3351 lines
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- *139310 - GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-INHIBITING ACTIVITY POLYPEPTIDE 1; GNAI1
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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">*139310</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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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/139310">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</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=ENSG00000127955;t=ENST00000649796" 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=2770" 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=139310" 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=ENSG00000127955;t=ENST00000649796" 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_001256414,NM_002069" 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_002069" 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=139310" 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=00756&isoform_id=00756_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/GNAI1" 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/183191,386747,2897865,3005737,5650709,20072863,20147703,33946324,52000964,54696416,119597415,119597416,119597417,119597418,158259367,194385776,374081863,2104758941" 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/P63096" 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=2770" 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=ENSG00000127955;t=ENST00000649796" 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=GNAI1" 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=GNAI1" 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+2770" 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/GNAI1" 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:2770" 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/2770" 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=chr7&hgg_gene=ENST00000649796.2&hgg_start=80134831&hgg_end=80226181&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:4384" 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:4384" 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=139310[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=139310[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/GNAI1/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/ENSG00000127955" 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=GNAI1" 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=GNAI1" 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=GNAI1" 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=GNAI1&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/PA172" 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:4384" 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/FBgn0001104.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:95771" 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/GNAI1#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:95771" 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/2770/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=2770" 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="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001666;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001666 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001678;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001678 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-040426-1310" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:2770" 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=GNAI1&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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139310
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-INHIBITING ACTIVITY POLYPEPTIDE 1; GNAI1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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G PROTEIN, ALPHA-INHIBITING 1; Gi<br />
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INHIBITORY G PROTEIN<br />
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ADENYLATE CYCLASE INHIBITORY PROTEIN
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=GNAI1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GNAI1</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/7/372?start=-3&limit=10&highlight=372">7q21.11</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr7:80134831-80226181&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'})">7:80,134,831-80,226,181</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/7/372?start=-3&limit=10&highlight=372">
|
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7q21.11
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/619854"> 619854 </a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/139310" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/139310" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
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|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<p>Guanine nucleotide-binding proteins (G proteins) form a large family of signal-transducing molecules. They are found as heterotrimers made up of alpha, beta, and gamma subunits. Members of the G protein family have been characterized most extensively on the basis of the alpha subunit, which binds guanine nucleotide, is capable of hydrolyzing GTP, and interacts with specific receptor and effector molecules. The G protein family includes Gs (<a href="/entry/139320">139320</a>) and Gi, the stimulatory and inhibitory GTP-binding regulators of adenylate cyclase; Go, a protein abundant in brain (GNAO1; <a href="/entry/139311">139311</a>); and transducin-1 (GNAT1; <a href="/entry/139330">139330</a>) and transducin-2 (GNAT2; <a href="/entry/139340">139340</a>), proteins involved in phototransduction in retinal rods and cones, respectively (<a href="#11" class="mim-tip-reference" title="Sullivan, K. A., Liao, Y.-C., Alborzi, A., Beiderman, B., Chang, F.-H., Masters, S. B., Levinson, A. D., Bourne, H. R. <strong>Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains.</strong> Proc. Nat. Acad. Sci. 83: 6687-6691, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3092218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3092218</a>] [<a href="https://doi.org/10.1073/pnas.83.18.6687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3092218">Sullivan et al., 1986</a>; <a href="#3" class="mim-tip-reference" title="Bray, P., Carter, A., Guo, V., Puckett, C., Kamholz, J., Spiegel, A., Nirenberg, M. <strong>Human cDNA clones for an alpha subunit of G(i) signal-transduction protein.</strong> Proc. Nat. Acad. Sci. 84: 5115-5119, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3110783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3110783</a>] [<a href="https://doi.org/10.1073/pnas.84.15.5115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3110783">Bray et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3092218+3110783" 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="#10" class="mim-tip-reference" title="Suki, W. N., Abramowitz, J., Mattera, R., Codina, J., Birnbaumer, L. <strong>The human genome encodes at least three non-allelic G proteins with alpha-i-type subunits.</strong> FEBS Lett. 220: 187-192, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2440724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2440724</a>] [<a href="https://doi.org/10.1016/0014-5793(87)80900-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2440724">Suki et al. (1987)</a> concluded that the human genome contains at least 3 nonallelic genes for alpha-i-type subunits of G protein; see, e.g., GNAI2 (<a href="/entry/139360">139360</a>), GNAI3 (<a href="/entry/139370">139370</a>), and GNAIH (<a href="/entry/139180">139180</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2440724" 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="#11" class="mim-tip-reference" title="Sullivan, K. A., Liao, Y.-C., Alborzi, A., Beiderman, B., Chang, F.-H., Masters, S. B., Levinson, A. D., Bourne, H. R. <strong>Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains.</strong> Proc. Nat. Acad. Sci. 83: 6687-6691, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3092218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3092218</a>] [<a href="https://doi.org/10.1073/pnas.83.18.6687" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3092218">Sullivan et al. (1986)</a> used a cDNA encoding bovine alpha chain of transducin-1 to isolate and sequence murine cDNAs for alpha(s) and alpha(i). Homologies and differences among the deduced amino acid sequences of the G protein and transducin alpha chains pointed to specific regions that may interact with guanine nucleotides, receptors, effector enzymes, and the G protein beta-gamma complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3092218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bray, P., Carter, A., Guo, V., Puckett, C., Kamholz, J., Spiegel, A., Nirenberg, M. <strong>Human cDNA clones for an alpha subunit of G(i) signal-transduction protein.</strong> Proc. Nat. Acad. Sci. 84: 5115-5119, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3110783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3110783</a>] [<a href="https://doi.org/10.1073/pnas.84.15.5115" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3110783">Bray et al. (1987)</a> isolated cDNA clones corresponding to the alpha(i) subunit from a human brain cDNA library. The deduced 349-residue protein is identical to the bovine protein. Northern blot analysis identified a 3.8-kb mRNA transcript. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3110783" 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="#8" class="mim-tip-reference" title="Neer, E. J., Michel, T., Eddy, R., Shows, T., Seidman, J. G. <strong>Genes for two homologous G-protein alpha subunits map to different human chromosomes.</strong> Hum. Genet. 77: 259-262, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2824334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2824334</a>] [<a href="https://doi.org/10.1007/BF00284481" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2824334">Neer et al. (1987)</a> cloned and characterized cDNA encoding the predominant alpha(i) of brain, together with a very similar cDNA that encodes another putative G protein, alpha(h). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2824334" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By screening human genomic libraries with rat cDNAs for Gi-alpha as probes, <a href="#5" class="mim-tip-reference" title="Itoh, H., Toyama, R., Kozasa, T., Tsukamoto, T., Matsuoka, M., Kaziro, Y. <strong>Presence of three distinct molecular species of G(i) protein alpha subunit: structure of rat cDNAs and human genomic DNAs.</strong> J. Biol. Chem. 263: 6656-6664, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2834384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2834384</a>]" pmid="2834384">Itoh et al. (1988)</a> isolated 3 genes for the alpha subunit. Southern blot analysis indicated that a single copy of each of the 3 genes is present in the haploid human genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2834384" 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="#1" class="mim-tip-reference" title="Blatt, C., Eversole-Cire, P., Cohn, V. H., Zollman, S., Fournier, R. E. K., Mohandas, L. T., Nesbitt, M., Lugo, T., Jones, D. T., Reed, R. R., Weiner, L. P., Sparkes, R. S., Simon, M. I. <strong>Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human.</strong> Proc. Nat. Acad. Sci. 85: 7642-7646, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2902634/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2902634</a>] [<a href="https://doi.org/10.1073/pnas.85.20.7642" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2902634">Blatt et al. (1988)</a> mapped GNAI1 to chromosome 7 by hybridization of cDNA clones with DNA from human-mouse somatic cell hybrids. <a href="#2" class="mim-tip-reference" title="Bloch, D. B., Bloch, K. D., Iannuzzi, M., Collins, F. S., Neer, E. J., Seidman, J. G., Morton, C. C. <strong>The gene for the alpha-i-1 subunit of human guanine nucleotide binding protein maps near the cystic fibrosis locus.</strong> Am. J. Hum. Genet. 42: 884-888, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3130752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3130752</a>]" pmid="3130752">Bloch et al. (1988)</a> mapped the GNAI1 gene to chromosome 7q21 by in situ hybridization. They confirmed the regional location by studying human/mouse somatic cell hybrid lines containing portions of human chromosome 7. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2902634+3130752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By the study of restriction fragment length variation (RFLV) in an interspecific backcross between C57BL/6J and Mus spretus mice, <a href="#13" class="mim-tip-reference" title="Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G. <strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong> Nature Genet. 1: 85-91, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302014</a>] [<a href="https://doi.org/10.1038/ng0592-85" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1302014">Wilkie et al. (1992)</a> demonstrated that the corresponding murine gene is located on chromosome 5. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a bacterial expression system, <a href="#6" class="mim-tip-reference" title="Lan, K.-L., Sarvazyan, N. A., Taussig, R., Mackenzie, R. G., DiBello, P. R., Dohlman, H. G., Neubig, R. R. <strong>A point mutation in G-alpha-o and G-alpha-i1 blocks interaction with regulator of G protein signaling proteins.</strong> J. Biol. Chem. 273: 12794-12797, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9582306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9582306</a>] [<a href="https://doi.org/10.1074/jbc.273.21.12794" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9582306">Lan et al. (1998)</a> found that point mutations in the Gnai1 and Gnao1 genes, G183S and G184S, respectively, resulted in resistance to regulators of G protein signaling proteins (RGS). The mutant G-alpha proteins showed significantly decreased affinity for RGS4 (<a href="/entry/602516">602516</a>) and RGS7 (<a href="/entry/602517">602517</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9582306" 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="#9" class="mim-tip-reference" title="Ogden, S. K., Fei, D. L., Schilling, N. S., Ahmed, Y. F., Hwa, J., Robbins, D. J. <strong>G protein G-alpha-i functions immediately downstream of Smoothened in hedgehog signalling.</strong> Nature 456: 967-970, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18987629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18987629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18987629[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/nature07459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18987629">Ogden et al. (2008)</a> presented in vitro and in vivo evidence in Drosophila that Smoothened (<a href="/entry/601500">601500</a>) activates G-alpha-i to modulate intracellular cAMP levels in response to hedgehog (see <a href="/entry/600725">600725</a>). <a href="#9" class="mim-tip-reference" title="Ogden, S. K., Fei, D. L., Schilling, N. S., Ahmed, Y. F., Hwa, J., Robbins, D. J. <strong>G protein G-alpha-i functions immediately downstream of Smoothened in hedgehog signalling.</strong> Nature 456: 967-970, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18987629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18987629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18987629[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/nature07459" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18987629">Ogden et al. (2008)</a> concluded that Smoothened functions as a canonical G protein-coupled receptor, which signals through Gnai1 to regulate hedgehog pathway activation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18987629" 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 8 unrelated patients with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), the <a href="#4" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Prevalence and architecture of de novo mutations in developmental disorders.</strong> Nature 542: 433-438, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28135719[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/nature21062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135719">Deciphering Developmental Disorders Study (2017)</a> identified de novo heterozygous mutations in the GNAI1 gene (see, e.g., <a href="#0001">139310.0001</a>). There were 5 missense mutations and 3 in-frame intragenic deletions. The patients were ascertained from large cohorts of thousands of individuals with developmental delay who underwent exome sequencing. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28135719" 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 24 unrelated patients with NEDHISB, <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> identified 16 different heterozygous mutations in the GNAI1 gene (see, e.g., <a href="#0001">139310.0001</a>-<a href="#0005">139310.0005</a>). The patients were ascertained through international collaboration after exome sequencing identified the mutations. Thirteen of the patients had previously been reported (see, e.g., <a href="#4" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Prevalence and architecture of de novo mutations in developmental disorders.</strong> Nature 542: 433-438, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28135719[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/nature21062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135719">Deciphering Developmental Disorders Study, 2017</a>). There were 12 missense mutations, 3 small in-frame deletions, and 1 frameshift mutation; none were present in the gnomAD database. The frameshift mutation was predicted to escape nonsense-mediated mRNA decay as it occurred in the penultimate exon. The mutations occurred de novo in all except 1 patient who inherited it from an unaffected mosaic mother. Although functional studies of the variants were not performed, structural modeling predicted that most would affect guanine nucleotide (GDP and GTP) binding motifs in GAI1 and disrupt proper GAI1 function. There were no obvious genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28135719+33473207" 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 pair of monozygotic twin boys with NEDHISB, <a href="#12" class="mim-tip-reference" title="Wayhelova, M., Vallova, V., Broz, P., Mikulasova, A., Loubalova, D., Filkova, H., Smetana, J., Drabova, K., Gaillyova, R., Kuglik, P. <strong>Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.</strong> J. Hum. Genet. 67: 209-214, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34819662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34819662</a>] [<a href="https://doi.org/10.1038/s10038-021-00988-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34819662">Wayhelova et al. (2022)</a> identified a de novo heterozygous missense mutation in the GNAI1 gene (D272G; <a href="#0006">139310.0006</a>). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; it was classified as pathogenic according to ACMG criteria. Functional studies of the variant were not performed. The authors noted that the GNAI1 gene is expressed in multiple fetal and postnatal brain structures and that disruption of gene function may lead to impaired neural development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34819662" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=139310[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
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<p>In a female patient (268385) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), the <a href="#4" class="mim-tip-reference" title="Deciphering Developmental Disorders Study. <strong>Prevalence and architecture of de novo mutations in developmental disorders.</strong> Nature 542: 433-438, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28135719[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/nature21062" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28135719">Deciphering Developmental Disorders study (2017)</a> identified a de novo heterozygous c.995T-A transversion (c.995T-A, ENST00000351004) in the GNAI1 gene, resulting in a val332-to-glu (V332E) substitution. The patient was ascertained from a large cohort of thousands of individuals with developmental delay who underwent exome sequencing. Functional studies of the variant were not performed. This same patient was reported by <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> as an 18-year-old woman (P24) who was nonverbal and nonambulatory with severe-to-profound intellectual disability, hypertonia, and obesity. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28135719+33473207" 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 2 unrelated patients (P3 and P4) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> identified a de novo heterozygous c.118G-T transversion (c.118G-T, NM_002069.5) in the GNAI1 gene, resulting in a gly40-to-cys (G40C) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred de novo in P4 and was inherited from a mother who was mosaic (6%) in P3. Both patients had early-onset seizures and were essentially nonverbal. P3 had autistic features and P4 was nonambulatory with spastic tetraparesis at age 11 years. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33473207" 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">rs1788434338 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1788434338;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=rs1788434338" 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=rs1788434338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 3 unrelated patients (P6, P7, and P8) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> identified a de novo heterozygous c.143C-A transversion (c.143C-A, NM_002069.5) in the GNAI1 gene, resulting in a thr48-to-lys (T48K) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. The patients had global developmental delay with delayed or absent speech; 2 were noted to have profound intellectual disability. All had hypotonia and various types of seizures, including intractable seizures necessitating temporal lobectomy in P8. Brain imaging was abnormal in the 2 patients studied, showing global atrophy and delayed myelination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33473207" 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">rs1788864590 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1788864590;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=rs1788864590" 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=rs1788864590" 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=RCV001569146 OR RCV002246432" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001569146, RCV002246432" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001569146...</a>
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<p>In 2 unrelated girls (P17 and P18) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> identified a de novo heterozygous c.671G-A transition (c.671G-A, NM_002069.5) in the GNAI1 gene, resulting in a cys224-to-tyr (C224Y) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. P17 was an 11.5-year-old girl with global developmental delay, poor speech, moderate-to-severe intellectual disability, poor eye contact, autistic features, hypotonia, and early-onset hypomotor generalized epilepsy that resolved by age 4 years. P18 was 12-year-old girl with moderate intellectual disability and autism who could speak well and attend a special school. She had hypotonia and dysmorphic features; she did not have seizures. Brain imaging was normal in both patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33473207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</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">rs2115712676 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2115712676;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=rs2115712676" 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=rs2115712676" 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=RCV002248391 OR RCV004973381" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248391, RCV004973381" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248391...</a>
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<p>In 2 unrelated patients (P19 and P20) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), <a href="#7" class="mim-tip-reference" title="Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others. <strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong> Genet. Med. 23: 881-887s, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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/s41436-020-01076-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33473207">Muir et al. (2021)</a> identified a de novo heterozygous c.809A-G transition (c.809A-G, NM_002069.5) in the GNAI1 gene, resulting in a lys270-to-arg (K270R) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. The patients had early-onset seizures, hypotonia, and dysmorphic facial features. Brain imaging was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33473207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</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">rs2115712712 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2115712712;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=rs2115712712" 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=rs2115712712" 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=RCV002248392" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV002248392" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV002248392</a>
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<p>In a pair of monozygotic twin boys with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; <a href="/entry/619854">619854</a>), <a href="#12" class="mim-tip-reference" title="Wayhelova, M., Vallova, V., Broz, P., Mikulasova, A., Loubalova, D., Filkova, H., Smetana, J., Drabova, K., Gaillyova, R., Kuglik, P. <strong>Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.</strong> J. Hum. Genet. 67: 209-214, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34819662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34819662</a>] [<a href="https://doi.org/10.1038/s10038-021-00988-w" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34819662">Wayhelova et al. (2022)</a> identified a de novo heterozygous c.815A-G transition (c.815A-G, NM_002069.6) at the distal part of exon 7 of the GNAI1 gene, resulting in an asp272-to-gly (D272G) substitution at a highly conserved guanine nucleotide binding site. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; it was classified as pathogenic according to ACMG criteria. Functional studies of the variant were not performed. The patients had global developmental delay with severe speech impairment and clumsy motor skills. Seizures were not reported and brain imaging was normal. Twin B developed acute lymphoblastic leukemia that was treated with chemotherapy. Genetic analysis also identified a heterozygous 5-bp deletion in the ATM gene (<a href="/entry/607585">607585</a>) in both boys that was inherited from their father. The ATM variant (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555092477;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs1555092477</a>) was classified as pathogenic and may have contributed to the development of acute lymphoblastic leukemia in twin B. Microarray analysis identified a familial heterozygous 8q24.23-q24.3 duplication and a heterozygous 5q13.2 deletion that were not thought to contribute to the neurodevelopmental phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34819662" 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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Blatt, C., Eversole-Cire, P., Cohn, V. H., Zollman, S., Fournier, R. E. K., Mohandas, L. T., Nesbitt, M., Lugo, T., Jones, D. T., Reed, R. R., Weiner, L. P., Sparkes, R. S., Simon, M. I.
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<strong>Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human.</strong>
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Proc. Nat. Acad. Sci. 85: 7642-7646, 1988.
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[<a href="https://doi.org/10.1073/pnas.85.20.7642" target="_blank">Full Text</a>]
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Bloch, D. B., Bloch, K. D., Iannuzzi, M., Collins, F. S., Neer, E. J., Seidman, J. G., Morton, C. C.
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<strong>The gene for the alpha-i-1 subunit of human guanine nucleotide binding protein maps near the cystic fibrosis locus.</strong>
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Am. J. Hum. Genet. 42: 884-888, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3130752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3130752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3130752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Bray, P., Carter, A., Guo, V., Puckett, C., Kamholz, J., Spiegel, A., Nirenberg, M.
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<strong>Human cDNA clones for an alpha subunit of G(i) signal-transduction protein.</strong>
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Proc. Nat. Acad. Sci. 84: 5115-5119, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3110783/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3110783</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3110783" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Deciphering Developmental Disorders Study.
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<strong>Prevalence and architecture of de novo mutations in developmental disorders.</strong>
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Nature 542: 433-438, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28135719/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28135719</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=28135719[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=28135719" 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/nature21062" target="_blank">Full Text</a>]
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<strong>Presence of three distinct molecular species of G(i) protein alpha subunit: structure of rat cDNAs and human genomic DNAs.</strong>
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J. Biol. Chem. 263: 6656-6664, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2834384/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2834384</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2834384" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Lan, K.-L., Sarvazyan, N. A., Taussig, R., Mackenzie, R. G., DiBello, P. R., Dohlman, H. G., Neubig, R. R.
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<strong>A point mutation in G-alpha-o and G-alpha-i1 blocks interaction with regulator of G protein signaling proteins.</strong>
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J. Biol. Chem. 273: 12794-12797, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9582306/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9582306</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9582306" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others.
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<strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong>
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Genet. Med. 23: 881-887s, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33473207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33473207</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33473207[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=33473207" 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/s41436-020-01076-8" target="_blank">Full Text</a>]
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<a id="Neer1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Neer, E. J., Michel, T., Eddy, R., Shows, T., Seidman, J. G.
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<strong>Genes for two homologous G-protein alpha subunits map to different human chromosomes.</strong>
|
|
Hum. Genet. 77: 259-262, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2824334/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2824334</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2824334" 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/10.1007/BF00284481" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Ogden2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ogden, S. K., Fei, D. L., Schilling, N. S., Ahmed, Y. F., Hwa, J., Robbins, D. J.
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<strong>G protein G-alpha-i functions immediately downstream of Smoothened in hedgehog signalling.</strong>
|
|
Nature 456: 967-970, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18987629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18987629</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=18987629[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=18987629" 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/nature07459" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Suki1987" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Suki, W. N., Abramowitz, J., Mattera, R., Codina, J., Birnbaumer, L.
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<strong>The human genome encodes at least three non-allelic G proteins with alpha-i-type subunits.</strong>
|
|
FEBS Lett. 220: 187-192, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2440724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2440724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2440724" 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(87)80900-6" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Sullivan1986" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sullivan, K. A., Liao, Y.-C., Alborzi, A., Beiderman, B., Chang, F.-H., Masters, S. B., Levinson, A. D., Bourne, H. R.
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|
<strong>Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains.</strong>
|
|
Proc. Nat. Acad. Sci. 83: 6687-6691, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3092218/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3092218</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3092218" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.83.18.6687" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Wayhelova2022" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wayhelova, M., Vallova, V., Broz, P., Mikulasova, A., Loubalova, D., Filkova, H., Smetana, J., Drabova, K., Gaillyova, R., Kuglik, P.
|
|
<strong>Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.</strong>
|
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J. Hum. Genet. 67: 209-214, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34819662/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34819662</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34819662" 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/s10038-021-00988-w" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Wilkie1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G.
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<strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong>
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Nature Genet. 1: 85-91, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1302014/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1302014</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1302014" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng0592-85" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<a id="contributors" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 04/26/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Ada Hamosh - updated : 2/18/2009<br>Cassandra L. Kniffin - updated : 6/5/2006
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 05/02/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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ckniffin : 04/26/2022<br>carol : 08/07/2013<br>alopez : 2/20/2009<br>terry : 2/18/2009<br>carol : 6/29/2006<br>ckniffin : 6/5/2006<br>alopez : 6/13/2001<br>carol : 7/2/1998<br>carol : 3/28/1998<br>mark : 9/3/1997<br>carol : 5/19/1992<br>supermim : 3/16/1992<br>carol : 3/4/1992<br>carol : 2/29/1992<br>supermim : 3/20/1990<br>ddp : 10/27/1989
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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<div class="col-md-8 col-md-offset-1">
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<div>
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<div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 139310
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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GUANINE NUCLEOTIDE-BINDING PROTEIN, ALPHA-INHIBITING ACTIVITY POLYPEPTIDE 1; GNAI1
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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G PROTEIN, ALPHA-INHIBITING 1; Gi<br />
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INHIBITORY G PROTEIN<br />
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ADENYLATE CYCLASE INHIBITORY PROTEIN
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: GNAI1</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 7q21.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 7:80,134,831-80,226,181 </span>
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</em>
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
|
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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7q21.11
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</span>
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</td>
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<td>
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<span class="mim-font">
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Neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
619854
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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Autosomal dominant
|
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
3
|
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Guanine nucleotide-binding proteins (G proteins) form a large family of signal-transducing molecules. They are found as heterotrimers made up of alpha, beta, and gamma subunits. Members of the G protein family have been characterized most extensively on the basis of the alpha subunit, which binds guanine nucleotide, is capable of hydrolyzing GTP, and interacts with specific receptor and effector molecules. The G protein family includes Gs (139320) and Gi, the stimulatory and inhibitory GTP-binding regulators of adenylate cyclase; Go, a protein abundant in brain (GNAO1; 139311); and transducin-1 (GNAT1; 139330) and transducin-2 (GNAT2; 139340), proteins involved in phototransduction in retinal rods and cones, respectively (Sullivan et al., 1986; Bray et al., 1987). </p><p>Suki et al. (1987) concluded that the human genome contains at least 3 nonallelic genes for alpha-i-type subunits of G protein; see, e.g., GNAI2 (139360), GNAI3 (139370), and GNAIH (139180). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Sullivan et al. (1986) used a cDNA encoding bovine alpha chain of transducin-1 to isolate and sequence murine cDNAs for alpha(s) and alpha(i). Homologies and differences among the deduced amino acid sequences of the G protein and transducin alpha chains pointed to specific regions that may interact with guanine nucleotides, receptors, effector enzymes, and the G protein beta-gamma complex. </p><p>Bray et al. (1987) isolated cDNA clones corresponding to the alpha(i) subunit from a human brain cDNA library. The deduced 349-residue protein is identical to the bovine protein. Northern blot analysis identified a 3.8-kb mRNA transcript. </p><p>Neer et al. (1987) cloned and characterized cDNA encoding the predominant alpha(i) of brain, together with a very similar cDNA that encodes another putative G protein, alpha(h). </p><p>By screening human genomic libraries with rat cDNAs for Gi-alpha as probes, Itoh et al. (1988) isolated 3 genes for the alpha subunit. Southern blot analysis indicated that a single copy of each of the 3 genes is present in the haploid human genome. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Mapping</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
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<p>Blatt et al. (1988) mapped GNAI1 to chromosome 7 by hybridization of cDNA clones with DNA from human-mouse somatic cell hybrids. Bloch et al. (1988) mapped the GNAI1 gene to chromosome 7q21 by in situ hybridization. They confirmed the regional location by studying human/mouse somatic cell hybrid lines containing portions of human chromosome 7. </p><p>By the study of restriction fragment length variation (RFLV) in an interspecific backcross between C57BL/6J and Mus spretus mice, Wilkie et al. (1992) demonstrated that the corresponding murine gene is located on chromosome 5. </p>
|
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</span>
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<div>
|
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<br />
|
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Gene Function</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
|
|
<p>In a bacterial expression system, Lan et al. (1998) found that point mutations in the Gnai1 and Gnao1 genes, G183S and G184S, respectively, resulted in resistance to regulators of G protein signaling proteins (RGS). The mutant G-alpha proteins showed significantly decreased affinity for RGS4 (602516) and RGS7 (602517). </p><p>Ogden et al. (2008) presented in vitro and in vivo evidence in Drosophila that Smoothened (601500) activates G-alpha-i to modulate intracellular cAMP levels in response to hedgehog (see 600725). Ogden et al. (2008) concluded that Smoothened functions as a canonical G protein-coupled receptor, which signals through Gnai1 to regulate hedgehog pathway activation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 8 unrelated patients with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), the Deciphering Developmental Disorders Study (2017) identified de novo heterozygous mutations in the GNAI1 gene (see, e.g., 139310.0001). There were 5 missense mutations and 3 in-frame intragenic deletions. The patients were ascertained from large cohorts of thousands of individuals with developmental delay who underwent exome sequencing. Functional studies of the variants were not performed. </p><p>In 24 unrelated patients with NEDHISB, Muir et al. (2021) identified 16 different heterozygous mutations in the GNAI1 gene (see, e.g., 139310.0001-139310.0005). The patients were ascertained through international collaboration after exome sequencing identified the mutations. Thirteen of the patients had previously been reported (see, e.g., Deciphering Developmental Disorders Study, 2017). There were 12 missense mutations, 3 small in-frame deletions, and 1 frameshift mutation; none were present in the gnomAD database. The frameshift mutation was predicted to escape nonsense-mediated mRNA decay as it occurred in the penultimate exon. The mutations occurred de novo in all except 1 patient who inherited it from an unaffected mosaic mother. Although functional studies of the variants were not performed, structural modeling predicted that most would affect guanine nucleotide (GDP and GTP) binding motifs in GAI1 and disrupt proper GAI1 function. There were no obvious genotype/phenotype correlations. </p><p>In a pair of monozygotic twin boys with NEDHISB, Wayhelova et al. (2022) identified a de novo heterozygous missense mutation in the GNAI1 gene (D272G; 139310.0006). The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; it was classified as pathogenic according to ACMG criteria. Functional studies of the variant were not performed. The authors noted that the GNAI1 gene is expressed in multiple fetal and postnatal brain structures and that disruption of gene function may lead to impaired neural development. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNAI1, VAL332GLU
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<br />
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SNP: rs2115727431,
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ClinVar: RCV002248390
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a female patient (268385) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), the Deciphering Developmental Disorders study (2017) identified a de novo heterozygous c.995T-A transversion (c.995T-A, ENST00000351004) in the GNAI1 gene, resulting in a val332-to-glu (V332E) substitution. The patient was ascertained from a large cohort of thousands of individuals with developmental delay who underwent exome sequencing. Functional studies of the variant were not performed. This same patient was reported by Muir et al. (2021) as an 18-year-old woman (P24) who was nonverbal and nonambulatory with severe-to-profound intellectual disability, hypertonia, and obesity. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNAI1, GLY40CYS
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<br />
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SNP: rs2116052322,
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ClinVar: RCV002249061
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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 (P3 and P4) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), Muir et al. (2021) identified a de novo heterozygous c.118G-T transversion (c.118G-T, NM_002069.5) in the GNAI1 gene, resulting in a gly40-to-cys (G40C) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. The mutation occurred de novo in P4 and was inherited from a mother who was mosaic (6%) in P3. Both patients had early-onset seizures and were essentially nonverbal. P3 had autistic features and P4 was nonambulatory with spastic tetraparesis at age 11 years. Functional studies of the variant 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>.0003 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNAI1, THR48LYS
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<br />
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SNP: rs1788434338,
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ClinVar: RCV001095673, RCV002249684
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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 3 unrelated patients (P6, P7, and P8) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), Muir et al. (2021) identified a de novo heterozygous c.143C-A transversion (c.143C-A, NM_002069.5) in the GNAI1 gene, resulting in a thr48-to-lys (T48K) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. The patients had global developmental delay with delayed or absent speech; 2 were noted to have profound intellectual disability. All had hypotonia and various types of seizures, including intractable seizures necessitating temporal lobectomy in P8. Brain imaging was abnormal in the 2 patients studied, showing global atrophy and delayed myelination. </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>.0004 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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GNAI1, CYS224TYR
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<br />
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SNP: rs1788864590,
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ClinVar: RCV001569146, RCV002246432
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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 2 unrelated girls (P17 and P18) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), Muir et al. (2021) identified a de novo heterozygous c.671G-A transition (c.671G-A, NM_002069.5) in the GNAI1 gene, resulting in a cys224-to-tyr (C224Y) substitution. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. P17 was an 11.5-year-old girl with global developmental delay, poor speech, moderate-to-severe intellectual disability, poor eye contact, autistic features, hypotonia, and early-onset hypomotor generalized epilepsy that resolved by age 4 years. P18 was 12-year-old girl with moderate intellectual disability and autism who could speak well and attend a special school. She had hypotonia and dysmorphic features; she did not have seizures. Brain imaging was normal in both patients. </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>.0005 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
|
|
</span>
|
|
</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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|
GNAI1, LYS270ARG
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<br />
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SNP: rs2115712676,
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ClinVar: RCV002248391, RCV004973381
|
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</span>
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 unrelated patients (P19 and P20) with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), Muir et al. (2021) identified a de novo heterozygous c.809A-G transition (c.809A-G, NM_002069.5) in the GNAI1 gene, resulting in a lys270-to-arg (K270R) substitution in the GDP-binding domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant were not performed. The patients had early-onset seizures, hypotonia, and dysmorphic facial features. Brain imaging was normal. </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 NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, IMPAIRED SPEECH, AND BEHAVIORAL ABNORMALITIES</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
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|
|
GNAI1, ASP272GLY
|
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|
|
<br />
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|
|
SNP: rs2115712712,
|
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|
|
|
|
|
|
ClinVar: RCV002248392
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a pair of monozygotic twin boys with neurodevelopmental disorder with hypotonia, impaired speech, and behavioral abnormalities (NEDHISB; 619854), Wayhelova et al. (2022) identified a de novo heterozygous c.815A-G transition (c.815A-G, NM_002069.6) at the distal part of exon 7 of the GNAI1 gene, resulting in an asp272-to-gly (D272G) substitution at a highly conserved guanine nucleotide binding site. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing; it was classified as pathogenic according to ACMG criteria. Functional studies of the variant were not performed. The patients had global developmental delay with severe speech impairment and clumsy motor skills. Seizures were not reported and brain imaging was normal. Twin B developed acute lymphoblastic leukemia that was treated with chemotherapy. Genetic analysis also identified a heterozygous 5-bp deletion in the ATM gene (607585) in both boys that was inherited from their father. The ATM variant (rs1555092477) was classified as pathogenic and may have contributed to the development of acute lymphoblastic leukemia in twin B. Microarray analysis identified a familial heterozygous 8q24.23-q24.3 duplication and a heterozygous 5q13.2 deletion that were not thought to contribute to the neurodevelopmental phenotype. </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>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
|
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Blatt, C., Eversole-Cire, P., Cohn, V. H., Zollman, S., Fournier, R. E. K., Mohandas, L. T., Nesbitt, M., Lugo, T., Jones, D. T., Reed, R. R., Weiner, L. P., Sparkes, R. S., Simon, M. I.
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<strong>Chromosomal localization of genes encoding guanine nucleotide-binding protein subunits in mouse and human.</strong>
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Proc. Nat. Acad. Sci. 85: 7642-7646, 1988.
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[PubMed: 2902634]
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[Full Text: https://doi.org/10.1073/pnas.85.20.7642]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Bloch, D. B., Bloch, K. D., Iannuzzi, M., Collins, F. S., Neer, E. J., Seidman, J. G., Morton, C. C.
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<strong>The gene for the alpha-i-1 subunit of human guanine nucleotide binding protein maps near the cystic fibrosis locus.</strong>
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Am. J. Hum. Genet. 42: 884-888, 1988.
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[PubMed: 3130752]
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<p class="mim-text-font">
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Bray, P., Carter, A., Guo, V., Puckett, C., Kamholz, J., Spiegel, A., Nirenberg, M.
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<strong>Human cDNA clones for an alpha subunit of G(i) signal-transduction protein.</strong>
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Proc. Nat. Acad. Sci. 84: 5115-5119, 1987.
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[PubMed: 3110783]
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[Full Text: https://doi.org/10.1073/pnas.84.15.5115]
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<li>
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<p class="mim-text-font">
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Deciphering Developmental Disorders Study.
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<strong>Prevalence and architecture of de novo mutations in developmental disorders.</strong>
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Nature 542: 433-438, 2017.
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[PubMed: 28135719]
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[Full Text: https://doi.org/10.1038/nature21062]
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</p>
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</li>
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<p class="mim-text-font">
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Itoh, H., Toyama, R., Kozasa, T., Tsukamoto, T., Matsuoka, M., Kaziro, Y.
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<strong>Presence of three distinct molecular species of G(i) protein alpha subunit: structure of rat cDNAs and human genomic DNAs.</strong>
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J. Biol. Chem. 263: 6656-6664, 1988.
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[PubMed: 2834384]
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<li>
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<p class="mim-text-font">
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Lan, K.-L., Sarvazyan, N. A., Taussig, R., Mackenzie, R. G., DiBello, P. R., Dohlman, H. G., Neubig, R. R.
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<strong>A point mutation in G-alpha-o and G-alpha-i1 blocks interaction with regulator of G protein signaling proteins.</strong>
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J. Biol. Chem. 273: 12794-12797, 1998.
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[PubMed: 9582306]
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[Full Text: https://doi.org/10.1074/jbc.273.21.12794]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Muir, A. M., Gardner, J. F., van Jaarsveld, R. H., de Lange, I. M., van der Smagt, J. J., Wilson, G. N., Dubbs, H., Goldberg, E. M., Zitano, L., Bupp, C., Martinez, J., Srour, M., and 44 others.
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<strong>Variants in GNAI1 cause a syndrome associated with variable features including developmental delay, seizures, and hypotonia.</strong>
|
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Genet. Med. 23: 881-887s, 2021.
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[PubMed: 33473207]
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[Full Text: https://doi.org/10.1038/s41436-020-01076-8]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Neer, E. J., Michel, T., Eddy, R., Shows, T., Seidman, J. G.
|
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<strong>Genes for two homologous G-protein alpha subunits map to different human chromosomes.</strong>
|
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Hum. Genet. 77: 259-262, 1987.
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[PubMed: 2824334]
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[Full Text: https://doi.org/10.1007/BF00284481]
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</p>
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<li>
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<p class="mim-text-font">
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Ogden, S. K., Fei, D. L., Schilling, N. S., Ahmed, Y. F., Hwa, J., Robbins, D. J.
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<strong>G protein G-alpha-i functions immediately downstream of Smoothened in hedgehog signalling.</strong>
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Nature 456: 967-970, 2008.
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[PubMed: 18987629]
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[Full Text: https://doi.org/10.1038/nature07459]
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<li>
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<p class="mim-text-font">
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Suki, W. N., Abramowitz, J., Mattera, R., Codina, J., Birnbaumer, L.
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<strong>The human genome encodes at least three non-allelic G proteins with alpha-i-type subunits.</strong>
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FEBS Lett. 220: 187-192, 1987.
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[PubMed: 2440724]
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[Full Text: https://doi.org/10.1016/0014-5793(87)80900-6]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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|
Sullivan, K. A., Liao, Y.-C., Alborzi, A., Beiderman, B., Chang, F.-H., Masters, S. B., Levinson, A. D., Bourne, H. R.
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<strong>Inhibitory and stimulatory G proteins of adenylate cyclase: cDNA and amino acid sequences of the alpha chains.</strong>
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Proc. Nat. Acad. Sci. 83: 6687-6691, 1986.
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[PubMed: 3092218]
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[Full Text: https://doi.org/10.1073/pnas.83.18.6687]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Wayhelova, M., Vallova, V., Broz, P., Mikulasova, A., Loubalova, D., Filkova, H., Smetana, J., Drabova, K., Gaillyova, R., Kuglik, P.
|
|
<strong>Novel de novo pathogenic variant in the GNAI1 gene as a cause of severe disorders of intellectual development.</strong>
|
|
J. Hum. Genet. 67: 209-214, 2022.
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[PubMed: 34819662]
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[Full Text: https://doi.org/10.1038/s10038-021-00988-w]
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Wilkie, T. M., Gilbert, D. J., Olsen, A. S., Chen, X.-N., Amatruda, T. T., Korenberg, J. R., Trask, B. J., de Jong, P., Reed, R. R., Simon, M. I., Jenkins, N. A., Copeland, N. G.
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<strong>Evolution of the mammalian G protein alpha subunit multigene family.</strong>
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Nature Genet. 1: 85-91, 1992.
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[PubMed: 1302014]
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[Full Text: https://doi.org/10.1038/ng0592-85]
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Cassandra L. Kniffin - updated : 04/26/2022<br>Ada Hamosh - updated : 2/18/2009<br>Cassandra L. Kniffin - updated : 6/5/2006
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Victor A. McKusick : 6/4/1986
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