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Entry
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- *601646 - PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B (B56), DELTA; PPP2R5D
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- OMIM
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<p>
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<span class="h4">*601646</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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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="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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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/601646">Table View</a>
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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 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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<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=ENSG00000112640;t=ENST00000485511" 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=5528" 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=601646" 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=ENSG00000112640;t=ENST00000485511" 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_001270476,NM_006245,NM_180976,NM_180977" 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_006245" 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=601646" 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=09039&isoform_id=09039_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/PPP2R5D" 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/1130543,1478068,2189947,2189949,5453954,7387495,12654527,12654673,14715057,31083280,31083288,62089308,119624535,119624536,119624537,119624538,119624539,158254640,158257026,194389164,197692385,197692415,394582140" 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/Q14738" 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=5528" 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=ENSG00000112640;t=ENST00000485511" 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=PPP2R5D" 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=PPP2R5D" 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+5528" 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/PPP2R5D" 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:5528" 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/5528" 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=ENST00000485511.6&hgg_start=42984570&hgg_end=43012342&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:9312" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:9312" 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://medlineplus.gov/genetics/gene/ppp2r5d" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=601646[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 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=601646[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/PPP2R5D/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000112640" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=PPP2R5D" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=PPP2R5D" 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=PPP2R5D" 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=PPP2R5D&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/PA33676" 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:9312" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0042693.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2388481" 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/PPP2R5D#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:2388481" 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/5528/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=5528" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00007554;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-2568" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:5528" 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=PPP2R5D&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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601646
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B (B56), DELTA; PPP2R5D
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PPP2R5D" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PPP2R5D</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/6/510?start=-3&limit=10&highlight=510">6p21.1</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:42984570-43012342&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'})">6:42,984,570-43,012,342</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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<a href="/geneMap/6/510?start=-3&limit=10&highlight=510">
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6p21.1
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Houge-Janssens syndrome 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/616355"> 616355 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<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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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/601646" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/601646" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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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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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<p>The PPP2R5D gene encodes a B56 regulatory subunit of protein phosphatase-2A (PP2A), an intracellular serine/threonine phosphatase (summary by <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al., 2015</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" 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>For background information on PP2A and its subunits, see <a href="/entry/601643">601643</a>.</p>
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<p><a href="#6" class="mim-tip-reference" title="McCright, B., Rivers, A. M., Audlin, S., Virshup, D. M. <strong>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</strong> J. Biol. Chem. 271: 22081-22089, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8703017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8703017</a>] [<a href="https://doi.org/10.1074/jbc.271.36.22081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8703017">McCright et al. (1996)</a> cloned the B56-delta gene from a human fetal brain cDNA library using a partial cDNA sequence. They found that B56-delta encoded a 602-amino acid protein with a predicted molecular mass of 69,947 Da. This subunit is able to form a functional trimeric PP2A phosphatase when combined with an A and a C subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8703017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Louis, J. V., Martens, E., Borghgraef, P., Lambrecht, C., Sents, W., Longin, S., Zwaenepoel, K., Pijnenborg, R., Landrieu, I., Lippens, G., Ledermann, B., Gotz, J., Van Leuven, F., Goris, J., Janssens, V. <strong>Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3-beta.</strong> Proc. Nat. Acad. Sci. 108: 6957-6962, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21482799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21482799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21482799[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.1018777108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21482799">Louis et al. (2011)</a> found expression of the Ppp2r5d gene in various brain regions in the mouse: expression was highest in the striatum and thalamus, intermediate in the brainstem and hippocampus, and weak in the cortex and cerebellum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21482799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="McCright, B., Rivers, A. M., Audlin, S., Virshup, D. M. <strong>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</strong> J. Biol. Chem. 271: 22081-22089, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8703017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8703017</a>] [<a href="https://doi.org/10.1074/jbc.271.36.22081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8703017">McCright et al. (1996)</a> observed that the location of B56-delta varies with the cell cycle, being present in both cytoplasm and nucleus in interphase cells but concentrated in the nucleus of mitotic and recently divided cells. Both B56-beta (<a href="/entry/601644">601644</a>) and B56-delta are highly expressed in the adult brain, and mRNA for these isoforms increases 3- to 5-fold when neuroblastoma cell lines are induced to differentiate by retinoic acid treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8703017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="McCright, B., Brothman, A. R., Virshup, D. M. <strong>Assignment of human protein phosphatase 2A regulatory subunit genes B56-alpha, B56-beta, B56-gamma, B56-delta, and B56-epsilon (PPP2R5A--PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2-to-p12.</strong> Genomics 36: 168-170, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8812429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8812429</a>] [<a href="https://doi.org/10.1006/geno.1996.0438" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8812429">McCright et al. (1996)</a> mapped the gene for the delta subunit of protein phosphatase-2A, designated PPP2R5D, to chromosome 6p21.1 by fluorescence in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8812429" 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>The <a href="#1" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified 4 patients with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>) who had heterozygous de novo missense mutations in the PPP2R5D gene. Three patients carried the same mutation (E198K; <a href="#0001">601646.0001</a>), and the fourth carried a different mutation (P201R; <a href="#0002">601646.0002</a>). The authors suggested that these mutations may perturb interactions between subunits of the protein phosphatase-2 complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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 7 unrelated patients with MRD35, <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified 5 different de novo heterozygous missense mutations in the PPP2R5D gene (<a href="#0001">601646.0001</a>-<a href="#0005">601646.0005</a>). Three of the patients carried the same E198K mutation. The mutations were found by parent-child trio exome sequencing and confirmed by Sanger sequencing. All mutations clustered in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex, except one (P53S; <a href="#0003">601646.0003</a>). In vitro functional expression studies in HEK293 cells showed that all mutations, except P53S, showed deficient holoenzyme formation of PP2A with decreased association of the mutant PPP2R5D subunit to the A or C subunits, consistent with a dominant-negative effect. <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> suggested that disruption of normal phosphorylation in the brain may result in brain dysfunction, perhaps by having far-reaching consequences for regulation of localized signaling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> identified 2 different heterozygous missense mutations in the PPP2R5D gene (<a href="#0001">601646.0001</a> and <a href="#0004">601646.0004</a>) in 3 unrelated patients with MRD35 associated with overgrowth, mainly macrocephaly. Functional studies of the variants were not performed, but <a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> postulated that they could plausibly alter the ability of PP2A to dephosphorylate target substrates. The first 2 patients were ascertained from a larger cohort of 111 parent-child trios with overgrowth syndrome, often associated with intellectual disability, who underwent exome sequencing. The third patient was ascertained from a cohort of 152 individuals with overgrowth phenotypes for whom parental DNA was not available. <a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> postulated that the mutations may disrupt the PI3K (see <a href="/entry/171834">171834</a>)/AKT1 (<a href="/entry/164730">164730</a>) growth regulatory cascade. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25972378" 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="Louis, J. V., Martens, E., Borghgraef, P., Lambrecht, C., Sents, W., Longin, S., Zwaenepoel, K., Pijnenborg, R., Landrieu, I., Lippens, G., Ledermann, B., Gotz, J., Van Leuven, F., Goris, J., Janssens, V. <strong>Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3-beta.</strong> Proc. Nat. Acad. Sci. 108: 6957-6962, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21482799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21482799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21482799[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.1018777108" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21482799">Louis et al. (2011)</a> found that Ppp2r5d-null mice developed a progressive increase in phosphorylated tau (MAPT; <a href="/entry/157140">157140</a>) in the brainstem and spinal cord compared to wildtype mice. However, neurofibrillary tangles did not develop. These changes were associated with progressive sensorimotor deficits, but not cognitive dysfunction. Knockout mice also showed decreased phosphorylation and increased activity of GSK3-beta (GSK3B; <a href="/entry/605004">605004</a>), as well as decreased CKD5 (<a href="/entry/123831">123831</a>) activity and absence of its activator p35 (CDK5R1; <a href="/entry/603460">603460</a>). The findings implied that disruption of a proper kinase-phosphatase balance may underlie the tau neuropathology of these mutant mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21482799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimAllelicVariantsToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>5 Selected Examples</a>):</strong>
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<a href="/allelicVariants/601646" class="btn btn-default" role="button"> Table View </a>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=601646[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000170482 OR RCV000202079 OR RCV000623917 OR RCV001255395 OR RCV001261364 OR RCV001420208 OR RCV002273972" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170482, RCV000202079, RCV000623917, RCV001255395, RCV001261364, RCV001420208, RCV002273972" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170482...</a>
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<p>In 3 unrelated patients with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>), the <a href="#1" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified a heterozygous de novo missense mutation in the PPP2R5D gene, a G-to-A transition at chromosome coordinate g.42,975,003 (chr6.42,975,003G-A, GRCh37) resulting in a glu198-to-lys (E198K) substitution. No functional studies were performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified a de novo heterozygous E198K mutation, resulting from a c.592G-A transition (c.592G-A, NM_006245.2), in 3 unrelated patients with MRD35. The mutation occurred in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. Overexpression of E198K in HEK293 cells resulted in increased phosphorylation of a PPP2R5D substrate, consistent with a dominant-negative effect. The patients with the E198K mutation had a more severe phenotype compared to patients with other PPP2R5D mutations, reflecting the greater impact of the mutation on binding to subunit A and C of the PP2A holocomplex demonstrated in in vitro cellular studies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> identified a de novo heterozygous E198K mutation (c.592G-A, NM_006245) in a patient (COG1744) with MRD35 associated with overgrowth, including increased head circumference. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present among 1,000 population controls or in the ExAC browser. Functional studies of the variant were not performed, but the mutation occurred in the substrate specificity loop, and <a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> postulated that it could plausibly alter the ability of PP2A to dephosphorylate target substrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25972378" 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>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</strong>
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PPP2R5D, PRO201ARG
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs876657383 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876657383;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=rs876657383" 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=rs876657383" 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=RCV000170483 OR RCV000521503" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170483, RCV000521503" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170483...</a>
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<p>In a patient with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>), the <a href="#1" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong> Nature 519: 223-228, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533962[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nature14135" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25533962">Deciphering Developmental Disorders Study (2015)</a> identified a heterozygous C-to-G transversion at chromosome coordinate g.42,975,013 (chr6.42,975,013C-G, GRCh37) in the PPP2R5D gene, resulting in a pro201-to-arg (P201R) substitution. This mutation occurred as a de novo event. No functional studies were performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25533962" 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="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified a de novo heterozygous P201R mutation (c.602C-G, NM_006245.2) in a patient with MRD35. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs757369209 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs757369209;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/rs757369209?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=rs757369209" 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=rs757369209" 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 patient with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>), <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified a de novo heterozygous c.157C-T transition (c.157C-T, NM_006245.2) in the PPP2R5D gene, resulting in a pro53-to-ser (P53S) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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">rs863225079 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs863225079;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=rs863225079" 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=rs863225079" 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=RCV000201454 OR RCV000202069 OR RCV001265718 OR RCV004737321" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201454, RCV000202069, RCV001265718, RCV004737321" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201454...</a>
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<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>), <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified a de novo heterozygous c.598G-A transition (c.598G-A, NM_006245.2) in the PPP2R5D gene, resulting in a glu200-to-lys (E200K) substitution in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> identified a heterozygous E200K mutation (c.598G-A, NM_006245) in 2 unrelated patients (COG1674 and COG0328) with MRD35 associated with overgrowth, mainly macrocephaly. The mutation in 1 of the patients was proven to have occurred de novo. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present among 1,000 population controls or in the ExAC browser. Functional studies of the variant were not performed, but the mutation occurred in the substrate specificity loop, and <a href="#4" class="mim-tip-reference" title="Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N. <strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong> Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>] [<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25972378">Loveday et al. (2015)</a> postulated that it could plausibly alter the ability of PP2A to dephosphorylate target substrates. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25972378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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">rs869320691 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869320691;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=rs869320691" 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=rs869320691" 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=RCV000201477 OR RCV004760433" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000201477, RCV004760433" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000201477...</a>
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<p>In a patient with autosomal dominant intellectual developmental disorder-35 (MRD35; <a href="/entry/616355">616355</a>), <a href="#2" class="mim-tip-reference" title="Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others. <strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong> J. Clin. Invest. 125: 3051-3062, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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/JCI79860" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26168268">Houge et al. (2015)</a> identified a de novo heterozygous c.619T-A transversion (c.619T-A, NM_006245.2) in the PPP2R5D gene, resulting in a trp207-to-arg (W207R) substitution in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26168268" 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>REFERENCES</strong>
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<a id="{Deciphering Developmental Disorders Study}2015" class="mim-anchor"></a>
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Deciphering Developmental Disorders Study.
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<strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong>
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Nature 519: 223-228, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25533962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25533962</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25533962[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=25533962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nature14135" target="_blank">Full Text</a>]
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Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others.
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<strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong>
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J. Clin. Invest. 125: 3051-3062, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26168268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26168268</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26168268[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=26168268" 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/10.1172/JCI79860" target="_blank">Full Text</a>]
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Louis, J. V., Martens, E., Borghgraef, P., Lambrecht, C., Sents, W., Longin, S., Zwaenepoel, K., Pijnenborg, R., Landrieu, I., Lippens, G., Ledermann, B., Gotz, J., Van Leuven, F., Goris, J., Janssens, V.
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<strong>Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3-beta.</strong>
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Proc. Nat. Acad. Sci. 108: 6957-6962, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21482799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21482799</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21482799[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=21482799" 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.1018777108" target="_blank">Full Text</a>]
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Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N.
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<strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong>
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Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25972378/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25972378</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25972378" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddv182" target="_blank">Full Text</a>]
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<strong>Assignment of human protein phosphatase 2A regulatory subunit genes B56-alpha, B56-beta, B56-gamma, B56-delta, and B56-epsilon (PPP2R5A--PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2-to-p12.</strong>
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Genomics 36: 168-170, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8812429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8812429</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8812429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1996.0438" target="_blank">Full Text</a>]
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McCright, B., Rivers, A. M., Audlin, S., Virshup, D. M.
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<strong>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</strong>
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J. Biol. Chem. 271: 22081-22089, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8703017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8703017</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8703017" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Ada Hamosh - updated : 5/12/2015<br>Jennifer P. Macke - updated : 5/5/1997
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carol : 10/02/2019<br>alopez : 11/02/2015<br>ckniffin : 10/28/2015<br>alopez : 5/12/2015<br>alopez : 4/27/2010<br>alopez : 4/27/2010<br>mgross : 2/4/2009<br>alopez : 12/1/1999<br>alopez : 5/5/1997<br>alopez : 5/5/1997<br>alopez : 5/5/1997<br>alopez : 4/8/1997<br>mark : 2/10/1997<br>jenny : 1/28/1997<br>jenny : 1/28/1997<br>mark : 1/23/1997
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 601646
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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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PROTEIN PHOSPHATASE 2, REGULATORY SUBUNIT B (B56), DELTA; PPP2R5D
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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: PPP2R5D</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 6p21.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 6:42,984,570-43,012,342 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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6p21.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Houge-Janssens syndrome 1
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</span>
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</td>
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<td>
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<span class="mim-font">
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616355
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The PPP2R5D gene encodes a B56 regulatory subunit of protein phosphatase-2A (PP2A), an intracellular serine/threonine phosphatase (summary by Houge et al., 2015). </p><p>For background information on PP2A and its subunits, see 601643.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>McCright et al. (1996) cloned the B56-delta gene from a human fetal brain cDNA library using a partial cDNA sequence. They found that B56-delta encoded a 602-amino acid protein with a predicted molecular mass of 69,947 Da. This subunit is able to form a functional trimeric PP2A phosphatase when combined with an A and a C subunit. </p><p>Louis et al. (2011) found expression of the Ppp2r5d gene in various brain regions in the mouse: expression was highest in the striatum and thalamus, intermediate in the brainstem and hippocampus, and weak in the cortex and cerebellum. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>McCright et al. (1996) observed that the location of B56-delta varies with the cell cycle, being present in both cytoplasm and nucleus in interphase cells but concentrated in the nucleus of mitotic and recently divided cells. Both B56-beta (601644) and B56-delta are highly expressed in the adult brain, and mRNA for these isoforms increases 3- to 5-fold when neuroblastoma cell lines are induced to differentiate by retinoic acid treatment. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>McCright et al. (1996) mapped the gene for the delta subunit of protein phosphatase-2A, designated PPP2R5D, to chromosome 6p21.1 by fluorescence in situ hybridization. </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>The Deciphering Developmental Disorders Study (2015) identified 4 patients with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355) who had heterozygous de novo missense mutations in the PPP2R5D gene. Three patients carried the same mutation (E198K; 601646.0001), and the fourth carried a different mutation (P201R; 601646.0002). The authors suggested that these mutations may perturb interactions between subunits of the protein phosphatase-2 complex. </p><p>In 7 unrelated patients with MRD35, Houge et al. (2015) identified 5 different de novo heterozygous missense mutations in the PPP2R5D gene (601646.0001-601646.0005). Three of the patients carried the same E198K mutation. The mutations were found by parent-child trio exome sequencing and confirmed by Sanger sequencing. All mutations clustered in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex, except one (P53S; 601646.0003). In vitro functional expression studies in HEK293 cells showed that all mutations, except P53S, showed deficient holoenzyme formation of PP2A with decreased association of the mutant PPP2R5D subunit to the A or C subunits, consistent with a dominant-negative effect. Houge et al. (2015) suggested that disruption of normal phosphorylation in the brain may result in brain dysfunction, perhaps by having far-reaching consequences for regulation of localized signaling. </p><p>Loveday et al. (2015) identified 2 different heterozygous missense mutations in the PPP2R5D gene (601646.0001 and 601646.0004) in 3 unrelated patients with MRD35 associated with overgrowth, mainly macrocephaly. Functional studies of the variants were not performed, but Loveday et al. (2015) postulated that they could plausibly alter the ability of PP2A to dephosphorylate target substrates. The first 2 patients were ascertained from a larger cohort of 111 parent-child trios with overgrowth syndrome, often associated with intellectual disability, who underwent exome sequencing. The third patient was ascertained from a cohort of 152 individuals with overgrowth phenotypes for whom parental DNA was not available. Loveday et al. (2015) postulated that the mutations may disrupt the PI3K (see 171834)/AKT1 (164730) growth regulatory cascade. </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>Louis et al. (2011) found that Ppp2r5d-null mice developed a progressive increase in phosphorylated tau (MAPT; 157140) in the brainstem and spinal cord compared to wildtype mice. However, neurofibrillary tangles did not develop. These changes were associated with progressive sensorimotor deficits, but not cognitive dysfunction. Knockout mice also showed decreased phosphorylation and increased activity of GSK3-beta (GSK3B; 605004), as well as decreased CKD5 (123831) activity and absence of its activator p35 (CDK5R1; 603460). The findings implied that disruption of a proper kinase-phosphatase balance may underlie the tau neuropathology of these mutant mice. </p>
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</span>
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
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</span>
|
|
<strong>5 Selected Examples):</strong>
|
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</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
|
<div>
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
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<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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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|
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PPP2R5D, GLU198LYS
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<br />
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ClinVar: RCV000170482, RCV000202079, RCV000623917, RCV001255395, RCV001261364, RCV001420208, RCV002273972
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</span>
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</div>
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|
|
<div>
|
|
<span class="mim-text-font">
|
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<p>In 3 unrelated patients with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355), the Deciphering Developmental Disorders Study (2015) identified a heterozygous de novo missense mutation in the PPP2R5D gene, a G-to-A transition at chromosome coordinate g.42,975,003 (chr6.42,975,003G-A, GRCh37) resulting in a glu198-to-lys (E198K) substitution. No functional studies were performed. </p><p>Houge et al. (2015) identified a de novo heterozygous E198K mutation, resulting from a c.592G-A transition (c.592G-A, NM_006245.2), in 3 unrelated patients with MRD35. The mutation occurred in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. Overexpression of E198K in HEK293 cells resulted in increased phosphorylation of a PPP2R5D substrate, consistent with a dominant-negative effect. The patients with the E198K mutation had a more severe phenotype compared to patients with other PPP2R5D mutations, reflecting the greater impact of the mutation on binding to subunit A and C of the PP2A holocomplex demonstrated in in vitro cellular studies. </p><p>Loveday et al. (2015) identified a de novo heterozygous E198K mutation (c.592G-A, NM_006245) in a patient (COG1744) with MRD35 associated with overgrowth, including increased head circumference. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present among 1,000 population controls or in the ExAC browser. Functional studies of the variant were not performed, but the mutation occurred in the substrate specificity loop, and Loveday et al. (2015) postulated that it could plausibly alter the ability of PP2A to dephosphorylate target substrates. </p>
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</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
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<strong>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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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|
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PPP2R5D, PRO201ARG
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<br />
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|
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SNP: rs876657383,
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ClinVar: RCV000170483, RCV000521503
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</span>
|
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</div>
|
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|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355), the Deciphering Developmental Disorders Study (2015) identified a heterozygous C-to-G transversion at chromosome coordinate g.42,975,013 (chr6.42,975,013C-G, GRCh37) in the PPP2R5D gene, resulting in a pro201-to-arg (P201R) substitution. This mutation occurred as a de novo event. No functional studies were performed. </p><p>Houge et al. (2015) identified a de novo heterozygous P201R mutation (c.602C-G, NM_006245.2) in a patient with MRD35. </p>
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</span>
|
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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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PPP2R5D, PRO53SER
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<br />
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SNP: rs757369209,
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gnomAD: rs757369209,
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ClinVar: RCV000201513
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355), Houge et al. (2015) identified a de novo heterozygous c.157C-T transition (c.157C-T, NM_006245.2) in the PPP2R5D gene, resulting in a pro53-to-ser (P53S) substitution. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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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PPP2R5D, GLU200LYS
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<br />
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SNP: rs863225079,
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ClinVar: RCV000201454, RCV000202069, RCV001265718, RCV004737321
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355), Houge et al. (2015) identified a de novo heterozygous c.598G-A transition (c.598G-A, NM_006245.2) in the PPP2R5D gene, resulting in a glu200-to-lys (E200K) substitution in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. </p><p>Loveday et al. (2015) identified a heterozygous E200K mutation (c.598G-A, NM_006245) in 2 unrelated patients (COG1674 and COG0328) with MRD35 associated with overgrowth, mainly macrocephaly. The mutation in 1 of the patients was proven to have occurred de novo. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present among 1,000 population controls or in the ExAC browser. Functional studies of the variant were not performed, but the mutation occurred in the substrate specificity loop, and Loveday et al. (2015) postulated that it could plausibly alter the ability of PP2A to dephosphorylate target substrates. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 35</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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PPP2R5D, TRP207ARG
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<br />
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SNP: rs869320691,
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ClinVar: RCV000201477, RCV004760433
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with autosomal dominant intellectual developmental disorder-35 (MRD35; 616355), Houge et al. (2015) identified a de novo heterozygous c.619T-A transversion (c.619T-A, NM_006245.2) in the PPP2R5D gene, resulting in a trp207-to-arg (W207R) substitution in a highly conserved acidic loop that faces the A and C subunits of the PP2A complex. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<p class="mim-text-font">
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Deciphering Developmental Disorders Study.
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<strong>Large-scale discovery of novel genetic causes of developmental disorders.</strong>
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Nature 519: 223-228, 2015.
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[PubMed: 25533962]
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[Full Text: https://doi.org/10.1038/nature14135]
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Houge, G., Haesen, D., Vissers, L. E. L. M., Mehta, S., Parker, M. J., Wright, M., Vogt, J., McKee, S., Tolmie, J. L., Cordeiro, N., Kleefstra, T., Willemsen, M. H., and 17 others.
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<strong>B56-delta-related protein phosphatase 2A dysfunction identified in patients with intellectual disability.</strong>
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J. Clin. Invest. 125: 3051-3062, 2015.
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[PubMed: 26168268]
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[Full Text: https://doi.org/10.1172/JCI79860]
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</p>
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</li>
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<p class="mim-text-font">
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Louis, J. V., Martens, E., Borghgraef, P., Lambrecht, C., Sents, W., Longin, S., Zwaenepoel, K., Pijnenborg, R., Landrieu, I., Lippens, G., Ledermann, B., Gotz, J., Van Leuven, F., Goris, J., Janssens, V.
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<strong>Mice lacking phosphatase PP2A subunit PR61/B'delta (Ppp2r5d) develop spatially restricted tauopathy by deregulation of CDK5 and GSK3-beta.</strong>
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Proc. Nat. Acad. Sci. 108: 6957-6962, 2011.
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[PubMed: 21482799]
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[Full Text: https://doi.org/10.1073/pnas.1018777108]
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<li>
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Loveday, C., Tatton-Brown, K., Clarke, M., Westwood, I., Renwick, A., Ramsay, E., Nemeth, A., Campbell, J., Joss, S., Gardner, M., Zachariou, A., Elliott, A., Ruark, E., van Montfort, R., Childhood Overgrowth Collaboration, Rahman, N.
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<strong>Mutations in the PP2A regulatory subunit B family genes PPP2R5B, PPP2R5C and PPP2R5D cause human overgrowth.</strong>
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Hum. Molec. Genet. 24: 4775-4779, 2015. Note: Erratum: Hum. Molec. Genet. 28: 1578 only, 2019.
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[PubMed: 25972378]
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[Full Text: https://doi.org/10.1093/hmg/ddv182]
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</p>
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</li>
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McCright, B., Brothman, A. R., Virshup, D. M.
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<strong>Assignment of human protein phosphatase 2A regulatory subunit genes B56-alpha, B56-beta, B56-gamma, B56-delta, and B56-epsilon (PPP2R5A--PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2-to-p12.</strong>
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Genomics 36: 168-170, 1996.
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[PubMed: 8812429]
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[Full Text: https://doi.org/10.1006/geno.1996.0438]
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</p>
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McCright, B., Rivers, A. M., Audlin, S., Virshup, D. M.
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<strong>The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm.</strong>
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J. Biol. Chem. 271: 22081-22089, 1996.
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[PubMed: 8703017]
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[Full Text: https://doi.org/10.1074/jbc.271.36.22081]
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Cassandra L. Kniffin - updated : 10/28/2015<br>Ada Hamosh - updated : 5/12/2015<br>Jennifer P. Macke - updated : 5/5/1997
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Alan F. Scott : 1/23/1997
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