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<title>
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Entry
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- *173325 - JUNCTION PLAKOGLOBIN; JUP
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- OMIM
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</ul>
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</nav>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="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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<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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</form>
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<p />
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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">*173325</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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</li>
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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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/173325">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
|
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</a>
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</span>
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</span>
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</div>
|
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000173801;t=ENST00000393931" 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=3728" 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=173325" 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=ENSG00000173801;t=ENST00000393931" 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_001352773,NM_001352774,NM_001352775,NM_001352776,NM_001352777,NM_002230,NM_021991,XM_006721874,XM_006721875,XM_011524758,XM_017024590,XM_047435934,XM_047435935,XM_047435937,XM_047435938,XM_047435939,XM_047435940,XM_047435941,XM_047435942" 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_002230" 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=173325" 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=01414&isoform_id=01414_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/JUP" 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/762885,1122889,1127022,4504811,9886707,10334699,12056468,15080189,29650759,33875446,119581166,119581167,119581168,119581169,157391349,158065980,205371866,211637695,218102999,444732959,578830868,578830870,767994651,957949665,957949668,1034599580,1209185216,1209185242,1209185278,1209185288,1209185293,2217311605,2217311607,2217311609,2217311614,2217311616,2217311618,2217311620,2217311622,2462554990,2462554992,2462554994,2462554996,2462554998,2462555000,2462555002,2462555004,2462555006,2462555008,2462555010" 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/P14923" 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=3728" 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=ENSG00000173801;t=ENST00000393931" 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=JUP" 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=JUP" 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+3728" 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/JUP" 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:3728" 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/3728" 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=chr17&hgg_gene=ENST00000393931.8&hgg_start=41754609&hgg_end=41786711&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=173325[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=173325[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000173801" 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=JUP" 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=JUP" 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=JUP" 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://www.LOVD.nl/JUP" title="ARVD/C Genetic Variants Database (JUP)" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">ARVD/C Genetic Variants Da…</a></div><div style="margin-left: 0.5em;"><a href="http://www.arvcdatabase.info" title="ARVD/C Genes Variants Database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">ARVD/C Genes Variants Data…</a></div><div style="margin-left: 0.5em;"><a href="http://www.fsm.it/cardmoc/" title="Gene Connection for the Heart; Naxos disease database" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Gene Connection for the He…</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=JUP&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/PA30009" 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:6207" 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/FBgn0000117.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:96650" 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/JUP#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:96650" 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/3728/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=3728" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00001979;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-110407-10" 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:3728" 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=JUP&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 715535009<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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173325
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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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JUNCTION PLAKOGLOBIN; JUP
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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PLAKOGLOBIN; PKGB<br />
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DESMOPLAKIN III; DP3<br />
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DP III<br />
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CATENIN, GAMMA
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=JUP" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">JUP</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/17/555?start=-3&limit=10&highlight=555">17q21.2</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr17:41754609-41786711&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'})">17:41,754,609-41,786,711</a> </span>
|
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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?Arrhythmogenic right ventricular dysplasia 12
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/173325" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>Plakoglobin is a major cytoplasmic protein that occurs in a soluble and a membrane-associated form and is the only known constituent common to the submembranous plaques of both kinds of adhering junctions, the desmosomes and the intermediate junctions. It is a desmoplakin (see <a href="/entry/125647">125647</a>) and is referred to as DP III. DP I and DP II are splice variants of the same gene. Using a partial cDNA clone for bovine plakoglobin, <a href="#9" class="mim-tip-reference" title="Franke, W. W., Goldschmidt, M. D., Zimbelmann, R., Mueller, H. M., Schiller, D. L., Cowin, P. <strong>Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein.</strong> Proc. Nat. Acad. Sci. 86: 4027-4031, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2726765/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2726765</a>] [<a href="https://doi.org/10.1073/pnas.86.11.4027" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2726765">Franke et al. (1989)</a> isolated cDNAs encoding human plakoglobin, determined its nucleotide sequence, and deduced the complete amino acid sequence. The polypeptide encoded by the cDNA was synthesized by in vitro transcription and translation and identified by its comigration with authentic plakoglobin in 2-dimensional gel electrophoresis. The protein, which has 744 amino acids and a molecular weight of 81,750 Da, is highly conserved between human and bovine tissues. Only one kind of plakoglobin mRNA (3.4 kb) was found in most tissues, but an additional mRNA (3.7 kb) was detected in certain human tumor cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2726765" 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>Plakoglobin associates with the cytoplasmic region of desmoglein I (<a href="/entry/125670">125670</a>), one of the transmembrane desmosomal proteins (<a href="#14" class="mim-tip-reference" title="Mathur, M., Goodwin, L., Cowin, P. <strong>Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg1 with plakoglobin.</strong> J. Biol. Chem. 269: 14075-14080, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8188687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8188687</a>]" pmid="8188687">Mathur et al., 1994</a>). It also is a component of the cadherin (see <a href="/entry/192090">192090</a>)-catenin complex, which is predominantly localized where actin filaments anchor in adherens junctions of epithelial cells (<a href="#11" class="mim-tip-reference" title="Knudsen, K. A., Wheelock, M. J. <strong>Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin.</strong> J. Cell Biol. 118: 671-679, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1639850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1639850</a>] [<a href="https://doi.org/10.1083/jcb.118.3.671" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1639850">Knudsen and Wheelock, 1992</a>). <a href="#1" class="mim-tip-reference" title="Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R. <strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong> Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>] [<a href="https://doi.org/10.1073/pnas.92.14.6384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604000">Aberle et al. (1995)</a> stated that catenins are of central importance for cadherin function in that they mediate the connection of cadherins to actin filaments and are part of a higher order submembranous network by which cadherins are linked to other transmembrane and peripheral cytoplasmic proteins. Interaction of the cadherin-catenin complex with epidermal growth factor receptor (EGFR; <a href="/entry/131550">131550</a>) and the finding that beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>) and plakoglobin are substrates for tyrosine phosphorylation following EGF stimulation of cells, together with the finding that catenins are associated with the tumor suppressor protein APC (<a href="/entry/611731">611731</a>), open the possibility that catenins are involved in signaling pathways and tumorigenesis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1639850+7604000+8188687" 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>Beta-catenin and gamma-catenin, vertebrate homologs of Drosophila armadillo, function in cell adhesion and the Wnt (e.g., WNT1; <a href="/entry/164820">164820</a>) signaling pathway. In colon and other cancers, mutations in the APC tumor suppressor protein or beta-catenin's N terminus stabilize beta-catenin, enhancing its ability to activate transcription of TCF (e.g., TCF7; <a href="/entry/189908">189908</a>)/LEF (e.g., LEF1; <a href="/entry/153245">153245</a>) target genes. Beta- and gamma-catenin have analogous structures and functions and like binding to APC. <a href="#12" class="mim-tip-reference" title="Kolligs, F. T., Kolligs, B., Hajra, K. M., Hu, G., Tani, M., Cho, K. R., Fearon, E. R. <strong>Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin.</strong> Genes Dev. 14: 1319-1331, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10837025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10837025</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10837025[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10837025">Kolligs et al. (2000)</a> reported that APC regulates both beta- and gamma-catenin and gamma-catenin functions as an oncogene. In contrast to beta-catenin, for which only N-terminal mutated forms transform RK3E epithelial cells, wildtype and several N-terminal mutated forms of gamma-catenin had similar transforming activity. The transforming activity of gamma-catenin, like that of beta-catenin, was dependent on TCF/LEF function. However, in contrast to beta-catenin, gamma-catenin strongly activated c-myc (<a href="/entry/190080">190080</a>) expression and c-myc function was crucial for gamma-catenin transformation. <a href="#12" class="mim-tip-reference" title="Kolligs, F. T., Kolligs, B., Hajra, K. M., Hu, G., Tani, M., Cho, K. R., Fearon, E. R. <strong>Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin.</strong> Genes Dev. 14: 1319-1331, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10837025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10837025</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10837025[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>]" pmid="10837025">Kolligs et al. (2000)</a> suggested that APC mutations alter regulation of both beta- and gamma-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of beta-catenin mutations. Elevated c-myc expression in cancers with APC defects may be due to altered regulation of both beta- and gamma-catenin. Furthermore, the authors stated that their data imply beta- and gamma-catenin may have distinct roles in Wnt signaling and cancer via differential effects on downstream target genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10837025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Arnemann, J., Spurr, N. K., Wheeler, G. N., Parker, A. E., Buxton, R. S. <strong>Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP).</strong> Genomics 10: 640-645, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1889810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1889810</a>] [<a href="https://doi.org/10.1016/0888-7543(91)90446-l" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1889810">Arnemann et al. (1991)</a> established a PCR assay for the gene encoding plakoglobin and used it to test human/mouse and human/rat somatic cell hybrids with different contents of human chromosomes. In this way, they were able to assign DP3 to chromosome 7. By analysis of progeny from 2 interspecific backcrosses, <a href="#10" class="mim-tip-reference" title="Guenet, J.-L., Simon-Chazottes, D., Ringwald, M., Kemler, R. <strong>The genes coding for alpha and beta catenin (Catna1 and Catnb) and plakoglobin (Jup) map to mouse chromosomes 18, 9, and 11, respectively.</strong> Mammalian Genome 6: 363-366, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7626889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7626889</a>] [<a href="https://doi.org/10.1007/BF00364802" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7626889">Guenet et al. (1995)</a> mapped the Jup gene to mouse chromosome 11. Thus, the human JUP gene is probably on 7p because that is the portion of the chromosome showing homology of synteny to mouse 11. However, mouse 11 shows much more extensive homology to human chromosome 17 and, indeed, <a href="#1" class="mim-tip-reference" title="Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R. <strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong> Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>] [<a href="https://doi.org/10.1073/pnas.92.14.6384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604000">Aberle et al. (1995)</a> mapped the plakoglobin gene to 17q12-q22 by analysis of DNA from human/hamster or human/mouse hybrid cell lines that contained only human chromosome 17 or parts thereof. Because of evolutionary conservation, human plakoglobin cDNA hybridized also to mouse and hamster DNA; however, the results obtained with DNA from hybrid cells unambiguously demonstrated that the human gene maps to chromosome 17q12-q22. The previously reported localization to chromosome 7 was based on PCR analysis using synthetic oligonucleotides and was not confirmed by independent work by <a href="#1" class="mim-tip-reference" title="Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R. <strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong> Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>] [<a href="https://doi.org/10.1073/pnas.92.14.6384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604000">Aberle et al. (1995)</a>. Using a monochromosomal human-rodent somatic cell hybrid panel, <a href="#7" class="mim-tip-reference" title="Cowley, C. M. E., Simrak, D., Spurr, N. K., Arnemann, J., Buxton, R. S. <strong>The plakophilin 1 (PKP1) and plakoglobin (JUP) genes map to human chromosomes 1q and 17, respectively.</strong> Hum. Genet. 100: 486-488, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9272178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9272178</a>] [<a href="https://doi.org/10.1007/s004390050539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9272178">Cowley et al. (1997)</a> likewise showed that the JUP gene is located on chromosome 17. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7626889+7604000+9272178+1889810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using the high-density map of polymorphic markers and genes in 17q12-q21 provided by the studies to elucidate the genetic basis of familial breast cancer, <a href="#1" class="mim-tip-reference" title="Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R. <strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong> Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>] [<a href="https://doi.org/10.1073/pnas.92.14.6384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604000">Aberle et al. (1995)</a> found linkage between plakoglobin and BRCA1 (<a href="/entry/113705">113705</a>)-linked markers. Meiotic recombinants in the 17q region showed that the plakoglobin gene lies between KRT10 (<a href="/entry/148080">148080</a>) and D17S858, an interval that also contains the BRCA1 gene. A single recombination event was found separating the plakoglobin gene from the BRCA1 gene. Three plakoglobin-positive cosmid clones were found to contain both the plakoglobin gene and the 17q21 marker locus UM8, in close proximity (less than 40 kb). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7604000" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Naxos Disease</em></strong></p><p>
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In affected members of 9 families and 3 sporadic patients with Naxos disease (NXD; <a href="/entry/601214">601214</a>) <a href="#15" class="mim-tip-reference" title="McKoy, G., Protonotarios, N., Crosby, A., Tsatsopoulou, A., Anastasakis, A., Coonar, A., Norman, M., Baboonian, C., Jeffery, S., McKenna, W. J. <strong>Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).</strong> Lancet 355: 2119-2124, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10902626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10902626</a>] [<a href="https://doi.org/10.1016/S0140-6736(00)02379-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10902626">McKoy et al. (2000)</a> identified homozygosity for a 2-bp deletion in the plakoglobin gene (<a href="#0001">173325.0001</a>). All of the patients, who were from the neighboring Greek islands of Naxos and Minos, had arrhythmogenic right ventricular cardiomyopathy (ARVC), palmoplantar keratoderma (PPK), and woolly hair. The finding of a deletion in plakoglobin in ARVC suggests that the proteins involved in cell-cell adhesion play an important role in maintaining myocyte integrity and that when junctions are disrupted, cell death with fatty and fibrous tissue replacement occurs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10902626" 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 3 unrelated Argentinian boys with skin fragility, PPK, and woolly hair, <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a> identified homozygosity for a nonsense mutation in the JUP gene (S24X; <a href="#0003">173325.0003</a>). A similarly affected Kuwaiti sister and brother with predominantly sparse hair were homozygous for a splice site mutation in JUP (<a href="#0004">173325.0004</a>). The mutations segregated with disease in each of the families and were not found in 108 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20130592" 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 female infant with generalized epidermolysis, alopecia, and onycholysis who died at day 12 of life due to sepsis and respiratory failure, <a href="#17" class="mim-tip-reference" title="Pigors, M., Kiritsi, D., Krumpelmann, S., Wagner, N., He, Y., Podda, M., Kohlhase, J., Hausser, I., Bruckner-Tuderman, L., Has, C. <strong>Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico-genetic entity.</strong> Hum. Molec. Genet. 20: 1811-1819, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21320868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21320868</a>] [<a href="https://doi.org/10.1093/hmg/ddr064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21320868">Pigors et al. (2011)</a> sequenced the candidate gene JUP and identified a homozygous nonsense mutation (Q539X; <a href="#0005">173325.0005</a>) for which her unaffected first-cousin parents were heterozygous. The authors demonstrated a complete lack of plakoglobin in patient skin; they suggested that this caused extreme skin fragility and did not allow skin barrier formation, thus resulting in a skin phenotype that was more severe than that previously associated with mutations in JUP. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21320868" 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 an uncle and nephew from a consanguineous Turkish family with ARVC, PPK, and alopecia mapping to chromosome 17q11.2-q21.32, <a href="#8" class="mim-tip-reference" title="Erken, H., Yariz, K. O., Duman, D., Kaya, C. T., Sayin, T., Heper, A. O., Tekin, M. <strong>Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK) is caused by a JUP mutation.</strong> Brit. J. Derm. 165: 917-921, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21668431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21668431</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2011.10455.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21668431">Erken et al. (2011)</a> sequenced the candidate gene JUP and identified homozygosity for a missense mutation (R265H; <a href="#0006">173325.0006</a>) that segregated with disease and was not found in controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21668431" 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 10-year-old Turkish boy with cutaneous and cardiac manifestations of Naxos disease, <a href="#16" class="mim-tip-reference" title="Oktem, A., Doolan, B. J., Akay, B. N., Onoufriadis, A., Okcu Heper, A., Kocak, O., Ersoy-Evans, S., McGrath, J. A. <strong>Autosomal recessive mutations in plakoglobin and risk of cardiac abnormalities.</strong> Clin. Exp. Derm. 45: 654-657, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32212272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32212272</a>] [<a href="https://doi.org/10.1111/ced.14201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32212272">Oktem et al. (2020)</a> identified homozygosity for the same splice site mutation (<a href="#0003">173325.0003</a>) previously identified in a Kuwaiti sister and brother by <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a>. Noting that the Turkish proband had only cutaneous manifestations when he presented at age 4 years, but exhibited right ventricular cardiomyopathy and right ventricular wall aneurysm on follow-up at age 10, <a href="#16" class="mim-tip-reference" title="Oktem, A., Doolan, B. J., Akay, B. N., Onoufriadis, A., Okcu Heper, A., Kocak, O., Ersoy-Evans, S., McGrath, J. A. <strong>Autosomal recessive mutations in plakoglobin and risk of cardiac abnormalities.</strong> Clin. Exp. Derm. 45: 654-657, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32212272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32212272</a>] [<a href="https://doi.org/10.1111/ced.14201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32212272">Oktem et al. (2020)</a> concluded that all JUP mutations involving cutaneous pathology have the potential to cause cardiac involvement, and suggested mandatory screening of cardiac function in all patients with mutations in JUP, even if cardiac disease is not clinically observed in early childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=32212272+20130592" 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>Arrhythmogenic Right Ventricular Cardiomyopathy</em></strong></p><p>
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<a href="#3" class="mim-tip-reference" title="Asimaki, A., Syrris, P., Wichter, T., Matthias, P., Saffitz, J. E., McKenna, W. J. <strong>A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy.</strong> Am. J. Hum. Genet. 81: 964-973, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17924338[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/10.1086/521633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17924338">Asimaki et al. (2007)</a> described a dominant mutation in the gene encoding plakoglobin in a German family with arrhythmogenic right ventricular cardiomyopathy but no cutaneous abnormalities (ARVC12; <a href="/entry/611528">611528</a>). The mutation (<a href="#0002">173325.0002</a>) was predicted to insert an extra serine residue at position 39 in the N terminus of plakoglobin. Analysis of a biopsy sample of the right ventricle from the proband showed markedly decreased localization of plakoglobin, desmoplakin (<a href="/entry/125647">125647</a>), and connexin-43 (<a href="/entry/121014">121014</a>) at intercalated discs in cardiac myocytes. Electron microscopy showed smaller and fewer desmosomes in cells expressing mutant plakoglobin. Taken together with other observations it was concluded that the insertion mutation affected the structure and distribution of mechanical and electrical cell junctions and could interfere with regulatory mechanisms mediated by Wnt signaling pathways. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17924338" 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>Other Variation</em></strong></p><p>
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<a href="#1" class="mim-tip-reference" title="Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R. <strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong> Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>] [<a href="https://doi.org/10.1073/pnas.92.14.6384" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7604000">Aberle et al. (1995)</a> identified an arginine/histidine polymorphism due to a substitution at nucleotide position 544 in exon 3 of the JUP gene, leading to replacement of arginine (CGC) by histidine (CAC) at amino acid position 142. This basepair substitution led to a loss of recognition sites for at least 2 restriction enzymes and thereby created an RFLP. The R142H substitution was found to represent a low-frequency polymorphism; from a total of 240 alleles examined, the arg142-to-his allele was found in 10 cases, giving an allele frequency of 0.042 +/- 0.013. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7604000" 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="#18" class="mim-tip-reference" title="Ruiz, P., Brinkmann, V., Ledermann, B., Behrend, M., Grund, C., Thalhammer, C., Vogel, F., Birchmeier, C., Gunthert, U., Franke, W. W., Birchmeier, W. <strong>Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.</strong> J. Cell Biol. 135: 215-225, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8858175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8858175</a>] [<a href="https://doi.org/10.1083/jcb.135.1.215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8858175">Ruiz et al. (1996)</a> generated mice deficient in plakoglobin (PG) by targeted disruption. Plakoglobin mutant mouse embryos showed decreased myofiber compliance and reduced cell-cell adhesion as a result of defects in the number and structure of desmosomes within the myocardium. Consequently, when myocardial cells undergo increased mechanical stress, e.g., at embryonic day 10.5 from the onset of embryonic blood circulation, the mice die from ventricular rupture. Plakoglobin-deficient C57BL/6 mice that survive longer, to around birth, show an additional skin phenotype. Epidermal desmosomes of these mice are disorganized and detached from the cytokeratin filaments, presenting features similar to the human blistering disease epidermolytic hyperkeratosis (<a href="#4" class="mim-tip-reference" title="Bierkamp, C., Mclaughlin, K. J., Schwarz, H., Huber, O., Kemler, R. <strong>Embryonic heart and skin defects in mice lacking plakoglobin.</strong> Dev. Biol. 180: 780-785, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8954745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8954745</a>] [<a href="https://doi.org/10.1006/dbio.1996.0346" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8954745">Bierkamp et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8858175+8954745" 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="Yin, T., Getsios, S., Caldelari, R., Kowalczyk, A. P., Muller, E. J., Jones, J. C. R., Green, K. J. <strong>Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms.</strong> Proc. Nat. Acad. Sci. 102: 5420-5425, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15805189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15805189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15805189[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.0501676102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15805189">Yin et al. (2005)</a> found that keratinocytes cultured from Pg-null mice exhibited weakened adhesion and increased motility. N- and C-terminally truncated Pg deletion mutants restored adhesion, but only the N-terminally deleted Pg suppressed single-cell migration. Both a chemical kinase inhibitor and a dominant-negative Src tyrosine kinase (<a href="/entry/190090">190090</a>) inhibited single-cell motility in Pg-null cells, whereas constitutively active Src overcame the inhibitory effect of Pg. <a href="#21" class="mim-tip-reference" title="Yin, T., Getsios, S., Caldelari, R., Kowalczyk, A. P., Muller, E. J., Jones, J. C. R., Green, K. J. <strong>Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms.</strong> Proc. Nat. Acad. Sci. 102: 5420-5425, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15805189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15805189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15805189[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.0501676102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15805189">Yin et al. (2005)</a> concluded that Pg strengthens adhesion and suppresses motility in mouse keratinocytes through both intercellular adhesion-dependent and -independent mechanisms, the latter of which may involve suppression of Src signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15805189" 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="#13" class="mim-tip-reference" title="Li, D., Zhang, W., Liu, Y., Haneline, L. S., Shou, W. <strong>Lack of plakoglobin in epidermis leads to keratoderma.</strong> J. Biol. Chem. 287: 10435-10443, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22315228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22315228</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22315228[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/10.1074/jbc.M111.299669" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22315228">Li et al. (2012)</a> created mice with conditional knockout of the Jup gene in epidermis. Jup mutants appeared normal at birth, but by 2 to 3 weeks of age, they became significantly smaller than controls and developed skin ulcerations near joint areas. All Jup-mutant mice died before weaning. Jup-mutant skin was markedly stiffer than that of controls, showing severe keratoderma, and hyperkeratosis in palms and soles. Thickening of Jup-mutant skin was accompanied by shedding of cornified and subcornified layers as well as detachment in the granular layer. Jup-mutant skin also showed excessive neutrophil infiltration, likely through wide spaces between adjacent Jup-mutant keratinocytes. Ultrastructural analysis of Jup mutants showed disturbed epidermal differentiation, with increased cell proliferation and apoptosis, and abnormal desmosomes and adherens junctions. Tight junctions appeared normal. Phosphorylation of beta-catenin (CTNNB1; <a href="/entry/116806">116806</a>) was reduced in Jup-mutant skin, but beta-catenin signaling appeared unaffected. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22315228" 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="#19" class="mim-tip-reference" title="Swope, D., Li, J., Muller, E. J., Radice, G. L. <strong>Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability.</strong> Genesis 50: 717-727, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22522917/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22522917</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22522917[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/10.1002/dvg.22034" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22522917">Swope et al. (2012)</a> created mice carrying a hypomorphic mutation in the Pg gene. About half of these animals were smaller than control littermates and died before weaning. The remaining mice carrying the hypomorphic mutation survived with no signs of cardiomyopathy or cardiac dysfunction, although they exhibited modest growth retardation compared to littermates. Beta-catenin expression was upregulated in hearts from mutant mice, but there was no change in beta-catenin reporter activity in mutant embryos. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22522917" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=173325[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs113994177 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994177;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=rs113994177" 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=rs113994177" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of 9 families and 3 sporadic patients with Naxos disease (NXD; <a href="/entry/601214">601214</a>), all from the neighboring Greek islands of Naxos and Minos, <a href="#15" class="mim-tip-reference" title="McKoy, G., Protonotarios, N., Crosby, A., Tsatsopoulou, A., Anastasakis, A., Coonar, A., Norman, M., Baboonian, C., Jeffery, S., McKenna, W. J. <strong>Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).</strong> Lancet 355: 2119-2124, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10902626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10902626</a>] [<a href="https://doi.org/10.1016/S0140-6736(00)02379-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10902626">McKoy et al. (2000)</a> identified a 2-bp deletion at the 3-prime end of the plakoglobin gene. The deletion of nucleotides 2157-2158 causes a frameshift and premature termination of translation. The frameshift alters the last 5 amino acids of the thirteenth armadillo repeat and truncates the C-terminal domain of the putative protein by 56 residues. Western blot analysis with an antiplakoglobin antibody confirmed the presence of mutant protein in a cardiac biopsy sample from a patient with the disease. This mutation destroys a Bst01 recognition site and was identified in homozygous state in 19 affected individuals. All of the patients had ARVC, PPK, and woolly hair. Twenty-nine clinically unaffected family members were heterozygous for the mutation; 20 unrelated individuals from Naxos and 43 autosomal dominant ARVC (<a href="/entry/107970">107970</a>) probands were homozygous for the normal allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10902626" 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> rs113994176 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs113994176;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/rs113994176?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=rs113994176" 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=rs113994176" 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=RCV000014570 OR RCV003764574" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014570, RCV003764574" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014570...</a>
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<p>In a German family in which a father and 3 sons had arrhythmogenic right ventricular cardiomyopathy (ARVD12; <a href="/entry/611528">611528</a>) but did not display any abnormalities of skin or hair, <a href="#3" class="mim-tip-reference" title="Asimaki, A., Syrris, P., Wichter, T., Matthias, P., Saffitz, J. E., McKenna, W. J. <strong>A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy.</strong> Am. J. Hum. Genet. 81: 964-973, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17924338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17924338</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17924338[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/10.1086/521633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17924338">Asimaki et al. (2007)</a> identified a heterozygous 3-bp insertion (118_119GCA) in the plakoglobin gene predicted to insert an extra serine residue at position 39 in the N terminus of the protein (S39_K40insS). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17924338" 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> rs782460555 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs782460555;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/rs782460555?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=rs782460555" 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=rs782460555" 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=RCV000194470" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000194470" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000194470</a>
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<p>In 3 unrelated Argentinian boys with skin fragility, palmoplantar keratoderma, and woolly hair (NXD; <a href="/entry/601214">601214</a>), 2 of whom were originally reported by <a href="#20" class="mim-tip-reference" title="Winik, B. C., Asial, R. A., McGrath, J. A., South, A. P., Boente, M. C. <strong>Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder.</strong> Brit. J. Derm. 160: 868-874, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19067702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19067702</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2008.08946.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19067702">Winik et al. (2009)</a>, <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a> identified homozygosity for a c.71C-A transversion in exon 2 of the JUP gene, resulting in a ser24-to-ter (S24X) substitution. The mutation was present in heterozygosity in the unaffected parents and was not found in 108 control chromosomes. RT-PCR analysis of patient and parent skin detected the presence of a mutant transcript in both, and Western blot analysis of skin proteins showed low levels of a truncated protein in both. Studies in dermal fibroblasts demonstrated efficient translation of S24X mRNA, suggesting that lack of membrane incorporation results in decreased protein stability; thus <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a> concluded that the first 42 amino acids of plakoglobin are essential for its efficient incorporation into desmosomes and adherens junctions of the skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20130592+19067702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Boente, M. D. C., Nanda, A., Baselaga, P. A., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Cardiomyopathy diagnosed in the eldest child harbouring p.S24X mutation in JUP.</strong> Brit. J. Derm. 175: 644-646, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27037756</a>] [<a href="https://doi.org/10.1111/bjd.14617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27037756">Boente et al. (2016)</a> provided follow-up on the oldest Argentinian patient originally reported by <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a>, who initially exhibited only cutaneous symptoms of Naxos disease. At age 17 years, however, echocardiography showed slight dilation of the left ventricle with normal systolic function, and by age 19, the cardiac involvement progressed to a diagnosis of left dilated cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20130592+27037756" 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> rs886037753 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037753;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/rs886037753?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=rs886037753" 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=rs886037753" 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=RCV000192505 OR RCV001208428 OR RCV002336520" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000192505, RCV001208428, RCV002336520" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000192505...</a>
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<p>In a Kuwaiti sister and brother with skin fragility, palmoplantar keratoderma, and sparse woolly hair (NXD; <a href="/entry/601214">601214</a>), <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a> identified homozygosity for a c.468G-A transition in exon 3 of the JUP gene, predicted to abolish the exon 3 donor splice site. The mutation was present in heterozygosity in the unaffected parents and was not found in 108 control chromosomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20130592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Boente, M. D. C., Nanda, A., Baselaga, P. A., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Cardiomyopathy diagnosed in the eldest child harbouring p.S24X mutation in JUP.</strong> Brit. J. Derm. 175: 644-646, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27037756</a>] [<a href="https://doi.org/10.1111/bjd.14617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27037756">Boente et al. (2016)</a> restudied the Kuwaiti family with Naxos disease originally described by <a href="#6" class="mim-tip-reference" title="Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong> J. Invest. Derm. 130: 1543-1550, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20130592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20130592</a>] [<a href="https://doi.org/10.1038/jid.2010.7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20130592">Cabral et al. (2010)</a>, and reported 2 new sibs affected by the same disorder. Although none of the sibs exhibited cardiac abnormalities at that time, <a href="#5" class="mim-tip-reference" title="Boente, M. D. C., Nanda, A., Baselaga, P. A., Kelsell, D. P., McGrath, J. A., South, A. P. <strong>Cardiomyopathy diagnosed in the eldest child harbouring p.S24X mutation in JUP.</strong> Brit. J. Derm. 175: 644-646, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27037756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27037756</a>] [<a href="https://doi.org/10.1111/bjd.14617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27037756">Boente et al. (2016)</a> predicted that patients with the c.468G-A mutation were likely to develop cardiac abnormalities similar to those seen in patients with the S24X mutation (<a href="#0003">173325.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=20130592+27037756" 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 10-year-old Turkish boy with cutaneous and cardiac manifestations of Naxos disease, <a href="#16" class="mim-tip-reference" title="Oktem, A., Doolan, B. J., Akay, B. N., Onoufriadis, A., Okcu Heper, A., Kocak, O., Ersoy-Evans, S., McGrath, J. A. <strong>Autosomal recessive mutations in plakoglobin and risk of cardiac abnormalities.</strong> Clin. Exp. Derm. 45: 654-657, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32212272/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32212272</a>] [<a href="https://doi.org/10.1111/ced.14201" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32212272">Oktem et al. (2020)</a> identified homozygosity for the c.468G-A splice site mutation, for which his unaffected consanguineous parents were heterozygous. The proband had only cutaneous manifestations when he presented at age 4 years, but exhibited right ventricular cardiomyopathy and right ventricular wall aneurysm on follow-up at age 10. The authors suggested mandatory screening of cardiac function in all patients with mutations in JUP, even if cardiac disease is not clinically observed in early childhood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32212272" 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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JUP, GLN539TER
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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> rs797046139 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797046139;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/rs797046139?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=rs797046139" 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=rs797046139" 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=RCV000193584" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000193584" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000193584</a>
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<p>In a female infant with generalized epidermolysis, alopecia, and onycholysis (NXD; <a href="/entry/601214">601214</a>) who died at day 12 of life due to sepsis and respiratory failure, <a href="#17" class="mim-tip-reference" title="Pigors, M., Kiritsi, D., Krumpelmann, S., Wagner, N., He, Y., Podda, M., Kohlhase, J., Hausser, I., Bruckner-Tuderman, L., Has, C. <strong>Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico-genetic entity.</strong> Hum. Molec. Genet. 20: 1811-1819, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21320868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21320868</a>] [<a href="https://doi.org/10.1093/hmg/ddr064" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21320868">Pigors et al. (2011)</a> identified homozygosity for a c.1615C-T transition (c.1615C-T, NM_002230.2) in exon 9 of the JUP gene, predicted to result in a gln539-to-ter (Q539X) substitution. Her unaffected first-cousin parents were heterozygous for the mutation; the mutation status of an alopecic younger brother was not reported. Quantitative PCR revealed an approximately 90% reduction in JUP transcript in patient skin compared to control, and immunofluorescence and immunoblot analysis demonstrated complete lack of plakoglobin in patient skin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21320868" 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> rs782440692 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs782440692;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/rs782440692?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=rs782440692" 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=rs782440692" 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=RCV000194635 OR RCV001853126 OR RCV002415828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000194635, RCV001853126, RCV002415828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000194635...</a>
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<p>In 2 men from a consanguineous Turkish family with arrhythmogenic right ventricular cardiomyopathy, mild palmoplantar keratoderma, and alopecia (NXD; <a href="/entry/601214">601214</a>), <a href="#8" class="mim-tip-reference" title="Erken, H., Yariz, K. O., Duman, D., Kaya, C. T., Sayin, T., Heper, A. O., Tekin, M. <strong>Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK) is caused by a JUP mutation.</strong> Brit. J. Derm. 165: 917-921, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21668431/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21668431</a>] [<a href="https://doi.org/10.1111/j.1365-2133.2011.10455.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21668431">Erken et al. (2011)</a> identified homozygosity for a c.794G-A transition in exon 4 of the JUP gene, resulting in an arg265-to-his (R265H) substitution at a highly conserved residue in the fourth armadillo repeat of plakoglobin. The mutation segregated fully with disease in the family and was not found in 192 Turkish controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21668431" 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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Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R.
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<strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong>
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Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7604000/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7604000</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7604000" 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.92.14.6384" target="_blank">Full Text</a>]
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Arnemann, J., Spurr, N. K., Wheeler, G. N., Parker, A. E., Buxton, R. S.
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<strong>Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP).</strong>
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Genomics 10: 640-645, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1889810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1889810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1889810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(91)90446-l" target="_blank">Full Text</a>]
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Asimaki, A., Syrris, P., Wichter, T., Matthias, P., Saffitz, J. E., McKenna, W. J.
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<strong>A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy.</strong>
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Am. J. Hum. Genet. 81: 964-973, 2007.
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[<a href="https://doi.org/10.1086/521633" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/dbio.1996.0346" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/bjd.14617" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/jid.2010.7" target="_blank">Full Text</a>]
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<strong>The plakophilin 1 (PKP1) and plakoglobin (JUP) genes map to human chromosomes 1q and 17, respectively.</strong>
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[<a href="https://doi.org/10.1007/s004390050539" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1365-2133.2011.10455.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.86.11.4027" target="_blank">Full Text</a>]
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<strong>The genes coding for alpha and beta catenin (Catna1 and Catnb) and plakoglobin (Jup) map to mouse chromosomes 18, 9, and 11, respectively.</strong>
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[<a href="https://doi.org/10.1007/BF00364802" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1083/jcb.118.3.671" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/S0140-6736(00)02379-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/ced.14201" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/dvg.22034" target="_blank">Full Text</a>]
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<a id="20" class="mim-anchor"></a>
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<a id="Winik2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Winik, B. C., Asial, R. A., McGrath, J. A., South, A. P., Boente, M. C.
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<strong>Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder.</strong>
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Brit. J. Derm. 160: 868-874, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19067702/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19067702</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19067702" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1365-2133.2008.08946.x" target="_blank">Full Text</a>]
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<a id="21" class="mim-anchor"></a>
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<a id="Yin2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yin, T., Getsios, S., Caldelari, R., Kowalczyk, A. P., Muller, E. J., Jones, J. C. R., Green, K. J.
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<strong>Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms.</strong>
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Proc. Nat. Acad. Sci. 102: 5420-5425, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15805189/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15805189</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15805189[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=15805189" 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.0501676102" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 05/03/2021
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Marla J. F. O'Neill - updated : 10/01/2015<br>Patricia A. Hartz - updated : 12/29/2014<br>Victor A. McKusick - updated : 10/10/2007<br>Patricia A. Hartz - updated : 6/30/2005<br>Ada Hamosh - updated : 8/4/2000<br>Patti M. Sherman - updated : 7/13/2000<br>Victor A. McKusick - updated : 8/27/1997
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 7/11/1990
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alopez : 05/03/2021
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alopez : 05/03/2021<br>alopez : 08/04/2016<br>carol : 10/01/2015<br>alopez : 12/29/2014<br>mcolton : 12/29/2014<br>ckniffin : 2/5/2008<br>alopez : 10/12/2007<br>terry : 10/10/2007<br>wwang : 8/4/2005<br>wwang : 7/21/2005<br>terry : 6/30/2005<br>carol : 8/4/2000<br>mcapotos : 8/3/2000<br>mcapotos : 7/27/2000<br>mcapotos : 7/21/2000<br>psherman : 7/13/2000<br>psherman : 11/2/1999<br>mark : 9/3/1997<br>terry : 8/27/1997<br>alopez : 7/30/1997<br>jenny : 7/9/1997<br>terry : 6/18/1996<br>terry : 6/3/1996<br>mark : 8/1/1995<br>supermim : 3/16/1992<br>carol : 6/20/1991<br>carol : 7/11/1990
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<span class="mim-font">
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<strong>*</strong> 173325
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<h3>
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JUNCTION PLAKOGLOBIN; JUP
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<em>Alternative titles; symbols</em>
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PLAKOGLOBIN; PKGB<br />
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DESMOPLAKIN III; DP3<br />
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DP III<br />
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CATENIN, GAMMA
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<strong><em>HGNC Approved Gene Symbol: JUP</em></strong>
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<strong>SNOMEDCT:</strong> 715535009;
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Cytogenetic location: 17q21.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 17:41,754,609-41,786,711 </span>
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</strong>
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<span class="small">(from NCBI)</span>
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<strong>Gene-Phenotype Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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<span class="mim-font">
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17q21.2
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<span class="mim-font">
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?Arrhythmogenic right ventricular dysplasia 12
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<span class="mim-font">
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611528
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Autosomal dominant
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<span class="mim-font">
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3
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<span class="mim-font">
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Naxos disease
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<span class="mim-font">
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601214
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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<span class="mim-font">
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<strong>TEXT</strong>
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<strong>Cloning and Expression</strong>
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<span class="mim-text-font">
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<p>Plakoglobin is a major cytoplasmic protein that occurs in a soluble and a membrane-associated form and is the only known constituent common to the submembranous plaques of both kinds of adhering junctions, the desmosomes and the intermediate junctions. It is a desmoplakin (see 125647) and is referred to as DP III. DP I and DP II are splice variants of the same gene. Using a partial cDNA clone for bovine plakoglobin, Franke et al. (1989) isolated cDNAs encoding human plakoglobin, determined its nucleotide sequence, and deduced the complete amino acid sequence. The polypeptide encoded by the cDNA was synthesized by in vitro transcription and translation and identified by its comigration with authentic plakoglobin in 2-dimensional gel electrophoresis. The protein, which has 744 amino acids and a molecular weight of 81,750 Da, is highly conserved between human and bovine tissues. Only one kind of plakoglobin mRNA (3.4 kb) was found in most tissues, but an additional mRNA (3.7 kb) was detected in certain human tumor cell lines. </p>
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<strong>Gene Function</strong>
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<span class="mim-text-font">
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<p>Plakoglobin associates with the cytoplasmic region of desmoglein I (125670), one of the transmembrane desmosomal proteins (Mathur et al., 1994). It also is a component of the cadherin (see 192090)-catenin complex, which is predominantly localized where actin filaments anchor in adherens junctions of epithelial cells (Knudsen and Wheelock, 1992). Aberle et al. (1995) stated that catenins are of central importance for cadherin function in that they mediate the connection of cadherins to actin filaments and are part of a higher order submembranous network by which cadherins are linked to other transmembrane and peripheral cytoplasmic proteins. Interaction of the cadherin-catenin complex with epidermal growth factor receptor (EGFR; 131550) and the finding that beta-catenin (CTNNB1; 116806) and plakoglobin are substrates for tyrosine phosphorylation following EGF stimulation of cells, together with the finding that catenins are associated with the tumor suppressor protein APC (611731), open the possibility that catenins are involved in signaling pathways and tumorigenesis. </p><p>Beta-catenin and gamma-catenin, vertebrate homologs of Drosophila armadillo, function in cell adhesion and the Wnt (e.g., WNT1; 164820) signaling pathway. In colon and other cancers, mutations in the APC tumor suppressor protein or beta-catenin's N terminus stabilize beta-catenin, enhancing its ability to activate transcription of TCF (e.g., TCF7; 189908)/LEF (e.g., LEF1; 153245) target genes. Beta- and gamma-catenin have analogous structures and functions and like binding to APC. Kolligs et al. (2000) reported that APC regulates both beta- and gamma-catenin and gamma-catenin functions as an oncogene. In contrast to beta-catenin, for which only N-terminal mutated forms transform RK3E epithelial cells, wildtype and several N-terminal mutated forms of gamma-catenin had similar transforming activity. The transforming activity of gamma-catenin, like that of beta-catenin, was dependent on TCF/LEF function. However, in contrast to beta-catenin, gamma-catenin strongly activated c-myc (190080) expression and c-myc function was crucial for gamma-catenin transformation. Kolligs et al. (2000) suggested that APC mutations alter regulation of both beta- and gamma-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of beta-catenin mutations. Elevated c-myc expression in cancers with APC defects may be due to altered regulation of both beta- and gamma-catenin. Furthermore, the authors stated that their data imply beta- and gamma-catenin may have distinct roles in Wnt signaling and cancer via differential effects on downstream target genes. </p>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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<span class="mim-text-font">
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<p>Arnemann et al. (1991) established a PCR assay for the gene encoding plakoglobin and used it to test human/mouse and human/rat somatic cell hybrids with different contents of human chromosomes. In this way, they were able to assign DP3 to chromosome 7. By analysis of progeny from 2 interspecific backcrosses, Guenet et al. (1995) mapped the Jup gene to mouse chromosome 11. Thus, the human JUP gene is probably on 7p because that is the portion of the chromosome showing homology of synteny to mouse 11. However, mouse 11 shows much more extensive homology to human chromosome 17 and, indeed, Aberle et al. (1995) mapped the plakoglobin gene to 17q12-q22 by analysis of DNA from human/hamster or human/mouse hybrid cell lines that contained only human chromosome 17 or parts thereof. Because of evolutionary conservation, human plakoglobin cDNA hybridized also to mouse and hamster DNA; however, the results obtained with DNA from hybrid cells unambiguously demonstrated that the human gene maps to chromosome 17q12-q22. The previously reported localization to chromosome 7 was based on PCR analysis using synthetic oligonucleotides and was not confirmed by independent work by Aberle et al. (1995). Using a monochromosomal human-rodent somatic cell hybrid panel, Cowley et al. (1997) likewise showed that the JUP gene is located on chromosome 17. </p><p>Using the high-density map of polymorphic markers and genes in 17q12-q21 provided by the studies to elucidate the genetic basis of familial breast cancer, Aberle et al. (1995) found linkage between plakoglobin and BRCA1 (113705)-linked markers. Meiotic recombinants in the 17q region showed that the plakoglobin gene lies between KRT10 (148080) and D17S858, an interval that also contains the BRCA1 gene. A single recombination event was found separating the plakoglobin gene from the BRCA1 gene. Three plakoglobin-positive cosmid clones were found to contain both the plakoglobin gene and the 17q21 marker locus UM8, in close proximity (less than 40 kb). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p><strong><em>Naxos Disease</em></strong></p><p>
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In affected members of 9 families and 3 sporadic patients with Naxos disease (NXD; 601214) McKoy et al. (2000) identified homozygosity for a 2-bp deletion in the plakoglobin gene (173325.0001). All of the patients, who were from the neighboring Greek islands of Naxos and Minos, had arrhythmogenic right ventricular cardiomyopathy (ARVC), palmoplantar keratoderma (PPK), and woolly hair. The finding of a deletion in plakoglobin in ARVC suggests that the proteins involved in cell-cell adhesion play an important role in maintaining myocyte integrity and that when junctions are disrupted, cell death with fatty and fibrous tissue replacement occurs. </p><p>In 3 unrelated Argentinian boys with skin fragility, PPK, and woolly hair, Cabral et al. (2010) identified homozygosity for a nonsense mutation in the JUP gene (S24X; 173325.0003). A similarly affected Kuwaiti sister and brother with predominantly sparse hair were homozygous for a splice site mutation in JUP (173325.0004). The mutations segregated with disease in each of the families and were not found in 108 control chromosomes. </p><p>In a female infant with generalized epidermolysis, alopecia, and onycholysis who died at day 12 of life due to sepsis and respiratory failure, Pigors et al. (2011) sequenced the candidate gene JUP and identified a homozygous nonsense mutation (Q539X; 173325.0005) for which her unaffected first-cousin parents were heterozygous. The authors demonstrated a complete lack of plakoglobin in patient skin; they suggested that this caused extreme skin fragility and did not allow skin barrier formation, thus resulting in a skin phenotype that was more severe than that previously associated with mutations in JUP. </p><p>In an uncle and nephew from a consanguineous Turkish family with ARVC, PPK, and alopecia mapping to chromosome 17q11.2-q21.32, Erken et al. (2011) sequenced the candidate gene JUP and identified homozygosity for a missense mutation (R265H; 173325.0006) that segregated with disease and was not found in controls. </p><p>In a 10-year-old Turkish boy with cutaneous and cardiac manifestations of Naxos disease, Oktem et al. (2020) identified homozygosity for the same splice site mutation (173325.0003) previously identified in a Kuwaiti sister and brother by Cabral et al. (2010). Noting that the Turkish proband had only cutaneous manifestations when he presented at age 4 years, but exhibited right ventricular cardiomyopathy and right ventricular wall aneurysm on follow-up at age 10, Oktem et al. (2020) concluded that all JUP mutations involving cutaneous pathology have the potential to cause cardiac involvement, and suggested mandatory screening of cardiac function in all patients with mutations in JUP, even if cardiac disease is not clinically observed in early childhood. </p><p><strong><em>Arrhythmogenic Right Ventricular Cardiomyopathy</em></strong></p><p>
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Asimaki et al. (2007) described a dominant mutation in the gene encoding plakoglobin in a German family with arrhythmogenic right ventricular cardiomyopathy but no cutaneous abnormalities (ARVC12; 611528). The mutation (173325.0002) was predicted to insert an extra serine residue at position 39 in the N terminus of plakoglobin. Analysis of a biopsy sample of the right ventricle from the proband showed markedly decreased localization of plakoglobin, desmoplakin (125647), and connexin-43 (121014) at intercalated discs in cardiac myocytes. Electron microscopy showed smaller and fewer desmosomes in cells expressing mutant plakoglobin. Taken together with other observations it was concluded that the insertion mutation affected the structure and distribution of mechanical and electrical cell junctions and could interfere with regulatory mechanisms mediated by Wnt signaling pathways. </p><p><strong><em>Other Variation</em></strong></p><p>
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Aberle et al. (1995) identified an arginine/histidine polymorphism due to a substitution at nucleotide position 544 in exon 3 of the JUP gene, leading to replacement of arginine (CGC) by histidine (CAC) at amino acid position 142. This basepair substitution led to a loss of recognition sites for at least 2 restriction enzymes and thereby created an RFLP. The R142H substitution was found to represent a low-frequency polymorphism; from a total of 240 alleles examined, the arg142-to-his allele was found in 10 cases, giving an allele frequency of 0.042 +/- 0.013. </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>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">
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<p>Ruiz et al. (1996) generated mice deficient in plakoglobin (PG) by targeted disruption. Plakoglobin mutant mouse embryos showed decreased myofiber compliance and reduced cell-cell adhesion as a result of defects in the number and structure of desmosomes within the myocardium. Consequently, when myocardial cells undergo increased mechanical stress, e.g., at embryonic day 10.5 from the onset of embryonic blood circulation, the mice die from ventricular rupture. Plakoglobin-deficient C57BL/6 mice that survive longer, to around birth, show an additional skin phenotype. Epidermal desmosomes of these mice are disorganized and detached from the cytokeratin filaments, presenting features similar to the human blistering disease epidermolytic hyperkeratosis (Bierkamp et al., 1996). </p><p>Yin et al. (2005) found that keratinocytes cultured from Pg-null mice exhibited weakened adhesion and increased motility. N- and C-terminally truncated Pg deletion mutants restored adhesion, but only the N-terminally deleted Pg suppressed single-cell migration. Both a chemical kinase inhibitor and a dominant-negative Src tyrosine kinase (190090) inhibited single-cell motility in Pg-null cells, whereas constitutively active Src overcame the inhibitory effect of Pg. Yin et al. (2005) concluded that Pg strengthens adhesion and suppresses motility in mouse keratinocytes through both intercellular adhesion-dependent and -independent mechanisms, the latter of which may involve suppression of Src signaling. </p><p>Li et al. (2012) created mice with conditional knockout of the Jup gene in epidermis. Jup mutants appeared normal at birth, but by 2 to 3 weeks of age, they became significantly smaller than controls and developed skin ulcerations near joint areas. All Jup-mutant mice died before weaning. Jup-mutant skin was markedly stiffer than that of controls, showing severe keratoderma, and hyperkeratosis in palms and soles. Thickening of Jup-mutant skin was accompanied by shedding of cornified and subcornified layers as well as detachment in the granular layer. Jup-mutant skin also showed excessive neutrophil infiltration, likely through wide spaces between adjacent Jup-mutant keratinocytes. Ultrastructural analysis of Jup mutants showed disturbed epidermal differentiation, with increased cell proliferation and apoptosis, and abnormal desmosomes and adherens junctions. Tight junctions appeared normal. Phosphorylation of beta-catenin (CTNNB1; 116806) was reduced in Jup-mutant skin, but beta-catenin signaling appeared unaffected. </p><p>Swope et al. (2012) created mice carrying a hypomorphic mutation in the Pg gene. About half of these animals were smaller than control littermates and died before weaning. The remaining mice carrying the hypomorphic mutation survived with no signs of cardiomyopathy or cardiac dysfunction, although they exhibited modest growth retardation compared to littermates. Beta-catenin expression was upregulated in hearts from mutant mice, but there was no change in beta-catenin reporter activity in mutant embryos. </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">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 NAXOS DISEASE</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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JUP, 2-BP DEL, 2157TG
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<br />
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SNP: rs113994177,
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ClinVar: RCV000014569, RCV000481302, RCV001731287, RCV003764573
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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 affected members of 9 families and 3 sporadic patients with Naxos disease (NXD; 601214), all from the neighboring Greek islands of Naxos and Minos, McKoy et al. (2000) identified a 2-bp deletion at the 3-prime end of the plakoglobin gene. The deletion of nucleotides 2157-2158 causes a frameshift and premature termination of translation. The frameshift alters the last 5 amino acids of the thirteenth armadillo repeat and truncates the C-terminal domain of the putative protein by 56 residues. Western blot analysis with an antiplakoglobin antibody confirmed the presence of mutant protein in a cardiac biopsy sample from a patient with the disease. This mutation destroys a Bst01 recognition site and was identified in homozygous state in 19 affected individuals. All of the patients had ARVC, PPK, and woolly hair. Twenty-nine clinically unaffected family members were heterozygous for the mutation; 20 unrelated individuals from Naxos and 43 autosomal dominant ARVC (107970) probands were homozygous for the normal allele. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 12 (1 family)</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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JUP, 3-BP INS, 118GCA
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<br />
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SNP: rs113994176,
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gnomAD: rs113994176,
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ClinVar: RCV000014570, RCV003764574
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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 German family in which a father and 3 sons had arrhythmogenic right ventricular cardiomyopathy (ARVD12; 611528) but did not display any abnormalities of skin or hair, Asimaki et al. (2007) identified a heterozygous 3-bp insertion (118_119GCA) in the plakoglobin gene predicted to insert an extra serine residue at position 39 in the N terminus of the protein (S39_K40insS). </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 NAXOS DISEASE</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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JUP, SER24TER
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<br />
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SNP: rs782460555,
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gnomAD: rs782460555,
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ClinVar: RCV000194470
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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 3 unrelated Argentinian boys with skin fragility, palmoplantar keratoderma, and woolly hair (NXD; 601214), 2 of whom were originally reported by Winik et al. (2009), Cabral et al. (2010) identified homozygosity for a c.71C-A transversion in exon 2 of the JUP gene, resulting in a ser24-to-ter (S24X) substitution. The mutation was present in heterozygosity in the unaffected parents and was not found in 108 control chromosomes. RT-PCR analysis of patient and parent skin detected the presence of a mutant transcript in both, and Western blot analysis of skin proteins showed low levels of a truncated protein in both. Studies in dermal fibroblasts demonstrated efficient translation of S24X mRNA, suggesting that lack of membrane incorporation results in decreased protein stability; thus Cabral et al. (2010) concluded that the first 42 amino acids of plakoglobin are essential for its efficient incorporation into desmosomes and adherens junctions of the skin. </p><p>Boente et al. (2016) provided follow-up on the oldest Argentinian patient originally reported by Cabral et al. (2010), who initially exhibited only cutaneous symptoms of Naxos disease. At age 17 years, however, echocardiography showed slight dilation of the left ventricle with normal systolic function, and by age 19, the cardiac involvement progressed to a diagnosis of left dilated cardiomyopathy. </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>.0004 NAXOS DISEASE</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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JUP, 468G-A
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<br />
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SNP: rs886037753,
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gnomAD: rs886037753,
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ClinVar: RCV000192505, RCV001208428, RCV002336520
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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 Kuwaiti sister and brother with skin fragility, palmoplantar keratoderma, and sparse woolly hair (NXD; 601214), Cabral et al. (2010) identified homozygosity for a c.468G-A transition in exon 3 of the JUP gene, predicted to abolish the exon 3 donor splice site. The mutation was present in heterozygosity in the unaffected parents and was not found in 108 control chromosomes. </p><p>Boente et al. (2016) restudied the Kuwaiti family with Naxos disease originally described by Cabral et al. (2010), and reported 2 new sibs affected by the same disorder. Although none of the sibs exhibited cardiac abnormalities at that time, Boente et al. (2016) predicted that patients with the c.468G-A mutation were likely to develop cardiac abnormalities similar to those seen in patients with the S24X mutation (173325.0003). </p><p>In a 10-year-old Turkish boy with cutaneous and cardiac manifestations of Naxos disease, Oktem et al. (2020) identified homozygosity for the c.468G-A splice site mutation, for which his unaffected consanguineous parents were heterozygous. The proband had only cutaneous manifestations when he presented at age 4 years, but exhibited right ventricular cardiomyopathy and right ventricular wall aneurysm on follow-up at age 10. The authors suggested mandatory screening of cardiac function in all patients with mutations in JUP, even if cardiac disease is not clinically observed in early childhood. </p>
|
|
</span>
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</div>
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<div>
|
|
<br />
|
|
</div>
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</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 NAXOS DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
JUP, GLN539TER
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|
|
<br />
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|
|
|
SNP: rs797046139,
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|
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|
|
gnomAD: rs797046139,
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|
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|
|
|
ClinVar: RCV000193584
|
|
|
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|
</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a female infant with generalized epidermolysis, alopecia, and onycholysis (NXD; 601214) who died at day 12 of life due to sepsis and respiratory failure, Pigors et al. (2011) identified homozygosity for a c.1615C-T transition (c.1615C-T, NM_002230.2) in exon 9 of the JUP gene, predicted to result in a gln539-to-ter (Q539X) substitution. Her unaffected first-cousin parents were heterozygous for the mutation; the mutation status of an alopecic younger brother was not reported. Quantitative PCR revealed an approximately 90% reduction in JUP transcript in patient skin compared to control, and immunofluorescence and immunoblot analysis demonstrated complete lack of plakoglobin in patient skin. </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>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 NAXOS DISEASE</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
JUP, ARG265HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs782440692,
|
|
|
|
|
|
gnomAD: rs782440692,
|
|
|
|
|
|
ClinVar: RCV000194635, RCV001853126, RCV002415828
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 men from a consanguineous Turkish family with arrhythmogenic right ventricular cardiomyopathy, mild palmoplantar keratoderma, and alopecia (NXD; 601214), Erken et al. (2011) identified homozygosity for a c.794G-A transition in exon 4 of the JUP gene, resulting in an arg265-to-his (R265H) substitution at a highly conserved residue in the fourth armadillo repeat of plakoglobin. The mutation segregated fully with disease in the family and was not found in 192 Turkish controls. </p>
|
|
</span>
|
|
</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Aberle, H., Bierkamp, C., Torchard, D., Serova, O., Wagner, T., Natt, E., Wirsching, J., Heidkamper, C., Montagna, M., Lynch, H. T., Lenoir, G. M., Scherer, G., Feunteun, J., Kemler, R.
|
|
<strong>The human plakoglobin gene localizes on chromosome 17q21 and is subjected to loss of heterozygosity in breast and ovarian cancers.</strong>
|
|
Proc. Nat. Acad. Sci. 92: 6384-6388, 1995.
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[PubMed: 7604000]
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[Full Text: https://doi.org/10.1073/pnas.92.14.6384]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Arnemann, J., Spurr, N. K., Wheeler, G. N., Parker, A. E., Buxton, R. S.
|
|
<strong>Chromosomal assignment of the human genes coding for the major proteins of the desmosome junction, desmoglein DGI (DSG), desmocollins DGII/III (DSC), desmoplakins DPI/II (DSP), and plakoglobin DPIII (JUP).</strong>
|
|
Genomics 10: 640-645, 1991.
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[PubMed: 1889810]
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[Full Text: https://doi.org/10.1016/0888-7543(91)90446-l]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Asimaki, A., Syrris, P., Wichter, T., Matthias, P., Saffitz, J. E., McKenna, W. J.
|
|
<strong>A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy.</strong>
|
|
Am. J. Hum. Genet. 81: 964-973, 2007.
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[PubMed: 17924338]
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[Full Text: https://doi.org/10.1086/521633]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Bierkamp, C., Mclaughlin, K. J., Schwarz, H., Huber, O., Kemler, R.
|
|
<strong>Embryonic heart and skin defects in mice lacking plakoglobin.</strong>
|
|
Dev. Biol. 180: 780-785, 1996.
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[PubMed: 8954745]
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[Full Text: https://doi.org/10.1006/dbio.1996.0346]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Boente, M. D. C., Nanda, A., Baselaga, P. A., Kelsell, D. P., McGrath, J. A., South, A. P.
|
|
<strong>Cardiomyopathy diagnosed in the eldest child harbouring p.S24X mutation in JUP.</strong>
|
|
Brit. J. Derm. 175: 644-646, 2016.
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[PubMed: 27037756]
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[Full Text: https://doi.org/10.1111/bjd.14617]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Cabral, R. M., Liu, L., Hogan, C., Dopping-Hepenstal, P. J. C., Winik, B. C., Asial, R. A., Dobson, R., Mein, C. A., Baselaga, P. A., Mellerio, J. E., Nanda, A., del Carmen Boente, M., Kelsell, D. P., McGrath, J. A., South, A. P.
|
|
<strong>Homozygous mutations in the 5-prime region of the JUP gene result in cutaneous disease but normal heart development in children.</strong>
|
|
J. Invest. Derm. 130: 1543-1550, 2010.
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[PubMed: 20130592]
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[Full Text: https://doi.org/10.1038/jid.2010.7]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Cowley, C. M. E., Simrak, D., Spurr, N. K., Arnemann, J., Buxton, R. S.
|
|
<strong>The plakophilin 1 (PKP1) and plakoglobin (JUP) genes map to human chromosomes 1q and 17, respectively.</strong>
|
|
Hum. Genet. 100: 486-488, 1997.
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|
|
[PubMed: 9272178]
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[Full Text: https://doi.org/10.1007/s004390050539]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Erken, H., Yariz, K. O., Duman, D., Kaya, C. T., Sayin, T., Heper, A. O., Tekin, M.
|
|
<strong>Cardiomyopathy with alopecia and palmoplantar keratoderma (CAPK) is caused by a JUP mutation.</strong>
|
|
Brit. J. Derm. 165: 917-921, 2011.
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|
[PubMed: 21668431]
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[Full Text: https://doi.org/10.1111/j.1365-2133.2011.10455.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Franke, W. W., Goldschmidt, M. D., Zimbelmann, R., Mueller, H. M., Schiller, D. L., Cowin, P.
|
|
<strong>Molecular cloning and amino acid sequence of human plakoglobin, the common junctional plaque protein.</strong>
|
|
Proc. Nat. Acad. Sci. 86: 4027-4031, 1989.
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|
[PubMed: 2726765]
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[Full Text: https://doi.org/10.1073/pnas.86.11.4027]
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Guenet, J.-L., Simon-Chazottes, D., Ringwald, M., Kemler, R.
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<strong>The genes coding for alpha and beta catenin (Catna1 and Catnb) and plakoglobin (Jup) map to mouse chromosomes 18, 9, and 11, respectively.</strong>
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Mammalian Genome 6: 363-366, 1995.
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[PubMed: 7626889]
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[Full Text: https://doi.org/10.1007/BF00364802]
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<li>
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<p class="mim-text-font">
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Knudsen, K. A., Wheelock, M. J.
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<strong>Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin.</strong>
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J. Cell Biol. 118: 671-679, 1992.
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[PubMed: 1639850]
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[Full Text: https://doi.org/10.1083/jcb.118.3.671]
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Kolligs, F. T., Kolligs, B., Hajra, K. M., Hu, G., Tani, M., Cho, K. R., Fearon, E. R.
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<strong>Gamma-catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of beta-catenin.</strong>
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Genes Dev. 14: 1319-1331, 2000.
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[PubMed: 10837025]
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Li, D., Zhang, W., Liu, Y., Haneline, L. S., Shou, W.
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<strong>Lack of plakoglobin in epidermis leads to keratoderma.</strong>
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J. Biol. Chem. 287: 10435-10443, 2012.
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[PubMed: 22315228]
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[Full Text: https://doi.org/10.1074/jbc.M111.299669]
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Mathur, M., Goodwin, L., Cowin, P.
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<strong>Interactions of the cytoplasmic domain of the desmosomal cadherin Dsg1 with plakoglobin.</strong>
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J. Biol. Chem. 269: 14075-14080, 1994.
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[PubMed: 8188687]
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McKoy, G., Protonotarios, N., Crosby, A., Tsatsopoulou, A., Anastasakis, A., Coonar, A., Norman, M., Baboonian, C., Jeffery, S., McKenna, W. J.
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<strong>Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).</strong>
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Lancet 355: 2119-2124, 2000.
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[PubMed: 10902626]
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[Full Text: https://doi.org/10.1016/S0140-6736(00)02379-5]
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Oktem, A., Doolan, B. J., Akay, B. N., Onoufriadis, A., Okcu Heper, A., Kocak, O., Ersoy-Evans, S., McGrath, J. A.
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<strong>Autosomal recessive mutations in plakoglobin and risk of cardiac abnormalities.</strong>
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Clin. Exp. Derm. 45: 654-657, 2020.
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[PubMed: 32212272]
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[Full Text: https://doi.org/10.1111/ced.14201]
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Pigors, M., Kiritsi, D., Krumpelmann, S., Wagner, N., He, Y., Podda, M., Kohlhase, J., Hausser, I., Bruckner-Tuderman, L., Has, C.
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<strong>Lack of plakoglobin leads to lethal congenital epidermolysis bullosa: a novel clinico-genetic entity.</strong>
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Hum. Molec. Genet. 20: 1811-1819, 2011.
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[PubMed: 21320868]
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[Full Text: https://doi.org/10.1093/hmg/ddr064]
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Ruiz, P., Brinkmann, V., Ledermann, B., Behrend, M., Grund, C., Thalhammer, C., Vogel, F., Birchmeier, C., Gunthert, U., Franke, W. W., Birchmeier, W.
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<strong>Targeted mutation of plakoglobin in mice reveals essential functions of desmosomes in the embryonic heart.</strong>
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J. Cell Biol. 135: 215-225, 1996.
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[PubMed: 8858175]
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[Full Text: https://doi.org/10.1083/jcb.135.1.215]
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Swope, D., Li, J., Muller, E. J., Radice, G. L.
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<strong>Analysis of a Jup hypomorphic allele reveals a critical threshold for postnatal viability.</strong>
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Genesis 50: 717-727, 2012.
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[PubMed: 22522917]
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[Full Text: https://doi.org/10.1002/dvg.22034]
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Winik, B. C., Asial, R. A., McGrath, J. A., South, A. P., Boente, M. C.
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<strong>Acantholytic ectodermal dysplasia: clinicopathological study of a new desmosomal disorder.</strong>
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Brit. J. Derm. 160: 868-874, 2009.
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[PubMed: 19067702]
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[Full Text: https://doi.org/10.1111/j.1365-2133.2008.08946.x]
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Yin, T., Getsios, S., Caldelari, R., Kowalczyk, A. P., Muller, E. J., Jones, J. C. R., Green, K. J.
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<strong>Plakoglobin suppresses keratinocyte motility through both cell-cell adhesion-dependent and -independent mechanisms.</strong>
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Proc. Nat. Acad. Sci. 102: 5420-5425, 2005.
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[PubMed: 15805189]
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[Full Text: https://doi.org/10.1073/pnas.0501676102]
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