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Entry
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- *137142 - GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-5; GABRA5
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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">*137142</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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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/137142">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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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=ENSG00000186297;t=ENST00000335625" 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=2558" 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=137142" 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=ENSG00000186297;t=ENST00000335625" 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_000810,NM_001165037,XM_005268258,XM_006720459,XM_017022055,XM_017022056,XM_047432338,XM_047432339" 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_000810" 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=137142" 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=08840&isoform_id=08840_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/GABRA5" 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/182916,399519,1247500,3420026,4503861,7417244,32880003,85567072,109731251,119578060,119578061,158261929,194376876,194383486,259013560,530405180,578826794,1034590210,1034590212,2217300671,2217300674,2462543523,2462543525,2462543527,2462543529,2462543531,2462543533" 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/P31644" 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=2558" 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=ENSG00000186297;t=ENST00000335625" 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=GABRA5" 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=GABRA5" 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+2558" 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/GABRA5" 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:2558" 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/2558" 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=chr15&hgg_gene=ENST00000335625.10&hgg_start=26866719&hgg_end=26949208&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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=137142[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=137142[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/GABRA5/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/ENSG00000186297" 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=GABRA5" 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=GABRA5" 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=GABRA5" 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=GABRA5&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/PA28493" 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:4079" 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/FBgn0001134.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:95617" 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/GABRA5#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:95617" 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/2558/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=2558" 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=WBGene00008551;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00008551 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00013914;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00013914 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-081104-30" 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:2558" 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=GABRA5&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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137142
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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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GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-5; GABRA5
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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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GABA-A RECEPTOR, ALPHA-5 POLYPEPTIDE
|
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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=GABRA5" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">GABRA5</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/15/37?start=-3&limit=10&highlight=37">15q12</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr15:26866719-26949208&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'})">15:26,866,719-26,949,208</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>
|
|
<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>
|
|
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">
|
|
<a href="/geneMap/15/37?start=-3&limit=10&highlight=37">
|
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15q12
|
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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">
|
|
Developmental and epileptic encephalopathy 79
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/618559"> 618559 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<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">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/137142" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/137142" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
|
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|
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<span class="mim-font">
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<p>Gamma-aminobutyric acid (GABA) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system. GABRA5 is a member of the GABA-A receptor gene family of heteromeric pentameric ligand-gated ion channels through which GABA, the major inhibitory neurotransmitter in the mammalian brain, acts. GABA-A receptors are the site of action of a number of important pharmacologic agents including barbiturates, benzodiazepines, and ethanol (summary by <a href="#11" class="mim-tip-reference" title="Whiting, P. J., Bonnert, T. P., McKernan, R. M., Farrar, S., le Bourdelles, B., Heavens, R. P., Smith, D. W., Hewson, L., Rigby, M. R., Sirinathsinghji, D. J. S., Thompson, S. A., Wafford, K. A. <strong>Molecular and functional diversity of the expanding GABA-A receptor gene family.</strong> Ann. N.Y. Acad. Sci. 868: 645-653, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10414349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10414349</a>] [<a href="https://doi.org/10.1111/j.1749-6632.1999.tb11341.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10414349">Whiting et al., 1999</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10414349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For additional general information about the GABA-A receptor gene family, see GABRA1 (<a href="/entry/137160">137160</a>).</p>
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<p><a href="#12" class="mim-tip-reference" title="Wingrove, P., Hadingham, K., Wafford, K., Kemp, J. A., Ragan, C. I., Whiting, P. <strong>Cloning and expression of a cDNA encoding the human GABA-A receptor alpha-5 subunit.</strong> Biochem. Soc. Trans. 20: 18S only, 1991."None>Wingrove et al. (1991)</a> reported the cloning and expression of a cDNA corresponding to GABRA5. Overall, the human protein has 94% amino acid sequence identity with the rat alpha-5 subunit, with most of the differences occurring in the signal peptide and the putative large cytoplasmic loop domain. Human alpha-5 has 57% sequence identity with human alpha-1, again most of the amino acid differences being in the signal peptide and the putative large cytoplasmic loop domain. The expression studies indicated that GABA-A receptor subtypes containing alpha-5, like their rat equivalent, have a unique benzodiazepine pharmacology.</p>
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<p>By fluorescence in situ hybridization, <a href="#7" class="mim-tip-reference" title="Knoll, J. H. M., Sinnett, D., Wagstaff, J., Glatt, K., Wilcox, A. S., Whiting, P., Wingrove, P., Sikela, J., Lalande, M. <strong>FISH ordering of DNA markers within the Angelman/Prader-Willi chromosomal regions: mapping of a second GABA-A receptor subunit gene, GABRA5. (Abstract)</strong> Am. J. Hum. Genet. 51 (suppl.): A9 only, 1992."None>Knoll et al. (1992)</a> mapped the GABRA5 gene to chromosome 15q11-q13.</p><p><a href="#10" class="mim-tip-reference" title="Russek, S. J., Farb, D. H. <strong>Mapping of the beta-2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABA-A receptor isoform.</strong> Genomics 23: 528-533, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851879</a>] [<a href="https://doi.org/10.1006/geno.1994.1539" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7851879">Russek and Farb (1994)</a> stated that the gene encoding the gamma-3 form of the GABA-A receptor (GABRG3; <a href="/entry/600233">600233</a>) is located on 15q11-q13 in a cluster with GABRA5 and GABRB3 (<a href="/entry/137192">137192</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#4" class="mim-tip-reference" title="Glatt, K., Glatt, H., Lalande, M. <strong>Structure and organization of GABRB3 and GABRA5.</strong> Genomics 41: 63-69, 1997. Note: Erratum: Genomics 44: 155 only, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126483</a>] [<a href="https://doi.org/10.1006/geno.1997.4639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9126483">Glatt et al. (1997)</a> reported that the GABRA5 gene contains 11 exons spanning 86 kb. There are 3 alternative first exons, a noncoding second exon, and a translation initiation site in exon 3. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using coding SNPs within the GABA receptor gene cluster on chromosome 15q11-q13, <a href="#6" class="mim-tip-reference" title="Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H., Lasalle, J. M. <strong>15q11-13 GABA(A) receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders.</strong> Hum. Molec. Genet. 16: 691-703, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17339270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17339270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17339270[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddm014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17339270">Hogart et al. (2007)</a> demonstrated that the GABRG3, GABRB3, and GABRA5 genes were biallelically expressed in the cerebral cortex of 21 postmortem human brain samples. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17339270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Glatt, K. A., Sinnett, D., Lalande, M. <strong>Dinucleotide repeat polymorphism at the GABA-A receptor alpha-5 (GABRA5) locus at chromosome 15q11-q13.</strong> Hum. Molec. Genet. 1: 348 only, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338907</a>] [<a href="https://doi.org/10.1093/hmg/1.5.348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1338907">Glatt et al. (1992)</a> demonstrated a dinucleotide repeat polymorphism at the GABRA5 locus. A single maternal allele was observed in classic Prader-Willi syndrome (<a href="/entry/176270">176270</a>) cases and a single paternal allele in classic Angelman syndrome (<a href="/entry/105830">105830</a>) cases in which deletions had previously been demonstrated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338907" 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="Ritchie, R. J., Mattei, M.-G., Lalande, M. <strong>A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications.</strong> Hum. Molec. Genet. 7: 1253-1260, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668167</a>] [<a href="https://doi.org/10.1093/hmg/7.8.1253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9668167">Ritchie et al. (1998)</a> reported a partial duplication of GABRA5 within the imprinted 15q11-q13 region. The duplicated locus mapped to the pericentromeric region of 15q, proximal to the large deletions associated Angelman and Prader-Willi syndromes. They also observed variation in the number of copies of this locus in different individuals, indicating that the duplication is part of the variable repeat. Investigation of the duplication in individuals with a normal karyotype revealed between 1 and 4 copies of the repeat on each chromosome 15, whereas from 8 to 20 copies were found in individuals possessing a cytogenetically detectable elongation of the 15q region. The variable region is roughly 1 Mb long and contains 2 other nonprocessed duplications, the immunoglobulin heavy chain (IgH) D segment gene (IGHD; <a href="/entry/147170">147170</a>) on 14q and the NF1 gene (<a href="/entry/613113">613113</a>) on chromosome 17. One unit of the pericentromeric repeat is thus composed of duplications of genes from different chromosomal regions. <a href="#9" class="mim-tip-reference" title="Ritchie, R. J., Mattei, M.-G., Lalande, M. <strong>A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications.</strong> Hum. Molec. Genet. 7: 1253-1260, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668167</a>] [<a href="https://doi.org/10.1093/hmg/7.8.1253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9668167">Ritchie et al. (1998)</a> also found replication asynchrony across the GABRA5 duplication, suggesting for the first time that the imprinted part of chromosome 15q extends proximal of the region commonly deleted in Angelman and Prader-Willi syndromes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9668167" 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="Papadimitriou, G. N., Dikeos, D. G., Karadima, G., Avramopoulos, D., Daskalopoulou, E. G., Vassilopoulos, D., Stefanis, C. N. <strong>Association between the GABA-A receptor alpha-5 subunit gene locus (GABRA5) and bipolar affective disorder.</strong> Am. J. Med. Genet. 81: 73-80, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9514592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9514592</a>]" pmid="9514592">Papadimitriou et al. (1998)</a> found an association between a 282-bp CA repeat in the gene encoding GABRA5 and bipolar affective disorder in 48 unrelated southern Greek patients but not in 50 healthy individuals drawn from the same population. No association was seen in another sample of 40 unipolar patients in the same specimen. Even though the authors applied the Bonferroni correction for the total numbers of genes tested, they cautioned that the level of significance in association studies is still a matter of debate. They believed that the 282-bp allele is unlikely to have functional significance but does not represent stratification in their sample. Rather, they considered that the allele may be in linkage disequilibrium with a functional mutation elsewhere in the GABRA5 gene or another gene in close proximity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9514592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Developmental and Epileptic Encephalopathy 79</em></strong></p><p>
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In a 2-year-old boy (patient 1), born of unrelated parents, with developmental and epileptic encephalopathy-79 (DEE79; <a href="/entry/618559">618559</a>), <a href="#1" class="mim-tip-reference" title="Butler, K. M., Moody, O. A., Schuler, E., Coryell, J., Alexander, J. J., Jenkins, A., Escayg, A. <strong>De novo variations in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy.</strong> Brain 141: 2392-2405, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29961870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29961870</a>] [<a href="https://doi.org/10.1093/brain/awy171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29961870">Butler et al. (2018)</a> identified a de novo heterozygous missense mutation in the GABRA5 gene (V294L; <a href="#0001">137142.0001</a>). The mutation, which was found by trio-based whole-genome sequencing and confirmed by Sanger sequencing, occurred in the pore-forming transmembrane domain and was not found in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29961870" 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 2 unrelated children (patients 1 and 2) with DEE79, <a href="#5" class="mim-tip-reference" title="Hernandez, C. C., XiangWei, W., Hu, N., Shen, D., Shen, W., Lagrange, A. H., Zhang, Y., Dai, L., Ding, C., Sun, Z., Hu, J., Zhu, H., Jiang, Y., Macdonald, R. L. <strong>Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.</strong> Brain 142: 1938-1954, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31056671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31056671</a>] [<a href="https://doi.org/10.1093/brain/awz123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31056671">Hernandez et al. (2019)</a> identified de novo heterozygous mutations in the GABRA5 gene (V294F, <a href="#0002">137142.0002</a> and S413F, <a href="#0003">137142.0003</a>). The mutations, which were found by next-generation sequencing of a targeted gene panel of 480 candidate genes in a cohort of 1,969 patients with a similar phenotype, were confirmed by Sanger sequencing and not present in the gnomAD database. In vitro functional expression studies of the mutations in rat primary hippocampal neurons and HEK293 cells showed variable abnormalities, including decreased expression of the mutant V294F protein at dendritic GABAergic synapses compared to wildtype; both variants resulted in decreased GABA-evoked current amplitudes compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31056671" 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 mice, <a href="#2" class="mim-tip-reference" title="Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., Carmichael, S. T. <strong>Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.</strong> Nature 468: 305-309, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21048709[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/nature09511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048709">Clarkson et al. (2010)</a> showed that after a stroke, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA-A receptors and is caused by an impairment in GABA transporter function. To counteract the heightened inhibition, <a href="#2" class="mim-tip-reference" title="Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., Carmichael, S. T. <strong>Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.</strong> Nature 468: 305-309, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21048709[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/nature09511" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21048709">Clarkson et al. (2010)</a> administered in vivo a benzodiazepine inverse agonist specific for alpha-5-subunit-containing extrasynaptic GABA-A receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of alpha-5- or delta-subunit (GABRD; <a href="/entry/137163">137163</a>)-containing GABA-A receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA-A receptor function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21048709" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=137142[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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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1595438243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595438243;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=rs1595438243" 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=rs1595438243" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 2-year-old boy (patient 1), born of unrelated parents, with developmental and epileptic encephalopathy-79 (DEE79; <a href="/entry/618559">618559</a>), <a href="#1" class="mim-tip-reference" title="Butler, K. M., Moody, O. A., Schuler, E., Coryell, J., Alexander, J. J., Jenkins, A., Escayg, A. <strong>De novo variations in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy.</strong> Brain 141: 2392-2405, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29961870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29961870</a>] [<a href="https://doi.org/10.1093/brain/awy171" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29961870">Butler et al. (2018)</a> identified a de novo heterozygous c.880G-C transversion (c.880G-C, NM_000810) in the GABRA5 gene, resulting in a val294-to-leu (V294L) substitution at a highly conserved residue in the pore-forming M2 transmembrane domain. The mutation, which was found by trio-based whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. The patient had onset of various types of seizures at 4 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29961870" 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">rs1595438243 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595438243;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=rs1595438243" 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=rs1595438243" 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=RCV000850106 OR RCV002279564" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000850106, RCV002279564" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000850106...</a>
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<p>In a 4-year-old boy (patient 1) with developmental and epileptic encephalopathy-79 (DEE79; <a href="/entry/618559">618559</a>), <a href="#5" class="mim-tip-reference" title="Hernandez, C. C., XiangWei, W., Hu, N., Shen, D., Shen, W., Lagrange, A. H., Zhang, Y., Dai, L., Ding, C., Sun, Z., Hu, J., Zhu, H., Jiang, Y., Macdonald, R. L. <strong>Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.</strong> Brain 142: 1938-1954, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31056671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31056671</a>] [<a href="https://doi.org/10.1093/brain/awz123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31056671">Hernandez et al. (2019)</a> identified a de novo heterozygous c.880G-T transversion (c.880G-T, NM_000810.3) in the GABRA5 gene, resulting in a val294-to-phe (V294F) substitution at a conserved residue in the M2 pore domain. The mutation, which was found by next-generation sequencing of a targeted gene panel and confirmed by Sanger sequencing, was not found in the gnomAD database. Expression of the mutation in rat primary hippocampal neurons resulted in decreased expression of the mutant protein at dendritic GABAergic synapses compared to wildtype. The mutant protein showed aberrant accumulation within the soma of neurons and localization to the ER, suggesting a possible trafficking defect. Functional studies in neurons and HEK293 cells showed decreased cell surface expression of the mutant subunit and decreased GABA-evoked current amplitudes compared to wildtype. The patient presented with onset of multifocal seizures at 4 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31056671" 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">rs1595441329 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1595441329;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=rs1595441329" 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=rs1595441329" 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=RCV000850107" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000850107" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000850107</a>
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<p>In a 7-year-old boy (patient 2) with developmental and epileptic encephalopathy-79 (DEE79; <a href="/entry/618559">618559</a>), <a href="#5" class="mim-tip-reference" title="Hernandez, C. C., XiangWei, W., Hu, N., Shen, D., Shen, W., Lagrange, A. H., Zhang, Y., Dai, L., Ding, C., Sun, Z., Hu, J., Zhu, H., Jiang, Y., Macdonald, R. L. <strong>Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.</strong> Brain 142: 1938-1954, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31056671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31056671</a>] [<a href="https://doi.org/10.1093/brain/awz123" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31056671">Hernandez et al. (2019)</a> identified a de novo heterozygous c.1238C-T transition (c.1238C-T, NM_000810.3) in the GABRA5 gene, resulting in a ser413-to-phe (S413F) substitution at a nonconserved residue in the intracellular N tail of the M4 domain. The mutation, which was found by next-generation sequencing of a targeted gene panel and confirmed by Sanger sequencing, was not found in the gnomAD database. Expression of the mutation into rat primary hippocampal neurons resulted in normal expression of the mutant protein at dendritic GABAergic synapses similar to wildtype. Functional studies in neurons and HEK293 cells showed that the mutation was associated with decreased GABA-evoked current amplitudes compared to wildtype. The S413F mutation also showed a dominant-negative effect by decreasing the trafficking of the partnering GABRB3 (<a href="/entry/137192">137192</a>) subunit to the cell surface, with no effect on other subunits. The patient had onset of epileptic spasms and focal and tonic seizures at 3 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31056671" 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>De novo variations in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy.</strong>
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Brain 141: 2392-2405, 2018.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29961870/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29961870</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29961870" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awy171" target="_blank">Full Text</a>]
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<strong>Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.</strong>
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Nature 468: 305-309, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21048709/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21048709</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21048709[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=21048709" 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/nature09511" target="_blank">Full Text</a>]
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Glatt, K. A., Sinnett, D., Lalande, M.
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<strong>Dinucleotide repeat polymorphism at the GABA-A receptor alpha-5 (GABRA5) locus at chromosome 15q11-q13.</strong>
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Hum. Molec. Genet. 1: 348 only, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1338907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1338907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1338907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/1.5.348" target="_blank">Full Text</a>]
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<a id="4" class="mim-anchor"></a>
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<a id="Glatt1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Glatt, K., Glatt, H., Lalande, M.
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|
<strong>Structure and organization of GABRB3 and GABRA5.</strong>
|
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Genomics 41: 63-69, 1997. Note: Erratum: Genomics 44: 155 only, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9126483/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9126483</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9126483" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1997.4639" 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="5" class="mim-anchor"></a>
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<a id="Hernandez2019" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hernandez, C. C., XiangWei, W., Hu, N., Shen, D., Shen, W., Lagrange, A. H., Zhang, Y., Dai, L., Ding, C., Sun, Z., Hu, J., Zhu, H., Jiang, Y., Macdonald, R. L.
|
|
<strong>Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.</strong>
|
|
Brain 142: 1938-1954, 2019.
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|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31056671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31056671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31056671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awz123" 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="6" class="mim-anchor"></a>
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<a id="Hogart2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H., Lasalle, J. M.
|
|
<strong>15q11-13 GABA(A) receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders.</strong>
|
|
Hum. Molec. Genet. 16: 691-703, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17339270/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17339270</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17339270[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=17339270" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddm014" 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="7" class="mim-anchor"></a>
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<a id="Knoll1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Knoll, J. H. M., Sinnett, D., Wagstaff, J., Glatt, K., Wilcox, A. S., Whiting, P., Wingrove, P., Sikela, J., Lalande, M.
|
|
<strong>FISH ordering of DNA markers within the Angelman/Prader-Willi chromosomal regions: mapping of a second GABA-A receptor subunit gene, GABRA5. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A9 only, 1992.
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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="8" class="mim-anchor"></a>
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<a id="Papadimitriou1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Papadimitriou, G. N., Dikeos, D. G., Karadima, G., Avramopoulos, D., Daskalopoulou, E. G., Vassilopoulos, D., Stefanis, C. N.
|
|
<strong>Association between the GABA-A receptor alpha-5 subunit gene locus (GABRA5) and bipolar affective disorder.</strong>
|
|
Am. J. Med. Genet. 81: 73-80, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9514592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9514592</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9514592" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</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="9" class="mim-anchor"></a>
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<a id="Ritchie1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Ritchie, R. J., Mattei, M.-G., Lalande, M.
|
|
<strong>A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications.</strong>
|
|
Hum. Molec. Genet. 7: 1253-1260, 1998.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9668167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9668167</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9668167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/7.8.1253" 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="Russek1994" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Russek, S. J., Farb, D. H.
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<strong>Mapping of the beta-2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABA-A receptor isoform.</strong>
|
|
Genomics 23: 528-533, 1994.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7851879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7851879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7851879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1994.1539" 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="11" class="mim-anchor"></a>
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<a id="Whiting1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Whiting, P. J., Bonnert, T. P., McKernan, R. M., Farrar, S., le Bourdelles, B., Heavens, R. P., Smith, D. W., Hewson, L., Rigby, M. R., Sirinathsinghji, D. J. S., Thompson, S. A., Wafford, K. A.
|
|
<strong>Molecular and functional diversity of the expanding GABA-A receptor gene family.</strong>
|
|
Ann. N.Y. Acad. Sci. 868: 645-653, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10414349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10414349</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10414349" 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/10.1111/j.1749-6632.1999.tb11341.x" 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="12" class="mim-anchor"></a>
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<a id="Wingrove1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Wingrove, P., Hadingham, K., Wafford, K., Kemp, J. A., Ragan, C. I., Whiting, P.
|
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<strong>Cloning and expression of a cDNA encoding the human GABA-A receptor alpha-5 subunit.</strong>
|
|
Biochem. Soc. Trans. 20: 18S only, 1991.
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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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</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 : 08/29/2019
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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 : 11/30/2010<br>Cassandra L. Kniffin - updated : 7/13/2010<br>Victor A. McKusick - updated : 11/6/1998<br>Rebekah S. Rasooly - updated : 5/29/1998<br>Orest Hurko - updated : 5/11/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<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 : 9/28/1992
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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 : 11/25/2020
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</span>
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</div>
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</div>
|
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<div class="row collapse" id="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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joanna : 11/13/2020<br>alopez : 09/04/2019<br>ckniffin : 08/29/2019<br>terry : 05/25/2012<br>alopez : 12/2/2010<br>terry : 11/30/2010<br>wwang : 7/14/2010<br>ckniffin : 7/13/2010<br>carol : 12/3/2009<br>carol : 11/23/2009<br>carol : 11/16/1998<br>terry : 11/6/1998<br>carol : 7/23/1998<br>alopez : 5/29/1998<br>terry : 5/28/1998<br>terry : 5/11/1998<br>mark : 4/10/1997<br>carol : 10/29/1992<br>carol : 10/23/1992<br>carol : 10/14/1992<br>carol : 10/9/1992<br>carol : 9/28/1992
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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> 137142
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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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GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-5; GABRA5
|
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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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GABA-A RECEPTOR, ALPHA-5 POLYPEPTIDE
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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: GABRA5</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: 15q12
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Genomic coordinates <span class="small">(GRCh38)</span> : 15:26,866,719-26,949,208 </span>
|
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</em>
|
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</strong>
|
|
<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">
|
|
<span class="mim-font">
|
|
15q12
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Developmental and epileptic encephalopathy 79
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
618559
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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">
|
|
<strong>TEXT</strong>
|
|
</span>
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</h4>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<p>Gamma-aminobutyric acid (GABA) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system. GABRA5 is a member of the GABA-A receptor gene family of heteromeric pentameric ligand-gated ion channels through which GABA, the major inhibitory neurotransmitter in the mammalian brain, acts. GABA-A receptors are the site of action of a number of important pharmacologic agents including barbiturates, benzodiazepines, and ethanol (summary by Whiting et al., 1999). </p><p>For additional general information about the GABA-A receptor gene family, see GABRA1 (137160).</p>
|
|
</span>
|
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<div>
|
|
<br />
|
|
</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>Cloning and Expression</strong>
|
|
</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>Wingrove et al. (1991) reported the cloning and expression of a cDNA corresponding to GABRA5. Overall, the human protein has 94% amino acid sequence identity with the rat alpha-5 subunit, with most of the differences occurring in the signal peptide and the putative large cytoplasmic loop domain. Human alpha-5 has 57% sequence identity with human alpha-1, again most of the amino acid differences being in the signal peptide and the putative large cytoplasmic loop domain. The expression studies indicated that GABA-A receptor subtypes containing alpha-5, like their rat equivalent, have a unique benzodiazepine pharmacology.</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By fluorescence in situ hybridization, Knoll et al. (1992) mapped the GABRA5 gene to chromosome 15q11-q13.</p><p>Russek and Farb (1994) stated that the gene encoding the gamma-3 form of the GABA-A receptor (GABRG3; 600233) is located on 15q11-q13 in a cluster with GABRA5 and GABRB3 (137192). </p>
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</span>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Glatt et al. (1997) reported that the GABRA5 gene contains 11 exons spanning 86 kb. There are 3 alternative first exons, a noncoding second exon, and a translation initiation site in exon 3. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using coding SNPs within the GABA receptor gene cluster on chromosome 15q11-q13, Hogart et al. (2007) demonstrated that the GABRG3, GABRB3, and GABRA5 genes were biallelically expressed in the cerebral cortex of 21 postmortem human brain samples. </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>Glatt et al. (1992) demonstrated a dinucleotide repeat polymorphism at the GABRA5 locus. A single maternal allele was observed in classic Prader-Willi syndrome (176270) cases and a single paternal allele in classic Angelman syndrome (105830) cases in which deletions had previously been demonstrated. </p><p>Ritchie et al. (1998) reported a partial duplication of GABRA5 within the imprinted 15q11-q13 region. The duplicated locus mapped to the pericentromeric region of 15q, proximal to the large deletions associated Angelman and Prader-Willi syndromes. They also observed variation in the number of copies of this locus in different individuals, indicating that the duplication is part of the variable repeat. Investigation of the duplication in individuals with a normal karyotype revealed between 1 and 4 copies of the repeat on each chromosome 15, whereas from 8 to 20 copies were found in individuals possessing a cytogenetically detectable elongation of the 15q region. The variable region is roughly 1 Mb long and contains 2 other nonprocessed duplications, the immunoglobulin heavy chain (IgH) D segment gene (IGHD; 147170) on 14q and the NF1 gene (613113) on chromosome 17. One unit of the pericentromeric repeat is thus composed of duplications of genes from different chromosomal regions. Ritchie et al. (1998) also found replication asynchrony across the GABRA5 duplication, suggesting for the first time that the imprinted part of chromosome 15q extends proximal of the region commonly deleted in Angelman and Prader-Willi syndromes. </p><p>Papadimitriou et al. (1998) found an association between a 282-bp CA repeat in the gene encoding GABRA5 and bipolar affective disorder in 48 unrelated southern Greek patients but not in 50 healthy individuals drawn from the same population. No association was seen in another sample of 40 unipolar patients in the same specimen. Even though the authors applied the Bonferroni correction for the total numbers of genes tested, they cautioned that the level of significance in association studies is still a matter of debate. They believed that the 282-bp allele is unlikely to have functional significance but does not represent stratification in their sample. Rather, they considered that the allele may be in linkage disequilibrium with a functional mutation elsewhere in the GABRA5 gene or another gene in close proximity. </p><p><strong><em>Developmental and Epileptic Encephalopathy 79</em></strong></p><p>
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In a 2-year-old boy (patient 1), born of unrelated parents, with developmental and epileptic encephalopathy-79 (DEE79; 618559), Butler et al. (2018) identified a de novo heterozygous missense mutation in the GABRA5 gene (V294L; 137142.0001). The mutation, which was found by trio-based whole-genome sequencing and confirmed by Sanger sequencing, occurred in the pore-forming transmembrane domain and was not found in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. </p><p>In 2 unrelated children (patients 1 and 2) with DEE79, Hernandez et al. (2019) identified de novo heterozygous mutations in the GABRA5 gene (V294F, 137142.0002 and S413F, 137142.0003). The mutations, which were found by next-generation sequencing of a targeted gene panel of 480 candidate genes in a cohort of 1,969 patients with a similar phenotype, were confirmed by Sanger sequencing and not present in the gnomAD database. In vitro functional expression studies of the mutations in rat primary hippocampal neurons and HEK293 cells showed variable abnormalities, including decreased expression of the mutant V294F protein at dendritic GABAergic synapses compared to wildtype; both variants resulted in decreased GABA-evoked current amplitudes compared to wildtype. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In mice, Clarkson et al. (2010) showed that after a stroke, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABA-A receptors and is caused by an impairment in GABA transporter function. To counteract the heightened inhibition, Clarkson et al. (2010) administered in vivo a benzodiazepine inverse agonist specific for alpha-5-subunit-containing extrasynaptic GABA-A receptors at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of alpha-5- or delta-subunit (GABRD; 137163)-containing GABA-A receptors responsible for tonic inhibition also proved beneficial for recovery after stroke, consistent with the therapeutic potential of diminishing extrasynaptic GABA-A receptor function. </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>3 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 79</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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GABRA5, VAL294LEU
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<br />
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SNP: rs1595438243,
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ClinVar: RCV000850105
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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 2-year-old boy (patient 1), born of unrelated parents, with developmental and epileptic encephalopathy-79 (DEE79; 618559), Butler et al. (2018) identified a de novo heterozygous c.880G-C transversion (c.880G-C, NM_000810) in the GABRA5 gene, resulting in a val294-to-leu (V294L) substitution at a highly conserved residue in the pore-forming M2 transmembrane domain. The mutation, which was found by trio-based whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. In vitro functional expression studies in HEK293 cells showed that the mutant subunit was expressed at the surface and incorporated into the channel, but the mutant channel was 10 times more sensitive to GABA compared to wildtype. This increased sensitization resulted in increased receptor desensitization to GABA, with a reduced maximal GABA-evoked current and impaired capacity to pass GABAergic chloride current. The patient had onset of various types of seizures at 4 months of age. </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>.0002 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 79</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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GABRA5, VAL294PHE
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<br />
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SNP: rs1595438243,
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ClinVar: RCV000850106, RCV002279564
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 4-year-old boy (patient 1) with developmental and epileptic encephalopathy-79 (DEE79; 618559), Hernandez et al. (2019) identified a de novo heterozygous c.880G-T transversion (c.880G-T, NM_000810.3) in the GABRA5 gene, resulting in a val294-to-phe (V294F) substitution at a conserved residue in the M2 pore domain. The mutation, which was found by next-generation sequencing of a targeted gene panel and confirmed by Sanger sequencing, was not found in the gnomAD database. Expression of the mutation in rat primary hippocampal neurons resulted in decreased expression of the mutant protein at dendritic GABAergic synapses compared to wildtype. The mutant protein showed aberrant accumulation within the soma of neurons and localization to the ER, suggesting a possible trafficking defect. Functional studies in neurons and HEK293 cells showed decreased cell surface expression of the mutant subunit and decreased GABA-evoked current amplitudes compared to wildtype. The patient presented with onset of multifocal seizures at 4 months of age. </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>.0003 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 79</strong>
|
|
</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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GABRA5, SER413PHE
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<br />
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SNP: rs1595441329,
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|
ClinVar: RCV000850107
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|
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
|
<p>In a 7-year-old boy (patient 2) with developmental and epileptic encephalopathy-79 (DEE79; 618559), Hernandez et al. (2019) identified a de novo heterozygous c.1238C-T transition (c.1238C-T, NM_000810.3) in the GABRA5 gene, resulting in a ser413-to-phe (S413F) substitution at a nonconserved residue in the intracellular N tail of the M4 domain. The mutation, which was found by next-generation sequencing of a targeted gene panel and confirmed by Sanger sequencing, was not found in the gnomAD database. Expression of the mutation into rat primary hippocampal neurons resulted in normal expression of the mutant protein at dendritic GABAergic synapses similar to wildtype. Functional studies in neurons and HEK293 cells showed that the mutation was associated with decreased GABA-evoked current amplitudes compared to wildtype. The S413F mutation also showed a dominant-negative effect by decreasing the trafficking of the partnering GABRB3 (137192) subunit to the cell surface, with no effect on other subunits. The patient had onset of epileptic spasms and focal and tonic seizures at 3 months of age. </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 />
|
|
</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">
|
|
Butler, K. M., Moody, O. A., Schuler, E., Coryell, J., Alexander, J. J., Jenkins, A., Escayg, A.
|
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<strong>De novo variations in GABRA2 and GABRA5 alter receptor function and contribute to early-onset epilepsy.</strong>
|
|
Brain 141: 2392-2405, 2018.
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[PubMed: 29961870]
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[Full Text: https://doi.org/10.1093/brain/awy171]
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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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Clarkson, A. N., Huang, B. S., MacIsaac, S. E., Mody, I., Carmichael, S. T.
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<strong>Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke.</strong>
|
|
Nature 468: 305-309, 2010.
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[PubMed: 21048709]
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[Full Text: https://doi.org/10.1038/nature09511]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Glatt, K. A., Sinnett, D., Lalande, M.
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|
<strong>Dinucleotide repeat polymorphism at the GABA-A receptor alpha-5 (GABRA5) locus at chromosome 15q11-q13.</strong>
|
|
Hum. Molec. Genet. 1: 348 only, 1992.
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[PubMed: 1338907]
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[Full Text: https://doi.org/10.1093/hmg/1.5.348]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Glatt, K., Glatt, H., Lalande, M.
|
|
<strong>Structure and organization of GABRB3 and GABRA5.</strong>
|
|
Genomics 41: 63-69, 1997. Note: Erratum: Genomics 44: 155 only, 1997.
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[PubMed: 9126483]
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[Full Text: https://doi.org/10.1006/geno.1997.4639]
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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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Hernandez, C. C., XiangWei, W., Hu, N., Shen, D., Shen, W., Lagrange, A. H., Zhang, Y., Dai, L., Ding, C., Sun, Z., Hu, J., Zhu, H., Jiang, Y., Macdonald, R. L.
|
|
<strong>Altered inhibitory synapses in de novo GABRA5 and GABRA1 mutations associated with early onset epileptic encephalopathies.</strong>
|
|
Brain 142: 1938-1954, 2019.
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[PubMed: 31056671]
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[Full Text: https://doi.org/10.1093/brain/awz123]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Hogart, A., Nagarajan, R. P., Patzel, K. A., Yasui, D. H., Lasalle, J. M.
|
|
<strong>15q11-13 GABA(A) receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders.</strong>
|
|
Hum. Molec. Genet. 16: 691-703, 2007.
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[PubMed: 17339270]
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[Full Text: https://doi.org/10.1093/hmg/ddm014]
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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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Knoll, J. H. M., Sinnett, D., Wagstaff, J., Glatt, K., Wilcox, A. S., Whiting, P., Wingrove, P., Sikela, J., Lalande, M.
|
|
<strong>FISH ordering of DNA markers within the Angelman/Prader-Willi chromosomal regions: mapping of a second GABA-A receptor subunit gene, GABRA5. (Abstract)</strong>
|
|
Am. J. Hum. Genet. 51 (suppl.): A9 only, 1992.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Papadimitriou, G. N., Dikeos, D. G., Karadima, G., Avramopoulos, D., Daskalopoulou, E. G., Vassilopoulos, D., Stefanis, C. N.
|
|
<strong>Association between the GABA-A receptor alpha-5 subunit gene locus (GABRA5) and bipolar affective disorder.</strong>
|
|
Am. J. Med. Genet. 81: 73-80, 1998.
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[PubMed: 9514592]
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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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Ritchie, R. J., Mattei, M.-G., Lalande, M.
|
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<strong>A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications.</strong>
|
|
Hum. Molec. Genet. 7: 1253-1260, 1998.
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[PubMed: 9668167]
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[Full Text: https://doi.org/10.1093/hmg/7.8.1253]
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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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Russek, S. J., Farb, D. H.
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<strong>Mapping of the beta-2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABA-A receptor isoform.</strong>
|
|
Genomics 23: 528-533, 1994.
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[PubMed: 7851879]
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[Full Text: https://doi.org/10.1006/geno.1994.1539]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Whiting, P. J., Bonnert, T. P., McKernan, R. M., Farrar, S., le Bourdelles, B., Heavens, R. P., Smith, D. W., Hewson, L., Rigby, M. R., Sirinathsinghji, D. J. S., Thompson, S. A., Wafford, K. A.
|
|
<strong>Molecular and functional diversity of the expanding GABA-A receptor gene family.</strong>
|
|
Ann. N.Y. Acad. Sci. 868: 645-653, 1999.
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[PubMed: 10414349]
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[Full Text: https://doi.org/10.1111/j.1749-6632.1999.tb11341.x]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Wingrove, P., Hadingham, K., Wafford, K., Kemp, J. A., Ragan, C. I., Whiting, P.
|
|
<strong>Cloning and expression of a cDNA encoding the human GABA-A receptor alpha-5 subunit.</strong>
|
|
Biochem. Soc. Trans. 20: 18S only, 1991.
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</p>
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</li>
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</ol>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<div class="row">
|
|
<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
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<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/29/2019<br>Ada Hamosh - updated : 11/30/2010<br>Cassandra L. Kniffin - updated : 7/13/2010<br>Victor A. McKusick - updated : 11/6/1998<br>Rebekah S. Rasooly - updated : 5/29/1998<br>Orest Hurko - updated : 5/11/1998
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Victor A. McKusick : 9/28/1992
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