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Entry
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- *602021 - PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 12A; PPP1R12A
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- OMIM
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<p>
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<span class="h4">*602021</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<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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<a href="#mapping">Mapping</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/602021">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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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000058272;t=ENST00000450142" 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=4659" 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=602021" 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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<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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</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=ENSG00000058272;t=ENST00000450142" 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_001143885,NM_001143886,NM_001244990,NM_001244992,NM_002480" 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_002480" 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=602021" 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=03606&isoform_id=03606_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/PPP1R12A" 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/2443338,4505317,13365493,15530294,21360806,28839799,37181056,41017262,62204186,84627432,119617757,119617758,119617759,119617760,119617761,119617762,189054352,194380308,219842212,219842214,350529366,350529370" 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/O14974" 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=4659" 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=ENSG00000058272;t=ENST00000450142" 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=PPP1R12A" 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=PPP1R12A" 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+4659" 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/PPP1R12A" 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:4659" 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/4659" 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=chr12&hgg_gene=ENST00000450142.7&hgg_start=79773563&hgg_end=79935460&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:7618" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=602021[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=602021[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/PPP1R12A/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/ENSG00000058272" 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=PPP1R12A" 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=PPP1R12A" 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=PPP1R12A" 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=PPP1R12A&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/PA33617" 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:7618" 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/FBgn0005536.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:1309528" 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/PPP1R12A#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:1309528" 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/4659/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=4659" 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=WBGene00003196;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-041011-3" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:4659" 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=PPP1R12A&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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602021
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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 1, REGULATORY SUBUNIT 12A; PPP1R12A
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
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MYOSIN PHOSPHATASE TARGET SUBUNIT 1; MYPT1<br />
|
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MYOSIN PHOSPHATASE, MYOSIN-BINDING SUBUNIT
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=PPP1R12A" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">PPP1R12A</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/12/648?start=-3&limit=10&highlight=648">12q21.2-q21.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr12:79773563-79935460&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'})">12:79,773,563-79,935,460</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/12/648?start=-3&limit=10&highlight=648">
|
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12q21.2-q21.31
|
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</a>
|
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</span>
|
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</td>
|
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|
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<td>
|
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<span class="mim-font">
|
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Genitourinary and/or/brain malformation syndrome
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/618820"> 618820 </a>
|
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|
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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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|
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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">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/602021" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/602021" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<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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<p>PPP1R12A is a regulatory subunit of myosin light chain phosphatase, which plays an essential role in smooth muscle contraction (<a href="#4" class="mim-tip-reference" title="Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S. <strong>Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure.</strong> J. Biol. Chem. 289: 22512-22523, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24951589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24951589</a>] [<a href="https://doi.org/10.1074/jbc.M113.525444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24951589">Qiao et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24951589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using the rat Mypt1 cDNA as probe, <a href="#5" class="mim-tip-reference" title="Takahashi, N., Ito, M., Tanaka, J., Nakano, T., Kaibuchi, K., Odai, H., Takemura, K. <strong>Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1) to human chromosome 12q15-q21.</strong> Genomics 44: 150-152, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9286714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9286714</a>] [<a href="https://doi.org/10.1006/geno.1997.4859" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9286714">Takahashi et al. (1997)</a> cloned a 4,855-bp cDNA for a human gene they symbolized MYPT1. Sequencing analysis showed that human MYPT1 contains 1,030 amino acids with a calculated molecular mass of approximately 115 kD. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9286714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By fluorescence in situ hybridization, <a href="#3" class="mim-tip-reference" title="Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., Kaibuchi, K. <strong>Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase).</strong> Science 273: 245-248, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8662509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8662509</a>] [<a href="https://doi.org/10.1126/science.273.5272.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8662509">Kimura et al. (1996)</a> mapped the MYPT1 gene to chromosome 12q15-q21.2. By radiation hybrid analysis, they showed that MYPT1 is located close to a highly polymorphic marker that lies between D12S350 and D12S106. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8662509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#6" class="mim-tip-reference" title="Terrak, M., Kerff, F., Langsetmo, K., Tao, T., Dominguez, R. <strong>Structural basis of protein phosphatase 1 regulation.</strong> Nature 429: 780-784, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15164081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15164081</a>] [<a href="https://doi.org/10.1038/nature02582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15164081">Terrak et al. (2004)</a> determined the crystal structure at 2.7-angstrom resolution of the complex between protein phosphatase-1 (PP1; see <a href="/entry/176875">176875</a>) and a 34-kD N-terminal domain of the myosin phosphatase targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the RVXF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping of the catalytic cleft of PP1, contributing to the increased myosin specificity of this complex. <a href="#6" class="mim-tip-reference" title="Terrak, M., Kerff, F., Langsetmo, K., Tao, T., Dominguez, R. <strong>Structural basis of protein phosphatase 1 regulation.</strong> Nature 429: 780-784, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15164081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15164081</a>] [<a href="https://doi.org/10.1038/nature02582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15164081">Terrak et al. (2004)</a> concluded that the structure has general implications for the control of PP1 activity by other regulatory subunits. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15164081" 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="Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., Kaibuchi, K. <strong>Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase).</strong> Science 273: 245-248, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8662509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8662509</a>] [<a href="https://doi.org/10.1126/science.273.5272.245" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8662509">Kimura et al. (1996)</a> demonstrated that myosin phosphatase regulates the interaction of actin (see <a href="/entry/102540">102540</a>) and myosin (see <a href="/entry/160710">160710</a>) downstream of the guanosine triphosphatase Rho. Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8662509" 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="Jin, H., Sperka, T., Herrlich, P., Morrison, H. <strong>Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.</strong> Nature 442: 576-579, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885985</a>] [<a href="https://doi.org/10.1038/nature04856" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885985">Jin et al. (2006)</a> identified MYPT1 as the enzyme that activates the tumor suppressor function of merlin, encoded by the NF2 gene (<a href="/entry/607379">607379</a>). The cellular MYPT1-PP1-delta (<a href="/entry/600590">600590</a>)-specific inhibitor CPI17 (<a href="/entry/608153">608153</a>) caused a loss of merlin function characterized by merlin phosphorylation, Ras activation, and transformation. Constitutively active merlin containing the mutation S518A reversed CPI17-induced transformation, showing that merlin is the decisive substrate of MYPT1-PP1-delta in tumor suppression. In addition <a href="#2" class="mim-tip-reference" title="Jin, H., Sperka, T., Herrlich, P., Morrison, H. <strong>Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.</strong> Nature 442: 576-579, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885985</a>] [<a href="https://doi.org/10.1038/nature04856" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885985">Jin et al. (2006)</a> showed that CPI17 levels are raised in several human tumor cell lines and that the downregulation of CPI17 induces merlin dephosphorylation, inhibits Ras activation, and abolishes the transformed phenotype. <a href="#2" class="mim-tip-reference" title="Jin, H., Sperka, T., Herrlich, P., Morrison, H. <strong>Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.</strong> Nature 442: 576-579, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16885985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16885985</a>] [<a href="https://doi.org/10.1038/nature04856" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16885985">Jin et al. (2006)</a> concluded that MYPT1 and its substrate merlin are part of a previously undescribed tumor suppressor cascade that can be hindered in 2 ways, by mutation of the NF2 gene and by upregulation of the oncoprotein CPI17. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16885985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 12 unrelated patients with genitourinary and/or brain malformations (GUBS; <a href="/entry/618820">618820</a>), <a href="#1" class="mim-tip-reference" title="Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others. <strong>Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital anomalies.</strong> Am. J. Hum. Genet. 106: 121-128, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31883643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31883643</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31883643">Hughes et al. (2020)</a> identified heterozygosity for de novo premature termination codon (PTC) variants in the PPP1R12A gene (see, e.g., <a href="#0001">602021.0001</a>-<a href="#0003">602021.0003</a>). The authors noted that the patients exhibited a broad spectrum of clinical manifestations, and that the PPP1R12A variants occurred across multiple exons and 1 intron, with no clear genotype-phenotype correlation observed with specific variants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31883643" 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="#4" class="mim-tip-reference" title="Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S. <strong>Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure.</strong> J. Biol. Chem. 289: 22512-22523, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24951589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24951589</a>] [<a href="https://doi.org/10.1074/jbc.M113.525444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24951589">Qiao et al. (2014)</a> generated conditional knockout mice lacking Mypt1 specifically in smooth muscle cells. Western blot analysis confirmed that mesenteric, femoral, and aortic smooth muscle tissues from mutant mice contained only trace or undetectable amounts of Mypt1 protein. Mypt1 deletion resulted in enhanced myosin regulatory light chain phosphorylation and contractility of vascular smooth muscle in response to a variety of vasoactive stimuli. Mutant mice exhibited permanent hypertension without changes in vascular structure, suggesting that the hypertension may have resulted from enhanced arterial contractile responses. <a href="#4" class="mim-tip-reference" title="Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S. <strong>Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure.</strong> J. Biol. Chem. 289: 22512-22523, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24951589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24951589</a>] [<a href="https://doi.org/10.1074/jbc.M113.525444" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24951589">Qiao et al. (2014)</a> concluded that MYPT1 modulates vascular smooth muscle contractility and contributes to blood pressure maintenance in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24951589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs1356631664 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1356631664;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/rs1356631664?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=rs1356631664" 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=rs1356631664" 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 6-year-old 46,XY boy (patient 6) with genitourinary and brain malformations (GUBS; <a href="/entry/618820">618820</a>), <a href="#1" class="mim-tip-reference" title="Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others. <strong>Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital anomalies.</strong> Am. J. Hum. Genet. 106: 121-128, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31883643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31883643</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31883643">Hughes et al. (2020)</a> identified heterozygosity for a de novo c.1510C-T transition (c.1510C-T, NM_002480.3) in the PPP1R12A gene, resulting in an arg504-to-ter (R504X) substitution. The patient had glandular hypospadias and chordee; encephalocele noted on prenatal ultrasound was repaired shortly after birth. Brain MRI showed dysgenesis of the corpus callosum, absent septum pellucidum, Chiari malformation, cortical dysplasia/polymicrogyria, and gray matter heterotopia. Examination revealed global developmental delay, intellectual disability with limited speech, autistic features, appendicular hypotonia with foot pronation, and unsteady gait. He also exhibited minor facial dysmorphisms such as low-set ears and micrognathia, and had short stature, patent ductus arteriosus, and ophthalmologic abnormalities including strabismus, astigmatism, and hyperopia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31883643" 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 GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME</strong>
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PPP1R12A, 1-BP DEL, 1189A
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1592661703 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1592661703;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=rs1592661703" 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=rs1592661703" 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=RCV001027736" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001027736" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001027736</a>
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<p>In a 30-year-old 46,XY female (patient 11) with genitourinary malformations and developmental delay (GUBS; <a href="/entry/618820">618820</a>), <a href="#1" class="mim-tip-reference" title="Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others. <strong>Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital anomalies.</strong> Am. J. Hum. Genet. 106: 121-128, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31883643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31883643</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31883643">Hughes et al. (2020)</a> identified heterozygosity for a de novo 1-bp deletion (c.1189delA, NM_002480.3) in the PPP1R12A gene, causing a frameshift predicted to result in a premature termination codon (Thr397HisfsTer42). She exhibited gonadal dysgenesis, including streak gonads, rudimentary fallopian tubes, and urogenital sinus with no uterus. Other features included alopecia totalis, obesity, acanthosis nigricans, and developmental delay. Brain MRI was unremarkable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31883643" 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 GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME</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">rs1592629980 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1592629980;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=rs1592629980" 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=rs1592629980" 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=RCV001027737" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001027737" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001027737</a>
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<p>In a 15-year-old 46,XX girl (patient 1) with brain malformations (GUBS; <a href="/entry/618820">618820</a>), <a href="#1" class="mim-tip-reference" title="Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others. <strong>Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital anomalies.</strong> Am. J. Hum. Genet. 106: 121-128, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31883643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31883643</a>] [<a href="https://doi.org/10.1016/j.ajhg.2019.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31883643">Hughes et al. (2020)</a> identified heterozygosity for a de novo 2-bp deletion (c.2033_2034delCT, NM_002480.3), causing a frameshift predicted to result in a premature termination codon (ser678 to ter; S678X). The patient had intellectual disability, attention-deficit/hyperactivity disorder, and seizures; brain MRI showed syntelencephaly/middle interhemispheric variant of holoprosencephaly, polymicrogyria, and Chiari I malformation. Genitourinary evaluation was not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31883643" 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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Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others.
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<strong>Loss-of-function variants in PPP1R12A: from isolated sex reversal to holoprosencephaly spectrum and urogenital anomalies.</strong>
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Am. J. Hum. Genet. 106: 121-128, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31883643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31883643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31883643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2019.12.004" target="_blank">Full Text</a>]
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Jin, H., Sperka, T., Herrlich, P., Morrison, H.
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<strong>Tumorigenic transformation by CPI-17 through inhibition of a merlin phosphatase.</strong>
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Nature 442: 576-579, 2006.
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[<a href="https://doi.org/10.1038/nature04856" target="_blank">Full Text</a>]
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Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., Kaibuchi, K.
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<strong>Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase).</strong>
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Science 273: 245-248, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8662509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8662509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8662509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S.
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<strong>Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24951589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24951589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24951589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Takahashi, N., Ito, M., Tanaka, J., Nakano, T., Kaibuchi, K., Odai, H., Takemura, K.
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<strong>Localization of the gene coding for myosin phosphatase, target subunit 1 (MYPT1) to human chromosome 12q15-q21.</strong>
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Genomics 44: 150-152, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9286714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9286714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9286714" 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.1997.4859" target="_blank">Full Text</a>]
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Terrak, M., Kerff, F., Langsetmo, K., Tao, T., Dominguez, R.
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<strong>Structural basis of protein phosphatase 1 regulation.</strong>
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Nature 429: 780-784, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15164081/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15164081</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15164081" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Marla J. F. O'Neill - updated : 03/19/2020
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Jane A. Welch - updated : 02/02/2018<br>Ada Hamosh - updated : 9/8/2006<br>Ada Hamosh - updated : 6/11/2004
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</span>
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</div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 9/26/1997
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 08/03/2020
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 03/19/2020<br>mgross : 02/02/2018<br>alopez : 09/11/2006<br>alopez : 9/11/2006<br>terry : 9/8/2006<br>terry : 6/22/2004<br>alopez : 6/15/2004<br>terry : 6/11/2004<br>carol : 8/21/2001<br>terry : 10/7/1997<br>mark : 9/26/1997
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602021
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<div>
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<h3>
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<span class="mim-font">
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PROTEIN PHOSPHATASE 1, REGULATORY SUBUNIT 12A; PPP1R12A
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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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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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MYOSIN PHOSPHATASE TARGET SUBUNIT 1; MYPT1<br />
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MYOSIN PHOSPHATASE, MYOSIN-BINDING SUBUNIT
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</span>
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</h4>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: PPP1R12A</em></strong>
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</span>
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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: 12q21.2-q21.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 12:79,773,563-79,935,460 </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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<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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Location
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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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<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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12q21.2-q21.31
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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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Genitourinary and/or/brain malformation syndrome
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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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618820
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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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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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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>PPP1R12A is a regulatory subunit of myosin light chain phosphatase, which plays an essential role in smooth muscle contraction (Qiao et al., 2014). </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>Using the rat Mypt1 cDNA as probe, Takahashi et al. (1997) cloned a 4,855-bp cDNA for a human gene they symbolized MYPT1. Sequencing analysis showed that human MYPT1 contains 1,030 amino acids with a calculated molecular mass of approximately 115 kD. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>By fluorescence in situ hybridization, Kimura et al. (1996) mapped the MYPT1 gene to chromosome 12q15-q21.2. By radiation hybrid analysis, they showed that MYPT1 is located close to a highly polymorphic marker that lies between D12S350 and D12S106. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Crystal Structure</em></strong></p><p>
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Terrak et al. (2004) determined the crystal structure at 2.7-angstrom resolution of the complex between protein phosphatase-1 (PP1; see 176875) and a 34-kD N-terminal domain of the myosin phosphatase targeting subunit MYPT1. MYPT1 is the protein that regulates PP1 function in smooth muscle relaxation. Structural elements amino- and carboxy-terminal to the RVXF motif of MYPT1 are positioned in a way that leads to a pronounced reshaping of the catalytic cleft of PP1, contributing to the increased myosin specificity of this complex. Terrak et al. (2004) concluded that the structure has general implications for the control of PP1 activity by other regulatory subunits. </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>Kimura et al. (1996) demonstrated that myosin phosphatase regulates the interaction of actin (see 102540) and myosin (see 160710) downstream of the guanosine triphosphatase Rho. Rho appears to inhibit myosin phosphatase through the action of Rho-kinase. </p><p>Jin et al. (2006) identified MYPT1 as the enzyme that activates the tumor suppressor function of merlin, encoded by the NF2 gene (607379). The cellular MYPT1-PP1-delta (600590)-specific inhibitor CPI17 (608153) caused a loss of merlin function characterized by merlin phosphorylation, Ras activation, and transformation. Constitutively active merlin containing the mutation S518A reversed CPI17-induced transformation, showing that merlin is the decisive substrate of MYPT1-PP1-delta in tumor suppression. In addition Jin et al. (2006) showed that CPI17 levels are raised in several human tumor cell lines and that the downregulation of CPI17 induces merlin dephosphorylation, inhibits Ras activation, and abolishes the transformed phenotype. Jin et al. (2006) concluded that MYPT1 and its substrate merlin are part of a previously undescribed tumor suppressor cascade that can be hindered in 2 ways, by mutation of the NF2 gene and by upregulation of the oncoprotein CPI17. </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>In 12 unrelated patients with genitourinary and/or brain malformations (GUBS; 618820), Hughes et al. (2020) identified heterozygosity for de novo premature termination codon (PTC) variants in the PPP1R12A gene (see, e.g., 602021.0001-602021.0003). The authors noted that the patients exhibited a broad spectrum of clinical manifestations, and that the PPP1R12A variants occurred across multiple exons and 1 intron, with no clear genotype-phenotype correlation observed with specific variants. </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>Qiao et al. (2014) generated conditional knockout mice lacking Mypt1 specifically in smooth muscle cells. Western blot analysis confirmed that mesenteric, femoral, and aortic smooth muscle tissues from mutant mice contained only trace or undetectable amounts of Mypt1 protein. Mypt1 deletion resulted in enhanced myosin regulatory light chain phosphorylation and contractility of vascular smooth muscle in response to a variety of vasoactive stimuli. Mutant mice exhibited permanent hypertension without changes in vascular structure, suggesting that the hypertension may have resulted from enhanced arterial contractile responses. Qiao et al. (2014) concluded that MYPT1 modulates vascular smooth muscle contractility and contributes to blood pressure maintenance in vivo. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>3 Selected Examples):</strong>
|
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</span>
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</h4>
|
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<div>
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<p />
|
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0001 GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME</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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PPP1R12A, ARG504TER
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<br />
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SNP: rs1356631664,
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gnomAD: rs1356631664,
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ClinVar: RCV001027735
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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 6-year-old 46,XY boy (patient 6) with genitourinary and brain malformations (GUBS; 618820), Hughes et al. (2020) identified heterozygosity for a de novo c.1510C-T transition (c.1510C-T, NM_002480.3) in the PPP1R12A gene, resulting in an arg504-to-ter (R504X) substitution. The patient had glandular hypospadias and chordee; encephalocele noted on prenatal ultrasound was repaired shortly after birth. Brain MRI showed dysgenesis of the corpus callosum, absent septum pellucidum, Chiari malformation, cortical dysplasia/polymicrogyria, and gray matter heterotopia. Examination revealed global developmental delay, intellectual disability with limited speech, autistic features, appendicular hypotonia with foot pronation, and unsteady gait. He also exhibited minor facial dysmorphisms such as low-set ears and micrognathia, and had short stature, patent ductus arteriosus, and ophthalmologic abnormalities including strabismus, astigmatism, and hyperopia. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0002 GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME</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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PPP1R12A, 1-BP DEL, 1189A
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<br />
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SNP: rs1592661703,
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ClinVar: RCV001027736
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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 30-year-old 46,XY female (patient 11) with genitourinary malformations and developmental delay (GUBS; 618820), Hughes et al. (2020) identified heterozygosity for a de novo 1-bp deletion (c.1189delA, NM_002480.3) in the PPP1R12A gene, causing a frameshift predicted to result in a premature termination codon (Thr397HisfsTer42). She exhibited gonadal dysgenesis, including streak gonads, rudimentary fallopian tubes, and urogenital sinus with no uterus. Other features included alopecia totalis, obesity, acanthosis nigricans, and developmental delay. Brain MRI was unremarkable. </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 GENITOURINARY AND/OR BRAIN MALFORMATION SYNDROME</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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PPP1R12A, 2-BP DEL, 2033CT
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<br />
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SNP: rs1592629980,
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ClinVar: RCV001027737
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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 15-year-old 46,XX girl (patient 1) with brain malformations (GUBS; 618820), Hughes et al. (2020) identified heterozygosity for a de novo 2-bp deletion (c.2033_2034delCT, NM_002480.3), causing a frameshift predicted to result in a premature termination codon (ser678 to ter; S678X). The patient had intellectual disability, attention-deficit/hyperactivity disorder, and seizures; brain MRI showed syntelencephaly/middle interhemispheric variant of holoprosencephaly, polymicrogyria, and Chiari I malformation. Genitourinary evaluation was not performed. </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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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
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Hughes, J. J., Alkhunaizi, E., Kruszka, P., Pyle, L. C., Grange, D. K., Berger, S. I., Payne, K. K., Masser-Frye, D., Hu, T., CHristie, M. R., Clegg, N. J., Everson, J. L., and 18 others.
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Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S.
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