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Entry
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- *137165 - SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GABA), MEMBER 1; SLC6A1
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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">*137165</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</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/137165">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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<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=ENSG00000157103;t=ENST00000287766" 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=6529" 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=137165" 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=ENSG00000157103;t=ENST00000287766" 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_001348250,NM_001348251,NM_001348252,NM_001348253,NM_003042,XM_005265411,XM_011534027,XM_017007071,XM_017007072" 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_003042" 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=137165" 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=00664&isoform_id=00664_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/SLC6A1" 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/31658,21707908,119584492,119584493,119584494,188528618,221040968,229462780,530373037,767924077,1034635178,1034635180,1134612281,1134612286,1134612297,1134612312,2462592069,2462592071,2462592073,2462592075,2462592077,2462592079" 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/P30531" 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=6529" 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=ENSG00000157103;t=ENST00000287766" 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=SLC6A1" 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=SLC6A1" 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+6529" 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/SLC6A1" 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:6529" 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/6529" 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=chr3&hgg_gene=ENST00000287766.10&hgg_start=10992748&hgg_end=11039247&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:11042" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=137165[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=137165[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/SLC6A1/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/ENSG00000157103" 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=SLC6A1" 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=SLC6A1" 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=SLC6A1" 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=SLC6A1&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/PA309" 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:11042" 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/FBgn0039915.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:95627" 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/SLC6A1#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:95627" 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/6529/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=6529" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00004910;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041114-57" 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="mimCellLines">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
|
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:137165" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</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:6529" 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=SLC6A1&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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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 230421008<br />
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<strong>ICD10CM:</strong> G40.4<br />
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">ICD+</a>
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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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137165
|
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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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SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GABA), MEMBER 1; SLC6A1
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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>
|
|
<h4>
|
|
<span class="mim-font">
|
|
GAMMA-AMINOBUTYRIC ACID TRANSPORTER<br />
|
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GABA TRANSPORTER; GABATR<br />
|
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GABATHG
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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>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SLC6A1" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC6A1</a></em></strong>
|
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</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/3/60?start=-3&limit=10&highlight=60">3p25.3</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr3:10992748-11039247&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'})">3:10,992,748-11,039,247</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
|
|
|
|
|
|
|
</span>
|
|
</p>
|
|
</div>
|
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/3/60?start=-3&limit=10&highlight=60">
|
|
3p25.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
Myoclonic-atonic epilepsy
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/616421"> 616421 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
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<p>The SLC6A1 gene encodes a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft (<a href="#3" class="mim-tip-reference" title="Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A. <strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong> Pharmacogenet. Genomics 19: 53-65, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19077666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19077666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19077666[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/10.1097/FPC.0b013e328318b21a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19077666">Hirunsatit et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19077666" 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="#7" class="mim-tip-reference" title="Nelson, H., Mandiyan, S., Nelson, N. <strong>Cloning of the human brain GABA transporter.</strong> FEBS Lett. 269: 181-184, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387399</a>] [<a href="https://doi.org/10.1016/0014-5793(90)81149-i" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2387399">Nelson et al. (1990)</a> cloned and sequenced a cDNA clone encoding the transporter for the neurotransmitter gamma-aminobutyric acid in human brain. The cDNA contained an open reading frame encoding a hydrophobic protein of 599 amino acids with a calculated molecular weight of 67,022 daltons. Hydropathy analysis showed 12 potential transmembrane segments. The human protein is highly homologous to that from rat brain. Northern hybridization demonstrated a ubiquitous distribution of the transporter in various parts of the brain. This gene, which they called GABATHG, was also cloned and sequenced by <a href="#6" class="mim-tip-reference" title="Lam, D. M.-K., Fei, J., Zhang, X.-Y., Tam, A. C. W., Zhu, L.-H., Huang, F., King, S. C., Guo, L.-H. <strong>Molecular cloning and structure of the human (GABATHG) GABA transporter gene.</strong> Molec. Brain Res. 19: 227-232, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8412566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8412566</a>] [<a href="https://doi.org/10.1016/0169-328x(93)90032-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8412566">Lam et al. (1993)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2387399+8412566" 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="#6" class="mim-tip-reference" title="Lam, D. M.-K., Fei, J., Zhang, X.-Y., Tam, A. C. W., Zhu, L.-H., Huang, F., King, S. C., Guo, L.-H. <strong>Molecular cloning and structure of the human (GABATHG) GABA transporter gene.</strong> Molec. Brain Res. 19: 227-232, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8412566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8412566</a>] [<a href="https://doi.org/10.1016/0169-328x(93)90032-k" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8412566">Lam et al. (1993)</a> determined that the SLC6A1 gene contains 15 exons and is approximately 25 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8412566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A. <strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong> Pharmacogenet. Genomics 19: 53-65, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19077666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19077666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19077666[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/10.1097/FPC.0b013e328318b21a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19077666">Hirunsatit et al. (2009)</a> stated that the SLC6A1 gene contains 16 exons. There are 2 main transcripts generated by alternative splicing: 1 includes exons 1 through 16, and the other includes exons 2 through 16. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19077666" 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="#8" class="mim-tip-reference" title="Zomot, E., Bendahan, A., Quick, M., Zhao, Y., Javitch, J. A., Kanner, B. I. <strong>Mechanism of chloride interaction with neurotransmitter:sodium symporters.</strong> Nature 449: 726-730, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704762</a>] [<a href="https://doi.org/10.1038/nature06133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704762">Zomot et al. (2007)</a> showed that introduction of a negatively charged amino acid at or near 1 of the 2 putative sodium binding sites of the GABA transporter GAT1 from rat brain (also called SLC6A1) renders both net flux and exchange of GABA largely chloride independent. In contrast to wildtype GAT1, a marked stimulation of the rate of net flux, but not of exchange, was observed when the internal pH was lowered. Equivalent mutations introduced in the mouse GABA transporter GAT4 (SLC6A11; <a href="/entry/607952">607952</a>) and the human dopamine transporter DAT (SLC6A3; <a href="/entry/126455">126455</a>) also result in chloride-independent transport, whereas the reciprocal mutations in LeuT and Tyt1 render substrate binding and/or uptake by these bacterial neurotransmitter:sodium symporters chloride independent. <a href="#8" class="mim-tip-reference" title="Zomot, E., Bendahan, A., Quick, M., Zhao, Y., Javitch, J. A., Kanner, B. I. <strong>Mechanism of chloride interaction with neurotransmitter:sodium symporters.</strong> Nature 449: 726-730, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704762</a>] [<a href="https://doi.org/10.1038/nature06133" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17704762">Zomot et al. (2007)</a> concluded that the negative charge, provided either by chloride or by the transporter itself, is required during binding and translocation of the neurotransmitter, probably to counterbalance the charge of the cotransported sodium ions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704762" 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="#5" class="mim-tip-reference" title="Huang, F., Shi, L. J., Heng, H. H. Q., Fei, J., Guo, L.-H. <strong>Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25.</strong> Genomics 29: 302-304, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8530094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8530094</a>] [<a href="https://doi.org/10.1006/geno.1995.1253" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8530094">Huang et al. (1995)</a> used fluorescence in situ hybridization to map the SLC6A1 gene to chromosome 3p25-p24. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8530094" 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="Hirunsatit, R., Ilomaki, R., Malison, R., Rasanen, P., Ilomaki, E., Kranzler, H. R., Kosten, T., Sughondhabirom, A., Thavichachart, N., Tangwongchai, S., Listman, J., Mutirangura, A., Gelernter, J., Lappalainen, J. <strong>Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research.</strong> BMC Genet. 8: 71, 2007. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17941974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17941974</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17941974[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/10.1186/1471-2156-8-71" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17941974">Hirunsatit et al. (2007)</a> identified a 21-bp insertion polymorphism in the predicted promoter region of the SLC6A1 gene upstream of exon 1 that creates a second tandem copy of the sequence. The insertion represents a variable number of tandem repeat (VNTR) polymorphism. The insertion allele was detected only in individuals of African descent, with a frequency of 39%. By in vitro functional expression studies, <a href="#3" class="mim-tip-reference" title="Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A. <strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong> Pharmacogenet. Genomics 19: 53-65, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19077666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19077666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19077666[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/10.1097/FPC.0b013e328318b21a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19077666">Hirunsatit et al. (2009)</a> showed that the SLC6A1 insertion promoter (2 copies of the sequence) had significantly greater promoter activity than the noninsertion (1 copy of the sequence) promoter, which in turn had greater activity than a promoterless control. The 2-copy insertion polymorphism created an enhancer element. Studies of postmortem hippocampus from 69 African American individuals showed that the SLC6A1 promoter genotype predicted SLC6A1 RNA expression and that overall SLC6A1 expression decreased with age. The allele frequency for the insertion was 14.5% in the African American postmortem sample and 18.1% in a sample of 69 Tanzanian individuals. <a href="#3" class="mim-tip-reference" title="Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A. <strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong> Pharmacogenet. Genomics 19: 53-65, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19077666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19077666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19077666[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/10.1097/FPC.0b013e328318b21a" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19077666">Hirunsatit et al. (2009)</a> postulated that this genetic variation may affect clinical response to drugs that bind the SLC6A1 receptor in populations of African descent. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=17941974+19077666" 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>Myoclonic-Atonic Epilepsy</em></strong></p><p>
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In 7 patients, including a mother and daughter, with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified 6 different heterozygous mutations in the SLC6A1 gene (see, e.g., <a href="#0001">137165.0001</a>-<a href="#0005">137165.0005</a>). One additional patient had a heterozygous deletion of chromosome 3p25 that included part of the SLC6A1 gene. Four of the mutations and the deletion occurred de novo; 1 affected child inherited the mutation from an affected mother, and another affected child inherited the mutation from an unaffected mother who was somatic mosaic for the mutation. Functional studies of the variants were not performed, but <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> postulated that the mutations resulted in a loss of function and disrupted the transport of GABA from the extracellular space into the presynaptic terminal. The mutations were found by direct sequencing of the SLC6A1 gene in 2 cohorts: the first 4 mutations were found in 4 of 569 individuals with epileptic encephalopathies, and the remaining 2 mutations were found in 2 of 75 individuals with myotonic-atonic epilepsy. Overall, SLC6A1 mutations occurred in 6 (4%) of 160 probands with MAE, suggesting that mutations in this gene result in a specific epilepsy syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" 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="#2" class="mim-tip-reference" title="Cope, D. W., Di Giovanni, G., Fyson, S. J., Orban, G., Errington, A. C., Lorincz, M. L., Gould, T. M., Carter, D. A., Crunelli, V. <strong>Enhanced tonic GABA-A inhibition in typical absence epilepsy.</strong> Nature Med. 15: 1392-1398, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966779[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966779">Cope et al. (2009)</a> found that Slc6a1-knockout mice developed spike-wave discharges characteristic of absence seizures (see, e.g., ECA1, <a href="/entry/600131">600131</a>). The activation of peri- or extrasynaptic GABA receptors by ambient GABA causes a persistently active, or tonic, inhibitory current. Extrasynaptic GABA-A receptors in thalamocortical neurons contain the delta subunit (GABRD; <a href="/entry/137163">137163</a>). In an established rat model of absence epilepsy with spontaneous spike-wave discharges called GAERS (genetic absence epilepsy rats from Strasbourg), <a href="#2" class="mim-tip-reference" title="Cope, D. W., Di Giovanni, G., Fyson, S. J., Orban, G., Errington, A. C., Lorincz, M. L., Gould, T. M., Carter, D. A., Crunelli, V. <strong>Enhanced tonic GABA-A inhibition in typical absence epilepsy.</strong> Nature Med. 15: 1392-1398, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966779[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/nm.2058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19966779">Cope et al. (2009)</a> found increased tonic current amplitude at thalamocortical GABA-A receptors beginning at postnatal day 17 compared to controls. Similarly increased tonic GABA-A receptor activation was observed in other mouse strains of absence epilepsy, including stargazer and lethargic mice, but not in tottering mice. Increased tonic inhibition was due to compromised GABA uptake by the GABA transporter GAT1 in the thalamus. Blockade or knockout of GAT1 in normal animals induced absence-like seizures. Mice without thalamic GABA-A receptors were resistant to pharmacologically induced seizures. Overall, these results showed that enhanced extrasynaptic GABA-A receptor activation in the thalamus may underlie absence seizures. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19966779" 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=137165[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">rs794726859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794726859;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=rs794726859" 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=rs794726859" 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=RCV001092965 OR RCV003156080 OR RCV003444212" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001092965, RCV003156080, RCV003444212" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001092965...</a>
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<p>In an 8-year-old girl with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified a de novo heterozygous c.131G-A transition (c.131G-A, NM_003042.3) in the SLC6A1 gene, resulting in an arg44-to-gln (R44Q) substitution at a highly conserved residue in the cytoplasmic domain. The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" 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">rs876657400 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876657400;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=rs876657400" 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=rs876657400" 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 16-year-old girl with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified a de novo heterozygous c.889G-A transition (c.889G-A, NM_003042.3) in the SLC6A1 gene, resulting in a gly297-to-arg (G297R) substitution at a highly conserved residue in transmembrane domain 6, which clusters around the GABA-binding pocket. The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MYOCLONIC-ATONIC EPILEPSY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs749240316 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs749240316;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs749240316?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs749240316" 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=rs749240316" 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 10-year-old girl with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified a heterozygous c.1000G-C transversion (c.1000G-C, NM_003042.3) in the SLC6A1 gene, resulting in an ala334-to-pro (A334P) substitution at a highly conserved residue in transmembrane domain 7, which clusters around the GABA-binding pocket. The mutation was inherited from the unaffected mother, who was somatic mosaic (18% mutation load in white cells). The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" 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>.0004 MYOCLONIC-ATONIC EPILEPSY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs876657401 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs876657401;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=rs876657401" 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=rs876657401" 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=RCV003444215" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003444215" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003444215</a>
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<p>In a 10-year-old boy with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified a de novo heterozygous 2-bp deletion (c.1369_1370delGG, NM_003042.3) in the SLC6A1 gene, resulting in a frameshift and premature termination (Gly457HisfsTer10). The mutation, which was found by direct sequencing of SLC6A1 gene, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MYOCLONIC-ATONIC EPILEPSY</strong>
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SLC6A1, ALA288VAL
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs794726860 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs794726860;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=rs794726860" 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=rs794726860" 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=RCV000414233 OR RCV000622292 OR RCV002508925 OR RCV003444216" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000414233, RCV000622292, RCV002508925, RCV003444216" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000414233...</a>
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<p>In a mother and daughter with myoclonic-atonic epilepsy (MAE; <a href="/entry/616421">616421</a>), <a href="#1" class="mim-tip-reference" title="Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others. <strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong> Am. J. Hum. Genet. 96: 808-815, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>] [<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25865495">Carvill et al. (2015)</a> identified a heterozygous c.863C-T transition (c.863C-T, NM_003042.3) in the SLC6A1 gene, resulting in an ala288-to-val (A288V) substitution at a highly conserved residue adjacent to transmembrane domain 6. The mutation was found by direct sequencing of SLC6A1. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Carvill2015" class="mim-anchor"></a>
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Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others.
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<strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong>
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Am. J. Hum. Genet. 96: 808-815, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25865495/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25865495</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25865495" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2015.02.016" target="_blank">Full Text</a>]
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<a id="Cope2009" class="mim-anchor"></a>
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Cope, D. W., Di Giovanni, G., Fyson, S. J., Orban, G., Errington, A. C., Lorincz, M. L., Gould, T. M., Carter, D. A., Crunelli, V.
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<strong>Enhanced tonic GABA-A inhibition in typical absence epilepsy.</strong>
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Nature Med. 15: 1392-1398, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19966779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19966779</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19966779[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=19966779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/nm.2058" target="_blank">Full Text</a>]
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<a id="Hirunsatit2009" class="mim-anchor"></a>
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Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A.
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<strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong>
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Pharmacogenet. Genomics 19: 53-65, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19077666/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19077666</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19077666[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=19077666" 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/10.1097/FPC.0b013e328318b21a" target="_blank">Full Text</a>]
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<a id="Hirunsatit2007" class="mim-anchor"></a>
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Hirunsatit, R., Ilomaki, R., Malison, R., Rasanen, P., Ilomaki, E., Kranzler, H. R., Kosten, T., Sughondhabirom, A., Thavichachart, N., Tangwongchai, S., Listman, J., Mutirangura, A., Gelernter, J., Lappalainen, J.
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<strong>Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research.</strong>
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BMC Genet. 8: 71, 2007. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17941974/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17941974</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17941974[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=17941974" 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/10.1186/1471-2156-8-71" target="_blank">Full Text</a>]
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<a id="Huang1995" class="mim-anchor"></a>
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Huang, F., Shi, L. J., Heng, H. H. Q., Fei, J., Guo, L.-H.
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<strong>Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25.</strong>
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Genomics 29: 302-304, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8530094/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8530094</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8530094" 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.1995.1253" target="_blank">Full Text</a>]
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<a id="Lam1993" class="mim-anchor"></a>
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Lam, D. M.-K., Fei, J., Zhang, X.-Y., Tam, A. C. W., Zhu, L.-H., Huang, F., King, S. C., Guo, L.-H.
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<strong>Molecular cloning and structure of the human (GABATHG) GABA transporter gene.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8412566/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8412566</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8412566" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0169-328x(93)90032-k" target="_blank">Full Text</a>]
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Nelson, H., Mandiyan, S., Nelson, N.
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<strong>Cloning of the human brain GABA transporter.</strong>
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FEBS Lett. 269: 181-184, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2387399/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2387399</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2387399" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0014-5793(90)81149-i" target="_blank">Full Text</a>]
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Zomot, E., Bendahan, A., Quick, M., Zhao, Y., Javitch, J. A., Kanner, B. I.
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<strong>Mechanism of chloride interaction with neurotransmitter:sodium symporters.</strong>
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Nature 449: 726-730, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17704762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17704762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17704762" 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/nature06133" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/15/2015
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Cassandra L. Kniffin - updated : 12/17/2009<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Ada Hamosh - updated : 10/26/2007
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Victor A. McKusick : 10/30/1990
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 11/20/2020
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 06/19/2015<br>mcolton : 6/18/2015<br>ckniffin : 6/15/2015<br>wwang : 1/6/2010<br>ckniffin : 12/17/2009<br>wwang : 7/22/2009<br>ckniffin : 6/18/2009<br>ckniffin : 6/18/2009<br>wwang : 4/17/2009<br>alopez : 11/1/2007<br>terry : 10/26/2007<br>carol : 3/8/2002<br>terry : 3/8/2002<br>mark : 4/1/1996<br>terry : 10/30/1995<br>mark : 10/3/1995<br>supermim : 3/16/1992<br>carol : 10/30/1990
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 137165
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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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SOLUTE CARRIER FAMILY 6 (NEUROTRANSMITTER TRANSPORTER, GABA), MEMBER 1; SLC6A1
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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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<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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GAMMA-AMINOBUTYRIC ACID TRANSPORTER<br />
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GABA TRANSPORTER; GABATR<br />
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GABATHG
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</span>
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</h4>
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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: SLC6A1</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 230421008;
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<strong>ICD10CM:</strong> G40.4;
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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: 3p25.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 3:10,992,748-11,039,247 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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<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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<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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</tr>
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</thead>
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<tbody>
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<td rowspan="1">
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<span class="mim-font">
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3p25.3
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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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Myoclonic-atonic epilepsy
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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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616421
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</td>
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<td>
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<span class="mim-font">
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Autosomal dominant
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The SLC6A1 gene encodes a gamma-aminobutyric acid (GABA) transporter, which removes GABA from the synaptic cleft (Hirunsatit et al., 2009). </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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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Nelson et al. (1990) cloned and sequenced a cDNA clone encoding the transporter for the neurotransmitter gamma-aminobutyric acid in human brain. The cDNA contained an open reading frame encoding a hydrophobic protein of 599 amino acids with a calculated molecular weight of 67,022 daltons. Hydropathy analysis showed 12 potential transmembrane segments. The human protein is highly homologous to that from rat brain. Northern hybridization demonstrated a ubiquitous distribution of the transporter in various parts of the brain. This gene, which they called GABATHG, was also cloned and sequenced by Lam et al. (1993). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Structure</strong>
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</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>Lam et al. (1993) determined that the SLC6A1 gene contains 15 exons and is approximately 25 kb. </p><p>Hirunsatit et al. (2009) stated that the SLC6A1 gene contains 16 exons. There are 2 main transcripts generated by alternative splicing: 1 includes exons 1 through 16, and the other includes exons 2 through 16. </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>Zomot et al. (2007) showed that introduction of a negatively charged amino acid at or near 1 of the 2 putative sodium binding sites of the GABA transporter GAT1 from rat brain (also called SLC6A1) renders both net flux and exchange of GABA largely chloride independent. In contrast to wildtype GAT1, a marked stimulation of the rate of net flux, but not of exchange, was observed when the internal pH was lowered. Equivalent mutations introduced in the mouse GABA transporter GAT4 (SLC6A11; 607952) and the human dopamine transporter DAT (SLC6A3; 126455) also result in chloride-independent transport, whereas the reciprocal mutations in LeuT and Tyt1 render substrate binding and/or uptake by these bacterial neurotransmitter:sodium symporters chloride independent. Zomot et al. (2007) concluded that the negative charge, provided either by chloride or by the transporter itself, is required during binding and translocation of the neurotransmitter, probably to counterbalance the charge of the cotransported sodium ions. </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>Huang et al. (1995) used fluorescence in situ hybridization to map the SLC6A1 gene to chromosome 3p25-p24. </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>Hirunsatit et al. (2007) identified a 21-bp insertion polymorphism in the predicted promoter region of the SLC6A1 gene upstream of exon 1 that creates a second tandem copy of the sequence. The insertion represents a variable number of tandem repeat (VNTR) polymorphism. The insertion allele was detected only in individuals of African descent, with a frequency of 39%. By in vitro functional expression studies, Hirunsatit et al. (2009) showed that the SLC6A1 insertion promoter (2 copies of the sequence) had significantly greater promoter activity than the noninsertion (1 copy of the sequence) promoter, which in turn had greater activity than a promoterless control. The 2-copy insertion polymorphism created an enhancer element. Studies of postmortem hippocampus from 69 African American individuals showed that the SLC6A1 promoter genotype predicted SLC6A1 RNA expression and that overall SLC6A1 expression decreased with age. The allele frequency for the insertion was 14.5% in the African American postmortem sample and 18.1% in a sample of 69 Tanzanian individuals. Hirunsatit et al. (2009) postulated that this genetic variation may affect clinical response to drugs that bind the SLC6A1 receptor in populations of African descent. </p><p><strong><em>Myoclonic-Atonic Epilepsy</em></strong></p><p>
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|
In 7 patients, including a mother and daughter, with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified 6 different heterozygous mutations in the SLC6A1 gene (see, e.g., 137165.0001-137165.0005). One additional patient had a heterozygous deletion of chromosome 3p25 that included part of the SLC6A1 gene. Four of the mutations and the deletion occurred de novo; 1 affected child inherited the mutation from an affected mother, and another affected child inherited the mutation from an unaffected mother who was somatic mosaic for the mutation. Functional studies of the variants were not performed, but Carvill et al. (2015) postulated that the mutations resulted in a loss of function and disrupted the transport of GABA from the extracellular space into the presynaptic terminal. The mutations were found by direct sequencing of the SLC6A1 gene in 2 cohorts: the first 4 mutations were found in 4 of 569 individuals with epileptic encephalopathies, and the remaining 2 mutations were found in 2 of 75 individuals with myotonic-atonic epilepsy. Overall, SLC6A1 mutations occurred in 6 (4%) of 160 probands with MAE, suggesting that mutations in this gene result in a specific epilepsy syndrome. </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>Cope et al. (2009) found that Slc6a1-knockout mice developed spike-wave discharges characteristic of absence seizures (see, e.g., ECA1, 600131). The activation of peri- or extrasynaptic GABA receptors by ambient GABA causes a persistently active, or tonic, inhibitory current. Extrasynaptic GABA-A receptors in thalamocortical neurons contain the delta subunit (GABRD; 137163). In an established rat model of absence epilepsy with spontaneous spike-wave discharges called GAERS (genetic absence epilepsy rats from Strasbourg), Cope et al. (2009) found increased tonic current amplitude at thalamocortical GABA-A receptors beginning at postnatal day 17 compared to controls. Similarly increased tonic GABA-A receptor activation was observed in other mouse strains of absence epilepsy, including stargazer and lethargic mice, but not in tottering mice. Increased tonic inhibition was due to compromised GABA uptake by the GABA transporter GAT1 in the thalamus. Blockade or knockout of GAT1 in normal animals induced absence-like seizures. Mice without thalamic GABA-A receptors were resistant to pharmacologically induced seizures. Overall, these results showed that enhanced extrasynaptic GABA-A receptor activation in the thalamus may underlie absence seizures. </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>5 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 MYOCLONIC-ATONIC EPILEPSY</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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SLC6A1, ARG44GLN
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<br />
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SNP: rs794726859,
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ClinVar: RCV001092965, RCV003156080, RCV003444212
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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 an 8-year-old girl with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified a de novo heterozygous c.131G-A transition (c.131G-A, NM_003042.3) in the SLC6A1 gene, resulting in an arg44-to-gln (R44Q) substitution at a highly conserved residue in the cytoplasmic domain. The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 MYOCLONIC-ATONIC EPILEPSY</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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SLC6A1, GLY297ARG
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<br />
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SNP: rs876657400,
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ClinVar: RCV001268638, RCV003444213
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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 16-year-old girl with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified a de novo heterozygous c.889G-A transition (c.889G-A, NM_003042.3) in the SLC6A1 gene, resulting in a gly297-to-arg (G297R) substitution at a highly conserved residue in transmembrane domain 6, which clusters around the GABA-binding pocket. The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 MYOCLONIC-ATONIC EPILEPSY</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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SLC6A1, ALA334PRO
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<br />
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SNP: rs749240316,
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gnomAD: rs749240316,
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ClinVar: RCV003444214
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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 10-year-old girl with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified a heterozygous c.1000G-C transversion (c.1000G-C, NM_003042.3) in the SLC6A1 gene, resulting in an ala334-to-pro (A334P) substitution at a highly conserved residue in transmembrane domain 7, which clusters around the GABA-binding pocket. The mutation was inherited from the unaffected mother, who was somatic mosaic (18% mutation load in white cells). The mutation, which was found by direct sequencing of SLC6A1, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 MYOCLONIC-ATONIC EPILEPSY</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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SLC6A1, 2-BP DEL, 1369GG
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<br />
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SNP: rs876657401,
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ClinVar: RCV003444215
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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 10-year-old boy with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified a de novo heterozygous 2-bp deletion (c.1369_1370delGG, NM_003042.3) in the SLC6A1 gene, resulting in a frameshift and premature termination (Gly457HisfsTer10). The mutation, which was found by direct sequencing of SLC6A1 gene, was not present in the Exome Aggregation Consortium database. Functional studies of the variant were not performed. </p>
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<span class="mim-font">
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<strong>.0005 MYOCLONIC-ATONIC EPILEPSY</strong>
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</h4>
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<span class="mim-text-font">
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SLC6A1, ALA288VAL
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<br />
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SNP: rs794726860,
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ClinVar: RCV000414233, RCV000622292, RCV002508925, RCV003444216
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<p>In a mother and daughter with myoclonic-atonic epilepsy (MAE; 616421), Carvill et al. (2015) identified a heterozygous c.863C-T transition (c.863C-T, NM_003042.3) in the SLC6A1 gene, resulting in an ala288-to-val (A288V) substitution at a highly conserved residue adjacent to transmembrane domain 6. The mutation was found by direct sequencing of SLC6A1. Functional studies of the variant were not performed. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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Carvill, G. L., McMahon, J. M., Schneider, A., Zemel, M., Myers, C. T., Saykally, J., Nguyen, J., Robbiano, A., Zara, F., Specchio, N., Mecarelli, O., Smith, R. L., and 13 others.
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<strong>Mutations in the GABA transporter SLC6A1 cause epilepsy with myoclonic-atonic seizures.</strong>
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Am. J. Hum. Genet. 96: 808-815, 2015.
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[PubMed: 25865495]
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[Full Text: https://doi.org/10.1016/j.ajhg.2015.02.016]
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</li>
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Cope, D. W., Di Giovanni, G., Fyson, S. J., Orban, G., Errington, A. C., Lorincz, M. L., Gould, T. M., Carter, D. A., Crunelli, V.
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<strong>Enhanced tonic GABA-A inhibition in typical absence epilepsy.</strong>
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Nature Med. 15: 1392-1398, 2009.
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[PubMed: 19966779]
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[Full Text: https://doi.org/10.1038/nm.2058]
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</li>
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<li>
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Hirunsatit, R., George, E. D., Lipska, B. K., Elwafi, H. M., Sander, L., Yrigollen, C. M., Gelernter, J., Grigoenko, E. L., Lappalainen, J., Mane, S., Nairn, A. C., Kleinman, J. E., Simen, A. A.
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<strong>Twenty-one-base-pair insertion polymorphism creates an enhancer element and potentiates SLC6A1 GABA transporter promoter activity.</strong>
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Pharmacogenet. Genomics 19: 53-65, 2009.
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[PubMed: 19077666]
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[Full Text: https://doi.org/10.1097/FPC.0b013e328318b21a]
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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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Hirunsatit, R., Ilomaki, R., Malison, R., Rasanen, P., Ilomaki, E., Kranzler, H. R., Kosten, T., Sughondhabirom, A., Thavichachart, N., Tangwongchai, S., Listman, J., Mutirangura, A., Gelernter, J., Lappalainen, J.
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<strong>Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research.</strong>
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BMC Genet. 8: 71, 2007. Note: Electronic Article.
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[PubMed: 17941974]
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[Full Text: https://doi.org/10.1186/1471-2156-8-71]
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</li>
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<p class="mim-text-font">
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Huang, F., Shi, L. J., Heng, H. H. Q., Fei, J., Guo, L.-H.
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<strong>Assignment of the human GABA transporter gene (GABATHG) locus to chromosome 3p24-p25.</strong>
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Genomics 29: 302-304, 1995.
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[PubMed: 8530094]
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[Full Text: https://doi.org/10.1006/geno.1995.1253]
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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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Lam, D. M.-K., Fei, J., Zhang, X.-Y., Tam, A. C. W., Zhu, L.-H., Huang, F., King, S. C., Guo, L.-H.
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<strong>Molecular cloning and structure of the human (GABATHG) GABA transporter gene.</strong>
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Molec. Brain Res. 19: 227-232, 1993.
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[PubMed: 8412566]
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[Full Text: https://doi.org/10.1016/0169-328x(93)90032-k]
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</li>
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<li>
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<p class="mim-text-font">
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Nelson, H., Mandiyan, S., Nelson, N.
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<strong>Cloning of the human brain GABA transporter.</strong>
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FEBS Lett. 269: 181-184, 1990.
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[PubMed: 2387399]
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[Full Text: https://doi.org/10.1016/0014-5793(90)81149-i]
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Zomot, E., Bendahan, A., Quick, M., Zhao, Y., Javitch, J. A., Kanner, B. I.
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<strong>Mechanism of chloride interaction with neurotransmitter:sodium symporters.</strong>
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Nature 449: 726-730, 2007.
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[PubMed: 17704762]
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[Full Text: https://doi.org/10.1038/nature06133]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 6/15/2015<br>Cassandra L. Kniffin - updated : 12/17/2009<br>Cassandra L. Kniffin - updated : 6/18/2009<br>Ada Hamosh - updated : 10/26/2007
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<span class="mim-text-font">
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Victor A. McKusick : 10/30/1990
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alopez : 11/20/2020<br>carol : 06/19/2015<br>mcolton : 6/18/2015<br>ckniffin : 6/15/2015<br>wwang : 1/6/2010<br>ckniffin : 12/17/2009<br>wwang : 7/22/2009<br>ckniffin : 6/18/2009<br>ckniffin : 6/18/2009<br>wwang : 4/17/2009<br>alopez : 11/1/2007<br>terry : 10/26/2007<br>carol : 3/8/2002<br>terry : 3/8/2002<br>mark : 4/1/1996<br>terry : 10/30/1995<br>mark : 10/3/1995<br>supermim : 3/16/1992<br>carol : 10/30/1990
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