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<title>
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Entry
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- *172405 - PHOSPHOLAMBAN; PLN
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="input-group">
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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<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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<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 style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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<p />
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</div>
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*172405</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
|
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<a href="/allelicVariants/172405">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=ENSG00000198523;t=ENST00000357525" 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=5350" 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=172405" 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=ENSG00000198523;t=ENST00000357525" 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_002667" 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_002667" 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=172405" 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=01395&isoform_id=01395_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/PLN" 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/130774,189943,190019,4505887,5916238,13528957,119568583,189053120" 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/P26678" 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=5350" 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=ENSG00000198523;t=ENST00000357525" 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=PLN" 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=PLN" 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+5350" 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/PLN" 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:5350" 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/5350" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000357525.6&hgg_start=118548296&hgg_end=118561716&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
|
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9080" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=172405[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=172405[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/ENSG00000198523" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=PLN" 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=PLN" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=PLN&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/PA272" 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:9080" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:97622" 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/PLN#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:97622" 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/5350/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://omia.org/OMIA002195/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5350" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-060503-603" 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">
|
|
<span class="small">
|
|
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<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:5350" 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=PLN&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
|
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<span class="h3">
|
|
<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
172405
|
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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>
|
|
<h3>
|
|
<span class="mim-font">
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PHOSPHOLAMBAN; PLN
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PLN" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PLN</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>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/6/815?start=-3&limit=10&highlight=815">6q22.31</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:118548296-118561716&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">6:118,548,296-118,561,716</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=609909,613874" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/6/815?start=-3&limit=10&highlight=815">
|
|
6q22.31
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1P
|
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|
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</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/609909"> 609909 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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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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<p>Phospholamban is expressed in the sarcoplasmic reticulum membrane as a 30-kD homopentamer. It controls cellular calcium levels by a mechanism that depends on its phosphorylation (summary by <a href="#17" class="mim-tip-reference" title="Oxenoid, K., Chou, J. J. <strong>The structure of phospholamban pentamer reveals a channel-like architecture in membranes.</strong> Proc. Nat. Acad. Sci. 102: 10870-10875, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16043693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16043693</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16043693[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.0504920102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16043693">Oxenoid and Chou, 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16043693" 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>Using dog and rabbit phospholamban cDNAs as probes, <a href="#3" class="mim-tip-reference" title="Fujii, J., Zarain-Herzberg, A., Willard, H. F., Tada, M., MacLennan, D. H. <strong>Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.</strong> J. Biol. Chem. 266: 11669-11675, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828805</a>]" pmid="1828805">Fujii et al. (1991)</a> cloned human phospholamban from a skeletal muscle cDNA library. The deduced 52-amino acid human protein differs from rabbit, dog, and pig at position 27 and from dog and pig at position 2. Northern blot analysis of rabbit tissues detected phospholamban transcripts in heart and soleus and in tissues rich in smooth muscle, such as uterus, small and large intestine, trachea, bladder, esophagus, and aorta. No expression was detected in plantaris, spleen, testis, brain, liver, and kidney. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1828805" 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="McTiernan, C. F., Frye, C. S., Lemster, B. H., Kinder, E. A., Ogletree-Hughes, M. L., Moravec, C. S., Feldman, A. M. <strong>The human phospholamban gene: structure and expression.</strong> J. Molec. Cell Cardiol. 31: 679-692, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10198197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10198197</a>] [<a href="https://doi.org/10.1006/jmcc.1998.0904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10198197">McTiernan et al. (1999)</a> found that human ventricle and quadriceps displayed high levels of phospholamban transcripts and proteins, with markedly lower expression in smooth muscles. The right atrium also expressed low levels of phospholamban. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10198197" 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="#3" class="mim-tip-reference" title="Fujii, J., Zarain-Herzberg, A., Willard, H. F., Tada, M., MacLennan, D. H. <strong>Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.</strong> J. Biol. Chem. 266: 11669-11675, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828805</a>]" pmid="1828805">Fujii et al. (1991)</a> found that the rabbit Pln gene spans 13.2 kb and contains only 1 intron, which separates exonic sequences in the 5-prime UTR. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1828805" 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="McTiernan, C. F., Frye, C. S., Lemster, B. H., Kinder, E. A., Ogletree-Hughes, M. L., Moravec, C. S., Feldman, A. M. <strong>The human phospholamban gene: structure and expression.</strong> J. Molec. Cell Cardiol. 31: 679-692, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10198197/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10198197</a>] [<a href="https://doi.org/10.1006/jmcc.1998.0904" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10198197">McTiernan et al. (1999)</a> reported that the structure of the human phospholamban gene closely resembles that reported for the chicken, rabbit, rat, and mouse genes. Comparison of the human to other mammalian phospholamban genes indicated a marked conservation of sequence for at least 217 bp upstream of the transcription start site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10198197" 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>Using a human phospholamban cDNA, <a href="#3" class="mim-tip-reference" title="Fujii, J., Zarain-Herzberg, A., Willard, H. F., Tada, M., MacLennan, D. H. <strong>Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.</strong> J. Biol. Chem. 266: 11669-11675, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828805</a>]" pmid="1828805">Fujii et al. (1991)</a> mapped the phospholamban gene to human chromosome 6. By fluorescence in situ hybridization, <a href="#16" class="mim-tip-reference" title="Otsu, K., Fujii, J., Periasamy, M., Difilippantonio, M., Uppender, M., Ward, D. C., MacLennan, D. H. <strong>Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes.</strong> Genomics 17: 507-509, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8406504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8406504</a>] [<a href="https://doi.org/10.1006/geno.1993.1357" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8406504">Otsu et al. (1993)</a> mapped the PLN gene to chromosome 6q22.1. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8406504+1828805" 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="#3" class="mim-tip-reference" title="Fujii, J., Zarain-Herzberg, A., Willard, H. F., Tada, M., MacLennan, D. H. <strong>Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6.</strong> J. Biol. Chem. 266: 11669-11675, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1828805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1828805</a>]" pmid="1828805">Fujii et al. (1991)</a> stated that phospholamban is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. Phospholamban is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a; see <a href="/entry/108740">108740</a>) in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta agonists. Phospholamban is also expressed in slow-twitch skeletal muscle and some smooth muscle cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1828805" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Asahi, M., Otsu, K., Nakayama, H., Hikoso, S., Takeda, T., Gramolini, A. O., Trivieri, M. G., Oudit, G. Y., Morita, T., Kusakari, Y., Hirano, S., Hongo, K., Hirotani, S., Yamaguchi, O., Peterson, A., Backx, P. H., Kurihara, S., Hori, M., MacLennan, D. H. <strong>Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) activity and impairs cardiac function in mice.</strong> Proc. Nat. Acad. Sci. 101: 9199-9204, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15201433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15201433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15201433[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.0402596101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15201433">Asahi et al. (2004)</a> generated mice with cardiac-specific overexpression of epitope-tagged rabbit sarcolipin (SLN; <a href="/entry/602203">602203</a>). Overexpression of Sln decreased the apparent affinity of Serca2a (<a href="/entry/108740">108740</a>) for calcium in transgenic hearts. The mice had altered calcium currents, impaired cardiac contractility with altered tension and relaxation times, and ventricular hypertrophy. Coimmunoprecipitation indicated that overexpressed Sln bound both Serca2a and Pln, forming a ternary complex. The results suggested that Sln overexpression inhibits Serca2a through stabilization of Serca2a-Pln interaction and through inhibition of Pln phosphorylation. <a href="#1" class="mim-tip-reference" title="Asahi, M., Otsu, K., Nakayama, H., Hikoso, S., Takeda, T., Gramolini, A. O., Trivieri, M. G., Oudit, G. Y., Morita, T., Kusakari, Y., Hirano, S., Hongo, K., Hirotani, S., Yamaguchi, O., Peterson, A., Backx, P. H., Kurihara, S., Hori, M., MacLennan, D. H. <strong>Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) activity and impairs cardiac function in mice.</strong> Proc. Nat. Acad. Sci. 101: 9199-9204, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15201433/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15201433</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15201433[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.0402596101" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15201433">Asahi et al. (2004)</a> concluded that inhibition of Serca2a impairs contractility and calcium cycling, but responsiveness to beta-adrenergic agonists may prevent progression to heart failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15201433" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By pairwise testing of fluorescence-labeled proteins, <a href="#19" class="mim-tip-reference" title="Phillips, T. A., Hauck, G. T., Pribadi, M. P., Cho, E. E., Cleary, S. R., Robia, S. L. <strong>Micropeptide hetero-oligomerization adds complexity to the calcium pump regulatory network.</strong> Biophys. J. 122: 301-309, 2023.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36523160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36523160</a>] [<a href="https://doi.org/10.1016/j.bpj.2022.12.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="36523160">Phillips et al. (2023)</a> showed that different SERCA-modulating membrane micropeptides, including PLN, formed heterooligomers with varying affinities. Moreover, each micropeptide also assembled into homooligomers, but the homooligomers did not interact with SERCA. The affinities of heterooligomerization of micropeptides depended on whether they were the minority or majority species, and SERCA interaction with individual monomeric micropeptides competed with micropeptide-micropeptide interactions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36523160" 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>Using NMR experiments, <a href="#17" class="mim-tip-reference" title="Oxenoid, K., Chou, J. J. <strong>The structure of phospholamban pentamer reveals a channel-like architecture in membranes.</strong> Proc. Nat. Acad. Sci. 102: 10870-10875, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16043693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16043693</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16043693[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.0504920102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16043693">Oxenoid and Chou (2005)</a> characterized the reconstituted human PLN pentamer. They found that PLN assembled by parallel packing into well-structured pentamers with 5-fold rotational symmetry. In the PLN pentamer, the positively-charged N-terminal domains formed alpha helices that repulsed one another via electrostatic charges and assumed a bellflower appearance. The linker regions of each subunit acquired dihedral angles characteristic of beta strands. The long, largely hydrophobic C-terminal transmembrane alpha helices engaged in leu/ile zipper interactions and formed a funnel-like pore with a diameter of about 3.6 angstroms at its narrowest point. <a href="#17" class="mim-tip-reference" title="Oxenoid, K., Chou, J. J. <strong>The structure of phospholamban pentamer reveals a channel-like architecture in membranes.</strong> Proc. Nat. Acad. Sci. 102: 10870-10875, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16043693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16043693</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16043693[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.0504920102" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16043693">Oxenoid and Chou (2005)</a> concluded that, like monomeric PLN, pentameric PLN can interact with the SERCA cytoplasmic domain due to the relative mobility of the N-terminal SERCA-interacting domains. They proposed that the entire PLN pentamer may have a dual function as a regulatory protein and as an ion channel. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16043693" 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>Dilated Cardiomyopathy 1P</em></strong></p><p>
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<a href="#20" class="mim-tip-reference" title="Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., Kranias, E. G., MacLennan, D. H., Seidman, J. G., Seidman, C. E. <strong>Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.</strong> Science 299: 1410-1413, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610310</a>] [<a href="https://doi.org/10.1126/science.1081578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610310">Schmitt et al. (2003)</a> sequenced the PLN gene in 20 unrelated individuals with inherited dilated cardiomyopathy and heart failure (see CMD1P, <a href="/entry/609909">609909</a>). In 1 sample, an arginine-to-cysteine substitution at codon 9 in the cytosolic PLN domain was identified and segregated with disease in that 4-generation family (R9C; <a href="#0001">172405.0001</a>). Affected individuals had increased chamber dimensions and decreased contractile function at age 20 to 30 years, with progression to heart failure within 5 to 10 years after symptom onset. Congestive heart failure was severe in 12 individuals, necessitating cardiac transplantation in 4. The average age at death of affected individuals was 25.1 +/- 12.7 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12610310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated families with CMD1P, <a href="#7" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G.-C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., Liggett, S. B., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.</strong> J. Clin. Invest. 111: 869-876, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12639993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12639993</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12639993[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/10.1172/JCI17892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12639993">Haghighi et al. (2003)</a> identified a nonsense mutation in the PLN gene (L39X; <a href="#0002">172405.0002</a>). The 2 homozygous individuals developed dilated cardiomyopathy and heart failure requiring cardiac transplantation at ages 16 and 27 years, respectively; 11 heterozygous individuals exhibited variable clinical findings, indicating incomplete penetrance of the cardiomyopathy phenotype. <a href="#7" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G.-C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., Liggett, S. B., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.</strong> J. Clin. Invest. 111: 869-876, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12639993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12639993</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12639993[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/10.1172/JCI17892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12639993">Haghighi et al. (2003)</a> concluded that in contrast to mice in which Pln deficiency enhances myocardial inotropy and lusitropy without adverse effects, PLN is essential for cardiac health in humans, and its absence results in lethal heart failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12639993" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a 7-generation family with CMD1P, <a href="#6" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Gamolini, A. O., Waggoner, J. R., Pater, L., Lynch, R. A., Fan, G.-C., Tsiapras, D., Parekh, R. R., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.</strong> Proc. Nat. Acad. Sci. 103: 1388-1393, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432188</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432188[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.0510519103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16432188">Haghighi et al. (2006)</a> identified heterozygosity for a 3-bp deletion in the PLN gene (<a href="#0003">172405.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16432188" 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="Haghighi, K., Chen, G., Sato, Y., Fan, G.-C., He, S., Kolokathis, F., Pater, L., Paraskevaidis, I., Jones, W. K., Dorn, G. W., II, Kremastinos, D. T., Kranias, E. G. <strong>A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids.</strong> Hum. Mutat. 29: 640-647, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18241046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18241046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18241046[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/humu.20692" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18241046">Haghighi et al. (2008)</a> analyzed the PLN gene in 381 CMD patients and 296 controls with no known cardiomyopathy history and identified a heterozygous -36A-C variant in the 5-prime untranslated region (<a href="#0006">172405.0006</a>) in 22 patients and 1 control. Functional analysis demonstrated that the -36A-C variant increased PLN activity by 24% compared to wildtype and that this alteration in the steroid receptor sequence for the glucocorticoid nuclear receptor/transcription factor resulted in enhanced binding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18241046" 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>Hypertrophic Cardiomyopathy 18</em></strong></p><p>
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<a href="#15" class="mim-tip-reference" title="Minamisawa, S., Sato, Y., Tatsuguchi, Y., Fujino, T., Imamura, S., Uetsuka, Y., Nakazawa, M., Matsuoka, R. <strong>Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 304: 1-4, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12705874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12705874</a>] [<a href="https://doi.org/10.1016/s0006-291x(03)00526-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12705874">Minamisawa et al. (2003)</a> analyzed the candidate gene PLN in 87 patients with hypertrophic cardiomyopathy (see CMH18; <a href="/entry/613874">613874</a>), 10 with dilated cardiomyopathy, and 2 patients with restrictive cardiomyopathy (RCM; see <a href="/entry/115210">115210</a>). In the proband of a 2-generation family with CMH, they identified heterozygosity for a mutation in the promoter region (<a href="#0004">172405.0004</a>) that increased transcriptional activity 1.5-fold compared to wildtype and was not found in 296 Japanese controls. No PLN mutations were identified in the remaining 98 cardiomyopathy patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12705874" 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="#14" class="mim-tip-reference" title="Medin, M., Hermida-Prieto, M., Monserrat, L., Laredo, R., Rodriguez-Rey, J. C., Fernandez, X., Castro-Beiras, A. <strong>Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN 42C-G mutation.</strong> Europ. J. Heart Fail. 9: 37-43, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16829191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16829191</a>] [<a href="https://doi.org/10.1016/j.ejheart.2006.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16829191">Medin et al. (2007)</a> performed SSCP mutation screening and DNA sequencing of the PLN gene in 101 CMH patients and 85 CMD patients and identified a point mutation in the promoter region (<a href="#0005">172405.0005</a>) in 1 CMH proband. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16829191" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Chiu, C., Tebo, M., Ingles, J., Yeates, L., Arthur, J. W., Lind, J. M., Semsarian, C. <strong>Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy.</strong> J. Molec. Cell. Cardiol. 43: 337-343, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17655857</a>] [<a href="https://doi.org/10.1016/j.yjmcc.2007.06.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17655857">Chiu et al. (2007)</a> screened an Australian cohort of 252 unrelated CMH patients for mutations in calcium regulatory genes and identified heterozygosity for the L39X mutation in the PLN gene in 1 proband (<a href="#0002">172405.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17655857" 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="#11" class="mim-tip-reference" title="Landstrom, A. P., Adekola, B. A., Bos, J. M., Ommen, S. R., Ackerman, M. J. <strong>PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.</strong> Am. Heart J. 161: 165-171, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21167350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21167350</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21167350[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ahj.2010.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21167350">Landstrom et al. (2011)</a> analyzed the PLN gene in a cohort of 1,064 CMH probands and identified heterozygosity for the L39X mutation in a 58-year-old male proband with CMH. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21167350" 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>Exclusion Studies</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="Kalemi, T., Efthimiadis, G., Zioutas, D., Lambropoulos, A., Mitakidou, A., Giannakoulas, G., Vassilikos, V., Karvounis, H., Kotsis, A., Parharidis, G., Louridas, G. <strong>Phospholamban gene mutations are not associated with hypertrophic cardiomyopathy in a northern Greek population.</strong> Biochem. Genet. 43: 637-642, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16382369/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16382369</a>] [<a href="https://doi.org/10.1007/s10528-005-9121-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16382369">Kalemi et al. (2005)</a> did not find mutations in the PLN gene in 53 Greek patients with CMH, but noted that because 95% of identified CMH-related mutations involve 4 genes, namely MYH7 (<a href="/entry/160760">160760</a>), TNNT2 (<a href="/entry/191045">191045</a>), MYBPC3 (<a href="/entry/600958">600958</a>), and TNNI3 (<a href="/entry/191044">191044</a>), a large cohort of CMH patients would be required to identify a novel CMH-causing gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16382369" 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="#18" class="mim-tip-reference" title="Petkow-Dimitrow, P., Kiec-Wilk, B., Kwasniak, M., Mikolajczyk, M., Dembinska-Kiec, A. <strong>Phospholamban gene mutations are not associated with hypertrophic cardiomyopathy in patients from southern Poland.</strong> Kardiol. Pol. 69: 134-137, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21332051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21332051</a>]" pmid="21332051">Petkow-Dimitrow et al. (2011)</a> screened 50 consecutive patients with CMH from southern Poland for the R9C (<a href="#0001">172405.0001</a>) and L39X (<a href="#0002">172405.0002</a>) mutations in the PLN gene but did not find those mutations in any patients or in 50 sex- and age-matched controls with normal echocardiograms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21332051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Luo, W., Grupp, I. L., Harrer, J., Ponniah, S., Grupp, G., Duffy, J. J., Doetschman, T., Kranias, E. G. <strong>Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.</strong> Circ. Res. 75: 401-409, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8062415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8062415</a>] [<a href="https://doi.org/10.1161/01.res.75.3.401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8062415">Luo et al. (1994)</a> generated Pln -/- mice, which exhibited significantly enhanced myocardial performance that was associated with an increase in the affinity of Serca2 for Ca(2+). Isoproterenol dose-response curves for contraction and relaxation in the Pln-null mice began at a maximum level and were not further increased by isoproterenol. <a href="#12" class="mim-tip-reference" title="Luo, W., Grupp, I. L., Harrer, J., Ponniah, S., Grupp, G., Duffy, J. J., Doetschman, T., Kranias, E. G. <strong>Targeted ablation of the phospholamban gene is associated with markedly enhanced myocardial contractility and loss of beta-agonist stimulation.</strong> Circ. Res. 75: 401-409, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8062415/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8062415</a>] [<a href="https://doi.org/10.1161/01.res.75.3.401" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8062415">Luo et al. (1994)</a> concluded that PLN acts as a critical repressor of basal myocardial contractility and may be the key phosphoprotein mediating in cardiac contractile responses to beta-adrenergic agonists. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8062415" 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 echocardiography to assess left ventricular function in Pln-null mice in vivo, <a href="#8" class="mim-tip-reference" title="Hoit, B. D., Khoury, S. F., Kranias, E. G., Ball, N., Walsh, R. A. <strong>In vivo echocardiographic detection of enhanced left ventricular function in gene-targeted mice with phospholamban deficiency.</strong> Circ. Res. 77: 632-637, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7641333/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7641333</a>] [<a href="https://doi.org/10.1161/01.res.77.3.632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7641333">Hoit et al. (1995)</a> observed significant increases in multiple physiologic parameters compared to wildtype controls (p less than 0.05) and concluded that PLN regulates basal left ventricular function in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7641333" 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 hamster model of progressive heart failure, <a href="#9" class="mim-tip-reference" title="Hoshijima, M., Ikeda, Y., Iwanaga, Y., Minamisawa, S, Date, M., Gu, Y., Iwatate, M., Li, M., Wang, L., Wilson, J. M., Wang, Y., Ross, J., Jr., Chien, K. R. <strong>Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.</strong> Nature Med. 8: 864-871, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12134142/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12134142</a>] [<a href="https://doi.org/10.1038/nm739" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12134142">Hoshijima et al. (2002)</a> used an in vivo transcoronary delivery system to administer recombinant adeno-associated virus expressing a pseudophosphorylated mutant of human PLN. The treatment suppressed progressive impairment of left ventricular systolic function and contractility for 28 to 30 weeks; low left ventricular systolic pressure and deterioration in left ventricular relaxation were also largely prevented, protecting the hamsters from myocardial cell loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12134142" 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="#20" class="mim-tip-reference" title="Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., Kranias, E. G., MacLennan, D. H., Seidman, J. G., Seidman, C. E. <strong>Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.</strong> Science 299: 1410-1413, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610310</a>] [<a href="https://doi.org/10.1126/science.1081578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610310">Schmitt et al. (2003)</a> generated transgenic mice expressing the PLN R9C mutation under the control of the alpha-cardiac myosin heavy chain (<a href="/entry/160710">160710</a>) promoter. Two independent lines with identical phenotype were generated: biventricular cardiac dilation began at age 4 months, and dilated cardiomyopathy was rapidly progressive. Cellular and biochemical studies revealed that, unlike wildtype PLN, PLN-R9C did not directly inhibit SERCA2a. Rather, PLN-R9C trapped protein kinase A (see <a href="/entry/176911">176911</a>), which blocked PKA-mediated phosphorylation of wildtype PLN and in turn delayed decay of calcium transients in myocytes. <a href="#20" class="mim-tip-reference" title="Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., Kranias, E. G., MacLennan, D. H., Seidman, J. G., Seidman, C. E. <strong>Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.</strong> Science 299: 1410-1413, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610310</a>] [<a href="https://doi.org/10.1126/science.1081578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610310">Schmitt et al. (2003)</a> concluded that myocellular calcium dysregulation can initiate human heart failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12610310" 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 transgenic mice with cardiac-specific overexpression of the PLN arg14 deletion, <a href="#6" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Gamolini, A. O., Waggoner, J. R., Pater, L., Lynch, R. A., Fan, G.-C., Tsiapras, D., Parekh, R. R., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.</strong> Proc. Nat. Acad. Sci. 103: 1388-1393, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432188</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432188[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.0510519103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16432188">Haghighi et al. (2006)</a> observed recapitulation of human cardiomyopathy, with similar histopathologic abnormalities and premature death. Coexpression of normal and mutant PLN in HEK293 cells resulted in superinhibition of sarcoplasmic reticulum Ca(2+)-ATPase activity, and the dominant effect of the arg14 deletion could not be fully removed, even upon phosphorylation by protein kinase A (see <a href="/entry/176911">176911</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16432188" 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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs111033559 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033559;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=rs111033559" 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=rs111033559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 4-generation family segregating autosomal dominant dilated cardiomyopathy with heart failure (CMD1P; <a href="/entry/609909">609909</a>), <a href="#20" class="mim-tip-reference" title="Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., Kranias, E. G., MacLennan, D. H., Seidman, J. G., Seidman, C. E. <strong>Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.</strong> Science 299: 1410-1413, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610310</a>] [<a href="https://doi.org/10.1126/science.1081578" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12610310">Schmitt et al. (2003)</a> identified a C-to-T transition at nucleotide 25 of the PLN gene, resulting in an arg9-to-cys (R9C) substitution in the cytosolic PLN domain. This mutation segregated absolutely with affected status in the family, occurred in a highly conserved residue, and was absent from more than 200 normal chromosomes. In the family, affected individuals had increased chamber dimensions and decreased contractile function at age 20 to 30 years, with progression to heart failure within 5 to 10 years after symptom onset. Congestive heart failure was severe in 12 individuals, necessitating cardiac transplantation in 4. The average age at death in affected individuals was 25.1 +/- 12.7 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12610310" 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 biochemical and biophysical techniques in vitro and in live cells, <a href="#4" class="mim-tip-reference" title="Ha, K. N., Masterson, L. R., Hou, Z., Verardi, R., Walsh, N., Veglia, G., Robia, S. L. <strong>Lethal arg9cys phospholamban mutation hinders Ca(2+)-ATPase regulation and phosphorylation by protein kinase A.</strong> Proc. Nat. Acad. Sci. 108: 2735-2740, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21282613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21282613</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21282613[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.1013987108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21282613">Ha et al. (2011)</a> found that the R9C mutation led to stabilization of pentameric PLN due to disulfide bridge formation between the cytoplasmic domains of individual PLN(R9C) subunits. Stabilization of the PLN pentamer inhibited the dissociation of the pentamer into PLN monomers and promoted the formation of PLN(R9C) dimers, particularly under oxidative conditions. PKA (see <a href="/entry/176911">176911</a>)-mediated phosphorylation of pentameric PLN(R9C) was significantly impaired due to this stabilization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21282613" 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> rs111033560 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033560;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/rs111033560?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=rs111033560" 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=rs111033560" 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=RCV000014607 OR RCV000022712 OR RCV000151666 OR RCV000157419 OR RCV000157420 OR RCV000171826 OR RCV000523391 OR RCV000621703 OR RCV000770226 OR RCV002467493 OR RCV003389232" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000014607, RCV000022712, RCV000151666, RCV000157419, RCV000157420, RCV000171826, RCV000523391, RCV000621703, RCV000770226, RCV002467493, RCV003389232" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000014607...</a>
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<p><strong><em>Dilated Cardiomyopathy 1P</em></strong></p><p>
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In 2 unrelated families with idiopathic dilated cardiomyopathy (CMD1P; <a href="/entry/609909">609909</a>), <a href="#7" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Pater, L., Lynch, R. A., Asahi, M., Gramolini, A. O., Fan, G.-C., Tsiapras, D., Hahn, H. S., Adamopoulos, S., Liggett, S. B., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>Human phospholamban null results in lethal dilated cardiomyopathy revealing a critical difference between mouse and human.</strong> J. Clin. Invest. 111: 869-876, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12639993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12639993</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=12639993[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/10.1172/JCI17892" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12639993">Haghighi et al. (2003)</a> identified a 116T-G transversion in the PLN gene, resulting in a leu39-to-ter (L39X) substitution that truncated the 52-amino acid protein in the highly conserved transmembrane domain II. The 2 homozygous individuals developed dilated cardiomyopathy and heart failure requiring cardiac transplantation at ages 16 and 27 years, respectively; 11 heterozygous individuals exhibited variable clinical findings indicating incomplete penetrance of the cardiomyopathy phenotype: 2 had dilated cardiomyopathy with ejection fractions of 25% or less, 4 had left ventricular hypertrophy with normal left ventricular systolic function, and 5 had normal echocardiograms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12639993" 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>Hypertrophic Cardiomyopathy 18</em></strong></p><p>
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In a 65-year-old Australian woman who was diagnosed with familial hypertrophic cardiomyopathy (CMH18; <a href="/entry/613874">613874</a>) at age 61 years, <a href="#2" class="mim-tip-reference" title="Chiu, C., Tebo, M., Ingles, J., Yeates, L., Arthur, J. W., Lind, J. M., Semsarian, C. <strong>Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy.</strong> J. Molec. Cell. Cardiol. 43: 337-343, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17655857/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17655857</a>] [<a href="https://doi.org/10.1016/j.yjmcc.2007.06.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17655857">Chiu et al. (2007)</a> identified heterozygosity for the L39X mutation in the PLN gene. Echocardiography revealed asymmetric septal hypertrophy with a maximum wall thickness of 20 mm, normal systolic contractile function, and no evidence of left ventricular dilation. Her mother had also been diagnosed with CMH and had died at age 80 of noncardiac causes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17655857" 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 58-year-old man with CMH18, <a href="#11" class="mim-tip-reference" title="Landstrom, A. P., Adekola, B. A., Bos, J. M., Ommen, S. R., Ackerman, M. J. <strong>PLN-encoded phospholamban mutation in a large cohort of hypertrophic cardiomyopathy cases: summary of the literature and implications for genetic testing.</strong> Am. Heart J. 161: 165-171, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21167350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21167350</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21167350[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ahj.2010.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21167350">Landstrom et al. (2011)</a> identified heterozygosity for the L39X mutation in the PLN gene. The mutation segregated with disease in the family and was not found in 300 controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21167350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 7-generation family with idiopathic dilated cardiomyopathy (CMD1P; <a href="/entry/609909">609909</a>) and ventricular tachycardia, <a href="#6" class="mim-tip-reference" title="Haghighi, K., Kolokathis, F., Gamolini, A. O., Waggoner, J. R., Pater, L., Lynch, R. A., Fan, G.-C., Tsiapras, D., Parekh, R. R., Dorn, G. W., II, MacLennan, D. H., Kremastinos, D. T., Kranias, E. G. <strong>A mutation in the human phospholamban gene, deleting arginine 14, results in lethal, hereditary cardiomyopathy.</strong> Proc. Nat. Acad. Sci. 103: 1388-1393, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16432188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16432188</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16432188[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.0510519103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16432188">Haghighi et al. (2006)</a> identified heterozygosity for a 3-bp deletion in the PLN gene, resulting in deletion of a highly conserved arg14 residue. By middle age, heterozygous individuals in this family developed left ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias, with overt heart failure in some cases. No homozygous individuals were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16432188" 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">rs920627366 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs920627366;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=rs920627366" 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=rs920627366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a woman who was diagnosed with hypertrophic cardiomyopathy (CMH18; <a href="/entry/613874">613874</a>) at 56 years of age, <a href="#15" class="mim-tip-reference" title="Minamisawa, S., Sato, Y., Tatsuguchi, Y., Fujino, T., Imamura, S., Uetsuka, Y., Nakazawa, M., Matsuoka, R. <strong>Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy.</strong> Biochem. Biophys. Res. Commun. 304: 1-4, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12705874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12705874</a>] [<a href="https://doi.org/10.1016/s0006-291x(03)00526-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12705874">Minamisawa et al. (2003)</a> identified heterozygosity for a -77A-G transition in the promoter region of the PLN gene. Functional analysis in transiently transfected neonatal rat cardiomyocytes demonstrated that the mutation resulted in a 1.5-fold increase in PLN transcription compared to wildtype. The mutation was not found in 296 Japanese controls. The proband's family history was consistent with a late-onset type of CMH: her father, who was diagnosed with cardiomyopathy, had died at age 82, and an older brother was also diagnosed with CMH at age 62 years. None of the family members were available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12705874" 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> rs188578681 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs188578681;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/rs188578681?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=rs188578681" 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=rs188578681" 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=RCV000022714 OR RCV000205657 OR RCV002494536 OR RCV004758672" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000022714, RCV000205657, RCV002494536, RCV004758672" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000022714...</a>
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<p>In an 85-year-old woman who was diagnosed with apical hypertrophic cardiomyopathy (CMH18; <a href="/entry/613874">613874</a>) at 67 years of age, <a href="#14" class="mim-tip-reference" title="Medin, M., Hermida-Prieto, M., Monserrat, L., Laredo, R., Rodriguez-Rey, J. C., Fernandez, X., Castro-Beiras, A. <strong>Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN 42C-G mutation.</strong> Europ. J. Heart Fail. 9: 37-43, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16829191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16829191</a>] [<a href="https://doi.org/10.1016/j.ejheart.2006.04.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16829191">Medin et al. (2007)</a> identified heterozygosity for a -42C-G transversion n the promoter region of the PLN gene that was not found in more than 100 control subjects. Mutations in 6 other known CMH genes were excluded in the proband. Transfection studies in the C6 glioma cell line and C2C12 muscle cells demonstrated a 43% and 47% decrease in transcriptional activity compared to wildtype, respectively. The proband's brother was diagnosed with apical CMH at 72 years of age and died suddenly at age 81 years. Screening of the proband's 3 asymptomatic sons revealed that 1 had apical hypertrophic cardiomyopathy with mild hypertrophy at age 59 years; the other 2 had normal electro- and echocardiograms. The affected son and a 55-year-old asymptomatic son were also heterozygous for the -42C-G mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16829191" 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> rs77186188 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs77186188;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/rs77186188?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=rs77186188" 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=rs77186188" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p><a href="#5" class="mim-tip-reference" title="Haghighi, K., Chen, G., Sato, Y., Fan, G.-C., He, S., Kolokathis, F., Pater, L., Paraskevaidis, I., Jones, W. K., Dorn, G. W., II, Kremastinos, D. T., Kranias, E. G. <strong>A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids.</strong> Hum. Mutat. 29: 640-647, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18241046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18241046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18241046[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/humu.20692" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18241046">Haghighi et al. (2008)</a> analyzed the PLN gene in 381 dilated cardiomyopathy patients and 296 controls with no known cardiomyopathy history and identified a heterozygous -36A-C transversion in the PLN promoter region in 22 patients with dilated cardiomyopathy-1P (CMD1P; <a href="/entry/609909">609909</a>) and 1 control. Luciferase reporter analysis in rat neonatal cardiomyocytes demonstrated that the -36A-C variant increased PLN activity by 24% compared to wildtype. In addition, the -36A-C alteration in the steroid receptor sequence for the glucocorticoid nuclear receptor/transcription factor resulted in enhanced binding. <a href="#5" class="mim-tip-reference" title="Haghighi, K., Chen, G., Sato, Y., Fan, G.-C., He, S., Kolokathis, F., Pater, L., Paraskevaidis, I., Jones, W. K., Dorn, G. W., II, Kremastinos, D. T., Kranias, E. G. <strong>A human phospholamban promoter polymorphism in dilated cardiomyopathy alters transcriptional regulation by glucocorticoids.</strong> Hum. Mutat. 29: 640-647, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18241046/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18241046</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18241046[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/humu.20692" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18241046">Haghighi et al. (2008)</a> suggested that this variant might contribute to depressed contractility and accelerate functional deterioration in heart failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18241046" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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[<a href="https://doi.org/10.1073/pnas.1013987108" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.20692" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0510519103" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI17892" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.res.77.3.632" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/nm739" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10528-005-9121-8" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ahj.2010.08.001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.res.75.3.401" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/jmcc.1998.0904" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ejheart.2006.04.007" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0006-291x(03)00526-6" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Otsu1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
|
Otsu, K., Fujii, J., Periasamy, M., Difilippantonio, M., Uppender, M., Ward, D. C., MacLennan, D. H.
|
|
<strong>Chromosome mapping of five human cardiac and skeletal muscle sarcoplasmic reticulum protein genes.</strong>
|
|
Genomics 17: 507-509, 1993.
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8406504/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8406504</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8406504" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1993.1357" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Oxenoid2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Oxenoid, K., Chou, J. J.
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|
<strong>The structure of phospholamban pentamer reveals a channel-like architecture in membranes.</strong>
|
|
Proc. Nat. Acad. Sci. 102: 10870-10875, 2005.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16043693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16043693</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16043693[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=16043693" 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.0504920102" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Petkow-Dimitrow2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Petkow-Dimitrow, P., Kiec-Wilk, B., Kwasniak, M., Mikolajczyk, M., Dembinska-Kiec, A.
|
|
<strong>Phospholamban gene mutations are not associated with hypertrophic cardiomyopathy in patients from southern Poland.</strong>
|
|
Kardiol. Pol. 69: 134-137, 2011.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21332051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21332051</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21332051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="19" class="mim-anchor"></a>
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<a id="Phillips2023" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Phillips, T. A., Hauck, G. T., Pribadi, M. P., Cho, E. E., Cleary, S. R., Robia, S. L.
|
|
<strong>Micropeptide hetero-oligomerization adds complexity to the calcium pump regulatory network.</strong>
|
|
Biophys. J. 122: 301-309, 2023.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36523160/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36523160</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36523160" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.bpj.2022.12.014" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="20" class="mim-anchor"></a>
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<a id="Schmitt2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schmitt, J. P., Kamisago, M., Asahi, M., Li, G. H., Ahmad, F., Mende, U., Kranias, E. G., MacLennan, D. H., Seidman, J. G., Seidman, C. E.
|
|
<strong>Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban.</strong>
|
|
Science 299: 1410-1413, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12610310/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12610310</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12610310" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1126/science.1081578" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
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Bao Lige - updated : 09/28/2023
|
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="mimCollapseContributors">
|
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Patricia A. Hartz - updated : 4/8/2011<br>Marla J. F. O'Neill - updated : 4/7/2011<br>Marla J. F. O'Neill - updated : 4/7/2011<br>Marla J. F. O'Neill - updated : 2/21/2006<br>Marla J. F. O'Neill - updated : 2/10/2005<br>Marla J. F. O'Neill - updated : 2/7/2005<br>Patricia A. Hartz - updated : 8/26/2004<br>Ada Hamosh - updated : 3/24/2003<br>Victor A. McKusick - updated : 7/13/1999
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
|
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<span class="text-nowrap mim-text-font">
|
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Creation Date:
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</span>
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
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Victor A. McKusick : 12/6/1991
|
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
|
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
|
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</span>
|
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</div>
|
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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|
mgross : 09/28/2023
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</span>
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</div>
|
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</div>
|
|
<div class="row collapse" id="mimCollapseEditHistory">
|
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
|
|
carol : 01/11/2023<br>carol : 01/10/2023<br>mgross : 05/20/2011<br>mgross : 5/20/2011<br>wwang : 5/13/2011<br>terry : 4/8/2011<br>wwang : 4/8/2011<br>wwang : 4/8/2011<br>terry : 4/7/2011<br>terry : 4/7/2011<br>terry : 4/7/2011<br>wwang : 2/22/2006<br>wwang : 2/21/2006<br>terry : 3/16/2005<br>wwang : 2/16/2005<br>wwang : 2/14/2005<br>terry : 2/10/2005<br>tkritzer : 2/8/2005<br>terry : 2/7/2005<br>mgross : 8/31/2004<br>terry : 8/26/2004<br>alopez : 3/24/2003<br>terry : 3/24/2003<br>carol : 7/23/1999<br>jlewis : 7/21/1999<br>jlewis : 7/21/1999<br>terry : 7/13/1999<br>carol : 8/19/1998<br>carol : 8/25/1993<br>supermim : 3/16/1992<br>carol : 12/19/1991<br>carol : 12/6/1991
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
|
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<span class="mim-font">
|
|
<strong>*</strong> 172405
|
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</span>
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</h3>
|
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</div>
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<div>
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<h3>
|
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<span class="mim-font">
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PHOSPHOLAMBAN; PLN
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: PLN</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: 6q22.31
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 6:118,548,296-118,561,716 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
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</p>
|
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
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</h4>
|
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<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
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</th>
|
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<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
6q22.31
|
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</span>
|
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</td>
|
|
|
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|
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<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, dilated, 1P
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
609909
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
|
<span class="mim-font">
|
|
Cardiomyopathy, hypertrophic, 18
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613874
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
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|
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</tbody>
|
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</table>
|
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</div>
|
|
</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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|
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|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Phospholamban is expressed in the sarcoplasmic reticulum membrane as a 30-kD homopentamer. It controls cellular calcium levels by a mechanism that depends on its phosphorylation (summary by Oxenoid and Chou, 2005). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using dog and rabbit phospholamban cDNAs as probes, Fujii et al. (1991) cloned human phospholamban from a skeletal muscle cDNA library. The deduced 52-amino acid human protein differs from rabbit, dog, and pig at position 27 and from dog and pig at position 2. Northern blot analysis of rabbit tissues detected phospholamban transcripts in heart and soleus and in tissues rich in smooth muscle, such as uterus, small and large intestine, trachea, bladder, esophagus, and aorta. No expression was detected in plantaris, spleen, testis, brain, liver, and kidney. </p><p>McTiernan et al. (1999) found that human ventricle and quadriceps displayed high levels of phospholamban transcripts and proteins, with markedly lower expression in smooth muscles. The right atrium also expressed low levels of phospholamban. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Fujii et al. (1991) found that the rabbit Pln gene spans 13.2 kb and contains only 1 intron, which separates exonic sequences in the 5-prime UTR. </p><p>McTiernan et al. (1999) reported that the structure of the human phospholamban gene closely resembles that reported for the chicken, rabbit, rat, and mouse genes. Comparison of the human to other mammalian phospholamban genes indicated a marked conservation of sequence for at least 217 bp upstream of the transcription start site. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using a human phospholamban cDNA, Fujii et al. (1991) mapped the phospholamban gene to human chromosome 6. By fluorescence in situ hybridization, Otsu et al. (1993) mapped the PLN gene to chromosome 6q22.1. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Fujii et al. (1991) stated that phospholamban is a major substrate for the cAMP-dependent protein kinase in cardiac muscle. Phospholamban is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a; see 108740) in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca(2+) pump leads to enhanced muscle relaxation rates, thereby contributing to the inotropic response elicited in heart by beta agonists. Phospholamban is also expressed in slow-twitch skeletal muscle and some smooth muscle cells. </p><p>Asahi et al. (2004) generated mice with cardiac-specific overexpression of epitope-tagged rabbit sarcolipin (SLN; 602203). Overexpression of Sln decreased the apparent affinity of Serca2a (108740) for calcium in transgenic hearts. The mice had altered calcium currents, impaired cardiac contractility with altered tension and relaxation times, and ventricular hypertrophy. Coimmunoprecipitation indicated that overexpressed Sln bound both Serca2a and Pln, forming a ternary complex. The results suggested that Sln overexpression inhibits Serca2a through stabilization of Serca2a-Pln interaction and through inhibition of Pln phosphorylation. Asahi et al. (2004) concluded that inhibition of Serca2a impairs contractility and calcium cycling, but responsiveness to beta-adrenergic agonists may prevent progression to heart failure. </p><p>By pairwise testing of fluorescence-labeled proteins, Phillips et al. (2023) showed that different SERCA-modulating membrane micropeptides, including PLN, formed heterooligomers with varying affinities. Moreover, each micropeptide also assembled into homooligomers, but the homooligomers did not interact with SERCA. The affinities of heterooligomerization of micropeptides depended on whether they were the minority or majority species, and SERCA interaction with individual monomeric micropeptides competed with micropeptide-micropeptide interactions. </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>Biochemical Features</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>Using NMR experiments, Oxenoid and Chou (2005) characterized the reconstituted human PLN pentamer. They found that PLN assembled by parallel packing into well-structured pentamers with 5-fold rotational symmetry. In the PLN pentamer, the positively-charged N-terminal domains formed alpha helices that repulsed one another via electrostatic charges and assumed a bellflower appearance. The linker regions of each subunit acquired dihedral angles characteristic of beta strands. The long, largely hydrophobic C-terminal transmembrane alpha helices engaged in leu/ile zipper interactions and formed a funnel-like pore with a diameter of about 3.6 angstroms at its narrowest point. Oxenoid and Chou (2005) concluded that, like monomeric PLN, pentameric PLN can interact with the SERCA cytoplasmic domain due to the relative mobility of the N-terminal SERCA-interacting domains. They proposed that the entire PLN pentamer may have a dual function as a regulatory protein and as an ion channel. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Dilated Cardiomyopathy 1P</em></strong></p><p>
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Schmitt et al. (2003) sequenced the PLN gene in 20 unrelated individuals with inherited dilated cardiomyopathy and heart failure (see CMD1P, 609909). In 1 sample, an arginine-to-cysteine substitution at codon 9 in the cytosolic PLN domain was identified and segregated with disease in that 4-generation family (R9C; 172405.0001). Affected individuals had increased chamber dimensions and decreased contractile function at age 20 to 30 years, with progression to heart failure within 5 to 10 years after symptom onset. Congestive heart failure was severe in 12 individuals, necessitating cardiac transplantation in 4. The average age at death of affected individuals was 25.1 +/- 12.7 years. </p><p>In 2 unrelated families with CMD1P, Haghighi et al. (2003) identified a nonsense mutation in the PLN gene (L39X; 172405.0002). The 2 homozygous individuals developed dilated cardiomyopathy and heart failure requiring cardiac transplantation at ages 16 and 27 years, respectively; 11 heterozygous individuals exhibited variable clinical findings, indicating incomplete penetrance of the cardiomyopathy phenotype. Haghighi et al. (2003) concluded that in contrast to mice in which Pln deficiency enhances myocardial inotropy and lusitropy without adverse effects, PLN is essential for cardiac health in humans, and its absence results in lethal heart failure. </p><p>In affected members of a 7-generation family with CMD1P, Haghighi et al. (2006) identified heterozygosity for a 3-bp deletion in the PLN gene (172405.0003). </p><p>Haghighi et al. (2008) analyzed the PLN gene in 381 CMD patients and 296 controls with no known cardiomyopathy history and identified a heterozygous -36A-C variant in the 5-prime untranslated region (172405.0006) in 22 patients and 1 control. Functional analysis demonstrated that the -36A-C variant increased PLN activity by 24% compared to wildtype and that this alteration in the steroid receptor sequence for the glucocorticoid nuclear receptor/transcription factor resulted in enhanced binding. </p><p><strong><em>Hypertrophic Cardiomyopathy 18</em></strong></p><p>
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|
Minamisawa et al. (2003) analyzed the candidate gene PLN in 87 patients with hypertrophic cardiomyopathy (see CMH18; 613874), 10 with dilated cardiomyopathy, and 2 patients with restrictive cardiomyopathy (RCM; see 115210). In the proband of a 2-generation family with CMH, they identified heterozygosity for a mutation in the promoter region (172405.0004) that increased transcriptional activity 1.5-fold compared to wildtype and was not found in 296 Japanese controls. No PLN mutations were identified in the remaining 98 cardiomyopathy patients. </p><p>Medin et al. (2007) performed SSCP mutation screening and DNA sequencing of the PLN gene in 101 CMH patients and 85 CMD patients and identified a point mutation in the promoter region (172405.0005) in 1 CMH proband. </p><p>Chiu et al. (2007) screened an Australian cohort of 252 unrelated CMH patients for mutations in calcium regulatory genes and identified heterozygosity for the L39X mutation in the PLN gene in 1 proband (172405.0002). </p><p>Landstrom et al. (2011) analyzed the PLN gene in a cohort of 1,064 CMH probands and identified heterozygosity for the L39X mutation in a 58-year-old male proband with CMH. </p><p><strong><em>Exclusion Studies</em></strong></p><p>
|
|
Kalemi et al. (2005) did not find mutations in the PLN gene in 53 Greek patients with CMH, but noted that because 95% of identified CMH-related mutations involve 4 genes, namely MYH7 (160760), TNNT2 (191045), MYBPC3 (600958), and TNNI3 (191044), a large cohort of CMH patients would be required to identify a novel CMH-causing gene. </p><p>Petkow-Dimitrow et al. (2011) screened 50 consecutive patients with CMH from southern Poland for the R9C (172405.0001) and L39X (172405.0002) mutations in the PLN gene but did not find those mutations in any patients or in 50 sex- and age-matched controls with normal echocardiograms. </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>Luo et al. (1994) generated Pln -/- mice, which exhibited significantly enhanced myocardial performance that was associated with an increase in the affinity of Serca2 for Ca(2+). Isoproterenol dose-response curves for contraction and relaxation in the Pln-null mice began at a maximum level and were not further increased by isoproterenol. Luo et al. (1994) concluded that PLN acts as a critical repressor of basal myocardial contractility and may be the key phosphoprotein mediating in cardiac contractile responses to beta-adrenergic agonists. </p><p>Using echocardiography to assess left ventricular function in Pln-null mice in vivo, Hoit et al. (1995) observed significant increases in multiple physiologic parameters compared to wildtype controls (p less than 0.05) and concluded that PLN regulates basal left ventricular function in vivo. </p><p>In a hamster model of progressive heart failure, Hoshijima et al. (2002) used an in vivo transcoronary delivery system to administer recombinant adeno-associated virus expressing a pseudophosphorylated mutant of human PLN. The treatment suppressed progressive impairment of left ventricular systolic function and contractility for 28 to 30 weeks; low left ventricular systolic pressure and deterioration in left ventricular relaxation were also largely prevented, protecting the hamsters from myocardial cell loss. </p><p>Schmitt et al. (2003) generated transgenic mice expressing the PLN R9C mutation under the control of the alpha-cardiac myosin heavy chain (160710) promoter. Two independent lines with identical phenotype were generated: biventricular cardiac dilation began at age 4 months, and dilated cardiomyopathy was rapidly progressive. Cellular and biochemical studies revealed that, unlike wildtype PLN, PLN-R9C did not directly inhibit SERCA2a. Rather, PLN-R9C trapped protein kinase A (see 176911), which blocked PKA-mediated phosphorylation of wildtype PLN and in turn delayed decay of calcium transients in myocytes. Schmitt et al. (2003) concluded that myocellular calcium dysregulation can initiate human heart failure. </p><p>In transgenic mice with cardiac-specific overexpression of the PLN arg14 deletion, Haghighi et al. (2006) observed recapitulation of human cardiomyopathy, with similar histopathologic abnormalities and premature death. Coexpression of normal and mutant PLN in HEK293 cells resulted in superinhibition of sarcoplasmic reticulum Ca(2+)-ATPase activity, and the dominant effect of the arg14 deletion could not be fully removed, even upon phosphorylation by protein kinase A (see 176911). </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 CARDIOMYOPATHY, DILATED, 1P</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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PLN, ARG9CYS
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<br />
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SNP: rs111033559,
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ClinVar: RCV000014606, RCV000183815, RCV000211844, RCV000769213
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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 4-generation family segregating autosomal dominant dilated cardiomyopathy with heart failure (CMD1P; 609909), Schmitt et al. (2003) identified a C-to-T transition at nucleotide 25 of the PLN gene, resulting in an arg9-to-cys (R9C) substitution in the cytosolic PLN domain. This mutation segregated absolutely with affected status in the family, occurred in a highly conserved residue, and was absent from more than 200 normal chromosomes. In the family, affected individuals had increased chamber dimensions and decreased contractile function at age 20 to 30 years, with progression to heart failure within 5 to 10 years after symptom onset. Congestive heart failure was severe in 12 individuals, necessitating cardiac transplantation in 4. The average age at death in affected individuals was 25.1 +/- 12.7 years. </p><p>Using biochemical and biophysical techniques in vitro and in live cells, Ha et al. (2011) found that the R9C mutation led to stabilization of pentameric PLN due to disulfide bridge formation between the cytoplasmic domains of individual PLN(R9C) subunits. Stabilization of the PLN pentamer inhibited the dissociation of the pentamer into PLN monomers and promoted the formation of PLN(R9C) dimers, particularly under oxidative conditions. PKA (see 176911)-mediated phosphorylation of pentameric PLN(R9C) was significantly impaired due to this stabilization. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0002 CARDIOMYOPATHY, DILATED, 1P</strong>
|
|
</span>
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</h4>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC 18, INCLUDED
|
|
</span>
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</div>
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<div>
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<span class="mim-text-font">
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|
PLN, LEU39TER
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<br />
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|
SNP: rs111033560,
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|
|
gnomAD: rs111033560,
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|
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|
|
ClinVar: RCV000014607, RCV000022712, RCV000151666, RCV000157419, RCV000157420, RCV000171826, RCV000523391, RCV000621703, RCV000770226, RCV002467493, RCV003389232
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p />
|
|
<p><strong><em>Dilated Cardiomyopathy 1P</em></strong></p><p>
|
|
In 2 unrelated families with idiopathic dilated cardiomyopathy (CMD1P; 609909), Haghighi et al. (2003) identified a 116T-G transversion in the PLN gene, resulting in a leu39-to-ter (L39X) substitution that truncated the 52-amino acid protein in the highly conserved transmembrane domain II. The 2 homozygous individuals developed dilated cardiomyopathy and heart failure requiring cardiac transplantation at ages 16 and 27 years, respectively; 11 heterozygous individuals exhibited variable clinical findings indicating incomplete penetrance of the cardiomyopathy phenotype: 2 had dilated cardiomyopathy with ejection fractions of 25% or less, 4 had left ventricular hypertrophy with normal left ventricular systolic function, and 5 had normal echocardiograms. </p><p><strong><em>Hypertrophic Cardiomyopathy 18</em></strong></p><p>
|
|
In a 65-year-old Australian woman who was diagnosed with familial hypertrophic cardiomyopathy (CMH18; 613874) at age 61 years, Chiu et al. (2007) identified heterozygosity for the L39X mutation in the PLN gene. Echocardiography revealed asymmetric septal hypertrophy with a maximum wall thickness of 20 mm, normal systolic contractile function, and no evidence of left ventricular dilation. Her mother had also been diagnosed with CMH and had died at age 80 of noncardiac causes. </p><p>In a 58-year-old man with CMH18, Landstrom et al. (2011) identified heterozygosity for the L39X mutation in the PLN gene. The mutation segregated with disease in the family and was not found in 300 controls. </p>
|
|
</span>
|
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</div>
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<div>
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|
<br />
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|
</div>
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|
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</div>
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<div>
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|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 CARDIOMYOPATHY, DILATED, 1P</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
PLN, 3-BP DEL, 39AGA
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|
|
<br />
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|
|
SNP: rs397516784,
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|
|
ClinVar: RCV000037582, RCV000183818, RCV000212833, RCV000233546, RCV000244830, RCV000491072, RCV001197004, RCV001787831
|
|
|
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</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-generation family with idiopathic dilated cardiomyopathy (CMD1P; 609909) and ventricular tachycardia, Haghighi et al. (2006) identified heterozygosity for a 3-bp deletion in the PLN gene, resulting in deletion of a highly conserved arg14 residue. By middle age, heterozygous individuals in this family developed left ventricular dilation, contractile dysfunction, and episodic ventricular arrhythmias, with overt heart failure in some cases. No homozygous individuals were identified. </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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 18</strong>
|
|
</span>
|
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</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
PLN, -77A-G
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|
|
<br />
|
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|
|
SNP: rs920627366,
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|
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|
|
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|
|
ClinVar: RCV000022713, RCV001852000
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a woman who was diagnosed with hypertrophic cardiomyopathy (CMH18; 613874) at 56 years of age, Minamisawa et al. (2003) identified heterozygosity for a -77A-G transition in the promoter region of the PLN gene. Functional analysis in transiently transfected neonatal rat cardiomyocytes demonstrated that the mutation resulted in a 1.5-fold increase in PLN transcription compared to wildtype. The mutation was not found in 296 Japanese controls. The proband's family history was consistent with a late-onset type of CMH: her father, who was diagnosed with cardiomyopathy, had died at age 82, and an older brother was also diagnosed with CMH at age 62 years. None of the family members were available for study. </p>
|
|
</span>
|
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</div>
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<div>
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|
<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 18</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
|
PLN, -42C-G, PROMOTER
|
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<br />
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|
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SNP: rs188578681,
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|
|
|
gnomAD: rs188578681,
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|
|
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ClinVar: RCV000022714, RCV000205657, RCV002494536, RCV004758672
|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 85-year-old woman who was diagnosed with apical hypertrophic cardiomyopathy (CMH18; 613874) at 67 years of age, Medin et al. (2007) identified heterozygosity for a -42C-G transversion n the promoter region of the PLN gene that was not found in more than 100 control subjects. Mutations in 6 other known CMH genes were excluded in the proband. Transfection studies in the C6 glioma cell line and C2C12 muscle cells demonstrated a 43% and 47% decrease in transcriptional activity compared to wildtype, respectively. The proband's brother was diagnosed with apical CMH at 72 years of age and died suddenly at age 81 years. Screening of the proband's 3 asymptomatic sons revealed that 1 had apical hypertrophic cardiomyopathy with mild hypertrophy at age 59 years; the other 2 had normal electro- and echocardiograms. The affected son and a 55-year-old asymptomatic son were also heterozygous for the -42C-G mutation. </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>.0006 CARDIOMYOPATHY, DILATED, 1P</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
PLN, -36A-C, PROMOTER
|
|
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|
|
|
<br />
|
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|
|
SNP: rs77186188,
|
|
|
|
|
|
gnomAD: rs77186188,
|
|
|
|
|
|
ClinVar: RCV000454553, RCV001516345, RCV001637028, RCV001803752
|
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|
</span>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>Haghighi et al. (2008) analyzed the PLN gene in 381 dilated cardiomyopathy patients and 296 controls with no known cardiomyopathy history and identified a heterozygous -36A-C transversion in the PLN promoter region in 22 patients with dilated cardiomyopathy-1P (CMD1P; 609909) and 1 control. Luciferase reporter analysis in rat neonatal cardiomyocytes demonstrated that the -36A-C variant increased PLN activity by 24% compared to wildtype. In addition, the -36A-C alteration in the steroid receptor sequence for the glucocorticoid nuclear receptor/transcription factor resulted in enhanced binding. Haghighi et al. (2008) suggested that this variant might contribute to depressed contractility and accelerate functional deterioration in heart failure. </p>
|
|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<p />
|
|
</div>
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<div>
|
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<ol>
|
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<li>
|
|
<p class="mim-text-font">
|
|
Asahi, M., Otsu, K., Nakayama, H., Hikoso, S., Takeda, T., Gramolini, A. O., Trivieri, M. G., Oudit, G. Y., Morita, T., Kusakari, Y., Hirano, S., Hongo, K., Hirotani, S., Yamaguchi, O., Peterson, A., Backx, P. H., Kurihara, S., Hori, M., MacLennan, D. H.
|
|
<strong>Cardiac-specific overexpression of sarcolipin inhibits sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA2a) activity and impairs cardiac function in mice.</strong>
|
|
Proc. Nat. Acad. Sci. 101: 9199-9204, 2004.
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[PubMed: 15201433]
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[Full Text: https://doi.org/10.1073/pnas.0402596101]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Chiu, C., Tebo, M., Ingles, J., Yeates, L., Arthur, J. W., Lind, J. M., Semsarian, C.
|
|
<strong>Genetic screening of calcium regulation genes in familial hypertrophic cardiomyopathy.</strong>
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