562283089" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009114" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009114" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009114</a>
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<p>In 11 affected members of a 5-generation Belgian family ('family 2') segregating autosomal dominant deafness (DFNA22; <a href="/entry/606346">606346</a>), <a href="#10" class="mim-tip-reference" title="Hilgert, N., Topsakal, V., van Dinther, J., Offeciers, E., Van de Heyning, P., Van Camp. G. <strong>A splice-site mutation and overexpression of MYO6 cause a similar phenotype in two families with autosomal dominant hearing loss.</strong> Europ. J. Hum. Genet. 16: 593-602, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18212818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18212818</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5202000" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18212818">Hilgert et al. (2008)</a> identified heterozygosity for a 2321T-G transversion in intron 23 of the MYO6 gene, creating a new splice donor site and resulting in the insertion of a 108-bp intronic fragment that causes a frameshift and a premature termination codon 16 nucleotides downstream of exon 23. The mutation was not found in unaffected family members or in 139 unrelated ethnically matched controls. Expression assays showed that patients had 80-85% of the MYO6 expression level of unaffected individuals, but the difference was not statistically significant. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18212818" 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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<br />
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<a id="references"class="mim-anchor"></a>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<p />
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="1" class="mim-anchor"></a>
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<a id="Ahituv2000" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ahituv, N., Sobe, T., Robertson, N. G., Morton, C. C., Taggart, R. T., Avraham, K. B.
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<strong>Genomic structure of the human unconventional myosin VI gene.</strong>
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Gene 261: 269-275, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11167014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11167014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11167014" 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/s0378-1119(00)00535-7" target="_blank">Full Text</a>]
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<a id="Ahmed2003" class="mim-anchor"></a>
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Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R.
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<strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong>
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Am. J. Hum. Genet. 72: 1315-1322, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12687499</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12687499[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=12687499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/375122" target="_blank">Full Text</a>]
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</p>
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<a id="3" class="mim-anchor"></a>
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<a id="Altman2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Altman, D., Sweeney, H. L., Spudich, J. A.
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<strong>The mechanism of myosin VI translocation and its load-induced anchoring.</strong>
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Cell 116: 737-749, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15006355/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15006355</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15006355" 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/s0092-8674(04)00211-9" target="_blank">Full Text</a>]
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</p>
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<a id="4" class="mim-anchor"></a>
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<a id="Avraham1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Avraham, K. B., Hasson, T., Sobe, T., Balsara, B., Testa, J. R., Skvorak, A. B., Morton, C. C., Copeland, N. G., Jenkins, N. A.
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<strong>Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice.</strong>
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Hum. Molec. Genet. 6: 1225-1231, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259267/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259267</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259267" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.8.1225" target="_blank">Full Text</a>]
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<a id="5" class="mim-anchor"></a>
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<a id="Avraham1995" class="mim-anchor"></a>
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<div class="">
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Avraham, K. B., Hasson, T., Steel, K. P., Kingsley, D. M., Russell, L. B., Mooseker, M. S., Copeland, N. G., Jenkins, N. A.
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<strong>The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells.</strong>
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Nature Genet. 11: 369-375, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7493015/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7493015</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7493015" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1295-369" target="_blank">Full Text</a>]
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<a id="Geisbrecht2002" class="mim-anchor"></a>
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Geisbrecht, E. R., Montell, D. J.
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<strong>Myosin VI is required for E-cadherin-mediated border cell migration.</strong>
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Nature Cell Biol. 4: 616-620, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12134162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12134162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12134162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ncb830" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Hasson1994" class="mim-anchor"></a>
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<strong>Porcine myosin-VI: characterization of a new mammalian unconventional myosin.</strong>
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J. Cell. Biol. 127: 425-440, 1994.
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[<a href="https://doi.org/10.1083/jcb.127.2.425" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Hasson1996" class="mim-anchor"></a>
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<div class="">
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Hasson, T., Skowron, J. F., Gilbert, D. J., Avraham, K. B., Perry, W. L., Bement, W. M., Anderson, B. L., Sherr, E. H., Chen, Z.-Y., Greene, L. A., Ward, D. C., Corey, D. P., Mooseker, M. S., Copeland, N. G., Jenkins, N. A.
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<strong>Mapping of unconventional myosins in mouse and human.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8884266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8884266</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8884266" 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.1996.0488" target="_blank">Full Text</a>]
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<a id="Heidrych2009" class="mim-anchor"></a>
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Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M.
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<strong>Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell.</strong>
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Hum. Molec. Genet. 18: 2779-2790, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19417007/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19417007</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19417007" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp213" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Hilgert2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hilgert, N., Topsakal, V., van Dinther, J., Offeciers, E., Van de Heyning, P., Van Camp. G.
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<strong>A splice-site mutation and overexpression of MYO6 cause a similar phenotype in two families with autosomal dominant hearing loss.</strong>
|
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Europ. J. Hum. Genet. 16: 593-602, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18212818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18212818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18212818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5202000" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Karolyi2003" class="mim-anchor"></a>
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<div class="">
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Karolyi, I. J., Probst, F. J., Beyer, L., Odeh, H., Dootz, G., Cha, K. B., Martin, D. M., Avraham, K. B., Kohrman, D., Dolan, D. F., Raphael, Y., Camper, S. A.
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<strong>Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.</strong>
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Hum. Molec. Genet. 12: 2797-2805, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12966030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12966030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12966030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddg308" target="_blank">Full Text</a>]
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<a id="Melchionda2001" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Melchionda, S., Ahituv, N., Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M. L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X., Avraham, K. B., Gasparini, P.
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<strong>MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.</strong>
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Am. J. Hum. Genet. 69: 635-640, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11468689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11468689</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11468689[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=11468689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/323156" target="_blank">Full Text</a>]
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<a id="Menetrey2005" class="mim-anchor"></a>
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<p class="mim-text-font">
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Menetrey, J., Bahloul, A., Wells, A. L., Yengo, C. M., Morris, C. A., Sweeney, H. L., Houdusse, A.
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<strong>The structure of the myosin VI motor reveals the mechanism of directionality reversal.</strong>
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Nature 435: 779-785, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944696/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944696</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944696[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=15944696" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature03592" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Mohiddin2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J.
|
|
<strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong>
|
|
J. Med. Genet. 41: 309-314, 2004.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15060111/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15060111</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15060111" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2003.011973" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Naccache2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Naccache, S. N., Hasson, T., Horowitz, A.
|
|
<strong>Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 12735-12740, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 15272 only, 2006.
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|
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16908842/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16908842</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16908842[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=16908842" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0605317103" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Rock2005" class="mim-anchor"></a>
|
|
<div class="">
|
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<p class="mim-text-font">
|
|
Rock, R. S., Ramamurthy, B., Dunn, A. R., Beccafico, S., Rami, B. R., Morris, C., Spink, B. J., Franzini-Armstrong, C., Spudich, J. A., Sweeney, H. L.
|
|
<strong>A flexible domain is essential for the large step size and processivity of myosin VI.</strong>
|
|
Molec. Cell 17: 603-609, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15721263/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15721263</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15721263" 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.molcel.2005.01.015" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Rock2001" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
|
Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A., Sweeney, H. L.
|
|
<strong>Myosin VI is a processive motor with a large step size.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 13655-13659, 2001.
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|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11707568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11707568</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11707568[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=11707568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.191512398" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Roux2009" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
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Roux, I., Hosie, S., Johnson, S. L., Bahloul, A., Cayet, N., Nouaille, S., Kros, C. J., Petit, C., Safieddine, S.
|
|
<strong>Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses.</strong>
|
|
Hum. Molec. Genet. 18: 4615-4628, 2009.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19744958/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19744958</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19744958" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp429" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Sanggaard2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sanggaard, K. M., Kjaer, K. W., Eiberg, H., Nurnberg, G., Nurnberg, P., Hoffman, K., Jensen, H., Sorum, C., Rendtorff, N. D., Tranebjaerg, L.
|
|
<strong>A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.</strong>
|
|
Am. J. Med. Genet. 146A: 1017-1025, 2008.
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|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18348273/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18348273</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18348273" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.32174" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="20" class="mim-anchor"></a>
|
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<a id="Sato2004" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Sato, O., White, H. D., Inoue, A., Belknap, B., Ikebe, R., Ikebe, M.
|
|
<strong>Human deafness mutation of myosin VI (C442Y) accelerates the ADP dissociation rate.</strong>
|
|
J. Biol. Chem. 279: 28844-28854, 2004.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15123708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15123708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15123708" 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.M314332200" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
|
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<a id="Vreugde2006" class="mim-anchor"></a>
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<div class="">
|
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<p class="mim-text-font">
|
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Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P. C., Crippa, M. P., Bussi, M., Biffo, S.
|
|
<strong>Nuclear myosin VI enhances RNA polymerase II-dependent transcription.</strong>
|
|
Molec. Cell 23: 749-755, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16949370/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16949370</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16949370" 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.molcel.2006.07.005" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="22" class="mim-anchor"></a>
|
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<a id="Wells1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wells, A. L., Lin, A. W., Chen, L.-Q., Safer, D., Cain, S. M., Hasson, T., Carragher, B. O., Milligan, R. A., Sweeney, H. L.
|
|
<strong>Myosin VI is an actin-based motor that moves backwards.</strong>
|
|
Nature 401: 505-508, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10519557/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10519557</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10519557" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/46835" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
|
|
</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
|
|
George E. Tiller - updated : 10/28/2010
|
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</span>
|
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</div>
|
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
George E. Tiller - updated : 6/23/2010<br>Marla J. F. O'Neill - updated : 12/18/2008<br>Kelly A. Przylepa - updated : 12/8/2008<br>Patricia A. Hartz - updated : 4/24/2007<br>Patricia A. Hartz - updated : 10/20/2006<br>Patricia A. Hartz - updated : 10/10/2006<br>Ada Hamosh - updated : 2/15/2006<br>George E. Tiller - updated : 1/31/2006<br>Cassandra L. Kniffin - updated : 7/16/2004<br>Stylianos E. Antonarakis - updated : 6/18/2004<br>Victor A. McKusick - updated : 4/29/2004<br>Victor A. McKusick - updated : 5/20/2003<br>Patricia A. Hartz - updated : 1/6/2003<br>Victor A. McKusick - updated : 1/7/2002<br>Victor A. McKusick - updated : 9/27/2001<br>Ada Hamosh - updated : 2/15/2000<br>Victor A. McKusick - updated : 8/22/1997
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
|
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</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
Victor A. McKusick : 1/5/1996
|
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
|
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
|
</span>
|
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</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 08/09/2024
|
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</span>
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
alopez : 05/24/2021<br>carol : 08/20/2018<br>alopez : 02/24/2016<br>wwang : 11/11/2010<br>terry : 10/28/2010<br>wwang : 7/1/2010<br>terry : 6/23/2010<br>wwang : 12/30/2008<br>terry : 12/18/2008<br>carol : 12/8/2008<br>terry : 12/8/2008<br>terry : 12/2/2008<br>terry : 12/2/2008<br>mgross : 4/25/2007<br>mgross : 4/24/2007<br>mgross : 4/24/2007<br>wwang : 12/1/2006<br>mgross : 11/6/2006<br>terry : 10/20/2006<br>wwang : 10/11/2006<br>terry : 10/10/2006<br>alopez : 2/15/2006<br>wwang : 2/7/2006<br>terry : 1/31/2006<br>tkritzer : 7/23/2004<br>ckniffin : 7/16/2004<br>mgross : 6/18/2004<br>tkritzer : 6/8/2004<br>tkritzer : 5/27/2004<br>terry : 4/29/2004<br>carol : 5/22/2003<br>terry : 5/20/2003<br>mgross : 1/7/2003<br>terry : 1/6/2003<br>carol : 1/17/2002<br>terry : 1/7/2002<br>carol : 10/2/2001<br>terry : 9/27/2001<br>alopez : 2/18/2000<br>alopez : 2/18/2000<br>terry : 2/15/2000<br>terry : 2/15/2000<br>terry : 8/22/1997<br>alopez : 7/30/1997<br>mark : 10/22/1996<br>terry : 10/14/1996<br>mark : 1/5/1996
|
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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|
|
<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
|
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<h3>
|
|
<span class="mim-font">
|
|
<strong>*</strong> 600970
|
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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 VI; MYO6
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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-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: MYO6</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>
|
|
Cytogenetic location: 6q14.1
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 6:75,749,239-75,919,537 </span>
|
|
</em>
|
|
</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>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="3">
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<span class="mim-font">
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6q14.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Deafness, autosomal dominant 22
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</span>
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</td>
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<td>
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<span class="mim-font">
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606346
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
|
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Deafness, autosomal dominant 22, with hypertrophic cardiomyopathy
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
606346
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Deafness, autosomal recessive 37
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
607821
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Myosin VI, one of the so-called unconventional myosins, is an actin-based molecular motor involved in intracellular vesicle and organelle transport (Rock et al., 2001; Hasson and Mooseker, 1994). Myosin VI participates in 2 steps of endocytic trafficking; it is recruited to both clathrin (see CLTC; 118955)-coated pits and to ensuing uncoated endocytic vesicles (Naccache et al., 2006). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Hasson and Mooseker (1994) characterized porcine myosin VI. Avraham et al. (1995) showed that the sequence of the mouse Myo6 gene is 87% identical to that of the pig. The mouse cDNA predicted a protein of 1,266 amino acids with a relative molecular mass of 142 kD. In the pig, rat, and mouse, myosin VI is widely expressed. In the mouse, within the cochlea of the inner ear, myosin VI is expressed specifically within the sensory hair cells. Avraham et al. (1995) found that the Myo6 gene is defective in the Snell's waltzer (sv) mouse mutant, which is associated with deafness. Together with the expression pattern in the sensory hair cells of the cochlea, this suggested to the authors that myosin VI is required for normal hearing and that the human homolog is a candidate for a human recessive deafness gene. </p><p>Avraham et al. (1997) cloned and characterized the human MYO6 cDNA. Expression of MYO6 in human fetal cochlea demonstrated the importance of myosin VI in the mammalian inner ear and supported its potential role in human inner ear pathology. </p><p>Vreugde et al. (2006) identified 5 putative monopartite nuclear localization signals and 1 putative bipartite nuclear localization signal in MYO6, mainly in the tail region. In the first part of the tail region, they identified a putative protein-protein interaction domain consisting of glutamic acid- and arginine-rich regions. Immunofluorescence and cellular fractionation of human and other mammalian cells revealed a proportion of MYO6 in the nucleus, where it colocalized with RNA polymerase II (see 180660) and nascent transcripts. MYO6 in the nuclear fraction had an apparent molecular mass of 150 kD. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Ahituv et al. (2000) determined that the MYO6 gene contains 32 exons and spans 70 kb. They found that exon 30, which contains a putative casein kinase II (see 115440) site, is alternatively spliced and appears only in fetal and adult brain. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Avraham et al. (1995) suggested that the human MYO6 gene may map to the centromeric region of chromosome 6, a region that shows syntenic homology with the portion of mouse chromosome 9 where the Snell's waltzer (sv) mouse mutation is located. On the basis of location of the Myo6 gene in the mouse, Hasson et al. (1996) predicted that the homologous human gene is located on 6p12-q16.3. By fluorescence in situ hybridization, Avraham et al. (1997) mapped the MYO6 gene to 6q13. In the mouse, Myo6 maps between Gsta and Htr1b; the human homologs, GSTA2 (138360) and HTR1B (182131), both map to chromosome 6. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
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</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Rock et al. (2001) noted that myosin VI moves toward the pointed end of actin (see 102560), whereas all other characterized myosins move toward the barbed end. They found that porcine myosin VI took much larger steps than expected. Unlike other characterized myosins, myosin VI stepping was highly irregular, with a broad distribution of step sizes. </p><p>Rock et al. (2005) showed that the proximal tail region of porcine myosin VI is a flexible domain that permits the myosin heads to separate and allows the large and variable step size of myosin VI. </p><p>MYO6 is thought to function as both a transporter and an anchor. Altman et al. (2004) noted that in vitro studies had suggested possible mechanisms for processive stepping, but a biochemical basis for anchoring had not been demonstrated. Using optical trapping, they observed MYO6 stepping against applied forces. Step size was not strongly affected by such loads. At saturating ATP, MYO6 kinetics showed little dependence on load until, at forces near stall, its stepping slowed dramatically as load increased. At subsaturating ATP or in the presence of ADP, stepping kinetics were significantly inhibited by load. </p><p>Naccache et al. (2006) found that Myo6 recruitment to uncoated endocytic vesicles in cultured mouse kidney epithelial cells was dependent on synectin (GIPC1; 605072). Myo6 bound a C-terminal domain of synectin, and Myo6 recruitment required the interaction between the PDZ-binding domains of engulfed receptors, such as megalin (LRP2; 600073), and the PDZ domain of synectin. </p><p>Vreugde et al. (2006) found that colocalization and interaction of MYO6 with RNA polymerase II required transcriptional activity. Pharmacologic blockade of transcription resulted in redistribution of nuclear MYO6 to the cytoplasm. Chromatin immunoprecipitation assays showed that MYO6 was recruited to the promoters and intragenic regions of active genes, but not to noncoding, nonregulatory intergenic regions. Downregulation of MYO6 reduced steady-state mRNA levels of the regulated genes in vivo, and antibodies to MYO6 reduced transcription in vitro. Vreugde et al. (2006) concluded that MYO6 modulates RNA polymerase II-dependent transcription of active genes and suggested that an actin-myosin-based mechanism may be involved in transcription. </p><p>Otoferlin (OTOF; 603681) has been proposed to be the calcium sensor in hair cell exocytosis, compensating for the classic synaptic fusion proteins synaptotagmin-1 (SYT1; 185605) and synaptotagmin-2 (SYT2; 600104). Heidrych et al. (2009) demonstrated in a yeast 2-hybrid assay that myosin VI is a novel otoferlin-binding partner. Coimmunoprecipitation assay and coexpression suggested an interaction of both proteins within the basolateral part of inner hair cells (IHCs). Comparison of Otof- and Myo6-mutant mice indicated noncomplementary and complementary roles of myosin VI and otoferlin for synaptic maturation. IHCs from Otof-mutant mice exhibited a decoupling of Ctbp2 (602619) and CaV1.3 (CACNA1D; 114206) and severe reduction of exocytosis. Myo6-mutant IHCs failed to transport BK channels to the membrane of the apical cell regions, and the exocytotic Ca(2+) efficiency did not mature. Otof- and Myo6-mutant IHCs showed a reduced basolateral synaptic surface area and altered active zone topography. Membrane infoldings in Otof-mutant IHCs indicated disturbed transport of endocytotic membranes and linked the above morphologic changes to a complementary role of otoferlin and myosin VI in transport of intracellular compartments to the basolateral inner hair cell membrane. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Biochemical Features</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Cryoelectron Microscopy</em></strong></p><p>
|
|
Wells et al. (1999) visualized the myosin VI construct bound to actin (see 102560) using cryoelectron microscopy and image analysis, and found that an ADP-mediated conformational change in the domain distal to the motor, a structure likely to be the effective lever arm, is in the opposite direction to that observed for other myosins. Wells et al. (1999) concluded that myosin VI achieves reverse-direction movement by rotating its lever arm in the opposite direction to conventional myosin lever arm movement. </p><p><strong><em>Crystal Structure</em></strong></p><p>
|
|
Menetrey et al. (2005) solved the crystal structure of a truncated version of the reverse-direction myosin motor, myosin VI, containing the motor domain and binding sites of 2 calmodulin (114180) molecules at a resolution of 2.4 angstroms. The structure revealed only minor differences in the motor domain from that in plus end-directed myosins, with the exception of 2 unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective lever arm of myosin VI, which includes a second calmodulin bound to an IQ motif, towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. Menetrey et al. (2005) proposed a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI. </p><p><strong><em>Electron Microscopy</em></strong></p><p>
|
|
Roux et al. (2009) showed that Myo6 was present at the synaptic active zone of IHCs by immunogold electron microscopy. In Myo6(sv/sv) mice, ionic currents and ribbon synapse maturation of IHCs proceeded normally until at least postnatal day 6. In adult Myo6(sv/sv) mice, however, the IHCs displayed immature potassium currents and still fired action potentials, as normally only observed in immature IHCs. In addition, the number of ribbons per IHC was reduced, and some of the remaining ribbons were morphologically immature. Calcium-dependent exocytosis was markedly reduced despite normal calcium currents and a large proportion of morphologically mature synapses. Yeast 2-hybrid assay, in vitro binding assays, and immunoprecipitation studies of transfected HEK-293 cells and mouse cochlear sensory epithelium showed direct interaction of Myo6 and otoferlin (OTOF; 603681). Immunogold electron microscopy showed that Myo6 and otoferlin colocalized at the edge of the synaptic active zone in mouse IHCs. Roux et al. (2009) suggested that MYO6/otoferlin interaction may be involved in the recycling of synaptic vesicles. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
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</h4>
|
|
</div>
|
|
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|
<span class="mim-text-font">
|
|
<p><strong><em>Deafness, Autosomal Dominant 22</em></strong></p><p>
|
|
In a large family segregating autosomal dominant nonsyndromic sensorineural hearing loss, Melchionda et al. (2001) demonstrated linkage of the disorder to 6q13 (DFNA22; 606346) and identified a missense mutation in the MYO6 gene (C442Y; 600970.0001) in all affected members. </p><p>In affected members of a kindred in which autosomal dominant sensorineural deafness cosegregated with familial hypertrophic cardiomyopathy, Mohiddin et al. (2004) identified a his246-to-arg mutation in the MYO6 gene (H246R; 600970.0005). </p><p>In a large Danish family with 18 affected members segregating autosomal dominant nonsyndromic hearing loss (DFNA22; 606346), Sanggaard et al. (2008) detected heterozygosity for a nonsense mutation in the MYO6 gene (R849X; 600970.0006). </p><p>Hilgert et al. (2008) analyzed the MYO6 gene in 2 Belgian families with autosomal dominant deafness mapping to the DFNA22 locus and identified a splice site mutation (600970.0007) in 'family 2.' No mutation was identified in 'family 1,' although quantitative real-time PCR revealed 1.5- to 1.8-fold overexpression of MYO6 in patients compared to controls. After exclusion of gene duplication, the authors suggested that most likely the overexpression in 'family 1' involved a mutation in an as yet unidentified regulatory region of the MYO6 gene. </p><p><strong><em>Deafness, Autosomal Dominant 22, with Hypertrophic Cardiomyopathy</em></strong></p><p>
|
|
In affected members of a kindred in which autosomal dominant sensorineural deafness cosegregated with familial hypertrophic cardiomyopathy (see 606346), Mohiddin et al. (2004) identified a heterozygous missense mutation in the MYO6 gene (H246R; 600970.0005). </p><p><strong><em>Deafness, Autosomal Recessive 37</em></strong></p><p>
|
|
Ahmed et al. (2003) identified mutations in the MYO6 gene in 3 families segregating autosomal recessive congenital sensorineural deafness (DFNB37; 607821); see 600970.0002-600970.0004. </p>
|
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>Geisbrecht and Montell (2002) found that depletion of Myo6 from a small group of migratory follicle cells of Drosophila, known as border cells, inhibited their migration. Cells lacking Myo6 also lacked E-cadherin (192090) and beta-catenin (116806). Conversely, cells lacking E-cadherin or beta-catenin showed reduced levels of Myo6. Geisbrecht and Montell (2002) concluded that, in Drosophila, Myo6 is required for border cell migration where it stabilizes E-cadherin and beta-catenin. </p><p>The MYO15 (602666), MYO6, and MYO7A (276903) genes are essential for hearing in both humans and mice. Despite widespread expression, homozygosity for mutations in these genes only results in auditory or ocular dysfunction. The pirouette (pi) mouse exhibits deafness and inner ear pathology resembling that of Myo15 mutant mice. Karolyi et al. (2003) crossed Myo15 mutant mice to Myo6, Myo7a, and pi mutant mouse strains. Viable double-mutant homozygotes were obtained from each cross, and hearing in doubly heterozygous mice was similar to singly heterozygous mice. All critical cell types of the cochlear sensory epithelium were present in double-mutant mice, and cochlear stereocilia exhibited a superimposition of single-mutant phenotypes. Karolyi et al. (2003) suggested that the function of Myo15 is distinct from that of Myo6, Myo7a, or pi in development and/or maintenance of stereocilia. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>7 Selected Examples):</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DEAFNESS, AUTOSOMAL DOMINANT 22</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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MYO6, CYS442TYR
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<br />
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SNP: rs121912557,
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ClinVar: RCV000009108
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>Melchionda et al. (2001) studied a large Italian kindred affected by progressive, postlingual sensorineural deafness linked to chromosome 6q13 (606346). Mutation analysis of the MYO6 gene demonstrated that all affected members of the family had a G-to-A transition in exon 12 at position 1325 of the cDNA sequence (relative to the ATG, designated +1), which replaces a cysteine (TGT) with a tyrosine (TAT) at residue 442 of the protein (C442Y). </p><p>By in vitro expression studies, Sato et al. (2004) found that the C442Y mutation caused several major changes in myosin VI mechanoenzymatic function. The C442Y mutant protein had an approximately 10-fold increase in the rate of ADP dissociation from myosin VI, and there was an approximately 10-fold increase in the ATPase rate in the absence of actin compared to wildtype. There was a 2-fold increase in the actin gliding velocity of the mutant protein compared to wildtype. The findings suggested that the mutation impedes the processive movement of myosin VI. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0002 DEAFNESS, AUTOSOMAL RECESSIVE 37</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MYO6, 1-BP INS, 36T
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<br />
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SNP: rs1562201376,
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ClinVar: RCV000009109
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; 607821), Ahmed et al. (2003) identified homozygosity for a 1-bp insertion (36insT) in exon 2 of the MYO6 gene in all 6 affected individuals. The insertion was predicted to cause a frameshift and premature translation termination after the first 12 amino acids of myosin VI. The oldest affected child also had congenital stationary night blindness and retinal pigment epithelial changes; the other 5 affected children with profound deafness were less than 30 months of age. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0003 DEAFNESS, AUTOSOMAL RECESSIVE 37</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MYO6, ARG1166TER
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<br />
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SNP: rs121912558,
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ClinVar: RCV000009110, RCV001582472
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; 607821), Ahmed et al. (2003) identified homozygosity for a 3496C-T transition in exon 32 of the MYO6 gene, resulting in an arg1166-to-ter (R1166X) substitution, in all affected members. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 DEAFNESS, AUTOSOMAL RECESSIVE 37</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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MYO6, GLU216VAL
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<br />
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|
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SNP: rs121912559,
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gnomAD: rs121912559,
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|
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ClinVar: RCV000009111, RCV000767071, RCV000987740
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|
</span>
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|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a Pakistani family segregating autosomal recessive congenital profound sensorineural deafness (DFNB37; 607821), Ahmed et al. (2003) identified homozygosity for a 647A-T transversion in the MYO6 gene, resulting in a glu216-to-val (E216V) substitution, in the single affected member. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 DEAFNESS, AUTOSOMAL DOMINANT 22, WITH HYPERTROPHIC CARDIOMYOPATHY</strong>
|
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</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
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MYO6, HIS246ARG
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<br />
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|
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SNP: rs121912560,
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gnomAD: rs121912560,
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|
|
|
|
ClinVar: RCV000219073, RCV001582473, RCV004691086
|
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|
|
|
|
</span>
|
|
</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In affected members of a kindred in which autosomal dominant deafness-22 cosegregated with familial hypertrophic cardiomyopathy (see 606346), Mohiddin et al. (2004) identified a 737A-G transition in the MYO6 gene, resulting in a his246-to-arg (H246R) mutation within the highly conserved motor domain of the protein. The sensorineural hearing loss, which was progressive and late in onset, was present in 10 members, 4 of whom also had hypertrophic cardiomyopathy. Six had sensorineural hearing loss without echocardiographic evidence of left ventricular hypertrophy; 4 of these 6 patients, however, had abnormalities on 12-lead ECG, and 3 of the 6 had prolongation of the QT interval. Cardiac symptoms were mild or absent in most affected family members. Mohiddin et al. (2004) suggested that the cardiac manifestations may have escaped detection in affected members of previously reported pedigrees with MYO6-associated sensorineural hearing loss. </p>
|
|
</span>
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</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 DEAFNESS, AUTOSOMAL DOMINANT 22</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
MYO6, ARG849TER
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<br />
|
|
|
|
SNP: rs121912561,
|
|
|
|
|
|
gnomAD: rs121912561,
|
|
|
|
|
|
ClinVar: RCV000009113, RCV000605133, RCV003555982
|
|
|
|
|
|
</span>
|
|
</div>
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|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Danish family with postlingual sensorineural hearing loss mapping to chromosome 6p12.1-q16.1 (606346), Sanggaard et al. (2008) identified a heterozygous 2545C-T transition in exon 25 of the MYO6 gene, resulting in an arg849-to-ter (R849X) mutation. </p>
|
|
</span>
|
|
</div>
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<div>
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|
<br />
|
|
</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>.0007 DEAFNESS, AUTOSOMAL DOMINANT 22</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
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|
MYO6, IVS23, T-G, +2321
|
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|
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<br />
|
|
|
|
SNP: rs1562283089,
|
|
|
|
|
|
|
|
ClinVar: RCV000009114
|
|
|
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|
|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 11 affected members of a 5-generation Belgian family ('family 2') segregating autosomal dominant deafness (DFNA22; 606346), Hilgert et al. (2008) identified heterozygosity for a 2321T-G transversion in intron 23 of the MYO6 gene, creating a new splice donor site and resulting in the insertion of a 108-bp intronic fragment that causes a frameshift and a premature termination codon 16 nucleotides downstream of exon 23. The mutation was not found in unaffected family members or in 139 unrelated ethnically matched controls. Expression assays showed that patients had 80-85% of the MYO6 expression level of unaffected individuals, but the difference was not statistically significant. </p>
|
|
</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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<div>
|
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<ol>
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<li>
|
|
<p class="mim-text-font">
|
|
Ahituv, N., Sobe, T., Robertson, N. G., Morton, C. C., Taggart, R. T., Avraham, K. B.
|
|
<strong>Genomic structure of the human unconventional myosin VI gene.</strong>
|
|
Gene 261: 269-275, 2000.
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|
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|
|
[PubMed: 11167014]
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[Full Text: https://doi.org/10.1016/s0378-1119(00)00535-7]
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</p>
|
|
</li>
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<li>
|
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<p class="mim-text-font">
|
|
Ahmed, Z. M., Morell, R. J., Riazuddin, S., Gropman, A., Shaukat, S., Ahmad, M. M., Mohiddin, S. A., Fananapazir, L., Caruso, R. C., Husnain, T., Khan, S. N., Riazuddin, S., Griffith, A. J., Friedman, T. B., Wilcox, E. R.
|
|
<strong>Mutations of MYO6 are associated with recessive deafness, DFNB37.</strong>
|
|
Am. J. Hum. Genet. 72: 1315-1322, 2003.
|
|
|
|
|
|
[PubMed: 12687499]
|
|
|
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|
|
[Full Text: https://doi.org/10.1086/375122]
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</p>
|
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</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Altman, D., Sweeney, H. L., Spudich, J. A.
|
|
<strong>The mechanism of myosin VI translocation and its load-induced anchoring.</strong>
|
|
Cell 116: 737-749, 2004.
|
|
|
|
|
|
[PubMed: 15006355]
|
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|
|
[Full Text: https://doi.org/10.1016/s0092-8674(04)00211-9]
|
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</p>
|
|
</li>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Avraham, K. B., Hasson, T., Sobe, T., Balsara, B., Testa, J. R., Skvorak, A. B., Morton, C. C., Copeland, N. G., Jenkins, N. A.
|
|
<strong>Characterization of unconventional MYO6, the human homologue of the gene responsible for deafness in Snell's waltzer mice.</strong>
|
|
Hum. Molec. Genet. 6: 1225-1231, 1997.
|
|
|
|
|
|
[PubMed: 9259267]
|
|
|
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|
|
[Full Text: https://doi.org/10.1093/hmg/6.8.1225]
|
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|
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</p>
|
|
</li>
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Avraham, K. B., Hasson, T., Steel, K. P., Kingsley, D. M., Russell, L. B., Mooseker, M. S., Copeland, N. G., Jenkins, N. A.
|
|
<strong>The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cells.</strong>
|
|
Nature Genet. 11: 369-375, 1995.
|
|
|
|
|
|
[PubMed: 7493015]
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|
|
|
|
|
[Full Text: https://doi.org/10.1038/ng1295-369]
|
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</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Geisbrecht, E. R., Montell, D. J.
|
|
<strong>Myosin VI is required for E-cadherin-mediated border cell migration.</strong>
|
|
Nature Cell Biol. 4: 616-620, 2002.
|
|
|
|
|
|
[PubMed: 12134162]
|
|
|
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|
|
[Full Text: https://doi.org/10.1038/ncb830]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hasson, T., Mooseker, M. S.
|
|
<strong>Porcine myosin-VI: characterization of a new mammalian unconventional myosin.</strong>
|
|
J. Cell. Biol. 127: 425-440, 1994.
|
|
|
|
|
|
[PubMed: 7929586]
|
|
|
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|
|
[Full Text: https://doi.org/10.1083/jcb.127.2.425]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hasson, T., Skowron, J. F., Gilbert, D. J., Avraham, K. B., Perry, W. L., Bement, W. M., Anderson, B. L., Sherr, E. H., Chen, Z.-Y., Greene, L. A., Ward, D. C., Corey, D. P., Mooseker, M. S., Copeland, N. G., Jenkins, N. A.
|
|
<strong>Mapping of unconventional myosins in mouse and human.</strong>
|
|
Genomics 36: 431-439, 1996.
|
|
|
|
|
|
[PubMed: 8884266]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0488]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heidrych, P., Zimmermann, U., Kuhn, S., Franz, C., Engel, J., Duncker, S. V., Hirt, B., Pusch, C. M., Ruth, P., Pfister, M., Marcotti, W., Blin, N., Knipper, M.
|
|
<strong>Otoferlin interacts with myosin VI: implications for maintenance of the basolateral synaptic structure of the inner hair cell.</strong>
|
|
Hum. Molec. Genet. 18: 2779-2790, 2009.
|
|
|
|
|
|
[PubMed: 19417007]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp213]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hilgert, N., Topsakal, V., van Dinther, J., Offeciers, E., Van de Heyning, P., Van Camp. G.
|
|
<strong>A splice-site mutation and overexpression of MYO6 cause a similar phenotype in two families with autosomal dominant hearing loss.</strong>
|
|
Europ. J. Hum. Genet. 16: 593-602, 2008.
|
|
|
|
|
|
[PubMed: 18212818]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/sj.ejhg.5202000]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Karolyi, I. J., Probst, F. J., Beyer, L., Odeh, H., Dootz, G., Cha, K. B., Martin, D. M., Avraham, K. B., Kohrman, D., Dolan, D. F., Raphael, Y., Camper, S. A.
|
|
<strong>Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.</strong>
|
|
Hum. Molec. Genet. 12: 2797-2805, 2003.
|
|
|
|
|
|
[PubMed: 12966030]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddg308]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Melchionda, S., Ahituv, N., Bisceglia, L., Sobe, T., Glaser, F., Rabionet, R., Arbones, M. L., Notarangelo, A., Di Iorio, E., Carella, M., Zelante, L., Estivill, X., Avraham, K. B., Gasparini, P.
|
|
<strong>MYO6, the human homologue of the gene responsible for deafness in Snell's Waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss.</strong>
|
|
Am. J. Hum. Genet. 69: 635-640, 2001.
|
|
|
|
|
|
[PubMed: 11468689]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1086/323156]
|
|
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Menetrey, J., Bahloul, A., Wells, A. L., Yengo, C. M., Morris, C. A., Sweeney, H. L., Houdusse, A.
|
|
<strong>The structure of the myosin VI motor reveals the mechanism of directionality reversal.</strong>
|
|
Nature 435: 779-785, 2005.
|
|
|
|
|
|
[PubMed: 15944696]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1038/nature03592]
|
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|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mohiddin, S. A., Ahmed, Z. M., Griffith, A. J., Tripodi, D., Friedman, T. B., Fananapazir, L., Morell, R. J.
|
|
<strong>Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6). (Letter)</strong>
|
|
J. Med. Genet. 41: 309-314, 2004.
|
|
|
|
|
|
[PubMed: 15060111]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1136/jmg.2003.011973]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Naccache, S. N., Hasson, T., Horowitz, A.
|
|
<strong>Binding of internalized receptors to the PDZ domain of GIPC/synectin recruits myosin VI to endocytic vesicles.</strong>
|
|
Proc. Nat. Acad. Sci. 103: 12735-12740, 2006. Note: Erratum: Proc. Nat. Acad. Sci. 103: 15272 only, 2006.
|
|
|
|
|
|
[PubMed: 16908842]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.0605317103]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rock, R. S., Ramamurthy, B., Dunn, A. R., Beccafico, S., Rami, B. R., Morris, C., Spink, B. J., Franzini-Armstrong, C., Spudich, J. A., Sweeney, H. L.
|
|
<strong>A flexible domain is essential for the large step size and processivity of myosin VI.</strong>
|
|
Molec. Cell 17: 603-609, 2005.
|
|
|
|
|
|
[PubMed: 15721263]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.molcel.2005.01.015]
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Rock, R. S., Rice, S. E., Wells, A. L., Purcell, T. J., Spudich, J. A., Sweeney, H. L.
|
|
<strong>Myosin VI is a processive motor with a large step size.</strong>
|
|
Proc. Nat. Acad. Sci. 98: 13655-13659, 2001.
|
|
|
|
|
|
[PubMed: 11707568]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.191512398]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Roux, I., Hosie, S., Johnson, S. L., Bahloul, A., Cayet, N., Nouaille, S., Kros, C. J., Petit, C., Safieddine, S.
|
|
<strong>Myosin VI is required for the proper maturation and function of inner hair cell ribbon synapses.</strong>
|
|
Hum. Molec. Genet. 18: 4615-4628, 2009.
|
|
|
|
|
|
[PubMed: 19744958]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddp429]
|
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|
|
</p>
|
|
</li>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sanggaard, K. M., Kjaer, K. W., Eiberg, H., Nurnberg, G., Nurnberg, P., Hoffman, K., Jensen, H., Sorum, C., Rendtorff, N. D., Tranebjaerg, L.
|
|
<strong>A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic hearing loss in a Danish DFNA22 family.</strong>
|
|
Am. J. Med. Genet. 146A: 1017-1025, 2008.
|
|
|
|
|
|
[PubMed: 18348273]
|
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|
|
[Full Text: https://doi.org/10.1002/ajmg.a.32174]
|
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|
|
</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Sato, O., White, H. D., Inoue, A., Belknap, B., Ikebe, R., Ikebe, M.
|
|
<strong>Human deafness mutation of myosin VI (C442Y) accelerates the ADP dissociation rate.</strong>
|
|
J. Biol. Chem. 279: 28844-28854, 2004.
|
|
|
|
|
|
[PubMed: 15123708]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M314332200]
|
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|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Vreugde, S., Ferrai, C., Miluzio, A., Hauben, E., Marchisio, P. C., Crippa, M. P., Bussi, M., Biffo, S.
|
|
<strong>Nuclear myosin VI enhances RNA polymerase II-dependent transcription.</strong>
|
|
Molec. Cell 23: 749-755, 2006.
|
|
|
|
|
|
[PubMed: 16949370]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.molcel.2006.07.005]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Wells, A. L., Lin, A. W., Chen, L.-Q., Safer, D., Cain, S. M., Hasson, T., Carragher, B. O., Milligan, R. A., Sweeney, H. L.
|
|
<strong>Myosin VI is an actin-based motor that moves backwards.</strong>
|
|
Nature 401: 505-508, 1999.
|
|
|
|
|
|
[PubMed: 10519557]
|
|
|
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[Full Text: https://doi.org/10.1038/46835]
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George E. Tiller - updated : 10/28/2010<br>George E. Tiller - updated : 6/23/2010<br>Marla J. F. O'Neill - updated : 12/18/2008<br>Kelly A. Przylepa - updated : 12/8/2008<br>Patricia A. Hartz - updated : 4/24/2007<br>Patricia A. Hartz - updated : 10/20/2006<br>Patricia A. Hartz - updated : 10/10/2006<br>Ada Hamosh - updated : 2/15/2006<br>George E. Tiller - updated : 1/31/2006<br>Cassandra L. Kniffin - updated : 7/16/2004<br>Stylianos E. Antonarakis - updated : 6/18/2004<br>Victor A. McKusick - updated : 4/29/2004<br>Victor A. McKusick - updated : 5/20/2003<br>Patricia A. Hartz - updated : 1/6/2003<br>Victor A. McKusick - updated : 1/7/2002<br>Victor A. McKusick - updated : 9/27/2001<br>Ada Hamosh - updated : 2/15/2000<br>Victor A. McKusick - updated : 8/22/1997
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Victor A. McKusick : 1/5/1996
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