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Entry
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- *606152 - SOLUTE CARRIER FAMILY 19 (THIAMINE TRANSPORTER), MEMBER 3; SLC19A3
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- OMIM
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<p>
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<span class="h4">*606152</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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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/606152">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000135917;t=ENST00000644224" 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=80704" 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=606152" 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 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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<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=ENSG00000135917;t=ENST00000644224" 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_001371411,NM_001371412,NM_001371413,NM_001371414,NM_025243,XM_047445927" 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_025243" 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=606152" 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=07311&isoform_id=07311_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/SLC19A3" 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/12483888,13376856,14582572,21594843,62702231,74733486,119591281,119591282,189065532,221043640,1701108468,1701108470,1701108472,1701108488,2217331217" 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/Q9BZV2" 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=80704" 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=ENSG00000135917;t=ENST00000644224" 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=SLC19A3" 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=SLC19A3" 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+80704" 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/SLC19A3" 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:80704" 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/80704" 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=chr2&hgg_gene=ENST00000644224.2&hgg_start=227683763&hgg_end=227718028&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 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/genes/HGNC:16266" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/slc19a3" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=606152[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606152[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://gnomad.broadinstitute.org/gene/ENSG00000135917" 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=SLC19A3" 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=SLC19A3" 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=SLC19A3" 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=SLC19A3&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/PA38397" 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:16266" 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/FBgn0032449.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:1931307" 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/SLC19A3#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:1931307" 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/80704/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://omia.org/OMIA001097/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=80704" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00007388;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00007388 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00018138;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00018138 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00044738;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00044738 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-050419-166" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:80704" 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=SLC19A3&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> 703522009<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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606152
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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 19 (THIAMINE TRANSPORTER), MEMBER 3; SLC19A3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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THIAMINE TRANSPORTER 2; THTR2
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=SLC19A3" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">SLC19A3</a></em></strong>
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</span>
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</p>
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</div>
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<div>
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<a id="cytogeneticLocation" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: <a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075">2q36.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:227683763-227718028&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'})">2:227,683,763-227,718,028</a> </span>
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</em>
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</strong>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
|
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<span class="mim-font">
|
|
<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075">
|
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2q36.3
|
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type)
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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<a href="/entry/607483"> 607483 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<p>SLC19A3 encodes a thiamine transporter (<a href="#6" class="mim-tip-reference" title="Rajgopal, A., Edmondnson, A., Goldman, I. D., Zhao, R. <strong>SLC19A3 encodes a second thiamine transporter ThTr2.</strong> Biochim. Biophys. Acta 1537: 175-178, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11731220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11731220</a>] [<a href="https://doi.org/10.1016/s0925-4439(01)00073-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11731220">Rajgopal et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731220" 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>By EST database searching with the RFC1 (SLC19A1; <a href="/entry/600424">600424</a>) protein sequence as query, PCR, and screening of a human placenta cDNA library, <a href="#3" class="mim-tip-reference" title="Eudy, J. D., Spiegelstein, O., Barber, R. C., Wlodarczyk, B. J., Talbot, J., Finnell, R. H. <strong>Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes.</strong> Molec. Genet. Metab. 71: 581-590, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11136550/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11136550</a>] [<a href="https://doi.org/10.1006/mgme.2000.3112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11136550">Eudy et al. (2000)</a> cloned a full-length SLC19A3 cDNA encoding a 496-amino acid protein. They also cloned the mouse homolog from a kidney cDNA library. Human SLC19A3 shares 39%, 48%, and 68% amino acid sequence identity with human SLC19A1 and SLC19A2 (<a href="/entry/603941">603941</a>) and mouse Slc19a3, respectively. Northern blot analysis of human tissues detected 3 transcripts of approximately 3.5, 2.6, and 2.0 kb in placenta, kidney, and liver. Highest expression was observed in placenta, with all 3 transcripts exhibiting similar levels of expression. In the liver and kidney, the 3.5-kb transcript was the most abundant. PCR analysis detected SLC19A3 transcripts in almost all tissues tested. Northern blot analysis in mouse tissues detected a single transcript in brain, kidney, lung, small intestine, heart, and testis, with the highest abundance in kidney and brain. PCR analysis identified weak expression of the mouse gene beginning at embryonic day 8.5 which peaked at E19 just prior to parturition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11136550" 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="#5" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> found high SLC19A3 expression in human thalamus compared to other brain regions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Subramanya, S. B., Subramanian, V. S., Sekar, V. T., Said, H. M. <strong>Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure.</strong> Am. J. Physiol. Gastrointest. Liver Physiol. 301: G896-G904, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21868632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21868632</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21868632[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/10.1152/ajpgi.00308.2011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21868632">Subramanya et al. (2011)</a> found expression of both the Slc19a2 and Slc19a3 genes in rat pancreatic acinar cells, with Slc19a2 showing higher expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21868632" 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>By assaying transfected HeLa cells, <a href="#6" class="mim-tip-reference" title="Rajgopal, A., Edmondnson, A., Goldman, I. D., Zhao, R. <strong>SLC19A3 encodes a second thiamine transporter ThTr2.</strong> Biochim. Biophys. Acta 1537: 175-178, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11731220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11731220</a>] [<a href="https://doi.org/10.1016/s0925-4439(01)00073-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11731220">Rajgopal et al. (2001)</a> found that human SLC19A3 mediated transport of radiolabeled thiamine, but not folic acid, pyridoxine, niacin, methotrexate, or other organic cations examined. The pH optimum for thiamine transport was pH 7.4. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In cellular studies, <a href="#8" class="mim-tip-reference" title="Subramanian, V. S., Marchant, J. S., Said, H. M. <strong>Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.</strong> Am. J. Physiol. Cell Physiol. 291: C851-C859, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16790503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16790503</a>] [<a href="https://doi.org/10.1152/ajpcell.00105.2006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16790503">Subramanian et al. (2006)</a> demonstrated that SLC19A3 is a thiamine transporter expressed at the apical surface of polarized cells, but it does not function as a biotin transporter. SLC19A3 was also expressed in human glioma cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16790503" 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>Biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>), also known as thiamine metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is an autosomal recessive disorder with childhood onset that presents as a subacute encephalopathy and progresses to severe cogwheel rigidity, dystonia, quadriparesis, and eventually death if left untreated. <a href="#12" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[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/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> stated that all patients diagnosed to that time were of Saudi, Syrian, or Yemeni ancestry, and all had consanguineous parents. Using linkage analysis in 4 families, they mapped the genetic defect to 2q36.3 to a minimum candidate region of approximately 2 Mb on the basis of complete homozygosity. In this segment, each family displayed 1 of 2 different missense mutations that altered the coding sequence of SLC19A3 (<a href="#0001">606152.0001</a> and <a href="#0002">606152.0002</a>). The mutations were on different haplotypes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Portuguese brother and sister with BTBGD, <a href="#1" class="mim-tip-reference" title="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al. (2010)</a> identified compound heterozygosity for 2 truncating mutations in the SLC19A3 gene (<a href="#0005">606152.0005</a>-<a href="#0006">606152.0006</a>), confirming that the disorder results from loss of function of this transporter. Each unaffected parent was heterozygous for 1 of the mutations. One of the patients only showed a therapeutic response to thiamine. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20065143" 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="#5" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> reported 2 Japanese brothers with onset of encephalopathy in the second decade of life. Genetic analysis identified compound heterozygous mutations in the SLC19A3 gene (<a href="#0003">606152.0003</a>-<a href="#0004">606152.0004</a>) in both brothers. <a href="#5" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> stated that the phenotype differed from biotin-responsive basal ganglia disease because brain lesions were found in the thalamus and periaqueductal regions, not in the basal ganglia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In affected patients from 3 families from the Al Hoceima province in northern Morocco with BTBGD manifest as severe infantile-onset fatal encephalopathy and Leigh syndrome (see <a href="/entry/256000">256000</a>) on brain imaging, <a href="#4" class="mim-tip-reference" title="Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H. <strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong> Brain 136: 882-890, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>] [<a href="https://doi.org/10.1093/brain/awt013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23423671">Gerards et al. (2013)</a> identified the same homozygous truncating mutation in the SLC19A3 gene (S7X; <a href="#0007">606152.0007</a>). Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing; the mutations in the subsequent families were found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" 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="Reidling, J. C., Lambrecht, N., Kassir, M., Said, H. M. <strong>Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice.</strong> Gastroenterology 138: 1802-1809, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19879271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19879271</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19879271[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/10.1053/j.gastro.2009.10.042" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19879271">Reidling et al. (2010)</a> found that Slc19a3-null mice had reduced uptake of intestinal thiamine and decreased serum thiamine compared to wildtype mice. However, intestinal uptake of thiamine in Slc19a2-null mice was not significantly different from that of wildtype mice. Moreover, the level of expression of Slc19a2 was not altered in the intestine of Slc19a3-null mice, but the level of expression of Slc19a3 was upregulated in the intestine of Slc19a2-null mice, thus compensating for the defect. The findings suggested that Slc19a3 is required for normal uptake of thiamine in the intestine, and can fulfill normal levels of uptake in conditions associated with Slc19a2 dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19879271" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Subramanya, S. B., Subramanian, V. S., Sekar, V. T., Said, H. M. <strong>Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure.</strong> Am. J. Physiol. Gastrointest. Liver Physiol. 301: G896-G904, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21868632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21868632</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21868632[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/10.1152/ajpgi.00308.2011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21868632">Subramanya et al. (2011)</a> found expression of both the Slc19a2 and Slc19a3 genes in rat pancreatic acinar cells. Chronic alcohol feeding of rats resulted in significant inhibition of carrier-mediated thiamine uptake by pancreatic acinar cells, and was associated with a significant reduction in expression of Slc19a2 and Slc19a3 at the protein and mRNA levels. The results demonstrated that thiamine uptake by pancreatic acinar cells occurs through a carrier-mediated process, and that thiamine transporters are expressed in these cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21868632" 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>Alaskan Husky encephalopathy (AHE), a fatal brain disease in young Alaskan Husky dogs, presents as a multifocal central nervous system deficit with seizures, altered mentation, dysphagia, central blindness, hypermetria, proprioceptive positioning deficits, ataxia, and tetraparesis. Brain imaging shows abnormal intracranial lesions consistent with Leigh syndrome in humans. <a href="#10" class="mim-tip-reference" title="Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L. <strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong> PLoS One 8: e57195, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23469184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23469184</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23469184[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/10.1371/journal.pone.0057195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23469184">Vernau et al. (2013)</a> determined that AHE is caused by homozygosity for a 4-bp deletion and a single nucleotide change (c.624insTTGC, c.625C-A) in the Slc19a3.1 gene that is predicted to result in a protein truncation. Heterozygosity for the mutation was found in 15 of 41 healthy Alaskan Husky control dogs, but not in another 187 dogs of different breeds. Canines have 2 paralogs of SLC19A3, Slc19a3.1 and Slc19a3.2, resulting from gene duplication. Slc19a3.1 is primarily expressed in the cerebrum, cerebellum, spinal cord, kidney, and testes, whereas Slc19a3.2 is mainly expressed in the kidney and liver, suggesting tissue-specific expression of these paralogs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23469184" 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="#11" class="mim-tip-reference" title="Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C. <strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong> Brain Path. 25: 441-453, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25117056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25117056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25117056[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/10.1111/bpa.12188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25117056">Vernau et al. (2015)</a> found that the cerebral cortex and thalamus of 2 dogs with AHE were severely deficient in thiamine pyrophosphate (TPP)-dependent enzymes compared to controls. These decreases in enzymatic activity were accompanied by decreases in mitochondrial mass, mtDNA copy number, and oxidative phosphorylation, although the latter decreases did not meet the threshold for a mitochondrial respiratory chain disorder. Affected brain tissue also showed evidence of increased oxidative stress. The findings indicated that the phenotype results from a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25117056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=606152[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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> rs121917882 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121917882;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/rs121917882?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=rs121917882" 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=rs121917882" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 patients with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>) in a Yemeni family, <a href="#12" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[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/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> found a homozygous G-to-T change at nucleotide 68 in exon 2 of the SLC19A3 gene, which was predicted to alter a highly conserved glycine at codon 23 to valine (G23V). This mutation was predicted to alter the first transmembrane domain of the SLC19A3 protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In canine kidney cells and human duodenal cells, both polarized epithelial cell lines, <a href="#8" class="mim-tip-reference" title="Subramanian, V. S., Marchant, J. S., Said, H. M. <strong>Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.</strong> Am. J. Physiol. Cell Physiol. 291: C851-C859, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16790503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16790503</a>] [<a href="https://doi.org/10.1152/ajpcell.00105.2006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16790503">Subramanian et al. (2006)</a> showed that the G23V mutant protein localized normally to the apical plasma membrane, similar to the wildtype protein, but showed decreased expression. However, cells expressing the mutant SLC19A3 protein had significantly impaired thiamine transport, similar to untransfected cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16790503" 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=RCV000004825 OR RCV000489300 OR RCV002512775 OR RCV004527286" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004825, RCV000489300, RCV002512775, RCV004527286" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004825...</a>
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<p>In 3 families, all of Saudi origin, with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>), <a href="#12" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[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/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> identified an A-to-G transition at nucleotide position 1264 in exon 5 of the SLC19A3, predicted to result in a substitution of threonine at codon 422 to alanine (T422A). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Eichler, F. S., Swoboda, K. J., Hunt, A. L., Cestari, D. M., Rapalino, O. <strong>Case 38-2017: A 20-year-old woman with seizures and progressive dystonia.</strong> New Eng. J. Med. 377: 2376-2384, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29236641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29236641</a>] [<a href="https://doi.org/10.1056/NEJMcpc1706109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29236641">Eichler et al. (2017)</a> reported a 20-year-old Saudi woman with BTBGD who was homozygous for the T422A mutation in the SLC19A3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29236641" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In canine kidney cells and human duodenal cells, both polarized epithelial cell lines, <a href="#8" class="mim-tip-reference" title="Subramanian, V. S., Marchant, J. S., Said, H. M. <strong>Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.</strong> Am. J. Physiol. Cell Physiol. 291: C851-C859, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16790503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16790503</a>] [<a href="https://doi.org/10.1152/ajpcell.00105.2006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16790503">Subramanian et al. (2006)</a> showed that the T422A mutant protein, which is in transmembrane domain 11, localized normally to the apical plasma membrane, similar to the wildtype protein, but showed decreased expression. However, cells expressing the mutant SLC19A3 protein had significantly impaired thiamine transport, similar to untransfected cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16790503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852957 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852957;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/rs137852957?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=rs137852957" 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=rs137852957" 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=RCV000004827" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004827" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004827</a>
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<p>In 2 Japanese brothers with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>) characterized by diplopia, seizures, and white matter changes in the thalamus without serum thiamine deficiency, <a href="#5" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> identified compound heterozygosity for 2 mutations in the SLC19A3 gene: a 218A-G transition in exon 2, resulting in a lys44-to-glu (K44E) substitution, and a 1047G-C transversion in exon 3, resulting in a glu320-to-gln (E320Q; <a href="#0004">606152.0004</a>) substitution. These mutations were not present among 192 ethnically matched controls. In vitro functional cellular expression studies showed that most of the K44E-mutant protein was impaired in intracellular transport while remaining normal in the endoplasmic reticulum. The E320Q mutant was identical in cell surface localization to wildtype protein but showed significantly decreased intracellular thiamine uptake activity. Onset of symptoms was in the second decade of life. Both patients also had severe partial complex seizures that were responsive to high-dose thiamine. Magnetic resonance imaging (MRI) of the brain showed high-intensity signals in the bilateral medial thalamus and periaqueductal region, which were characteristic of findings in Wernicke encephalopathy (<a href="/entry/277730">277730</a>), but there was no history of chronic alcohol use. These changes became normal within 1 month after treatment. Subacute ophthalmoplegia with nystagmus and ataxia occurred repeatedly within several months after the discontinuation of 100 mg of thiamine per day. There were no extrapyramidal features. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" 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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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> rs137852958 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852958;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/rs137852958?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=rs137852958" 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=rs137852958" 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=RCV000004828" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000004828" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000004828</a>
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<p>For discussion of the glu320-to-gln (E320Q) mutation in the SLC19A3 gene that was found in compound heterozygous state in 2 Japanese brothers with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>) by <a href="#5" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a>, see <a href="#0003">606152.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" 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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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> rs786205213 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205213;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/rs786205213?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=rs786205213" 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=rs786205213" 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=RCV000170443 OR RCV000367514" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170443, RCV000367514" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170443...</a>
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<p>In a Portuguese brother and sister with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>) <a href="#1" class="mim-tip-reference" title="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al. (2010)</a> identified compound heterozygosity for 2 mutations in the SLC19A3 gene: a 1-bp duplication (74dupT) in exon 2, resulting in a frameshift and premature termination, and an A-to-G transition in intron 3 (980-14A-G; <a href="#0006">606152.0006</a>), resulting in the skipping of exon 4 and an aberrantly spliced transcript degraded by nonsense-mediated mRNA decay. Each unaffected parent was heterozygous for 1 of the mutations. The brother was treated with high-dose biotin, which resulted in improvement of clinical features and disappearance of signal abnormalities on follow-up MRI. The sister was treated with high-dose biotin after worsening of her epilepsy, but she did not show improvement until thiamine was added. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20065143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</strong>
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SLC19A3, IVS3AS, A-G, -14
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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> rs200542114 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200542114;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/rs200542114?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=rs200542114" 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=rs200542114" 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=RCV000514518 OR RCV000697912" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000514518, RCV000697912" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000514518...</a>
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<p>For discussion of the splice site mutation in the SLC19A3 gene (980-14A-G) that was found in compound heterozygous state in sibs with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>) by <a href="#1" class="mim-tip-reference" title="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al. (2010)</a>, see <a href="#0005">606152.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20065143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0007 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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">rs713993048 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs713993048;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=rs713993048" 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=rs713993048" 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=RCV000149551 OR RCV001310776" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000149551, RCV001310776" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000149551...</a>
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<p>In 9 patients from 3 unrelated Moroccan families with biotin-thiamine-responsive basal ganglia disease (BTBGD; <a href="/entry/607483">607483</a>), presenting as Leigh syndrome, <a href="#4" class="mim-tip-reference" title="Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H. <strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong> Brain 136: 882-890, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>] [<a href="https://doi.org/10.1093/brain/awt013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23423671">Gerards et al. (2013)</a> identified a homozygous c.20C-A transversion in the SLC19A3 gene, resulting in a ser7-to-ter (S7X) substitution. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing, confirmed by Sanger sequencing, and filtered against the dbSNP (build 132) and 1000 Genomes Project databases. The mutation, which segregated with the disorder in the family, was not present in 460 control alleles. The mutations in the other 2 Moroccan families were found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh syndrome. Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The families all came from the Al Hoceima region in northern Morocco; 2 of the families were consanguineous. In vitro functional expression studies showed that the S7X mutant protein had no thiamine transporter activity, consistent with a complete loss of function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" 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://doi.org/10.1001/archneurol.2009.293" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMcpc1706109" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/mgme.2000.3112" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awt013" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank">Full Text</a>]
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Rajgopal, A., Edmondnson, A., Goldman, I. D., Zhao, R.
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<strong>SLC19A3 encodes a second thiamine transporter ThTr2.</strong>
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Biochim. Biophys. Acta 1537: 175-178, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11731220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11731220</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11731220" 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/s0925-4439(01)00073-4" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19879271/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19879271</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19879271[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=19879271" 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/10.1053/j.gastro.2009.10.042" target="_blank">Full Text</a>]
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Subramanian, V. S., Marchant, J. S., Said, H. M.
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<strong>Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.</strong>
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Am. J. Physiol. Cell Physiol. 291: C851-C859, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16790503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16790503</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16790503" 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/10.1152/ajpcell.00105.2006" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21868632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21868632</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21868632[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=21868632" 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/10.1152/ajpgi.00308.2011" target="_blank">Full Text</a>]
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Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L.
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<strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23469184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23469184</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23469184[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=23469184" 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/10.1371/journal.pone.0057195" target="_blank">Full Text</a>]
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Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C.
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<strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25117056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25117056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25117056[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=25117056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/bpa.12188" target="_blank">Full Text</a>]
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Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F.
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<strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[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=15871139" 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/10.1086/431216" target="_blank">Full Text</a>]
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Carol A. Bocchini - updated : 12/14/2017
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Cassandra L. Kniffin - updated : 12/29/2014<br>Patricia A. Hartz - updated : 4/19/2012<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 3/17/2010<br>Cassandra L. Kniffin - updated : 4/27/2009<br>Victor A. McKusick - updated : 6/17/2005
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Carol A. Bocchini : 7/24/2001
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carol : 12/14/2017<br>carol : 07/01/2015<br>mcolton : 6/24/2015<br>mcolton : 6/18/2015<br>carol : 12/30/2014<br>mcolton : 12/29/2014<br>ckniffin : 12/29/2014<br>carol : 9/16/2013<br>mgross : 5/14/2012<br>terry : 4/19/2012<br>carol : 2/10/2012<br>carol : 2/10/2012<br>ckniffin : 2/8/2012<br>wwang : 3/23/2010<br>ckniffin : 3/17/2010<br>wwang : 5/12/2009<br>ckniffin : 4/27/2009<br>alopez : 6/17/2005<br>terry : 6/17/2005<br>cwells : 11/12/2003<br>mcapotos : 7/26/2001<br>carol : 7/24/2001
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<div class="col-md-8 col-md-offset-1">
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<h3>
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<span class="mim-font">
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<strong>*</strong> 606152
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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 19 (THIAMINE TRANSPORTER), MEMBER 3; SLC19A3
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</span>
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</h3>
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</div>
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<br />
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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THIAMINE TRANSPORTER 2; THTR2
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</span>
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</h4>
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</div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: SLC19A3</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 703522009;
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</p>
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<br />
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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: 2q36.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:227,683,763-227,718,028 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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2q36.3
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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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Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type)
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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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607483
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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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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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>SLC19A3 encodes a thiamine transporter (Rajgopal et al., 2001). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By EST database searching with the RFC1 (SLC19A1; 600424) protein sequence as query, PCR, and screening of a human placenta cDNA library, Eudy et al. (2000) cloned a full-length SLC19A3 cDNA encoding a 496-amino acid protein. They also cloned the mouse homolog from a kidney cDNA library. Human SLC19A3 shares 39%, 48%, and 68% amino acid sequence identity with human SLC19A1 and SLC19A2 (603941) and mouse Slc19a3, respectively. Northern blot analysis of human tissues detected 3 transcripts of approximately 3.5, 2.6, and 2.0 kb in placenta, kidney, and liver. Highest expression was observed in placenta, with all 3 transcripts exhibiting similar levels of expression. In the liver and kidney, the 3.5-kb transcript was the most abundant. PCR analysis detected SLC19A3 transcripts in almost all tissues tested. Northern blot analysis in mouse tissues detected a single transcript in brain, kidney, lung, small intestine, heart, and testis, with the highest abundance in kidney and brain. PCR analysis identified weak expression of the mouse gene beginning at embryonic day 8.5 which peaked at E19 just prior to parturition. </p><p>Kono et al. (2009) found high SLC19A3 expression in human thalamus compared to other brain regions. </p><p>Subramanya et al. (2011) found expression of both the Slc19a2 and Slc19a3 genes in rat pancreatic acinar cells, with Slc19a2 showing higher expression. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By radiation hybrid analysis, Eudy et al. (2000) mapped the human SLC19A3 gene to chromosome 2q37 and the mouse homolog to a region showing syntenic homology on chromosome 1. </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>By assaying transfected HeLa cells, Rajgopal et al. (2001) found that human SLC19A3 mediated transport of radiolabeled thiamine, but not folic acid, pyridoxine, niacin, methotrexate, or other organic cations examined. The pH optimum for thiamine transport was pH 7.4. </p><p>In cellular studies, Subramanian et al. (2006) demonstrated that SLC19A3 is a thiamine transporter expressed at the apical surface of polarized cells, but it does not function as a biotin transporter. SLC19A3 was also expressed in human glioma cells. </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>Biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483), also known as thiamine metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is an autosomal recessive disorder with childhood onset that presents as a subacute encephalopathy and progresses to severe cogwheel rigidity, dystonia, quadriparesis, and eventually death if left untreated. Zeng et al. (2005) stated that all patients diagnosed to that time were of Saudi, Syrian, or Yemeni ancestry, and all had consanguineous parents. Using linkage analysis in 4 families, they mapped the genetic defect to 2q36.3 to a minimum candidate region of approximately 2 Mb on the basis of complete homozygosity. In this segment, each family displayed 1 of 2 different missense mutations that altered the coding sequence of SLC19A3 (606152.0001 and 606152.0002). The mutations were on different haplotypes. </p><p>In a Portuguese brother and sister with BTBGD, Debs et al. (2010) identified compound heterozygosity for 2 truncating mutations in the SLC19A3 gene (606152.0005-606152.0006), confirming that the disorder results from loss of function of this transporter. Each unaffected parent was heterozygous for 1 of the mutations. One of the patients only showed a therapeutic response to thiamine. </p><p>Kono et al. (2009) reported 2 Japanese brothers with onset of encephalopathy in the second decade of life. Genetic analysis identified compound heterozygous mutations in the SLC19A3 gene (606152.0003-606152.0004) in both brothers. Kono et al. (2009) stated that the phenotype differed from biotin-responsive basal ganglia disease because brain lesions were found in the thalamus and periaqueductal regions, not in the basal ganglia. </p><p>In affected patients from 3 families from the Al Hoceima province in northern Morocco with BTBGD manifest as severe infantile-onset fatal encephalopathy and Leigh syndrome (see 256000) on brain imaging, Gerards et al. (2013) identified the same homozygous truncating mutation in the SLC19A3 gene (S7X; 606152.0007). Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing; the mutations in the subsequent families were found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh 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>Reidling et al. (2010) found that Slc19a3-null mice had reduced uptake of intestinal thiamine and decreased serum thiamine compared to wildtype mice. However, intestinal uptake of thiamine in Slc19a2-null mice was not significantly different from that of wildtype mice. Moreover, the level of expression of Slc19a2 was not altered in the intestine of Slc19a3-null mice, but the level of expression of Slc19a3 was upregulated in the intestine of Slc19a2-null mice, thus compensating for the defect. The findings suggested that Slc19a3 is required for normal uptake of thiamine in the intestine, and can fulfill normal levels of uptake in conditions associated with Slc19a2 dysfunction. </p><p>Subramanya et al. (2011) found expression of both the Slc19a2 and Slc19a3 genes in rat pancreatic acinar cells. Chronic alcohol feeding of rats resulted in significant inhibition of carrier-mediated thiamine uptake by pancreatic acinar cells, and was associated with a significant reduction in expression of Slc19a2 and Slc19a3 at the protein and mRNA levels. The results demonstrated that thiamine uptake by pancreatic acinar cells occurs through a carrier-mediated process, and that thiamine transporters are expressed in these cells. </p><p>Alaskan Husky encephalopathy (AHE), a fatal brain disease in young Alaskan Husky dogs, presents as a multifocal central nervous system deficit with seizures, altered mentation, dysphagia, central blindness, hypermetria, proprioceptive positioning deficits, ataxia, and tetraparesis. Brain imaging shows abnormal intracranial lesions consistent with Leigh syndrome in humans. Vernau et al. (2013) determined that AHE is caused by homozygosity for a 4-bp deletion and a single nucleotide change (c.624insTTGC, c.625C-A) in the Slc19a3.1 gene that is predicted to result in a protein truncation. Heterozygosity for the mutation was found in 15 of 41 healthy Alaskan Husky control dogs, but not in another 187 dogs of different breeds. Canines have 2 paralogs of SLC19A3, Slc19a3.1 and Slc19a3.2, resulting from gene duplication. Slc19a3.1 is primarily expressed in the cerebrum, cerebellum, spinal cord, kidney, and testes, whereas Slc19a3.2 is mainly expressed in the kidney and liver, suggesting tissue-specific expression of these paralogs. </p><p>Vernau et al. (2015) found that the cerebral cortex and thalamus of 2 dogs with AHE were severely deficient in thiamine pyrophosphate (TPP)-dependent enzymes compared to controls. These decreases in enzymatic activity were accompanied by decreases in mitochondrial mass, mtDNA copy number, and oxidative phosphorylation, although the latter decreases did not meet the threshold for a mitochondrial respiratory chain disorder. Affected brain tissue also showed evidence of increased oxidative stress. The findings indicated that the phenotype results from a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. </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>7 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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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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SLC19A3, GLY23VAL
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<br />
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SNP: rs121917882,
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gnomAD: rs121917882,
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ClinVar: RCV000004824, RCV001310775, RCV003242961
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 patients with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483) in a Yemeni family, Zeng et al. (2005) found a homozygous G-to-T change at nucleotide 68 in exon 2 of the SLC19A3 gene, which was predicted to alter a highly conserved glycine at codon 23 to valine (G23V). This mutation was predicted to alter the first transmembrane domain of the SLC19A3 protein. </p><p>In canine kidney cells and human duodenal cells, both polarized epithelial cell lines, Subramanian et al. (2006) showed that the G23V mutant protein localized normally to the apical plasma membrane, similar to the wildtype protein, but showed decreased expression. However, cells expressing the mutant SLC19A3 protein had significantly impaired thiamine transport, similar to untransfected cells. </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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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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SLC19A3, THR422ALA
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<br />
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SNP: rs121917884,
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ClinVar: RCV000004825, RCV000489300, RCV002512775, RCV004527286
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 3 families, all of Saudi origin, with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483), Zeng et al. (2005) identified an A-to-G transition at nucleotide position 1264 in exon 5 of the SLC19A3, predicted to result in a substitution of threonine at codon 422 to alanine (T422A). </p><p>Eichler et al. (2017) reported a 20-year-old Saudi woman with BTBGD who was homozygous for the T422A mutation in the SLC19A3 gene. </p><p>In canine kidney cells and human duodenal cells, both polarized epithelial cell lines, Subramanian et al. (2006) showed that the T422A mutant protein, which is in transmembrane domain 11, localized normally to the apical plasma membrane, similar to the wildtype protein, but showed decreased expression. However, cells expressing the mutant SLC19A3 protein had significantly impaired thiamine transport, similar to untransfected cells. </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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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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SLC19A3, LYS44GLU
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<br />
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SNP: rs137852957,
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gnomAD: rs137852957,
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ClinVar: RCV000004827
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Japanese brothers with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483) characterized by diplopia, seizures, and white matter changes in the thalamus without serum thiamine deficiency, Kono et al. (2009) identified compound heterozygosity for 2 mutations in the SLC19A3 gene: a 218A-G transition in exon 2, resulting in a lys44-to-glu (K44E) substitution, and a 1047G-C transversion in exon 3, resulting in a glu320-to-gln (E320Q; 606152.0004) substitution. These mutations were not present among 192 ethnically matched controls. In vitro functional cellular expression studies showed that most of the K44E-mutant protein was impaired in intracellular transport while remaining normal in the endoplasmic reticulum. The E320Q mutant was identical in cell surface localization to wildtype protein but showed significantly decreased intracellular thiamine uptake activity. Onset of symptoms was in the second decade of life. Both patients also had severe partial complex seizures that were responsive to high-dose thiamine. Magnetic resonance imaging (MRI) of the brain showed high-intensity signals in the bilateral medial thalamus and periaqueductal region, which were characteristic of findings in Wernicke encephalopathy (277730), but there was no history of chronic alcohol use. These changes became normal within 1 month after treatment. Subacute ophthalmoplegia with nystagmus and ataxia occurred repeatedly within several months after the discontinuation of 100 mg of thiamine per day. There were no extrapyramidal features. </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 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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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SLC19A3, GLU320GLN
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<br />
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SNP: rs137852958,
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gnomAD: rs137852958,
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ClinVar: RCV000004828
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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>For discussion of the glu320-to-gln (E320Q) mutation in the SLC19A3 gene that was found in compound heterozygous state in 2 Japanese brothers with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483) by Kono et al. (2009), see 606152.0003. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</strong>
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</h4>
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<span class="mim-text-font">
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SLC19A3, 1-BP DUP, 74T
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<br />
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SNP: rs786205213,
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gnomAD: rs786205213,
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ClinVar: RCV000170443, RCV000367514
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</span>
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<p>In a Portuguese brother and sister with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483) Debs et al. (2010) identified compound heterozygosity for 2 mutations in the SLC19A3 gene: a 1-bp duplication (74dupT) in exon 2, resulting in a frameshift and premature termination, and an A-to-G transition in intron 3 (980-14A-G; 606152.0006), resulting in the skipping of exon 4 and an aberrantly spliced transcript degraded by nonsense-mediated mRNA decay. Each unaffected parent was heterozygous for 1 of the mutations. The brother was treated with high-dose biotin, which resulted in improvement of clinical features and disappearance of signal abnormalities on follow-up MRI. The sister was treated with high-dose biotin after worsening of her epilepsy, but she did not show improvement until thiamine was added. </p>
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<span class="mim-font">
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<strong>.0006 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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SLC19A3, IVS3AS, A-G, -14
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<br />
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SNP: rs200542114,
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gnomAD: rs200542114,
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ClinVar: RCV000514518, RCV000697912
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<span class="mim-text-font">
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<p>For discussion of the splice site mutation in the SLC19A3 gene (980-14A-G) that was found in compound heterozygous state in sibs with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483) by Debs et al. (2010), see 606152.0005. </p>
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<h4>
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<span class="mim-font">
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<strong>.0007 BIOTIN-THIAMINE-RESPONSIVE BASAL GANGLIA DISEASE</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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SLC19A3, SER7TER
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<br />
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SNP: rs713993048,
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ClinVar: RCV000149551, RCV001310776
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</span>
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<span class="mim-text-font">
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<p>In 9 patients from 3 unrelated Moroccan families with biotin-thiamine-responsive basal ganglia disease (BTBGD; 607483), presenting as Leigh syndrome, Gerards et al. (2013) identified a homozygous c.20C-A transversion in the SLC19A3 gene, resulting in a ser7-to-ter (S7X) substitution. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing, confirmed by Sanger sequencing, and filtered against the dbSNP (build 132) and 1000 Genomes Project databases. The mutation, which segregated with the disorder in the family, was not present in 460 control alleles. The mutations in the other 2 Moroccan families were found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh syndrome. Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The families all came from the Al Hoceima region in northern Morocco; 2 of the families were consanguineous. In vitro functional expression studies showed that the S7X mutant protein had no thiamine transporter activity, consistent with a complete loss of function. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F.
|
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<strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong>
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Arch. Neurol. 67: 126-130, 2010.
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[PubMed: 20065143]
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[Full Text: https://doi.org/10.1001/archneurol.2009.293]
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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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Eichler, F. S., Swoboda, K. J., Hunt, A. L., Cestari, D. M., Rapalino, O.
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<strong>Case 38-2017: A 20-year-old woman with seizures and progressive dystonia.</strong>
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New Eng. J. Med. 377: 2376-2384, 2017.
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[PubMed: 29236641]
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[Full Text: https://doi.org/10.1056/NEJMcpc1706109]
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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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Eudy, J. D., Spiegelstein, O., Barber, R. C., Wlodarczyk, B. J., Talbot, J., Finnell, R. H.
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<strong>Identification and characterization of the human and mouse SLC19A3 gene: a novel member of the reduced folate family of micronutrient transporter genes.</strong>
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Molec. Genet. Metab. 71: 581-590, 2000.
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[PubMed: 11136550]
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[Full Text: https://doi.org/10.1006/mgme.2000.3112]
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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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Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H.
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<strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong>
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Brain 136: 882-890, 2013.
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[PubMed: 23423671]
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[Full Text: https://doi.org/10.1093/brain/awt013]
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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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Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H.
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<strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong>
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New. Eng. J. Med. 360: 1792-1794, 2009.
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[PubMed: 19387023]
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[Full Text: https://doi.org/10.1056/NEJMc0809100]
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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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Rajgopal, A., Edmondnson, A., Goldman, I. D., Zhao, R.
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<strong>SLC19A3 encodes a second thiamine transporter ThTr2.</strong>
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Biochim. Biophys. Acta 1537: 175-178, 2001.
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[PubMed: 11731220]
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[Full Text: https://doi.org/10.1016/s0925-4439(01)00073-4]
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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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Reidling, J. C., Lambrecht, N., Kassir, M., Said, H. M.
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<strong>Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice.</strong>
|
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Gastroenterology 138: 1802-1809, 2010.
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[PubMed: 19879271]
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[Full Text: https://doi.org/10.1053/j.gastro.2009.10.042]
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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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Subramanian, V. S., Marchant, J. S., Said, H. M.
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<strong>Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2.</strong>
|
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Am. J. Physiol. Cell Physiol. 291: C851-C859, 2006.
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[PubMed: 16790503]
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[Full Text: https://doi.org/10.1152/ajpcell.00105.2006]
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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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Subramanya, S. B., Subramanian, V. S., Sekar, V. T., Said, H. M.
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<strong>Thiamin uptake by pancreatic acinar cells: effect of chronic alcohol feeding/exposure.</strong>
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Am. J. Physiol. Gastrointest. Liver Physiol. 301: G896-G904, 2011.
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[PubMed: 21868632]
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[Full Text: https://doi.org/10.1152/ajpgi.00308.2011]
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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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Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L.
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<strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong>
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PLoS One 8: e57195, 2013. Note: Electronic Article.
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[PubMed: 23469184]
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[Full Text: https://doi.org/10.1371/journal.pone.0057195]
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<li>
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<p class="mim-text-font">
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Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C.
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<strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong>
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Brain Path. 25: 441-453, 2015.
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[PubMed: 25117056]
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[Full Text: https://doi.org/10.1111/bpa.12188]
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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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Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F.
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<strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong>
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Am. J. Hum. Genet. 77: 16-26, 2005.
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[PubMed: 15871139]
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[Full Text: https://doi.org/10.1086/431216]
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<span class="mim-text-font">
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Carol A. Bocchini - updated : 12/14/2017<br>Cassandra L. Kniffin - updated : 12/29/2014<br>Patricia A. Hartz - updated : 4/19/2012<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 3/17/2010<br>Cassandra L. Kniffin - updated : 4/27/2009<br>Victor A. McKusick - updated : 6/17/2005
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<span class="mim-text-font">
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Carol A. Bocchini : 7/24/2001
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carol : 02/22/2024<br>carol : 12/14/2017<br>carol : 07/01/2015<br>mcolton : 6/24/2015<br>mcolton : 6/18/2015<br>carol : 12/30/2014<br>mcolton : 12/29/2014<br>ckniffin : 12/29/2014<br>carol : 9/16/2013<br>mgross : 5/14/2012<br>terry : 4/19/2012<br>carol : 2/10/2012<br>carol : 2/10/2012<br>ckniffin : 2/8/2012<br>wwang : 3/23/2010<br>ckniffin : 3/17/2010<br>wwang : 5/12/2009<br>ckniffin : 4/27/2009<br>alopez : 6/17/2005<br>terry : 6/17/2005<br>cwells : 11/12/2003<br>mcapotos : 7/26/2001<br>carol : 7/24/2001
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<p>
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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