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Entry
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- *139380 - GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-1; GNB1
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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">*139380</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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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/139380">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</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=ENSG00000078369;t=ENST00000378609" 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=2782" 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=139380" 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=ENSG00000078369;t=ENST00000378609" 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_001282538,NM_001282539,NM_002074,XM_017001059,XM_017001060,XM_017001061,XM_024446495,XM_047418042,XM_047418043,XM_047418044,XM_047418045,XM_047418046,XM_047418049,XM_047418050,XM_047418054,XM_047418055,XM_047418056,XM_047418057,XM_047418058,XM_047418059,XM_047418060,XM_047418061,XM_047418062,XM_047418063,XM_047418067,XM_047418068,XM_047418069,XM_047418070,XM_047418071,XM_047418072,XM_047418073,XM_047418074,XM_047418076,XM_047418078" 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_002074" 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=139380" 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=00766&isoform_id=00766_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/GNB1" 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/31669,339937,3387975,3387984,11321585,13278843,13543458,14290452,20257498,30583449,48145685,51317302,91992949,119576551,119576552,119576553,119576554,189069163,193783832,332367586,543173167,543173169,1034557820,1034557822,1034557824,1341395370,1370452841,2104758969,2217266602,2217266605,2217266607,2217266609,2217266611,2217266613,2217266615,2217266617,2217266619,2217266621,2217266623,2217266625,2217266627,2217266629,2217266631,2217266633,2217266635,2217266639,2217266641,2217266643,2217266645,2217266647,2217266650,2217266652,2217266654,2217266656,2217266658,2462508046,2462508048,2462508050,2462508052,2462508054,2462508056,2462508058,2462508060,2462508062,2462508064,2462508066,2462508068,2462508070,2462508072,2462508074,2462508077,2462508079,2462508081,2462508083,2462508085,2462508087,2462508089,2462508091,2462508093,2462508095,2462508097,2462508099,2462508101,2462508103,2462508105,2462508107,2462508109" 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/P62873" 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=2782" 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=ENSG00000078369;t=ENST00000378609" 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=GNB1" 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=GNB1" 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+2782" 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/GNB1" 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:2782" 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/2782" 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=chr1&hgg_gene=ENST00000378609.9&hgg_start=1785286&hgg_end=1891087&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">
|
|
<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:4396" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:4396" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=139380[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=139380[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/GNB1/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/ENSG00000078369" 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=GNB1" 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=GNB1" 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=GNB1" 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=GNB1&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/PA28776" 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:4396" 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/FBgn0001105.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:95781" 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/GNB1#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:95781" 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/2782/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=2782" 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=WBGene00001679;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-030131-823" 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">
|
|
<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:2782" 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=GNB1&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>
|
|
139380
|
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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, BETA-1; GNB1
|
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</span>
|
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</h3>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="alternativeTitles" class="mim-anchor"></a>
|
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<div>
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<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
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</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TRANSDUCIN, BETA POLYPEPTIDE
|
|
</span>
|
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</h4>
|
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</div>
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GNB1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNB1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/1/58?start=-3&limit=10&highlight=58">1p36.33</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr1:1785286-1891087&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'})">1:1,785,286-1,891,087</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
|
</span>
|
|
</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=616973,613065,614286" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/1/58?start=-3&limit=10&highlight=58">
|
|
1p36.33
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, autosomal dominant 42
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616973"> 616973 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p>Heterotrimeric guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. Each subunit of the G protein complex is encoded by a member of 1 of 3 corresponding gene families, alpha, beta, and gamma (<a href="#5" class="mim-tip-reference" title="Hurowitz, E. H., Melnyk, J. M., Chen, Y.-J., Kouros-Mehr, H., Simon, M. I., Shizuya, H. <strong>Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes.</strong> DNA Res. 7: 111-120, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10819326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10819326</a>] [<a href="https://doi.org/10.1093/dnares/7.2.111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10819326">Hurowitz et al., 2000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10819326" 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>Retinal transducin is a guanine nucleotide regulatory protein that activates a cGMP phosphodiesterase in photoreceptor cells. <a href="#3" class="mim-tip-reference" title="Fong, H. K. W., Hurley, J. B., Hopkins, R. S., Miake-Lye, R., Johnson, M. S., Doolittle, R. F., Simon, M. I. <strong>Repetitive segmental structure of the transducin beta-subunit: homology with the CDC4 gene and identification of related mRNAs.</strong> Proc. Nat. Acad. Sci. 83: 2162-2166, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3083416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3083416</a>] [<a href="https://doi.org/10.1073/pnas.83.7.2162" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3083416">Fong et al. (1986)</a> identified and analyzed cDNA clones of the bovine transducin beta subunit and deduced the primary structure of a 340-amino acid protein. Significant homology was found with the yeast CDC4 gene product. The beta-subunit polypeptide, of relative molecular mass 37,375 Da, is encoded by a 2.9-kb mRNA. All mammalian tissues and clonal cell lines examined contained at least 2 beta-related mRNAs, usually 1.8 and 2.9 kb long. The authors suggested that there may be a diversity of beta subunit-related mRNAs that could encode different proteins. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3083416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Codina, J., Stengel, D., Woo, S. L. C., Birnbaumer, L. <strong>Beta-subunits of the human liver G(s)/G(i) signal-transducing proteins and those of bovine rod cell transducin are identical.</strong> FEBS Lett. 207: 187-192, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3095147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3095147</a>] [<a href="https://doi.org/10.1016/0014-5793(86)81486-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3095147">Codina et al. (1986)</a> cloned a full-length G protein beta-1 subunit (GNB1) from a human liver cDNA library. They found that the deduced 340-amino acid protein is identical to that encoded by bovine retinal rod cell cDNA of the beta subunit of transducin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3095147" 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 coprecipitation analysis, <a href="#13" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> showed that GNB1 formed dimers with all gamma subunits analyzed. The strength of the interaction was variable and was strongest between GNB1 and GNG3 (<a href="/entry/608941">608941</a>), GNG10 (<a href="/entry/604389">604389</a>), GNG12, and GNG13 (<a href="/entry/607298">607298</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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 immunoprecipitation, <a href="#10" class="mim-tip-reference" title="Murakami, T., Ruengsinpinya, L., Nakamura, E., Takahata, Y., Hata, K., Okae, H., Taniguchi, S., Takahashi, M., Nishimura, R. <strong>G protein subunit beta 1 negatively regulates NLRP3 inflammasome activation.</strong> J. Immun. 202: 1942-1947, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30777924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30777924</a>] [<a href="https://doi.org/10.4049/jimmunol.1801388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30777924">Murakami et al. (2019)</a> showed that Gnb1 interacted with the pyrin (608107) domain (PYD) of Nlrp3 (<a href="/entry/606416">606416</a>) following Nlrp3 activation in mouse bone marrow-derived macrophages. Through its interaction with Nlrp3, Gnb1 negatively regulated Nlrp3 inflammasome activation by suppressing Asc (PYCARD; <a href="/entry/606838">606838</a>) oligomerization induced by Nlrp3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30777924" 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="#13" class="mim-tip-reference" title="Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W. <strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong> FEBS Lett. 544: 27-32, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>] [<a href="https://doi.org/10.1016/s0014-5793(03)00441-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12782285">Rosskopf et al. (2003)</a> determined that the GNB1 gene has 12 exons. The first 2 exons and the last exon are noncoding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a cDNA probe against a mouse/human somatic cell hybrid panel, <a href="#14" class="mim-tip-reference" title="Sparkes, R. S., Cohn, V. H., Mohandas, T., Zollman, S., Cire-Eversole, P., Amatruda, T. T., Reed, R. R., Lochrie, M. A., Simon, M. I. <strong>Mapping of genes encoding the subunits of guanine nucleotide-binding protein (G-proteins) in humans. (Abstract)</strong> Cytogenet. Cell Genet. 46: 696 only, 1987."None>Sparkes et al. (1987)</a> mapped the human beta-1 polypeptide of G protein to human chromosome 1. <a href="#7" class="mim-tip-reference" title="Levine, M. A., Modi, W. S., O'Brien, S. J. <strong>Chromosomal localization of the genes encoding two forms of the G-protein beta polypeptide, beta-1 and beta-3, in man.</strong> Genomics 8: 380-386, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979057</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90296-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1979057">Levine et al. (1990)</a> confirmed the assignment to chromosome 1 by Southern analysis of somatic cell hybrids, and <a href="#7" class="mim-tip-reference" title="Levine, M. A., Modi, W. S., O'Brien, S. J. <strong>Chromosomal localization of the genes encoding two forms of the G-protein beta polypeptide, beta-1 and beta-3, in man.</strong> Genomics 8: 380-386, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979057</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90296-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1979057">Levine et al. (1990)</a> and <a href="#9" class="mim-tip-reference" title="Modi, W. S., O'Brien, S. J., Levine, M. A. <strong>Chromosomal assignment of 2 GTP binding protein subunit genes: the alpha subunit of adenylyl cyclase (GNAS) and the beta 1 polypeptide (GNB). (Abstract)</strong> Cytogenet. Cell Genet. 58: 1860 only, 1991."None>Modi et al. (1991)</a> regionalized the assignment to 1pter-p31.2 by in situ hybridization. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1979057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Danciger, M., Farber, D. B., Peyser, M., Kozak, C. A. <strong>The gene for the beta-subunit of retinal transducin (Gnb-1) maps to distal mouse chromosome 4, and related sequences map to mouse chromosomes 5 and 8.</strong> Genomics 6: 428-435, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2328987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2328987</a>] [<a href="https://doi.org/10.1016/0888-7543(90)90472-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2328987">Danciger et al. (1990)</a> mapped the mouse Gnb1 to distal chromosome 4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2328987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><strong><em>Intellectual Developmental Disorder 42, Autosomal Dominant</em></strong></p><p>
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In 13 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified 9 different de novo heterozygous missense mutations in the GNB1 gene (see, e.g., <a href="#0001">139380.0001</a>-<a href="#0005">139380.0005</a>). The mutations were identified by exome sequencing and confirmed by Sanger sequencing. The patients were ascertained from a cohort of 5,855 individuals with a presumed genetic disorder of unknown cause. Functional studies and studies of patient cells were not performed by <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a>. However, <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> noted that <a href="#16" class="mim-tip-reference" title="Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others. <strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong> Nature Med. 21: 71-75, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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/nm.3751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25485910">Yoda et al. (2015)</a> had identified somatic mutations in the GNB1 gene that were associated with hematologic transformation. Functional studies of 3 of the mutations (D76G, <a href="#0001">139380.0001</a>; I80T, <a href="#0002">139380.0002</a>; I80N, <a href="#0003">139380.0003</a>) that were also identified as germline mutations in the patients reported by <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> had reduced binding to almost all G-alpha subunits and/or conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. The mutations resulted in activation of the PI3K-AKT-mTOR and MAPK pathways, consistent with a gain of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27108799+25485910" 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 16 patients with MRD42, <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified 14 mutations in the GNB1 gene, including 2 frameshift (<a href="#0007">139380.0007</a> and <a href="#0008">139380.0008</a>), 2 splicing (<a href="#0006">139380.0006</a> and <a href="#0009">139380.0009</a>), and 10 missense (see, e.g., <a href="#0010">139380.0010</a>). The mutations were identified by whole-exome sequencing; 1 mutation was inherited from a parent, 10 were de novo, and the inheritance of 3 mutations could not be determined due to lack of parental samples. Using a cell-based bioluminescence resonance energy transfer (BRET) assay, <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> demonstrated that 7 of the missense mutations resulted in deficits in receptor-driven G protein activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others. <strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong> Am. J. Med. Genet. 176A: 2259-2275, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30194818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30194818</a>] [<a href="https://doi.org/10.1002/ajmg.a.40472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30194818">Hemati et al. (2018)</a> reported 18 patients with MRD42 and de novo heterozygous mutations in the GNB1 gene. Twelve patients had heterozygosity for previously identified mutations, including 8 patients with I80T (<a href="#0002">139380.0002</a>). One of the mutations (C114Y; <a href="#0011">139380.0011</a>) was identified in a somatic mosaic state. All of the mutations were found by trio whole-exome sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30194818" 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 4-year-old girl with MRD42, <a href="#15" class="mim-tip-reference" title="Szczaluba, K., Biernacka, A., Szymanska, K., Gasperowicz, P., Kosinska, J., Rydzanicz, M., Ploski, R. <strong>Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: clinical report and literature review.</strong> Europ. J. Med. Genet. 61: 157-160, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29174093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29174093</a>] [<a href="https://doi.org/10.1016/j.ejmg.2017.11.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29174093">Szczaluba et al. (2018)</a> identified a de novo heterozygous missense mutation (G77V; <a href="#0012">139380.0012</a>) in the GNB1 gene. The mutation was found by trio whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29174093" 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 in Cancer</em></strong></p><p>
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<a href="#16" class="mim-tip-reference" title="Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others. <strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong> Nature Med. 21: 71-75, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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/nm.3751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25485910">Yoda et al. (2015)</a> identified heterozygous somatic mutations in the GNB1 gene (see, e.g., D76G, <a href="#0001">139380.0001</a>; I80T, <a href="#0002">139380.0002</a>; I80N, <a href="#0003">139380.0003</a>) and GNB2 (<a href="/entry/139390">139390</a>) genes in tumor tissue derived from patients with various malignancies, both solid tumors and hematologic malignancies, including acute lymphoblastic leukemia (ALL; <a href="/entry/613065">613065</a>), myelodysplastic syndrome (MDS; <a href="/entry/614286">614286</a>), and chronic lymphocytic leukemia (CLL; <a href="/entry/151400">151400</a>). In vitro and in vivo functional studies showed that all of the mutations resulted in cytokine-independent growth and activation of canonical G protein signaling. Recurrent mutations affecting residues K57, K78, I80, K89, and M101 were located on the G-beta protein surface that interacts with G-alpha subunits and downstream effectors. In vitro studies showed that most mutant proteins had reduced binding to G-alpha subunits with subsequent activation of the PI3K-AKT-mTOR and MAPK signaling pathways. Eleven mutations that affected residue K57 were found in myeloid neoplasms, whereas 7 of 8 mutations affecting residue I80 were found in B-cell neoplasms. Transfection of several of the mutations into murine bone marrow resulted in the development of hematologic neoplasms, and pharmacologic inhibition of the PI3K-mTOR signaling pathway resulted in increased survival. However, in some tumors, GNB1 mutations co-occurred with oncogenic kinase alterations, such as changes in JAK2 (<a href="/entry/147796">147796</a>) or BRAF (<a href="/entry/164757">164757</a>), which conferred inhibitor resistance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25485910" 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 Rd4/+ mouse, autosomal dominant retinal degeneration cosegregates with a large inversion spanning nearly all of chromosome 4 (<a href="#12" class="mim-tip-reference" title="Roderick, T. H., Chang, B., Hawes, N. L., Heckenlively, J. R. <strong>A new dominant retinal degeneration (Rd4) associated with a chromosomal inversion in the mouse.</strong> Genomics 42: 393-396, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9205110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9205110</a>] [<a href="https://doi.org/10.1006/geno.1997.4717" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9205110">Roderick et al., 1997</a>). To identify the responsible gene for this phenotype, <a href="#6" class="mim-tip-reference" title="Kitamura, E., Danciger, M., Yamashita, C., Rao, N. P., Nusinowitz, S., Chang, B., Farber, D. B. <strong>Disruption of the gene encoding the beta-1-subunit of transducin in the Rd4/+ mouse.</strong> Invest. Ophthal. Vis. Sci. 47: 1293-1301, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16565360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16565360</a>] [<a href="https://doi.org/10.1167/iovs.05-1164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16565360">Kitamura et al. (2006)</a> focused on the distal breakpoint and found that it lay in the second intron of the Gnb1 gene, coding for the transducin-beta-1 protein, which is directly involved in phototransduction and in the normal maintenance of photoreceptors. <a href="#6" class="mim-tip-reference" title="Kitamura, E., Danciger, M., Yamashita, C., Rao, N. P., Nusinowitz, S., Chang, B., Farber, D. B. <strong>Disruption of the gene encoding the beta-1-subunit of transducin in the Rd4/+ mouse.</strong> Invest. Ophthal. Vis. Sci. 47: 1293-1301, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16565360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16565360</a>] [<a href="https://doi.org/10.1167/iovs.05-1164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16565360">Kitamura et al. (2006)</a> determined that before the beginning of retinal degeneration in the Rd4/+ retina, the levels of Gnb1 mRNA and transducin-beta-1 were 50% of those in wildtype retina. <a href="#6" class="mim-tip-reference" title="Kitamura, E., Danciger, M., Yamashita, C., Rao, N. P., Nusinowitz, S., Chang, B., Farber, D. B. <strong>Disruption of the gene encoding the beta-1-subunit of transducin in the Rd4/+ mouse.</strong> Invest. Ophthal. Vis. Sci. 47: 1293-1301, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16565360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16565360</a>] [<a href="https://doi.org/10.1167/iovs.05-1164" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16565360">Kitamura et al. (2006)</a> suggested that disruption of the Gnb1 gene is responsible for Rd4/+ retinal disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9205110+16565360" 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 an 8.5-year-old boy of Ashkenazi Jewish descent with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified a de novo heterozygous c.227A-G transition (c.227A-G, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an asp76-to-gly (D76G) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC databases (January 2015), or in 4,326 control individuals. Functional studies of the variant and studies of patient cells were not performed. <a href="#16" class="mim-tip-reference" title="Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others. <strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong> Nature Med. 21: 71-75, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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/nm.3751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25485910">Yoda et al. (2015)</a> had identified a somatic D76G mutation in association with acute lymphoblastic T-cell leukemia (ALL; <a href="/entry/613065">613065</a>). D76G conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27108799+25485910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</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> rs752746786 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs752746786;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/rs752746786?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=rs752746786" 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=rs752746786" 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=RCV000190738 OR RCV000208571 OR RCV000210259 OR RCV000225179 OR RCV000225295 OR RCV000418135 OR RCV000755055 OR RCV001007652 OR RCV001195548 OR RCV001255414 OR RCV001264641 OR RCV001544504 OR RCV001795309 OR RCV002273978 OR RCV004767128" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190738, RCV000208571, RCV000210259, RCV000225179, RCV000225295, RCV000418135, RCV000755055, RCV001007652, RCV001195548, RCV001255414, RCV001264641, RCV001544504, RCV001795309, RCV002273978, RCV004767128" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190738...</a>
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<p>In 3 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified a de novo heterozygous c.239T-C transition (c.239T-C, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an ile80-to-thr (I80T) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was filtered against the Exome Sequencing Project (March 2013) and ExAC (January 2015) databases. The substitution occurs along the GNB1 protein surface that interacts with G-alpha subunits and downstream effectors. <a href="#16" class="mim-tip-reference" title="Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others. <strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong> Nature Med. 21: 71-75, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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/nm.3751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25485910">Yoda et al. (2015)</a> had identified somatic I80T variants in association with hematologic transformation, including myelodysplastic syndrome (MDS; <a href="/entry/614286">614286</a>) and chronic lymphocytic leukemia (CLL; <a href="/entry/151400">151400</a>). I80T was demonstrated to have reduced binding to almost all G-alpha subunits, which conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> noted that I80T has been reported in the ExAC browser as a low-confidence variant, but suggested that it may be a technical artifact or a postzygotic mutation. Functional studies of the variant and studies of patient cells were not performed by <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a>. See <a href="#0003">139380.0003</a> for another mutation affecting this residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27108799+25485910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others. <strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong> Am. J. Med. Genet. 176A: 2259-2275, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30194818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30194818</a>] [<a href="https://doi.org/10.1002/ajmg.a.40472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30194818">Hemati et al. (2018)</a> identified de novo heterozygosity for the I80T mutation in the GNB1 gene in 8 patients with MRD42. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30194818" 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> rs752746786 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs752746786;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/rs752746786?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=rs752746786" 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=rs752746786" 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=RCV000210280 OR RCV000225195 OR RCV000225283 OR RCV000755054 OR RCV001540042" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000210280, RCV000225195, RCV000225283, RCV000755054, RCV001540042" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000210280...</a>
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<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified a de novo heterozygous c.239T-A transversion (c.239T-A, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an ile80-to-asn (I80N) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC (January 2015) databases, or in 4,326 control individuals. The substitution occurs along the GNB1 protein surface that interacts with G-alpha subunits and downstream effectors. <a href="#16" class="mim-tip-reference" title="Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others. <strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong> Nature Med. 21: 71-75, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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/nm.3751" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25485910">Yoda et al. (2015)</a> had identified somatic I80N variants in association with hematologic transformation, including acute lymphoblastic leukemia (ALL; <a href="/entry/613065">613065</a>). I80N was demonstrated to have reduced binding to almost all G-alpha subunits, which conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. Functional studies of the variant and studies of patient cells were not performed by <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a>. See <a href="#0002">139380.0002</a> for another mutation affecting this residue. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=27108799+25485910" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a 13-month-old boy with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified a de novo heterozygous c.233A-G transition (c.233A-G, NM_002074.4) in exon 6 of the GNB1 gene, resulting in a lys78-to-arg (K78R) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC (January 2015) databases, or in 4,326 control individuals. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27108799" 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">rs869312825 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs869312825;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=rs869312825" 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=rs869312825" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#11" class="mim-tip-reference" title="Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others. <strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong> Am. J. Hum. Genet. 98: 1001-1010, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>] [<a href="https://doi.org/10.1016/j.ajhg.2016.03.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27108799">Petrovski et al. (2016)</a> identified a de novo heterozygous c.301A-G transition (c.301A-G, NM_002074.4) in exon 7 of the GNB1 gene, resulting in a met101-to-val (M101V) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were filtered against the dbSNP, Exome Sequencing Project (March 2013), ExAC (January 2015), and 1000 Genome Project databases. Functional studies of the variant and studies of patient cells were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27108799" 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">rs2100699964 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2100699964;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=rs2100699964" 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=rs2100699964" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 2-year-old Saudi Arabian boy with autosomal dominant intellectual development disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified a de novo heterozygous c.268-1G-T transversion (c.268-1G-T, NM_002074) in intron 6 of the GNB1 gene, predicted to cause a splicing abnormality. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" 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">rs2100699881 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2100699881;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=rs2100699881" 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=rs2100699881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 5-year-old Israeli boy with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified a de novo heterozygous 4-bp deletion (c.272_275del, NM_002074) in exon 7 of the GNB1 gene, predicted to cause a frameshift. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" 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 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</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">rs2100479399 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2100479399;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=rs2100479399" 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=rs2100479399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an 8-year-old Saudi Arabian patient with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified a de novo heterozygous 2-bp deletion (c.915_916del, NM_002074) in exon 10 of the GNB1 gene, predicted to cause a frameshift. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" 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>.0009 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV001774823" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001774823" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001774823</a>
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<p>In a 6-year-old Indian girl with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified a de novo heterozygous c.917-1G-T transversion (c.917-1G-T, NM_002074) in intron 10 of the GNB1 gene, predicted to cause a splicing abnormality. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" 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>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
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<p>In 3 probands of Israeli, Indian, and Mexican ethnicity with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#8" class="mim-tip-reference" title="Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A. <strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong> Hum. Molec. Genet. 26: 1078-1086, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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/10.1093/hmg/ddx018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28087732">Lohmann et al. (2017)</a> identified de novo heterozygosity for the same c.287G-T transversion (c.287G-T, NM_002074) in the GNB1 gene, resulting in an arg96-to-leu (R96L) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28087732" 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>.0011 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</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">rs1313820360 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1313820360;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=rs1313820360" 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=rs1313820360" 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=RCV001774824" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001774824" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001774824</a>
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<p>In a 7-year-old Hispanic girl (patient 3) with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#4" class="mim-tip-reference" title="Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others. <strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong> Am. J. Med. Genet. 176A: 2259-2275, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30194818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30194818</a>] [<a href="https://doi.org/10.1002/ajmg.a.40472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30194818">Hemati et al. (2018)</a> identified mosaicism for a c.341G-A transition (c.341G-A, NM_002074.4) in the GNB1 gene, resulting in a cys114-to-tyr (C114Y) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was identified in the patient in 29 of 163 reads, representing an 18% allelic fraction. Functional studies were not performed. The patient had a relatively milder phenotype compared to other patients with MRD42, which <a href="#4" class="mim-tip-reference" title="Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others. <strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong> Am. J. Med. Genet. 176A: 2259-2275, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30194818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30194818</a>] [<a href="https://doi.org/10.1002/ajmg.a.40472" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30194818">Hemati et al. (2018)</a> attributed to the mosaic state of the C114Y mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30194818" 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>.0012 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</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">rs1135401746 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1135401746;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=rs1135401746" 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=rs1135401746" 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=RCV001774825 OR RCV003728005" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001774825, RCV003728005" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001774825...</a>
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<p>In a 4-year-old patient with autosomal dominant intellectual developmental disorder-42 (MRD42; <a href="/entry/616973">616973</a>), <a href="#15" class="mim-tip-reference" title="Szczaluba, K., Biernacka, A., Szymanska, K., Gasperowicz, P., Kosinska, J., Rydzanicz, M., Ploski, R. <strong>Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: clinical report and literature review.</strong> Europ. J. Med. Genet. 61: 157-160, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29174093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29174093</a>] [<a href="https://doi.org/10.1016/j.ejmg.2017.11.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29174093">Szczaluba et al. (2018)</a> identified heterozygosity for a c.230G-T transversion (c.230G-T, NM_001282539.1) in exon 6 of the GNB1 gene, resulting in a gly77-to-val (G77V) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not identified in her parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29174093" 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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Codina, J., Stengel, D., Woo, S. L. C., Birnbaumer, L.
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<strong>Beta-subunits of the human liver G(s)/G(i) signal-transducing proteins and those of bovine rod cell transducin are identical.</strong>
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FEBS Lett. 207: 187-192, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3095147/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3095147</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3095147" 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/10.1016/0014-5793(86)81486-7" target="_blank">Full Text</a>]
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Danciger, M., Farber, D. B., Peyser, M., Kozak, C. A.
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<strong>The gene for the beta-subunit of retinal transducin (Gnb-1) maps to distal mouse chromosome 4, and related sequences map to mouse chromosomes 5 and 8.</strong>
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Genomics 6: 428-435, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2328987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2328987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2328987" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90472-7" target="_blank">Full Text</a>]
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Fong, H. K. W., Hurley, J. B., Hopkins, R. S., Miake-Lye, R., Johnson, M. S., Doolittle, R. F., Simon, M. I.
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<strong>Repetitive segmental structure of the transducin beta-subunit: homology with the CDC4 gene and identification of related mRNAs.</strong>
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Proc. Nat. Acad. Sci. 83: 2162-2166, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3083416/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3083416</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3083416" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others.
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<strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong>
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Am. J. Med. Genet. 176A: 2259-2275, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30194818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30194818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30194818" 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/ajmg.a.40472" target="_blank">Full Text</a>]
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Hurowitz, E. H., Melnyk, J. M., Chen, Y.-J., Kouros-Mehr, H., Simon, M. I., Shizuya, H.
|
|
<strong>Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes.</strong>
|
|
DNA Res. 7: 111-120, 2000.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10819326/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10819326</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10819326" 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/dnares/7.2.111" target="_blank">Full Text</a>]
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<a id="Kitamura2006" class="mim-anchor"></a>
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|
|
Kitamura, E., Danciger, M., Yamashita, C., Rao, N. P., Nusinowitz, S., Chang, B., Farber, D. B.
|
|
<strong>Disruption of the gene encoding the beta-1-subunit of transducin in the Rd4/+ mouse.</strong>
|
|
Invest. Ophthal. Vis. Sci. 47: 1293-1301, 2006.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16565360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16565360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16565360" 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/10.1167/iovs.05-1164" target="_blank">Full Text</a>]
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|
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<a id="7" class="mim-anchor"></a>
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<a id="Levine1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Levine, M. A., Modi, W. S., O'Brien, S. J.
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<strong>Chromosomal localization of the genes encoding two forms of the G-protein beta polypeptide, beta-1 and beta-3, in man.</strong>
|
|
Genomics 8: 380-386, 1990.
|
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1979057/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1979057</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1979057" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0888-7543(90)90296-7" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
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<a id="Lohmann2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A.
|
|
<strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong>
|
|
Hum. Molec. Genet. 26: 1078-1086, 2017.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28087732/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28087732</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28087732[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=28087732" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddx018" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Modi1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Modi, W. S., O'Brien, S. J., Levine, M. A.
|
|
<strong>Chromosomal assignment of 2 GTP binding protein subunit genes: the alpha subunit of adenylyl cyclase (GNAS) and the beta 1 polypeptide (GNB). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 58: 1860 only, 1991.
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<a id="Murakami2019" class="mim-anchor"></a>
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|
Murakami, T., Ruengsinpinya, L., Nakamura, E., Takahata, Y., Hata, K., Okae, H., Taniguchi, S., Takahashi, M., Nishimura, R.
|
|
<strong>G protein subunit beta 1 negatively regulates NLRP3 inflammasome activation.</strong>
|
|
J. Immun. 202: 1942-1947, 2019.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30777924/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30777924</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30777924" 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/10.4049/jimmunol.1801388" target="_blank">Full Text</a>]
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<a id="Petrovski2016" class="mim-anchor"></a>
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Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others.
|
|
<strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong>
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|
Am. J. Hum. Genet. 98: 1001-1010, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27108799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27108799</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27108799" 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.2016.03.011" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
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<a id="Roderick1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Roderick, T. H., Chang, B., Hawes, N. L., Heckenlively, J. R.
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<strong>A new dominant retinal degeneration (Rd4) associated with a chromosomal inversion in the mouse.</strong>
|
|
Genomics 42: 393-396, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9205110/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9205110</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9205110" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1997.4717" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Rosskopf2003" class="mim-anchor"></a>
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Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W.
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<strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong>
|
|
FEBS Lett. 544: 27-32, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12782285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12782285</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12782285" 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/s0014-5793(03)00441-1" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Sparkes1987" class="mim-anchor"></a>
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Sparkes, R. S., Cohn, V. H., Mohandas, T., Zollman, S., Cire-Eversole, P., Amatruda, T. T., Reed, R. R., Lochrie, M. A., Simon, M. I.
|
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<strong>Mapping of genes encoding the subunits of guanine nucleotide-binding protein (G-proteins) in humans. (Abstract)</strong>
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Cytogenet. Cell Genet. 46: 696 only, 1987.
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<a id="Szczaluba2018" class="mim-anchor"></a>
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Szczaluba, K., Biernacka, A., Szymanska, K., Gasperowicz, P., Kosinska, J., Rydzanicz, M., Ploski, R.
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<strong>Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: clinical report and literature review.</strong>
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Europ. J. Med. Genet. 61: 157-160, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29174093/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29174093</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29174093" 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.ejmg.2017.11.010" target="_blank">Full Text</a>]
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<a id="Yoda2015" class="mim-anchor"></a>
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Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others.
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<strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong>
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Nature Med. 21: 71-75, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25485910/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25485910</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25485910[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=25485910" 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/nm.3751" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 03/10/2020
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Cassandra L. Kniffin - updated : 6/14/2016<br>Jane Kelly - updated : 10/31/2007<br>Carol A. Bocchini - updated : 10/31/2007<br>Patricia A. Hartz - updated : 3/14/2007<br>Victor A. McKusick - updated : 6/7/2000<br>Carol A. Bocchini - updated : 12/1/1999
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 9/22/1987
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carol : 11/03/2021
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carol : 11/02/2021<br>carol : 11/02/2021<br>carol : 12/14/2020<br>mgross : 03/10/2020<br>carol : 08/08/2016<br>carol : 06/17/2016<br>ckniffin : 6/14/2016<br>carol : 6/25/2012<br>carol : 10/31/2007<br>carol : 10/31/2007<br>wwang : 3/20/2007<br>terry : 3/14/2007<br>mcapotos : 6/28/2000<br>mcapotos : 6/23/2000<br>terry : 6/7/2000<br>terry : 12/1/1999<br>carol : 12/1/1999<br>alopez : 5/12/1998<br>supermim : 3/16/1992<br>carol : 2/22/1992<br>carol : 8/8/1991<br>carol : 8/7/1991<br>carol : 10/10/1990<br>carol : 7/7/1990
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<strong>*</strong> 139380
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<h3>
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GUANINE NUCLEOTIDE-BINDING PROTEIN, BETA-1; GNB1
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TRANSDUCIN, BETA POLYPEPTIDE
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<strong><em>HGNC Approved Gene Symbol: GNB1</em></strong>
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Cytogenetic location: 1p36.33
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : 1:1,785,286-1,891,087 </span>
|
|
</em>
|
|
</strong>
|
|
<span class="small">(from NCBI)</span>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="3">
|
|
<span class="mim-font">
|
|
1p36.33
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Intellectual developmental disorder, autosomal dominant 42
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
616973
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Autosomal dominant
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Leukemia, acute lymphoblastic, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
613065
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Myelodysplastic syndrome, somatic
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
614286
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</h4>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Heterotrimeric guanine nucleotide-binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. Each subunit of the G protein complex is encoded by a member of 1 of 3 corresponding gene families, alpha, beta, and gamma (Hurowitz et al., 2000). </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Retinal transducin is a guanine nucleotide regulatory protein that activates a cGMP phosphodiesterase in photoreceptor cells. Fong et al. (1986) identified and analyzed cDNA clones of the bovine transducin beta subunit and deduced the primary structure of a 340-amino acid protein. Significant homology was found with the yeast CDC4 gene product. The beta-subunit polypeptide, of relative molecular mass 37,375 Da, is encoded by a 2.9-kb mRNA. All mammalian tissues and clonal cell lines examined contained at least 2 beta-related mRNAs, usually 1.8 and 2.9 kb long. The authors suggested that there may be a diversity of beta subunit-related mRNAs that could encode different proteins. </p><p>Codina et al. (1986) cloned a full-length G protein beta-1 subunit (GNB1) from a human liver cDNA library. They found that the deduced 340-amino acid protein is identical to that encoded by bovine retinal rod cell cDNA of the beta subunit of transducin. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Function</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using coprecipitation analysis, Rosskopf et al. (2003) showed that GNB1 formed dimers with all gamma subunits analyzed. The strength of the interaction was variable and was strongest between GNB1 and GNG3 (608941), GNG10 (604389), GNG12, and GNG13 (607298). </p><p>Using immunoprecipitation, Murakami et al. (2019) showed that Gnb1 interacted with the pyrin (608107) domain (PYD) of Nlrp3 (606416) following Nlrp3 activation in mouse bone marrow-derived macrophages. Through its interaction with Nlrp3, Gnb1 negatively regulated Nlrp3 inflammasome activation by suppressing Asc (PYCARD; 606838) oligomerization induced by Nlrp3. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Rosskopf et al. (2003) determined that the GNB1 gene has 12 exons. The first 2 exons and the last exon are noncoding. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Mapping</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Using a cDNA probe against a mouse/human somatic cell hybrid panel, Sparkes et al. (1987) mapped the human beta-1 polypeptide of G protein to human chromosome 1. Levine et al. (1990) confirmed the assignment to chromosome 1 by Southern analysis of somatic cell hybrids, and Levine et al. (1990) and Modi et al. (1991) regionalized the assignment to 1pter-p31.2 by in situ hybridization. </p><p>Danciger et al. (1990) mapped the mouse Gnb1 to distal chromosome 4. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p><strong><em>Intellectual Developmental Disorder 42, Autosomal Dominant</em></strong></p><p>
|
|
In 13 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified 9 different de novo heterozygous missense mutations in the GNB1 gene (see, e.g., 139380.0001-139380.0005). The mutations were identified by exome sequencing and confirmed by Sanger sequencing. The patients were ascertained from a cohort of 5,855 individuals with a presumed genetic disorder of unknown cause. Functional studies and studies of patient cells were not performed by Petrovski et al. (2016). However, Petrovski et al. (2016) noted that Yoda et al. (2015) had identified somatic mutations in the GNB1 gene that were associated with hematologic transformation. Functional studies of 3 of the mutations (D76G, 139380.0001; I80T, 139380.0002; I80N, 139380.0003) that were also identified as germline mutations in the patients reported by Petrovski et al. (2016) had reduced binding to almost all G-alpha subunits and/or conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. The mutations resulted in activation of the PI3K-AKT-mTOR and MAPK pathways, consistent with a gain of function. </p><p>In 16 patients with MRD42, Lohmann et al. (2017) identified 14 mutations in the GNB1 gene, including 2 frameshift (139380.0007 and 139380.0008), 2 splicing (139380.0006 and 139380.0009), and 10 missense (see, e.g., 139380.0010). The mutations were identified by whole-exome sequencing; 1 mutation was inherited from a parent, 10 were de novo, and the inheritance of 3 mutations could not be determined due to lack of parental samples. Using a cell-based bioluminescence resonance energy transfer (BRET) assay, Lohmann et al. (2017) demonstrated that 7 of the missense mutations resulted in deficits in receptor-driven G protein activation. </p><p>Hemati et al. (2018) reported 18 patients with MRD42 and de novo heterozygous mutations in the GNB1 gene. Twelve patients had heterozygosity for previously identified mutations, including 8 patients with I80T (139380.0002). One of the mutations (C114Y; 139380.0011) was identified in a somatic mosaic state. All of the mutations were found by trio whole-exome sequencing. </p><p>In a 4-year-old girl with MRD42, Szczaluba et al. (2018) identified a de novo heterozygous missense mutation (G77V; 139380.0012) in the GNB1 gene. The mutation was found by trio whole-exome sequencing and confirmed by Sanger sequencing. </p><p><strong><em>Somatic Mutations in Cancer</em></strong></p><p>
|
|
Yoda et al. (2015) identified heterozygous somatic mutations in the GNB1 gene (see, e.g., D76G, 139380.0001; I80T, 139380.0002; I80N, 139380.0003) and GNB2 (139390) genes in tumor tissue derived from patients with various malignancies, both solid tumors and hematologic malignancies, including acute lymphoblastic leukemia (ALL; 613065), myelodysplastic syndrome (MDS; 614286), and chronic lymphocytic leukemia (CLL; 151400). In vitro and in vivo functional studies showed that all of the mutations resulted in cytokine-independent growth and activation of canonical G protein signaling. Recurrent mutations affecting residues K57, K78, I80, K89, and M101 were located on the G-beta protein surface that interacts with G-alpha subunits and downstream effectors. In vitro studies showed that most mutant proteins had reduced binding to G-alpha subunits with subsequent activation of the PI3K-AKT-mTOR and MAPK signaling pathways. Eleven mutations that affected residue K57 were found in myeloid neoplasms, whereas 7 of 8 mutations affecting residue I80 were found in B-cell neoplasms. Transfection of several of the mutations into murine bone marrow resulted in the development of hematologic neoplasms, and pharmacologic inhibition of the PI3K-mTOR signaling pathway resulted in increased survival. However, in some tumors, GNB1 mutations co-occurred with oncogenic kinase alterations, such as changes in JAK2 (147796) or BRAF (164757), which conferred inhibitor resistance. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Animal Model</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In the Rd4/+ mouse, autosomal dominant retinal degeneration cosegregates with a large inversion spanning nearly all of chromosome 4 (Roderick et al., 1997). To identify the responsible gene for this phenotype, Kitamura et al. (2006) focused on the distal breakpoint and found that it lay in the second intron of the Gnb1 gene, coding for the transducin-beta-1 protein, which is directly involved in phototransduction and in the normal maintenance of photoreceptors. Kitamura et al. (2006) determined that before the beginning of retinal degeneration in the Rd4/+ retina, the levels of Gnb1 mRNA and transducin-beta-1 were 50% of those in wildtype retina. Kitamura et al. (2006) suggested that disruption of the Gnb1 gene is responsible for Rd4/+ retinal disease. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>12 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
LEUKEMIA, ACUTE LYMPHOBLASTIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, ASP76GLY
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869312821,
|
|
|
|
|
|
|
|
ClinVar: RCV000210265, RCV000225254, RCV000225357, RCV000755052, RCV001556774
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8.5-year-old boy of Ashkenazi Jewish descent with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified a de novo heterozygous c.227A-G transition (c.227A-G, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an asp76-to-gly (D76G) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC databases (January 2015), or in 4,326 control individuals. Functional studies of the variant and studies of patient cells were not performed. Yoda et al. (2015) had identified a somatic D76G mutation in association with acute lymphoblastic T-cell leukemia (ALL; 613065). D76G conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
MYELODYSPLASTIC SYNDROME, SOMATIC, INCLUDED<br />
|
|
LEUKEMIA, CHRONIC LYMPHOCYTIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, ILE80THR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs752746786,
|
|
|
|
|
|
gnomAD: rs752746786,
|
|
|
|
|
|
ClinVar: RCV000190738, RCV000208571, RCV000210259, RCV000225179, RCV000225295, RCV000418135, RCV000755055, RCV001007652, RCV001195548, RCV001255414, RCV001264641, RCV001544504, RCV001795309, RCV002273978, RCV004767128
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified a de novo heterozygous c.239T-C transition (c.239T-C, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an ile80-to-thr (I80T) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was filtered against the Exome Sequencing Project (March 2013) and ExAC (January 2015) databases. The substitution occurs along the GNB1 protein surface that interacts with G-alpha subunits and downstream effectors. Yoda et al. (2015) had identified somatic I80T variants in association with hematologic transformation, including myelodysplastic syndrome (MDS; 614286) and chronic lymphocytic leukemia (CLL; 151400). I80T was demonstrated to have reduced binding to almost all G-alpha subunits, which conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. Petrovski et al. (2016) noted that I80T has been reported in the ExAC browser as a low-confidence variant, but suggested that it may be a technical artifact or a postzygotic mutation. Functional studies of the variant and studies of patient cells were not performed by Petrovski et al. (2016). See 139380.0003 for another mutation affecting this residue. </p><p>Hemati et al. (2018) identified de novo heterozygosity for the I80T mutation in the GNB1 gene in 8 patients with MRD42. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
LEUKEMIA, ACUTE LYMPHOBLASTIC, SOMATIC, INCLUDED
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, ILE80ASN
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs752746786,
|
|
|
|
|
|
gnomAD: rs752746786,
|
|
|
|
|
|
ClinVar: RCV000210280, RCV000225195, RCV000225283, RCV000755054, RCV001540042
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified a de novo heterozygous c.239T-A transversion (c.239T-A, NM_002074.4) in exon 6 of the GNB1 gene, resulting in an ile80-to-asn (I80N) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC (January 2015) databases, or in 4,326 control individuals. The substitution occurs along the GNB1 protein surface that interacts with G-alpha subunits and downstream effectors. Yoda et al. (2015) had identified somatic I80N variants in association with hematologic transformation, including acute lymphoblastic leukemia (ALL; 613065). I80N was demonstrated to have reduced binding to almost all G-alpha subunits, which conferred cytokine-independent growth and activation of canonical G protein downstream signaling through disruption of the G-alpha/G-beta/G-gamma interaction interface. Functional studies of the variant and studies of patient cells were not performed by Petrovski et al. (2016). See 139380.0002 for another mutation affecting this residue. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, LYS78ARG
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs869312823,
|
|
|
|
|
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|
|
ClinVar: RCV000210269, RCV000225134, RCV000523590, RCV000755053, RCV001249296, RCV001266591, RCV002287394
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 13-month-old boy with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified a de novo heterozygous c.233A-G transition (c.233A-G, NM_002074.4) in exon 6 of the GNB1 gene, resulting in a lys78-to-arg (K78R) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the Exome Sequencing Project (March 2013) or ExAC (January 2015) databases, or in 4,326 control individuals. Functional studies of the variant and studies of patient cells were not performed. </p>
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|
</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
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</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GNB1, MET101VAL
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<br />
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SNP: rs869312825,
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ClinVar: RCV000210283, RCV000225171, RCV000480671, RCV000755056
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 unrelated patients with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Petrovski et al. (2016) identified a de novo heterozygous c.301A-G transition (c.301A-G, NM_002074.4) in exon 7 of the GNB1 gene, resulting in a met101-to-val (M101V) substitution. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, were filtered against the dbSNP, Exome Sequencing Project (March 2013), ExAC (January 2015), and 1000 Genome Project databases. Functional studies of the variant and studies of patient cells were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GNB1, IVS6AS, G-T, -1
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<br />
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SNP: rs2100699964,
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ClinVar: RCV001774820
|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 2-year-old Saudi Arabian boy with autosomal dominant intellectual development disorder-42 (MRD42; 616973), Lohmann et al. (2017) identified a de novo heterozygous c.268-1G-T transversion (c.268-1G-T, NM_002074) in intron 6 of the GNB1 gene, predicted to cause a splicing abnormality. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. </p>
|
|
</span>
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|
</div>
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<div>
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<br />
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|
</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
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|
GNB1, 4-BP DEL, NT272
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<br />
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|
|
SNP: rs2100699881,
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|
|
ClinVar: RCV001774821
|
|
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|
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</span>
|
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</div>
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 5-year-old Israeli boy with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Lohmann et al. (2017) identified a de novo heterozygous 4-bp deletion (c.272_275del, NM_002074) in exon 7 of the GNB1 gene, predicted to cause a frameshift. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
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</div>
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</div>
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<div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
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<span class="mim-text-font">
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GNB1, 2-BP DEL, NT915
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|
<br />
|
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|
|
SNP: rs2100479399,
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|
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|
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|
|
ClinVar: RCV001774822
|
|
|
|
|
|
</span>
|
|
</div>
|
|
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|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an 8-year-old Saudi Arabian patient with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Lohmann et al. (2017) identified a de novo heterozygous 2-bp deletion (c.915_916del, NM_002074) in exon 10 of the GNB1 gene, predicted to cause a frameshift. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
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<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0009 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
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|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, IVS10AS, G-T, -1
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs2100451989,
|
|
|
|
|
|
|
|
ClinVar: RCV001774823
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 6-year-old Indian girl with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Lohmann et al. (2017) identified a de novo heterozygous c.917-1G-T transversion (c.917-1G-T, NM_002074) in intron 10 of the GNB1 gene, predicted to cause a splicing abnormality. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0010 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, ARG96LEU
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1646670990,
|
|
|
|
|
|
|
|
ClinVar: RCV001290215
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 3 probands of Israeli, Indian, and Mexican ethnicity with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Lohmann et al. (2017) identified de novo heterozygosity for the same c.287G-T transversion (c.287G-T, NM_002074) in the GNB1 gene, resulting in an arg96-to-leu (R96L) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not present in the ExAC database or in an in-house database of 4,361 exomes. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0011 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, CYS114TYR
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1313820360,
|
|
|
|
|
|
|
|
ClinVar: RCV001774824
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 7-year-old Hispanic girl (patient 3) with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Hemati et al. (2018) identified mosaicism for a c.341G-A transition (c.341G-A, NM_002074.4) in the GNB1 gene, resulting in a cys114-to-tyr (C114Y) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was identified in the patient in 29 of 163 reads, representing an 18% allelic fraction. Functional studies were not performed. The patient had a relatively milder phenotype compared to other patients with MRD42, which Hemati et al. (2018) attributed to the mosaic state of the C114Y mutation. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0012 INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 42</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
GNB1, GLY77VAL
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs1135401746,
|
|
|
|
|
|
|
|
ClinVar: RCV001774825, RCV003728005
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old patient with autosomal dominant intellectual developmental disorder-42 (MRD42; 616973), Szczaluba et al. (2018) identified heterozygosity for a c.230G-T transversion (c.230G-T, NM_001282539.1) in exon 6 of the GNB1 gene, resulting in a gly77-to-val (G77V) substitution. The mutation, which was found by trio whole-exome sequencing and confirmed by Sanger sequencing, was not identified in her parents. Functional studies were not performed. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
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|
|
<li>
|
|
<p class="mim-text-font">
|
|
Codina, J., Stengel, D., Woo, S. L. C., Birnbaumer, L.
|
|
<strong>Beta-subunits of the human liver G(s)/G(i) signal-transducing proteins and those of bovine rod cell transducin are identical.</strong>
|
|
FEBS Lett. 207: 187-192, 1986.
|
|
|
|
|
|
[PubMed: 3095147]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0014-5793(86)81486-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Danciger, M., Farber, D. B., Peyser, M., Kozak, C. A.
|
|
<strong>The gene for the beta-subunit of retinal transducin (Gnb-1) maps to distal mouse chromosome 4, and related sequences map to mouse chromosomes 5 and 8.</strong>
|
|
Genomics 6: 428-435, 1990.
|
|
|
|
|
|
[PubMed: 2328987]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90472-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fong, H. K. W., Hurley, J. B., Hopkins, R. S., Miake-Lye, R., Johnson, M. S., Doolittle, R. F., Simon, M. I.
|
|
<strong>Repetitive segmental structure of the transducin beta-subunit: homology with the CDC4 gene and identification of related mRNAs.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 2162-2166, 1986.
|
|
|
|
|
|
[PubMed: 3083416]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1073/pnas.83.7.2162]
|
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|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hemati, P., Revah-Politi, A., Bassan, H., Petrovski, S., Bilancia, C. G., Ramsey, K., Griffin, N. G., Bier, L., Cho, M. T., Rosello, M., Lynch, S. A., Colombo, S., and 42 others.
|
|
<strong>Refining the phenotype associated with GNB1 mutations: clinical data on 18 newly identified patients and review of the literature.</strong>
|
|
Am. J. Med. Genet. 176A: 2259-2275, 2018.
|
|
|
|
|
|
[PubMed: 30194818]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/ajmg.a.40472]
|
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|
|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hurowitz, E. H., Melnyk, J. M., Chen, Y.-J., Kouros-Mehr, H., Simon, M. I., Shizuya, H.
|
|
<strong>Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes.</strong>
|
|
DNA Res. 7: 111-120, 2000.
|
|
|
|
|
|
[PubMed: 10819326]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/dnares/7.2.111]
|
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|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Kitamura, E., Danciger, M., Yamashita, C., Rao, N. P., Nusinowitz, S., Chang, B., Farber, D. B.
|
|
<strong>Disruption of the gene encoding the beta-1-subunit of transducin in the Rd4/+ mouse.</strong>
|
|
Invest. Ophthal. Vis. Sci. 47: 1293-1301, 2006.
|
|
|
|
|
|
[PubMed: 16565360]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1167/iovs.05-1164]
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Levine, M. A., Modi, W. S., O'Brien, S. J.
|
|
<strong>Chromosomal localization of the genes encoding two forms of the G-protein beta polypeptide, beta-1 and beta-3, in man.</strong>
|
|
Genomics 8: 380-386, 1990.
|
|
|
|
|
|
[PubMed: 1979057]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0888-7543(90)90296-7]
|
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|
|
</p>
|
|
</li>
|
|
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|
<li>
|
|
<p class="mim-text-font">
|
|
Lohmann, K., Masuho, I., Patil, D. N., Baumann, H., Hebert, E., Steinrucke, S., Trujillano, D., Skamangas, N. K., Dobricic, V., Huning, I., Gillessen-Kaesbach, G., Westenberger, A., Savic-Pavicevic, D., Munchau, A., Oprea, G., Klein, C., Rolfs, A., Martemyanov, K. A.
|
|
<strong>Novel GNB1 mutations disrupt assembly and function of G protein heterotrimers and cause global developmental delay in humans.</strong>
|
|
Hum. Molec. Genet. 26: 1078-1086, 2017.
|
|
|
|
|
|
[PubMed: 28087732]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1093/hmg/ddx018]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Modi, W. S., O'Brien, S. J., Levine, M. A.
|
|
<strong>Chromosomal assignment of 2 GTP binding protein subunit genes: the alpha subunit of adenylyl cyclase (GNAS) and the beta 1 polypeptide (GNB). (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 58: 1860 only, 1991.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Murakami, T., Ruengsinpinya, L., Nakamura, E., Takahata, Y., Hata, K., Okae, H., Taniguchi, S., Takahashi, M., Nishimura, R.
|
|
<strong>G protein subunit beta 1 negatively regulates NLRP3 inflammasome activation.</strong>
|
|
J. Immun. 202: 1942-1947, 2019.
|
|
|
|
|
|
[PubMed: 30777924]
|
|
|
|
|
|
[Full Text: https://doi.org/10.4049/jimmunol.1801388]
|
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|
|
|
</p>
|
|
</li>
|
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|
<li>
|
|
<p class="mim-text-font">
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Petrovski, S., Kury, S., Myers, C. T., Anyane-Yeboa, K., Cogne, B., Bialer, M., Xia, F., Hemati, P., Riviello, J., Mehaffey, M., Besnard, T., Becraft, E., and 35 others.
|
|
<strong>Germline de novo mutations in GNB1 cause severe neurodevelopmental disability, hypotonia, and seizures.</strong>
|
|
Am. J. Hum. Genet. 98: 1001-1010, 2016.
|
|
|
|
|
|
[PubMed: 27108799]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ajhg.2016.03.011]
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|
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|
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Roderick, T. H., Chang, B., Hawes, N. L., Heckenlively, J. R.
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|
<strong>A new dominant retinal degeneration (Rd4) associated with a chromosomal inversion in the mouse.</strong>
|
|
Genomics 42: 393-396, 1997.
|
|
|
|
|
|
[PubMed: 9205110]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1006/geno.1997.4717]
|
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Rosskopf, D., Nikula, C., Manthey, I., Joisten, M., Frey, U., Kohnen, S., Siffert, W.
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<strong>The human G protein beta-4 subunit: gene structure, expression, G-gamma and effector interaction.</strong>
|
|
FEBS Lett. 544: 27-32, 2003.
|
|
|
|
|
|
[PubMed: 12782285]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0014-5793(03)00441-1]
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</li>
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Sparkes, R. S., Cohn, V. H., Mohandas, T., Zollman, S., Cire-Eversole, P., Amatruda, T. T., Reed, R. R., Lochrie, M. A., Simon, M. I.
|
|
<strong>Mapping of genes encoding the subunits of guanine nucleotide-binding protein (G-proteins) in humans. (Abstract)</strong>
|
|
Cytogenet. Cell Genet. 46: 696 only, 1987.
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</p>
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</li>
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<li>
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Szczaluba, K., Biernacka, A., Szymanska, K., Gasperowicz, P., Kosinska, J., Rydzanicz, M., Ploski, R.
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<strong>Novel GNB1 de novo mutation in a patient with neurodevelopmental disorder and cutaneous mastocytosis: clinical report and literature review.</strong>
|
|
Europ. J. Med. Genet. 61: 157-160, 2018.
|
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|
|
|
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[PubMed: 29174093]
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[Full Text: https://doi.org/10.1016/j.ejmg.2017.11.010]
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Yoda, A., Adelmant, G., Tamburini, J., Chapuy, B., Shindoh, N., Yoda, Y., Weigert, O., Kopp, N., Wu, S.-C., Kim, S. S., Liu, H., Tivey, T., and 17 others.
|
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<strong>Mutations in G protein beta subunits promote transformation and kinase inhibitor resistance.</strong>
|
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Nature Med. 21: 71-75, 2015.
|
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[PubMed: 25485910]
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[Full Text: https://doi.org/10.1038/nm.3751]
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Bao Lige - updated : 03/10/2020<br>Cassandra L. Kniffin - updated : 6/14/2016<br>Jane Kelly - updated : 10/31/2007<br>Carol A. Bocchini - updated : 10/31/2007<br>Patricia A. Hartz - updated : 3/14/2007<br>Victor A. McKusick - updated : 6/7/2000<br>Carol A. Bocchini - updated : 12/1/1999
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Victor A. McKusick : 9/22/1987
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