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Entry
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- *139313 - GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-11; GNA11
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*139313</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</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="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/139313">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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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000088256;t=ENST00000078429" 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=2767" 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=139313" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000088256;t=ENST00000078429" 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_002067" 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_002067" 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=139313" 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=00759&isoform_id=00759_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/GNA11" 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/183691,712833,2286217,3041682,3289982,20147693,48146125,52545539,57870232,62088450,64653190,64654319,64654324,115511049,119589745,119589746,2104758959" 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/P29992" 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=2767" 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=ENSG00000088256;t=ENST00000078429" 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=GNA11" 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=GNA11" 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+2767" 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/GNA11" 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:2767" 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/2767" 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=chr19&hgg_gene=ENST00000078429.9&hgg_start=3094362&hgg_end=3123999&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://medlineplus.gov/genetics/gene/gna11" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=139313[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 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=139313[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/GNA11/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/ENSG00000088256" 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=GNA11" 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=GNA11" 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=GNA11" 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=GNA11&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/PA28764" 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:4379" 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/FBgn0004435.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:95766" 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/GNA11#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:95766" 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/2767/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=2767" 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=WBGene00001196;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-041121-9" 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:2767" 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=GNA11&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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139313
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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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GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-11; GNA11
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GNA11" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNA11</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/19/100?start=-3&limit=10&highlight=100">19p13.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:3094362-3123999&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'})">19:3,094,362-3,123,999</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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<span class="hidden-sm hidden-xs pull-right">
|
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<a href="/clinicalSynopsis/table?mimNumber=615361,145981" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
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View Clinical Synopses
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</a>
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</span>
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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="2">
|
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<span class="mim-font">
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<a href="/geneMap/19/100?start=-3&limit=10&highlight=100">
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19p13.3
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Hypocalcemia, autosomal dominant 2
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/615361"> 615361 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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<tr>
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<td>
|
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<span class="mim-font">
|
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Hypocalciuric hypercalcemia, type II
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/145981"> 145981 </a>
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
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/139313" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/139313" 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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<p><a href="#12" class="mim-tip-reference" title="Strathmann, M. P., Simon, M. I. <strong>G-alpha-12 and G-alpha-13 subunits define a fourth class of G protein alpha subunits.</strong> Proc. Nat. Acad. Sci. 88: 5582-5586, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1905812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1905812</a>] [<a href="https://doi.org/10.1073/pnas.88.13.5582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1905812">Strathmann and Simon (1991)</a> described the Gna11 gene in the mouse. The human gene was cloned by <a href="#6" class="mim-tip-reference" title="Jiang, M., Pandey, S., Tran, V. T., Fong, H. K. <strong>Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells.</strong> Proc. Nat. Acad. Sci. 88: 3907-3911, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1902575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1902575</a>] [<a href="https://doi.org/10.1073/pnas.88.9.3907" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1902575">Jiang et al. (1991)</a> and found to be 359 amino acids long. Mouse Gna11 and Gna15 (<a href="/entry/139314">139314</a>) are tandemly duplicated in a head-to-tail array. <a href="#2" class="mim-tip-reference" title="Davignon, I., Barnard, M., Gavrilova, O., Sweet, K., Wilkie, T. M. <strong>Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.</strong> Genomics 31: 359-366, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838318</a>] [<a href="https://doi.org/10.1006/geno.1996.0059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8838318">Davignon et al. (1996)</a> showed that the upstream gene, Gna11, is ubiquitously expressed, whereas expression of the downstream gene, Gna15, is restricted to hematopoietic cells. There was no evidence for alternative splicing within the coding sequence of either gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1905812+8838318+1902575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#12" class="mim-tip-reference" title="Strathmann, M. P., Simon, M. I. <strong>G-alpha-12 and G-alpha-13 subunits define a fourth class of G protein alpha subunits.</strong> Proc. Nat. Acad. Sci. 88: 5582-5586, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1905812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1905812</a>] [<a href="https://doi.org/10.1073/pnas.88.13.5582" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1905812">Strathmann and Simon (1991)</a> found that mouse Gna11 and Gna15 (<a href="/entry/139314">139314</a>) are tandemly duplicated in a head-to-tail array, spanning approximately 43 kb. <a href="#2" class="mim-tip-reference" title="Davignon, I., Barnard, M., Gavrilova, O., Sweet, K., Wilkie, T. M. <strong>Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.</strong> Genomics 31: 359-366, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838318</a>] [<a href="https://doi.org/10.1006/geno.1996.0059" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8838318">Davignon et al., 1996</a> further studied the genomic structure of mouse Gna11 and Gna15. Gna11 and Gna15 each contain 7 exons interposed by 6 introns. Gna11 is upstream of Gna15, and the region separating the 2 genes is 6 kb long. Phylogenetic trees revealed an approximately 6-fold higher rate of change in Gna15 than in Gna11. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1905812+8838318" 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="#16" class="mim-tip-reference" title="Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G. <strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong> Nature Genet. 1: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302014</a>] [<a href="https://doi.org/10.1038/ng0592-85" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1302014">Wilkie et al. (1992)</a> demonstrated that the GNA11 gene is located on mouse chromosome 10 (by the study of RFLVs in an interspecific backcross) and on human 19p13 (by in situ hybridization). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302014" 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 mice lacking G-alpha subunits specifically in smooth muscle cells, <a href="#17" class="mim-tip-reference" title="Wirth, A., Benyo, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Orsy, P., Horvath, B., Maser-Gluth, C., Greiner, E., Lemmer, B., Schutz, G., Gutkind, J. S., Offermanns, S. <strong>G-12-G-13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension.</strong> Nature Med. 14: 64-68, 2008. Note: Erratum: Nature Med. 14: 222 only, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18084302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18084302</a>] [<a href="https://doi.org/10.1038/nm1666" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18084302">Wirth et al. (2008)</a> found that G-alpha-q (GNAQ; <a href="/entry/600998">600998</a>) and G-alpha-11 were required for maintenance of basal blood pressure and for development of salt-induced hypertension. In contrast, lack of G-alpha-12 (GNA12; <a href="/entry/604394">604394</a>) and G-alpha-13 (GNA13; <a href="/entry/604406">604406</a>) and their effector, Larg (ARHGEF12; <a href="/entry/604763">604763</a>), did not alter normal blood pressure regulation, but blocked development of salt-induced hypertension. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18084302" 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 the proband from a 4-generation kindred with hypocalciuric hypercalcemia mapping to chromosome 19p13 (HHC2; <a href="/entry/145981">145981</a>) and an unrelated proband with HHC, <a href="#10" class="mim-tip-reference" title="Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V. <strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong> New Eng. J. Med. 368: 2476-2486, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1300253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802516">Nesbit et al. (2013)</a> identified heterozygosity for a 3-bp in-frame deletion and a missense mutation, respectively (<a href="#0001">139313.0001</a>-<a href="#0002">139313.0002</a>). In addition, 2 unrelated patients with hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>) were found to be heterozygous for missense mutations in GNA11 (<a href="#0003">139313.0003</a> and <a href="#0004">139313.0004</a>). All 4 GNA11 mutations predicted disrupted protein structures, and functional analysis in HEK293 cells showed that family hypocalciuric hypercalcemia type II-associated mutations decrease the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia 2-associated mutations increase cell sensitivity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of 2 unrelated 4-generation families segregating autosomal dominant hypocalcemia, <a href="#9" class="mim-tip-reference" title="Mannstadt, M., Harris, M., Bravenboer, B., Chitturi, S., Dreijerink, K. M. A., Lambright, D. G., Lim, E. T., Daly, M. J., Gabriel, S., Juppner, H. <strong>Germline mutations affecting G-alpha-11 in hypoparathyroidism. (Letter)</strong> New Eng. J. Med. 368: 2532-2534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802536</a>] [<a href="https://doi.org/10.1056/NEJMc1300278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802536">Mannstadt et al. (2013)</a> identified heterozygous missense mutations (<a href="#0005">139313.0005</a> and <a href="#0006">139313.0006</a>) that segregated with disease in each family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802536" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected members of a large 4-generation family segregating autosomal dominant hypocalcemia, <a href="#8" class="mim-tip-reference" title="Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A. <strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong> J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2014-1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24823460">Li et al. (2014)</a> identified a heterozygous missense mutation in the GNA11 gene (R60L; <a href="#0007">139313.0007</a>) that segregated with disease in the family and was not found in 1,200 in-house whole-exome sequencing samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24823460" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 65-year-old woman of Indian origin with hypocalciuric hypercalcemia, who was negative for mutation in the CASR and AP2S1 genes, <a href="#3" class="mim-tip-reference" title="Gorvin, C. M., Cranston, T., Hannan, F. M., Rust, N., Qureshi, A., Nesbit, M. A., Thakker, R. V. <strong>A G-protein subunit-alpha11 loss-of-function mutation, thr54met, causes familial hypocalciuric hypercalcemia type 2 (FHH2).</strong> J. Bone Miner. Res. 31: 1200-1206, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26729423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26729423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26729423[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/jbmr.2778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26729423">Gorvin et al. (2016)</a> sequenced exons and adjacent splice sites of the GNA11 gene and identified heterozygosity for a missense mutation (T54M; <a href="#0008">139313.0008</a>). Family members were unavailable for segregation analysis. Functional studies demonstrated impairment of Ca(2+)-channel signaling with the mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26729423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Somatic Mutations</em></strong></p><p>
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By gene sequencing of exon 5 of the GNA11 gene, <a href="#14" class="mim-tip-reference" title="Van Raamsdonk, C. D., Griewank, K. G., Crosby, M. B., Garrido, M. C., Vemula, S., Wiesner, T., Obenauf, A. C., Wackernagel, W., Green, G., Bouvier, N., Sozen, M. M., Baimukanova, G., Roy, R., Heguy, A., Dolgalev, I., Khanin, R., Busam, K., Speicher, M. R., O'Brien, J., Bastian, B. C. <strong>Mutations in GNA11 in uveal melanoma.</strong> New Eng. J. Med. 363: 2191-2199, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21083380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21083380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21083380[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1000584" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21083380">Van Raamsdonk et al. (2010)</a> identified somatic mutations affecting residue Q209 in 7% of blue nevi (<a href="/entry/603670">603670</a>), 32% of primary uveal melanomas (<a href="/entry/155720">155720</a>), and 57% of uveal melanoma metastases. Mutations in the same codon (Q209) of the paralogue gene GNAQ (<a href="/entry/600998">600998</a>) were found in 55% of blue nevi, 45% of primary uveal melanomas, and 22% of uveal melanoma metastases. The sample group included a total of 713 melanocytic neoplasms. Sequencing of exon 4 of these genes, affecting residue R183, in 453 melanocytic neoplasms showed a lower prevalence of mutations: 2.1% of blue nevi and 4.9% of primary uveal melanomas. The mutations were mutually exclusive, except for a single tumor that carried mutations at both Q209 and R183 in GNA11. In total, 83% of all uveal melanomas examined had oncogenic mutations in either GNAQ or GNA11. Mice injected with cells transduced with the GNA11 Q209L mutation developed rapidly growing tumors and metastases, whereas injection with GNA11 R183C-transduced cells showed lesser potency. Western blot analysis of melanocytes transduced with Q209L showed constitutive activation of the MAPK pathway. Although GNA11 mutations appeared to have a more potent effect on melanocytes than did GNAQ mutations, there was no difference in patient survival among those with GNA11 mutations compared to those with GNAQ mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21083380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RNA-seq followed by filtering, <a href="#1" class="mim-tip-reference" title="Ayturk, U. M., Couto, J. A., Hann, S., Mulliken, J. B., Williams, K. L., Huang, A. Y., Fishman, S. J., Boyd, T. K., Kozakewich, H. P. W., Bischoff, J., Greene, A. K., Warman, M. L. <strong>Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma.</strong> Am. J. Hum. Genet. 98: 789-795, 2016. Note: Erratum: Am. J. Hum. Genet. 98: 1271 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27058448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27058448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27058448[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27058448">Ayturk et al. (2016)</a> analyzed congenital hemangioma samples from 8 individuals and identified GNAQ as the only gene with variants in 3 or more samples that were not found in controls. Reanalysis of the samples showed that 6 of the 8 had a somatic GNAQ mutation, all involving the glutamine at amino acid 209: Q209L in 4, Q309P in 1, and Q209H in 1; the remaining 2 samples had a GNA11 mutation at the same residue, Q209L. The mutations were confirmed in 6 samples by digital droplet PCR (ddPCR) and/or molecular inversion probe sequencing (MIP-seq), and the somatic nature of the variants was verified by ddPCR testing of saliva or blood from 4 participants. Using a combination of ddPCR and MIP-seq, the authors also tested 8 archival formalin-fixed, paraffin-embedded congenital hemangioma samples and 4 chorangioma samples, and found a likely GNAQ (Q209L and Q209P) or GNA11 (Q209L) mutation in 4 of the congenital hemangioma samples. <a href="#1" class="mim-tip-reference" title="Ayturk, U. M., Couto, J. A., Hann, S., Mulliken, J. B., Williams, K. L., Huang, A. Y., Fishman, S. J., Boyd, T. K., Kozakewich, H. P. W., Bischoff, J., Greene, A. K., Warman, M. L. <strong>Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma.</strong> Am. J. Hum. Genet. 98: 789-795, 2016. Note: Erratum: Am. J. Hum. Genet. 98: 1271 only, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27058448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27058448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27058448[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27058448">Ayturk et al. (2016)</a> noted that the same GNAQ or GNA11 mutation (Q209L) occurred in both rapidly involuting congenital hemangioma (RICH) samples and in noninvoluting congenital hemangioma (NICH) samples, suggesting that other genetic, epigenetic, and/or environmental factors likely account for the these tumors' different postnatal behaviors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27058448" 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 experiments in transfected HEK293-CASR cells, <a href="#8" class="mim-tip-reference" title="Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A. <strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong> J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2014-1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24823460">Li et al. (2014)</a> observed significant functional differences between protooncogenic mutations in GNA11 and those associated with hypocalcemia. The protooncogenic Q209L mutation produced far greater activation of ERK1/2 (MAPK3; <a href="/entry/601795">601795</a>/MAPK1; <a href="/entry/176948">176948</a>) than the hypocalcemia-associated R60L mutation, and Q209L also showed greater activation of p38 (MAPK14; <a href="/entry/600289">600289</a>) and JNK (MAPK8; <a href="/entry/601158">601158</a>). In addition, Q209L demonstrated constitutive activation of an SRE promoter-luciferase reporter, indicating enhanced downstream signaling through the MAPK pathway, whereas R60L produced only moderately increased ligand-dependent activation compared to wildtype. <a href="#8" class="mim-tip-reference" title="Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A. <strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong> J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2014-1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24823460">Li et al. (2014)</a> proposed that the reduced activity of R60L compared to Q209L might provide an explanation for survival of individuals carrying the R60L mutation in their germline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24823460" 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 gene targeting, <a href="#11" class="mim-tip-reference" title="Offermanns, S., Zhao, L.-P., Gohla, A., Sarosi, I., Simon, M. I., Wilkie, T. M. <strong>Embryonic cardiomyocyte hypoplasia and craniofacial defects in G-alpha-q/G-alpha-11-mutant mice.</strong> EMBO J. 17: 4304-4312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9687499</a>] [<a href="https://doi.org/10.1093/emboj/17.15.4304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9687499">Offermanns et al. (1998)</a> generated Gna11-deficient mice that were viable and fertile with no apparent behavioral or morphologic defects. They bred Gnaq-deficient mice with Gna11-deficient mice and observed gene dosage effects between Gnaq and Gna11. Embryos completely lacking both genes died in utero with heart malformations. Mice inheriting a single copy of either gene died within hours of birth with craniofacial and/or cardiac defects. <a href="#11" class="mim-tip-reference" title="Offermanns, S., Zhao, L.-P., Gohla, A., Sarosi, I., Simon, M. I., Wilkie, T. M. <strong>Embryonic cardiomyocyte hypoplasia and craniofacial defects in G-alpha-q/G-alpha-11-mutant mice.</strong> EMBO J. 17: 4304-4312, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9687499</a>] [<a href="https://doi.org/10.1093/emboj/17.15.4304" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9687499">Offermanns et al. (1998)</a> concluded that at least 2 active alleles of these genes are required for extrauterine life. Genetic, morphologic, and pharmacologic analyses of intercross offspring inheriting different combinations of these 2 mutations indicated that Gnaq and Gna11 have overlapping functions in embryonic cardiomyocyte proliferation and craniofacial development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9687499" 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 new class of dominant 'dark skin' (Dsk) mutations was discovered in a screen of approximately 30,000 mice in a large-scale mutagenesis study. These result from increased dermal melanin. <a href="#13" class="mim-tip-reference" title="Van Raamsdonk, C. D., Fitch, K. R., Fuchs, H., Hrabe de Angelis, M., Barsh, G. S. <strong>Effects of G-protein mutations on skin color.</strong> Nature Genet. 36: 961-968, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15322542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15322542</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15322542[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ng1412" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15322542">Van Raamsdonk et al. (2004)</a> identified 3 of 4 such mutations as hypermorphic alleles of Gnaq and Gna11, which encode widely expressed G-alpha-q subunits, act in an additive and quantitative manner, and require endothelin receptor, type B (EDNRB; <a href="/entry/131244">131244</a>). Interaction between Gq and Kit receptor tyrosine kinase (<a href="/entry/164920">164920</a>) signaling can mediate coordinate or independent control of skin and hair color. The results provided a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15322542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Wettschureck, N., van der Stelt, M., Tsubokawa, H., Krestel, H., Moers, A., Petrosino, S., Schutz, G., Di Marzo, V., Offermanns, S. <strong>Forebrain-specific inactivation of Gq/G11 family G proteins results in age-dependent epilepsy and impaired endocannabinoid formation.</strong> Molec. Cell. Biol. 26: 5888-5894, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16847339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16847339</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16847339[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1128/MCB.00397-06" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16847339">Wettschureck et al. (2006)</a> found that mice with forebrain-specific deletion of G-alpha-q and G-alpha-11 had spontaneous epileptic seizures starting at age 3 months, with increased frequency as they aged. Histologic and immunohistochemical analyses revealed neuronal degeneration and reactive gliosis in the hippocampal CA1 region of knockout mice. Pharmacologic and electrophysiologic analyses indicated that endocannabinoid-mediated protective mechanisms were intact in knockout mice, but endogenous cannabinoid synthesis was impaired, resulting in increased seizure susceptibility and impaired neuroprotection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16847339" 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="#7" class="mim-tip-reference" title="Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schutz, G., Offermanns, S. <strong>Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.</strong> J. Clin. Invest. 117: 2399-2407, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17694176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17694176</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17694176[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI30380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17694176">Kero et al. (2007)</a> generated mice with thyrocyte-specific Gna11/Gnaq deficiency and observed severely reduced iodine organification and thyroid hormone secretion in response to TSH, with many of the mice developing hypothyroidism within months after birth. In addition, these mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet. <a href="#7" class="mim-tip-reference" title="Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schutz, G., Offermanns, S. <strong>Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.</strong> J. Clin. Invest. 117: 2399-2407, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17694176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17694176</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17694176[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1172/JCI30380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17694176">Kero et al. (2007)</a> concluded that the GNA11/GNAQ pathway has an essential role in the adaptive growth of the thyroid gland. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17694176" 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">rs672601249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs672601249;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=rs672601249" 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=rs672601249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of a 4-generation family segregating autosomal dominant hypocalciuric hypercalcemia (HHC2; <a href="/entry/145981">145981</a>), originally studied by <a href="#4" class="mim-tip-reference" title="Heath, H., III, Leppert, M. F., Lifton, R. P., Penniston, J. T. <strong>Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I: Studies in four families.</strong> J. Clin. Endocr. Metab. 75: 846-851, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1517376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1517376</a>] [<a href="https://doi.org/10.1210/jcem.75.3.1517376" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1517376">Heath et al. (1992)</a> (kindred 11675), <a href="#10" class="mim-tip-reference" title="Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V. <strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong> New Eng. J. Med. 368: 2476-2486, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1300253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802516">Nesbit et al. (2013)</a> identified heterozygosity for a 3-bp deletion (c.598_600delATC) in the GNA11 gene, resulting in an in-frame deletion of the highly conserved ile200 residue (ile200del). The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 ile200del mutant induces a decrease in sensitivity to changes in extracellular calcium concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=23802516+1517376" 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 HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE II</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">rs587777019 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777019;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=rs587777019" 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=rs587777019" 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=RCV000054475" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054475" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054475</a>
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<p>In a man who presented at 54 years of age with hypocalciuric hypercalcemia (HHC2; <a href="/entry/145981">145981</a>), <a href="#10" class="mim-tip-reference" title="Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V. <strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong> New Eng. J. Med. 368: 2476-2486, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1300253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802516">Nesbit et al. (2013)</a> identified heterozygosity for a c.404T-A transversion in the GNA11 gene, resulting in a leu135-to-gln (L135Q) substitution at a highly conserved residue in the helical domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 L135Q mutant induces a decrease in sensitivity to changes in extracellular calcium concentrations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802516" 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">rs587777020 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777020;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=rs587777020" 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=rs587777020" 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=RCV000054476 OR RCV002514274" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054476, RCV002514274" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054476...</a>
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<p>In a woman who was diagnosed at 52 years of age with hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>), <a href="#10" class="mim-tip-reference" title="Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V. <strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong> New Eng. J. Med. 368: 2476-2486, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1300253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802516">Nesbit et al. (2013)</a> identified heterozygosity for a c.542G-A transition in the GNA11 gene, resulting in an arg181-to-gln (R181Q) substitution at a highly conserved residue in the alpha-F helix of the helical domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 R181Q mutant induces an increase in sensitivity to changes in extracellular calcium concentrations. The patient was asymptomatic, but was ascertained after another family member was diagnosed with hypocalcemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802516" 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> rs140749796 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs140749796;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/rs140749796?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=rs140749796" 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=rs140749796" 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=RCV000054477" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054477" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054477</a>
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<p>In a woman who presented at 39 years of age with hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>), <a href="#10" class="mim-tip-reference" title="Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V. <strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong> New Eng. J. Med. 368: 2476-2486, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1056/NEJMoa1300253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802516">Nesbit et al. (2013)</a> identified heterozygosity for a c.1023C-G transversion in the GNA11 gene, resulting in a phe341-to-leu (F341L) substitution at a highly conserved residue in the GTPase domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 F341L mutant induces an increase in sensitivity to changes in extracellular calcium concentrations. The patient reported a 10-year history of occasional paresthesias, muscle cramps, and carpopedal spasm. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</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">rs587777021 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777021;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=rs587777021" 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=rs587777021" 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=RCV000054478 OR RCV001853077 OR RCV002504951" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054478, RCV001853077, RCV002504951" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054478...</a>
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<p>In 6 affected members of a 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>), <a href="#9" class="mim-tip-reference" title="Mannstadt, M., Harris, M., Bravenboer, B., Chitturi, S., Dreijerink, K. M. A., Lambright, D. G., Lim, E. T., Daly, M. J., Gabriel, S., Juppner, H. <strong>Germline mutations affecting G-alpha-11 in hypoparathyroidism. (Letter)</strong> New Eng. J. Med. 368: 2532-2534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802536</a>] [<a href="https://doi.org/10.1056/NEJMc1300278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802536">Mannstadt et al. (2013)</a> identified heterozygosity for a c.178C-T transition in exon 2 of the GNA11 gene, resulting in an arg60-to-cys (R60C) substitution at a highly conserved residue. The mutation was not found in unaffected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802536" 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>.0006 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777022 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777022;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/rs587777022?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=rs587777022" 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=rs587777022" 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=RCV000054479" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054479" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054479</a>
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<p>In 9 affected members of a 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>), <a href="#9" class="mim-tip-reference" title="Mannstadt, M., Harris, M., Bravenboer, B., Chitturi, S., Dreijerink, K. M. A., Lambright, D. G., Lim, E. T., Daly, M. J., Gabriel, S., Juppner, H. <strong>Germline mutations affecting G-alpha-11 in hypoparathyroidism. (Letter)</strong> New Eng. J. Med. 368: 2532-2534, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802536</a>] [<a href="https://doi.org/10.1056/NEJMc1300278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23802536">Mannstadt et al. (2013)</a> identified heterozygosity for a c.632C-G transversion in exon 5 of the GNA11 gene, resulting in a ser211-to-trp (S211W) substitution at a highly conserved residue. The mutation was not found in unaffected family members. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802536" 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>.0007 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs587777707 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777707;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/rs587777707?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=rs587777707" 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=rs587777707" 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=RCV000144048 OR RCV005089664" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000144048, RCV005089664" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000144048...</a>
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<p>In 6 affected members of a large 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; <a href="/entry/615361">615361</a>), originally reported by <a href="#5" class="mim-tip-reference" title="Hunter, A. G. W., Heick, H., Poznanski, W. J., McLaine, P. N. <strong>Autosomal dominant hypoparathyroidism: a proband with concurrent nephrogenic diabetes insipidus.</strong> J. Med. Genet. 18: 431-435, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6278146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6278146</a>] [<a href="https://doi.org/10.1136/jmg.18.6.431" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6278146">Hunter et al. (1981)</a>, <a href="#8" class="mim-tip-reference" title="Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A. <strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong> J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2014-1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24823460">Li et al. (2014)</a> identified heterozygosity for a c.179G-T transversion in the GNA11 gene, resulting in an arg60-to-leu (R60L) substitution at a critical residue within the alpha-1 helix that forms a salt bridge with asp71 from the helical domain that stabilizes linker 1. The mutation segregated with disease in the family and was not found in 1,200 in-house whole-exome sequencing samples. Transfected HEK293 cells expressing the R60L mutant showed a leftward shift of the concentration-response curve, indicating enhanced sensitivity to changes in extracellular calcium concentrations consistent with a gain-of-function mutation. <a href="#8" class="mim-tip-reference" title="Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A. <strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong> J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1210/jc.2014-1029" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24823460">Li et al. (2014)</a> noted that all affected members of this family developed mild postnatal growth failure and were significantly shorter than their unaffected relatives. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24823460+6278146" 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>.0008 HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE II</strong>
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GNA11, THR54MET
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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> rs1335558363 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1335558363;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/rs1335558363?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=rs1335558363" 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=rs1335558363" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001706737 OR RCV005014615" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001706737, RCV005014615" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001706737...</a>
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<p>In a 65-year-old woman of Indian origin with hypocalciuric hypercalcemia (HHC2; <a href="/entry/145981">145981</a>), <a href="#3" class="mim-tip-reference" title="Gorvin, C. M., Cranston, T., Hannan, F. M., Rust, N., Qureshi, A., Nesbit, M. A., Thakker, R. V. <strong>A G-protein subunit-alpha11 loss-of-function mutation, thr54met, causes familial hypocalciuric hypercalcemia type 2 (FHH2).</strong> J. Bone Miner. Res. 31: 1200-1206, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26729423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26729423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26729423[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/jbmr.2778" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26729423">Gorvin et al. (2016)</a> identified heterozygosity for a c.161C-T transition (c.161C-T, NM_002067) in exon 2 of the GNA11 gene, resulting in a thr54-to-met (T54M) substitution at a highly conserved residue within the alpha-1 helix. Family members were unavailable for segregation analysis. The variant was not found in the NHLBI-ESP or ExAC databases. Functional studies in transiently transfected HEK293-CaSR cells demonstrated a rightward shift in the Ca(2+) concentration-response curve with significantly elevated mean EC(50) values for the T54M mutant compared to wildtype GNA11, consistent with impairment of CaSR signal transduction. In addition, cells expressing the T54M mutant had significantly reduced maximal signaling responses compared to cells expressing the wildtype protein or the previously reported L135Q mutant (<a href="#0002">139313.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26729423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Ayturk2016" class="mim-anchor"></a>
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Ayturk, U. M., Couto, J. A., Hann, S., Mulliken, J. B., Williams, K. L., Huang, A. Y., Fishman, S. J., Boyd, T. K., Kozakewich, H. P. W., Bischoff, J., Greene, A. K., Warman, M. L.
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<strong>Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma.</strong>
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Am. J. Hum. Genet. 98: 789-795, 2016. Note: Erratum: Am. J. Hum. Genet. 98: 1271 only, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27058448/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27058448</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27058448[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27058448" 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.2016.03.009" target="_blank">Full Text</a>]
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Davignon, I., Barnard, M., Gavrilova, O., Sweet, K., Wilkie, T. M.
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<strong>Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.</strong>
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Genomics 31: 359-366, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8838318/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8838318</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8838318" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1996.0059" target="_blank">Full Text</a>]
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<a id="Gorvin2016" class="mim-anchor"></a>
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Gorvin, C. M., Cranston, T., Hannan, F. M., Rust, N., Qureshi, A., Nesbit, M. A., Thakker, R. V.
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<strong>A G-protein subunit-alpha11 loss-of-function mutation, thr54met, causes familial hypocalciuric hypercalcemia type 2 (FHH2).</strong>
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J. Bone Miner. Res. 31: 1200-1206, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26729423/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26729423</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26729423[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26729423" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/jbmr.2778" target="_blank">Full Text</a>]
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<a id="Heath1992" class="mim-anchor"></a>
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Heath, H., III, Leppert, M. F., Lifton, R. P., Penniston, J. T.
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<strong>Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I: Studies in four families.</strong>
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J. Clin. Endocr. Metab. 75: 846-851, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1517376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1517376</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1517376" 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/10.1210/jcem.75.3.1517376" target="_blank">Full Text</a>]
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Hunter, A. G. W., Heick, H., Poznanski, W. J., McLaine, P. N.
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<strong>Autosomal dominant hypoparathyroidism: a proband with concurrent nephrogenic diabetes insipidus.</strong>
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J. Med. Genet. 18: 431-435, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6278146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6278146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6278146" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.18.6.431" target="_blank">Full Text</a>]
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<a id="Jiang1991" class="mim-anchor"></a>
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Jiang, M., Pandey, S., Tran, V. T., Fong, H. K.
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<strong>Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells.</strong>
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Proc. Nat. Acad. Sci. 88: 3907-3911, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1902575/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1902575</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1902575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.88.9.3907" target="_blank">Full Text</a>]
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<a id="Kero2007" class="mim-anchor"></a>
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Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schutz, G., Offermanns, S.
|
|
<strong>Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.</strong>
|
|
J. Clin. Invest. 117: 2399-2407, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17694176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17694176</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17694176[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17694176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1172/JCI30380" target="_blank">Full Text</a>]
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<a id="Li2014" class="mim-anchor"></a>
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Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A.
|
|
<strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong>
|
|
J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24823460/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24823460</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24823460[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24823460" 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/10.1210/jc.2014-1029" target="_blank">Full Text</a>]
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<a id="Mannstadt2013" class="mim-anchor"></a>
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Mannstadt, M., Harris, M., Bravenboer, B., Chitturi, S., Dreijerink, K. M. A., Lambright, D. G., Lim, E. T., Daly, M. J., Gabriel, S., Juppner, H.
|
|
<strong>Germline mutations affecting G-alpha-11 in hypoparathyroidism. (Letter)</strong>
|
|
New Eng. J. Med. 368: 2532-2534, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802536/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802536</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802536" 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/10.1056/NEJMc1300278" target="_blank">Full Text</a>]
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Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V.
|
|
<strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong>
|
|
New Eng. J. Med. 368: 2476-2486, 2013.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23802516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23802516</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23802516[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23802516" 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/10.1056/NEJMoa1300253" target="_blank">Full Text</a>]
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<a id="Offermanns1998" class="mim-anchor"></a>
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Offermanns, S., Zhao, L.-P., Gohla, A., Sarosi, I., Simon, M. I., Wilkie, T. M.
|
|
<strong>Embryonic cardiomyocyte hypoplasia and craniofacial defects in G-alpha-q/G-alpha-11-mutant mice.</strong>
|
|
EMBO J. 17: 4304-4312, 1998.
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|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9687499/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9687499</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9687499" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/emboj/17.15.4304" target="_blank">Full Text</a>]
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Strathmann, M. P., Simon, M. I.
|
|
<strong>G-alpha-12 and G-alpha-13 subunits define a fourth class of G protein alpha subunits.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 5582-5586, 1991.
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|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1905812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1905812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1905812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.88.13.5582" target="_blank">Full Text</a>]
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Van Raamsdonk, C. D., Fitch, K. R., Fuchs, H., Hrabe de Angelis, M., Barsh, G. S.
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<strong>Effects of G-protein mutations on skin color.</strong>
|
|
Nature Genet. 36: 961-968, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15322542/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15322542</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15322542[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15322542" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1412" target="_blank">Full Text</a>]
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Van Raamsdonk, C. D., Griewank, K. G., Crosby, M. B., Garrido, M. C., Vemula, S., Wiesner, T., Obenauf, A. C., Wackernagel, W., Green, G., Bouvier, N., Sozen, M. M., Baimukanova, G., Roy, R., Heguy, A., Dolgalev, I., Khanin, R., Busam, K., Speicher, M. R., O'Brien, J., Bastian, B. C.
|
|
<strong>Mutations in GNA11 in uveal melanoma.</strong>
|
|
New Eng. J. Med. 363: 2191-2199, 2010.
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|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21083380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21083380</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21083380[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21083380" 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/10.1056/NEJMoa1000584" target="_blank">Full Text</a>]
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<a id="Wettschureck2006" class="mim-anchor"></a>
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Wettschureck, N., van der Stelt, M., Tsubokawa, H., Krestel, H., Moers, A., Petrosino, S., Schutz, G., Di Marzo, V., Offermanns, S.
|
|
<strong>Forebrain-specific inactivation of Gq/G11 family G proteins results in age-dependent epilepsy and impaired endocannabinoid formation.</strong>
|
|
Molec. Cell. Biol. 26: 5888-5894, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16847339/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16847339</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16847339[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16847339" 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/10.1128/MCB.00397-06" target="_blank">Full Text</a>]
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Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G.
|
|
<strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong>
|
|
Nature Genet. 1: 85-91, 1992.
|
|
|
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0592-85" target="_blank">Full Text</a>]
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Wirth, A., Benyo, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Orsy, P., Horvath, B., Maser-Gluth, C., Greiner, E., Lemmer, B., Schutz, G., Gutkind, J. S., Offermanns, S.
|
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<strong>G-12-G-13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension.</strong>
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Nature Med. 14: 64-68, 2008. Note: Erratum: Nature Med. 14: 222 only, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18084302/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18084302</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18084302" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nm1666" target="_blank">Full Text</a>]
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Marla J. F. O'Neill - updated : 09/22/2021
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Bao Lige - updated : 02/13/2020<br>Marla J. F. O'Neill - updated : 5/10/2016<br>Marla J. F. O'Neill - updated : 9/12/2014<br>Marla J. F. O'Neill - updated : 8/12/2013<br>Cassandra L. Kniffin - updated : 12/20/2010<br>Patricia A. Hartz - updated : 3/6/2008<br>Marla J. F. O'Neill - updated : 11/6/2007<br>Victor A. McKusick - updated : 9/30/2004<br>Dawn Watkins-Chow - updated : 7/11/2002<br>John A. Phillips, III - updated : 5/12/1998
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Victor A. McKusick : 5/19/1992
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mgross : 02/13/2020<br>carol : 07/24/2018<br>carol : 06/15/2016<br>alopez : 5/10/2016<br>alopez : 9/12/2014<br>carol : 8/12/2013<br>terry : 8/6/2012<br>wwang : 12/27/2010<br>ckniffin : 12/20/2010<br>mgross : 3/6/2008<br>wwang : 11/12/2007<br>terry : 11/6/2007<br>alopez : 9/30/2004<br>mgross : 7/11/2002<br>alopez : 7/9/2001<br>carol : 6/28/1999<br>alopez : 5/12/1998<br>jamie : 1/8/1997<br>jamie : 1/7/1997<br>jamie : 1/7/1997<br>jamie : 1/7/1997<br>mark : 3/20/1996<br>terry : 3/11/1996<br>carol : 7/1/1992<br>carol : 5/19/1992
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GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-11; GNA11
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GNA11</em></strong>
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<strong>
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<em>
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Cytogenetic location: 19p13.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:3,094,362-3,123,999 </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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</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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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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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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</thead>
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<tbody>
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<tr>
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<td rowspan="2">
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<span class="mim-font">
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19p13.3
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</td>
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<td>
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<span class="mim-font">
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Hypocalcemia, autosomal dominant 2
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615361
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Autosomal dominant
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3
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<tr>
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<td>
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<span class="mim-font">
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Hypocalciuric hypercalcemia, type II
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145981
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Autosomal dominant
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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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</tr>
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</tbody>
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</table>
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</div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<strong>Cloning and Expression</strong>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Strathmann and Simon (1991) described the Gna11 gene in the mouse. The human gene was cloned by Jiang et al. (1991) and found to be 359 amino acids long. Mouse Gna11 and Gna15 (139314) are tandemly duplicated in a head-to-tail array. Davignon et al. (1996) showed that the upstream gene, Gna11, is ubiquitously expressed, whereas expression of the downstream gene, Gna15, is restricted to hematopoietic cells. There was no evidence for alternative splicing within the coding sequence of either gene. </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 Structure</strong>
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</h4>
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</div>
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<p>Strathmann and Simon (1991) found that mouse Gna11 and Gna15 (139314) are tandemly duplicated in a head-to-tail array, spanning approximately 43 kb. Davignon et al., 1996 further studied the genomic structure of mouse Gna11 and Gna15. Gna11 and Gna15 each contain 7 exons interposed by 6 introns. Gna11 is upstream of Gna15, and the region separating the 2 genes is 6 kb long. Phylogenetic trees revealed an approximately 6-fold higher rate of change in Gna15 than in Gna11. </p>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</h4>
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</div>
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<p>Wilkie et al. (1992) demonstrated that the GNA11 gene is located on mouse chromosome 10 (by the study of RFLVs in an interspecific backcross) and on human 19p13 (by in situ hybridization). </p>
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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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</h4>
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</div>
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<p>Using mice lacking G-alpha subunits specifically in smooth muscle cells, Wirth et al. (2008) found that G-alpha-q (GNAQ; 600998) and G-alpha-11 were required for maintenance of basal blood pressure and for development of salt-induced hypertension. In contrast, lack of G-alpha-12 (GNA12; 604394) and G-alpha-13 (GNA13; 604406) and their effector, Larg (ARHGEF12; 604763), did not alter normal blood pressure regulation, but blocked development of salt-induced hypertension. </p>
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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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</h4>
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<p>In the proband from a 4-generation kindred with hypocalciuric hypercalcemia mapping to chromosome 19p13 (HHC2; 145981) and an unrelated proband with HHC, Nesbit et al. (2013) identified heterozygosity for a 3-bp in-frame deletion and a missense mutation, respectively (139313.0001-139313.0002). In addition, 2 unrelated patients with hypocalcemia (HYPOC2; 615361) were found to be heterozygous for missense mutations in GNA11 (139313.0003 and 139313.0004). All 4 GNA11 mutations predicted disrupted protein structures, and functional analysis in HEK293 cells showed that family hypocalciuric hypercalcemia type II-associated mutations decrease the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia 2-associated mutations increase cell sensitivity. </p><p>In affected members of 2 unrelated 4-generation families segregating autosomal dominant hypocalcemia, Mannstadt et al. (2013) identified heterozygous missense mutations (139313.0005 and 139313.0006) that segregated with disease in each family. </p><p>In affected members of a large 4-generation family segregating autosomal dominant hypocalcemia, Li et al. (2014) identified a heterozygous missense mutation in the GNA11 gene (R60L; 139313.0007) that segregated with disease in the family and was not found in 1,200 in-house whole-exome sequencing samples. </p><p>In a 65-year-old woman of Indian origin with hypocalciuric hypercalcemia, who was negative for mutation in the CASR and AP2S1 genes, Gorvin et al. (2016) sequenced exons and adjacent splice sites of the GNA11 gene and identified heterozygosity for a missense mutation (T54M; 139313.0008). Family members were unavailable for segregation analysis. Functional studies demonstrated impairment of Ca(2+)-channel signaling with the mutant protein. </p><p><strong><em>Somatic Mutations</em></strong></p><p>
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By gene sequencing of exon 5 of the GNA11 gene, Van Raamsdonk et al. (2010) identified somatic mutations affecting residue Q209 in 7% of blue nevi (603670), 32% of primary uveal melanomas (155720), and 57% of uveal melanoma metastases. Mutations in the same codon (Q209) of the paralogue gene GNAQ (600998) were found in 55% of blue nevi, 45% of primary uveal melanomas, and 22% of uveal melanoma metastases. The sample group included a total of 713 melanocytic neoplasms. Sequencing of exon 4 of these genes, affecting residue R183, in 453 melanocytic neoplasms showed a lower prevalence of mutations: 2.1% of blue nevi and 4.9% of primary uveal melanomas. The mutations were mutually exclusive, except for a single tumor that carried mutations at both Q209 and R183 in GNA11. In total, 83% of all uveal melanomas examined had oncogenic mutations in either GNAQ or GNA11. Mice injected with cells transduced with the GNA11 Q209L mutation developed rapidly growing tumors and metastases, whereas injection with GNA11 R183C-transduced cells showed lesser potency. Western blot analysis of melanocytes transduced with Q209L showed constitutive activation of the MAPK pathway. Although GNA11 mutations appeared to have a more potent effect on melanocytes than did GNAQ mutations, there was no difference in patient survival among those with GNA11 mutations compared to those with GNAQ mutations. </p><p>Using RNA-seq followed by filtering, Ayturk et al. (2016) analyzed congenital hemangioma samples from 8 individuals and identified GNAQ as the only gene with variants in 3 or more samples that were not found in controls. Reanalysis of the samples showed that 6 of the 8 had a somatic GNAQ mutation, all involving the glutamine at amino acid 209: Q209L in 4, Q309P in 1, and Q209H in 1; the remaining 2 samples had a GNA11 mutation at the same residue, Q209L. The mutations were confirmed in 6 samples by digital droplet PCR (ddPCR) and/or molecular inversion probe sequencing (MIP-seq), and the somatic nature of the variants was verified by ddPCR testing of saliva or blood from 4 participants. Using a combination of ddPCR and MIP-seq, the authors also tested 8 archival formalin-fixed, paraffin-embedded congenital hemangioma samples and 4 chorangioma samples, and found a likely GNAQ (Q209L and Q209P) or GNA11 (Q209L) mutation in 4 of the congenital hemangioma samples. Ayturk et al. (2016) noted that the same GNAQ or GNA11 mutation (Q209L) occurred in both rapidly involuting congenital hemangioma (RICH) samples and in noninvoluting congenital hemangioma (NICH) samples, suggesting that other genetic, epigenetic, and/or environmental factors likely account for the these tumors' different postnatal behaviors. </p>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</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 experiments in transfected HEK293-CASR cells, Li et al. (2014) observed significant functional differences between protooncogenic mutations in GNA11 and those associated with hypocalcemia. The protooncogenic Q209L mutation produced far greater activation of ERK1/2 (MAPK3; 601795/MAPK1; 176948) than the hypocalcemia-associated R60L mutation, and Q209L also showed greater activation of p38 (MAPK14; 600289) and JNK (MAPK8; 601158). In addition, Q209L demonstrated constitutive activation of an SRE promoter-luciferase reporter, indicating enhanced downstream signaling through the MAPK pathway, whereas R60L produced only moderately increased ligand-dependent activation compared to wildtype. Li et al. (2014) proposed that the reduced activity of R60L compared to Q209L might provide an explanation for survival of individuals carrying the R60L mutation in their germline. </p>
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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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</h4>
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<p>Using gene targeting, Offermanns et al. (1998) generated Gna11-deficient mice that were viable and fertile with no apparent behavioral or morphologic defects. They bred Gnaq-deficient mice with Gna11-deficient mice and observed gene dosage effects between Gnaq and Gna11. Embryos completely lacking both genes died in utero with heart malformations. Mice inheriting a single copy of either gene died within hours of birth with craniofacial and/or cardiac defects. Offermanns et al. (1998) concluded that at least 2 active alleles of these genes are required for extrauterine life. Genetic, morphologic, and pharmacologic analyses of intercross offspring inheriting different combinations of these 2 mutations indicated that Gnaq and Gna11 have overlapping functions in embryonic cardiomyocyte proliferation and craniofacial development. </p><p>A new class of dominant 'dark skin' (Dsk) mutations was discovered in a screen of approximately 30,000 mice in a large-scale mutagenesis study. These result from increased dermal melanin. Van Raamsdonk et al. (2004) identified 3 of 4 such mutations as hypermorphic alleles of Gnaq and Gna11, which encode widely expressed G-alpha-q subunits, act in an additive and quantitative manner, and require endothelin receptor, type B (EDNRB; 131244). Interaction between Gq and Kit receptor tyrosine kinase (164920) signaling can mediate coordinate or independent control of skin and hair color. The results provided a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system. </p><p>Wettschureck et al. (2006) found that mice with forebrain-specific deletion of G-alpha-q and G-alpha-11 had spontaneous epileptic seizures starting at age 3 months, with increased frequency as they aged. Histologic and immunohistochemical analyses revealed neuronal degeneration and reactive gliosis in the hippocampal CA1 region of knockout mice. Pharmacologic and electrophysiologic analyses indicated that endocannabinoid-mediated protective mechanisms were intact in knockout mice, but endogenous cannabinoid synthesis was impaired, resulting in increased seizure susceptibility and impaired neuroprotection. </p><p>Kero et al. (2007) generated mice with thyrocyte-specific Gna11/Gnaq deficiency and observed severely reduced iodine organification and thyroid hormone secretion in response to TSH, with many of the mice developing hypothyroidism within months after birth. In addition, these mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet. Kero et al. (2007) concluded that the GNA11/GNAQ pathway has an essential role in the adaptive growth of the thyroid gland. </p>
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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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<strong>8 Selected Examples):</strong>
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</h4>
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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>.0001 HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE II</strong>
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</h4>
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GNA11, 3-BP DEL, 598ATC
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SNP: rs672601249,
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ClinVar: RCV000054474
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<span class="mim-text-font">
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<p>In affected members of a 4-generation family segregating autosomal dominant hypocalciuric hypercalcemia (HHC2; 145981), originally studied by Heath et al. (1992) (kindred 11675), Nesbit et al. (2013) identified heterozygosity for a 3-bp deletion (c.598_600delATC) in the GNA11 gene, resulting in an in-frame deletion of the highly conserved ile200 residue (ile200del). The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 ile200del mutant induces a decrease in sensitivity to changes in extracellular calcium concentrations. </p>
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<h4>
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<span class="mim-font">
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<strong>.0002 HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE II</strong>
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</h4>
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<span class="mim-text-font">
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GNA11, LEU135GLN
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SNP: rs587777019,
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ClinVar: RCV000054475
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<span class="mim-text-font">
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<p>In a man who presented at 54 years of age with hypocalciuric hypercalcemia (HHC2; 145981), Nesbit et al. (2013) identified heterozygosity for a c.404T-A transversion in the GNA11 gene, resulting in a leu135-to-gln (L135Q) substitution at a highly conserved residue in the helical domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 L135Q mutant induces a decrease in sensitivity to changes in extracellular calcium concentrations. </p>
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<h4>
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<span class="mim-font">
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<strong>.0003 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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GNA11, ARG181GLN
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SNP: rs587777020,
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ClinVar: RCV000054476, RCV002514274
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<span class="mim-text-font">
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<p>In a woman who was diagnosed at 52 years of age with hypocalcemia (HYPOC2; 615361), Nesbit et al. (2013) identified heterozygosity for a c.542G-A transition in the GNA11 gene, resulting in an arg181-to-gln (R181Q) substitution at a highly conserved residue in the alpha-F helix of the helical domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 R181Q mutant induces an increase in sensitivity to changes in extracellular calcium concentrations. The patient was asymptomatic, but was ascertained after another family member was diagnosed with hypocalcemia. </p>
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<h4>
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<span class="mim-font">
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<strong>.0004 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</strong>
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</h4>
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<span class="mim-text-font">
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GNA11, PHE341LEU
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SNP: rs140749796,
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gnomAD: rs140749796,
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ClinVar: RCV000054477
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<span class="mim-text-font">
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<p>In a woman who presented at 39 years of age with hypocalcemia (HYPOC2; 615361), Nesbit et al. (2013) identified heterozygosity for a c.1023C-G transversion in the GNA11 gene, resulting in a phe341-to-leu (F341L) substitution at a highly conserved residue in the GTPase domain. The mutation was not found in 55 controls or in 5,400 exomes from the NHLBI Exome Sequencing Project. Functional analysis in HEK293 cells stably expressing calcium-sensing receptors demonstrated that the GNA11 F341L mutant induces an increase in sensitivity to changes in extracellular calcium concentrations. The patient reported a 10-year history of occasional paresthesias, muscle cramps, and carpopedal spasm. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</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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GNA11, ARG60CYS
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<br />
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SNP: rs587777021,
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ClinVar: RCV000054478, RCV001853077, RCV002504951
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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 6 affected members of a 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; 615361), Mannstadt et al. (2013) identified heterozygosity for a c.178C-T transition in exon 2 of the GNA11 gene, resulting in an arg60-to-cys (R60C) substitution at a highly conserved residue. The mutation was not found in unaffected family members. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</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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GNA11, SER211TRP
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<br />
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SNP: rs587777022,
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gnomAD: rs587777022,
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ClinVar: RCV000054479
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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 9 affected members of a 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; 615361), Mannstadt et al. (2013) identified heterozygosity for a c.632C-G transversion in exon 5 of the GNA11 gene, resulting in a ser211-to-trp (S211W) substitution at a highly conserved residue. The mutation was not found in unaffected family members. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0007 HYPOCALCEMIA, AUTOSOMAL DOMINANT 2</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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GNA11, ARG60LEU
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<br />
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SNP: rs587777707,
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gnomAD: rs587777707,
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ClinVar: RCV000144048, RCV005089664
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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 6 affected members of a large 4-generation family segregating autosomal dominant hypocalcemia (HYPOC2; 615361), originally reported by Hunter et al. (1981), Li et al. (2014) identified heterozygosity for a c.179G-T transversion in the GNA11 gene, resulting in an arg60-to-leu (R60L) substitution at a critical residue within the alpha-1 helix that forms a salt bridge with asp71 from the helical domain that stabilizes linker 1. The mutation segregated with disease in the family and was not found in 1,200 in-house whole-exome sequencing samples. Transfected HEK293 cells expressing the R60L mutant showed a leftward shift of the concentration-response curve, indicating enhanced sensitivity to changes in extracellular calcium concentrations consistent with a gain-of-function mutation. Li et al. (2014) noted that all affected members of this family developed mild postnatal growth failure and were significantly shorter than their unaffected relatives. </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>.0008 HYPOCALCIURIC HYPERCALCEMIA, FAMILIAL, TYPE II</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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GNA11, THR54MET
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<br />
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SNP: rs1335558363,
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gnomAD: rs1335558363,
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ClinVar: RCV001706737, RCV005014615
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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 65-year-old woman of Indian origin with hypocalciuric hypercalcemia (HHC2; 145981), Gorvin et al. (2016) identified heterozygosity for a c.161C-T transition (c.161C-T, NM_002067) in exon 2 of the GNA11 gene, resulting in a thr54-to-met (T54M) substitution at a highly conserved residue within the alpha-1 helix. Family members were unavailable for segregation analysis. The variant was not found in the NHLBI-ESP or ExAC databases. Functional studies in transiently transfected HEK293-CaSR cells demonstrated a rightward shift in the Ca(2+) concentration-response curve with significantly elevated mean EC(50) values for the T54M mutant compared to wildtype GNA11, consistent with impairment of CaSR signal transduction. In addition, cells expressing the T54M mutant had significantly reduced maximal signaling responses compared to cells expressing the wildtype protein or the previously reported L135Q mutant (139313.0002). </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>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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Ayturk, U. M., Couto, J. A., Hann, S., Mulliken, J. B., Williams, K. L., Huang, A. Y., Fishman, S. J., Boyd, T. K., Kozakewich, H. P. W., Bischoff, J., Greene, A. K., Warman, M. L.
|
|
<strong>Somatic activating mutations in GNAQ and GNA11 are associated with congenital hemangioma.</strong>
|
|
Am. J. Hum. Genet. 98: 789-795, 2016. Note: Erratum: Am. J. Hum. Genet. 98: 1271 only, 2016.
|
|
|
|
|
|
[PubMed: 27058448]
|
|
|
|
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[Full Text: https://doi.org/10.1016/j.ajhg.2016.03.009]
|
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</p>
|
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</li>
|
|
|
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<li>
|
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<p class="mim-text-font">
|
|
Davignon, I., Barnard, M., Gavrilova, O., Sweet, K., Wilkie, T. M.
|
|
<strong>Gene structure of murine Gna11 and Gna15: tandemly duplicated Gq class G protein alpha subunit genes.</strong>
|
|
Genomics 31: 359-366, 1996.
|
|
|
|
|
|
[PubMed: 8838318]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1996.0059]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gorvin, C. M., Cranston, T., Hannan, F. M., Rust, N., Qureshi, A., Nesbit, M. A., Thakker, R. V.
|
|
<strong>A G-protein subunit-alpha11 loss-of-function mutation, thr54met, causes familial hypocalciuric hypercalcemia type 2 (FHH2).</strong>
|
|
J. Bone Miner. Res. 31: 1200-1206, 2016.
|
|
|
|
|
|
[PubMed: 26729423]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/jbmr.2778]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Heath, H., III, Leppert, M. F., Lifton, R. P., Penniston, J. T.
|
|
<strong>Genetic linkage analysis in familial benign hypercalcemia using a candidate gene strategy. I: Studies in four families.</strong>
|
|
J. Clin. Endocr. Metab. 75: 846-851, 1992.
|
|
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|
|
|
[PubMed: 1517376]
|
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|
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[Full Text: https://doi.org/10.1210/jcem.75.3.1517376]
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</p>
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Hunter, A. G. W., Heick, H., Poznanski, W. J., McLaine, P. N.
|
|
<strong>Autosomal dominant hypoparathyroidism: a proband with concurrent nephrogenic diabetes insipidus.</strong>
|
|
J. Med. Genet. 18: 431-435, 1981.
|
|
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|
|
[PubMed: 6278146]
|
|
|
|
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|
[Full Text: https://doi.org/10.1136/jmg.18.6.431]
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</p>
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</li>
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|
|
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<li>
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<p class="mim-text-font">
|
|
Jiang, M., Pandey, S., Tran, V. T., Fong, H. K.
|
|
<strong>Guanine nucleotide-binding regulatory proteins in retinal pigment epithelial cells.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 3907-3911, 1991.
|
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|
|
[PubMed: 1902575]
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[Full Text: https://doi.org/10.1073/pnas.88.9.3907]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schutz, G., Offermanns, S.
|
|
<strong>Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.</strong>
|
|
J. Clin. Invest. 117: 2399-2407, 2007.
|
|
|
|
|
|
[PubMed: 17694176]
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|
|
[Full Text: https://doi.org/10.1172/JCI30380]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Li, D., Opas, E. E., Tuluc, F., Metzger, D. L., Hou, C., Hakonarson, H., Levine, M. A.
|
|
<strong>Autosomal dominant hypoparathyroidism caused by germline mutation in GNA11: phenotypic and molecular characterization.</strong>
|
|
J. Clin. Endocr. Metab. 99: E1774-E1783, 2014.
|
|
|
|
|
|
[PubMed: 24823460]
|
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|
|
|
|
[Full Text: https://doi.org/10.1210/jc.2014-1029]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Mannstadt, M., Harris, M., Bravenboer, B., Chitturi, S., Dreijerink, K. M. A., Lambright, D. G., Lim, E. T., Daly, M. J., Gabriel, S., Juppner, H.
|
|
<strong>Germline mutations affecting G-alpha-11 in hypoparathyroidism. (Letter)</strong>
|
|
New Eng. J. Med. 368: 2532-2534, 2013.
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|
|
[PubMed: 23802536]
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[Full Text: https://doi.org/10.1056/NEJMc1300278]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Nesbit, M. A., Hannan, F. M., Howles, S. A., Babinsky, V. N., Head, R. A., Cranston, T., Rust, N., Hobbs, M. R., Heath, H., III, Thakker, R. V.
|
|
<strong>Mutations affecting G-protein subunit alpha-11 in hypercalcemia and hypocalcemia.</strong>
|
|
New Eng. J. Med. 368: 2476-2486, 2013.
|
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|
|
[PubMed: 23802516]
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[Full Text: https://doi.org/10.1056/NEJMoa1300253]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Offermanns, S., Zhao, L.-P., Gohla, A., Sarosi, I., Simon, M. I., Wilkie, T. M.
|
|
<strong>Embryonic cardiomyocyte hypoplasia and craniofacial defects in G-alpha-q/G-alpha-11-mutant mice.</strong>
|
|
EMBO J. 17: 4304-4312, 1998.
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|
[PubMed: 9687499]
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|
[Full Text: https://doi.org/10.1093/emboj/17.15.4304]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Strathmann, M. P., Simon, M. I.
|
|
<strong>G-alpha-12 and G-alpha-13 subunits define a fourth class of G protein alpha subunits.</strong>
|
|
Proc. Nat. Acad. Sci. 88: 5582-5586, 1991.
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|
[PubMed: 1905812]
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[Full Text: https://doi.org/10.1073/pnas.88.13.5582]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Van Raamsdonk, C. D., Fitch, K. R., Fuchs, H., Hrabe de Angelis, M., Barsh, G. S.
|
|
<strong>Effects of G-protein mutations on skin color.</strong>
|
|
Nature Genet. 36: 961-968, 2004.
|
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|
|
[PubMed: 15322542]
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[Full Text: https://doi.org/10.1038/ng1412]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Van Raamsdonk, C. D., Griewank, K. G., Crosby, M. B., Garrido, M. C., Vemula, S., Wiesner, T., Obenauf, A. C., Wackernagel, W., Green, G., Bouvier, N., Sozen, M. M., Baimukanova, G., Roy, R., Heguy, A., Dolgalev, I., Khanin, R., Busam, K., Speicher, M. R., O'Brien, J., Bastian, B. C.
|
|
<strong>Mutations in GNA11 in uveal melanoma.</strong>
|
|
New Eng. J. Med. 363: 2191-2199, 2010.
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|
|
[PubMed: 21083380]
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[Full Text: https://doi.org/10.1056/NEJMoa1000584]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Wettschureck, N., van der Stelt, M., Tsubokawa, H., Krestel, H., Moers, A., Petrosino, S., Schutz, G., Di Marzo, V., Offermanns, S.
|
|
<strong>Forebrain-specific inactivation of Gq/G11 family G proteins results in age-dependent epilepsy and impaired endocannabinoid formation.</strong>
|
|
Molec. Cell. Biol. 26: 5888-5894, 2006.
|
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|
|
|
[PubMed: 16847339]
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[Full Text: https://doi.org/10.1128/MCB.00397-06]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G.
|
|
<strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong>
|
|
Nature Genet. 1: 85-91, 1992.
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|
[PubMed: 1302014]
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[Full Text: https://doi.org/10.1038/ng0592-85]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
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Wirth, A., Benyo, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Orsy, P., Horvath, B., Maser-Gluth, C., Greiner, E., Lemmer, B., Schutz, G., Gutkind, J. S., Offermanns, S.
|
|
<strong>G-12-G-13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension.</strong>
|
|
Nature Med. 14: 64-68, 2008. Note: Erratum: Nature Med. 14: 222 only, 2008.
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|
[PubMed: 18084302]
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[Full Text: https://doi.org/10.1038/nm1666]
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
|
|
Marla J. F. O'Neill - updated : 09/22/2021<br>Bao Lige - updated : 02/13/2020<br>Marla J. F. O'Neill - updated : 5/10/2016<br>Marla J. F. O'Neill - updated : 9/12/2014<br>Marla J. F. O'Neill - updated : 8/12/2013<br>Cassandra L. Kniffin - updated : 12/20/2010<br>Patricia A. Hartz - updated : 3/6/2008<br>Marla J. F. O'Neill - updated : 11/6/2007<br>Victor A. McKusick - updated : 9/30/2004<br>Dawn Watkins-Chow - updated : 7/11/2002<br>John A. Phillips, III - updated : 5/12/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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alopez : 09/22/2021<br>mgross : 02/13/2020<br>carol : 07/24/2018<br>carol : 06/15/2016<br>alopez : 5/10/2016<br>alopez : 9/12/2014<br>carol : 8/12/2013<br>terry : 8/6/2012<br>wwang : 12/27/2010<br>ckniffin : 12/20/2010<br>mgross : 3/6/2008<br>wwang : 11/12/2007<br>terry : 11/6/2007<br>alopez : 9/30/2004<br>mgross : 7/11/2002<br>alopez : 7/9/2001<br>carol : 6/28/1999<br>alopez : 5/12/1998<br>jamie : 1/8/1997<br>jamie : 1/7/1997<br>jamie : 1/7/1997<br>jamie : 1/7/1997<br>mark : 3/20/1996<br>terry : 3/11/1996<br>carol : 7/1/1992<br>carol : 5/19/1992
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