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- *615403 - THO COMPLEX, SUBUNIT 6; THOC6
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- OMIM
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*615403</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/615403">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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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-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=ENSG00000131652;t=ENST00000326266" 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=79228" 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=615403" 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 class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000131652;t=ENST00000326266" 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_001142350,NM_001347703,NM_001347704,NM_024339" 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_024339" 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=615403" 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://www.proteinatlas.org/search/THOC6" 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/13111899,22761350,29792081,31543164,74759455,119605827,119605828,119605829,189054262,215272341,1112917094,1112917096" 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/Q86W42" 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=79228" 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=ENSG00000131652;t=ENST00000326266" 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=THOC6" 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=THOC6" 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+79228" 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/THOC6" 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:79228" 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/79228" 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=chr16&hgg_gene=ENST00000326266.13&hgg_start=3024035&hgg_end=3027750&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:28369" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=615403[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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</a>
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</span>
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</span>
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</div>
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<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=615403[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/THOC6/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000131652" 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.gwascentral.org/search?q=THOC6" 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=THOC6" 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=THOC6&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/PA142670592" 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:28369" 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/FBgn0036263.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:2677480" 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/THOC6#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:2677480" 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/79228/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=79228" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-041010-198" 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:79228" 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=THOC6&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> 773554009<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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615403
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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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THO COMPLEX, SUBUNIT 6; THOC6
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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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FUNCTIONAL SPLICEOSOME-ASSOCIATED PROTEIN, 35-KD; FSAP35
|
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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=THOC6" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">THOC6</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/16/129?start=-3&limit=10&highlight=129">16p13.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr16:3024035-3027750&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'})">16:3,024,035-3,027,750</a> </span>
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</em>
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</strong>
|
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
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</p>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</div>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
|
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<a href="/geneMap/16/129?start=-3&limit=10&highlight=129">
|
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16p13.3
|
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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">
|
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Beaulieu-Boycott-Innes syndrome
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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/613680"> 613680 </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>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/615403" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/615403" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
|
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</span>
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</h4>
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<div>
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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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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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>The THOC6 gene encodes a subunit of the THO complex, which is involved in coordinating mRNA processing with export. The THO complex is a component of the TREX (transcription/export) complex (summary by <a href="#4" class="mim-tip-reference" title="Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M. <strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong> Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23621916[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1750-1172-8-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621916">Beaulieu et al., 2013</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621916" 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 mass spectrometric analysis of proteins that coimmunoprecipitated with UAP56 (DDX39B; <a href="/entry/142560">142560</a>) from HeLa cell nuclear extracts, followed by PCR, <a href="#6" class="mim-tip-reference" title="Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R. <strong>Recruitment of the human TREX complex to mRNA during splicing.</strong> Genes Dev. 19: 1512-1517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15998806[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/10.1101/gad.1302205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15998806">Masuda et al. (2005)</a> cloned THOC6, which they designated FSAP35. The deduced protein contains a WD40 repeat domain. THOC6 had an apparent molecular mass of 35 kD by SDS-PAGE. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15998806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using immunoprecipitation and mass spectrometric analysis of HeLa cell nuclear extracts, <a href="#6" class="mim-tip-reference" title="Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R. <strong>Recruitment of the human TREX complex to mRNA during splicing.</strong> Genes Dev. 19: 1512-1517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15998806[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/10.1101/gad.1302205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15998806">Masuda et al. (2005)</a> found that the human TREX complex contained THO2 (THOC2; <a href="/entry/300395">300395</a>), FSAP79 (THOC5; <a href="/entry/612733">612733</a>), HPR1 (THOC1; <a href="/entry/606930">606930</a>), UAP56, TEX1 (THOC3; <a href="/entry/606929">606929</a>), FSAP35, ALY (THOC4; <a href="/entry/604171">604171</a>), and FSAP24 (THOC7; <a href="/entry/611965">611965</a>). Immunodepletion and gel-filtration analyses revealed that THO2, HPR1, FSAP79, FSAP35, and FSAP24 were tightly associated in the THO complex, whereas UAP56, ALY, and TEX1 were more loosely associated. Immunoprecipitation of any TREX component efficiently immunoprecipitated spliced mRNA and cDNA transcripts, but not unspliced pre-mRNAs. Immunodepletion of any component had no effect on spliceosome assembly, splicing, or RNA stability. The TREX complex assembled on every mRNA examined. Mutation analysis showed that the C terminus of ALY was required for binding of both UAP56 and the THO complex. The C terminus of UAP56 was sufficient for ALY binding. The N terminus of UAP56 interacted weakly with the THO complex and TEX1, suggesting that other regions of UAP56 are required for maximal binding. <a href="#6" class="mim-tip-reference" title="Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R. <strong>Recruitment of the human TREX complex to mRNA during splicing.</strong> Genes Dev. 19: 1512-1517, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15998806[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/10.1101/gad.1302205" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15998806">Masuda et al. (2005)</a> concluded that recruitment of the human TREX complex is not directly coupled to transcription, as in yeast. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15998806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 2 sets of sisters from related Dariusleut Hutterite families with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), a neurodevelopmental disorder, <a href="#4" class="mim-tip-reference" title="Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M. <strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong> Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23621916[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1750-1172-8-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621916">Beaulieu et al. (2013)</a> identified a homozygous missense mutation in the THOC6 gene (G46R; <a href="#0001">615403.0001</a>). The mutation, which was found by Sanger sequencing followed by exome sequencing, segregated with the disorder in the family and was not found in the NHLBI Exome Variant Server and dbSNP databases, in 435 control exomes, or in 150 controls from the general population. The variant was seen in the heterozygous state in 3% of 92 Dariusleut controls and in 2% of 120 Lehrerleut controls. It was not present in 500 Schmiedeleut controls. In vitro functional expression studies showed that the mutation caused abnormal intracellular localization; knockdown of THOC6 in HeLa cells caused an increase in apoptosis. No THOC6 mutations were found in 140 female patients with intellectual disability and microcephaly. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 4-year old Saudi boy with BBIS, born to first cousins once removed, <a href="#3" class="mim-tip-reference" title="Anazi, S., Alshammari, M., Moneis, D., Abouelhoda, M., Ibrahim, N., Alkuraya, F. S. <strong>Confirming the candidacy of THOC6 in the etiology of intellectual disability. (Letter)</strong> Am. J. Med. Genet. 170A: 1367-1369, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26739162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26739162</a>] [<a href="https://doi.org/10.1002/ajmg.a.37549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26739162">Anazi et al. (2016)</a> identified a homozygous nonsense mutation in the THOC6 gene (R87X; <a href="#0002">615403.0002</a>). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26739162" 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 3 unrelated patients from France, Iran, and the U.S. with BBIS, <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a> identified homozygous or compound heterozygous mutations in the THOC6 gene (<a href="#0002">615403.0002</a>-<a href="#0006">615403.0006</a>). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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 an Italian girl with BBIS, <a href="#1" class="mim-tip-reference" title="Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., Allegri, A. M. E., Mancardi, M. M., Maghnie, M., Severino, M., Telethon Undiagnosed Diseases Program, Nigro, V., Capra, V. <strong>Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome.</strong> Am. J. Med. Genet. 176A: 2835-2840, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30238602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30238602</a>] [<a href="https://doi.org/10.1002/ajmg.a.40534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30238602">Accogli et al. (2018)</a> identified compound heterozygosity for 2 loss-of-function mutations in the THOC6 gene (<a href="#0007">615403.0007</a>-<a href="#0008">615403.0008</a>). The mutations were found by trio exome sequencing and confirmed by Sanger sequence. Each parent was heterozygous for one of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30238602" 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="#7" class="mim-tip-reference" title="Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A. <strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong> Hum. Molec. Genet. 28: 952-960, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476144</a>] [<a href="https://doi.org/10.1093/hmg/ddy391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30476144">Mattioli et al. (2019)</a> used trio exome sequencing to evaluate 2 patients with BBIS. In the first patient, the authors identified homozygosity for a rare haplotype that included 3 amino acid changes (W100R, V234L, G275D; <a href="#0009">615403.0009</a>) in the THOC6 gene due to maternal uniparental disomy of chromosome 16, and in the second patient, they identified compound heterozygosity for the same haplotype, inherited from the mother, and a previously reported missense mutation (G190E; <a href="#0005">615403.0005</a>), inherited from the father. Both the triple mutant and G190E variants changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (<a href="/entry/606930">606930</a>) and THOC5 (<a href="/entry/612733">612733</a>). Two of the amino acid changes (W100R and G275D) from the 3-variant haplotype were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In zebrafish, <a href="#4" class="mim-tip-reference" title="Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M. <strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong> Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23621916[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1750-1172-8-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621916">Beaulieu et al. (2013)</a> found that the Thoc6 ortholog was present during embryonic neurodevelopment. The gene was highly expressed in the developing midbrain and the eyes at 24 hours postfertilization, and later became restricted to the posterior part of the midbrain and the midbrain-hindbrain boundary. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621916" 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> rs587777030 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs587777030;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/rs587777030?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=rs587777030" 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=rs587777030" 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=RCV000054832" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000054832" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000054832</a>
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<p>In 2 sets of sisters from related Dariusleut Hutterite families with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), <a href="#4" class="mim-tip-reference" title="Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M. <strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong> Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23621916[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1750-1172-8-62" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23621916">Beaulieu et al. (2013)</a> identified a homozygous c.136G-A transition in the THOC6 gene, resulting in a gly46-to-arg (G46R) substitution at a highly conserved residue. The mutation, which was found by Sanger sequencing followed by exome sequencing, segregated with the disorder in the family and was not found in the NHLBI Exome Variant Server and dbSNP databases, in 435 control exomes, or in 150 controls from the general population. The variant was seen in heterozygous state in 3% of 92 Dariusleut controls and in 2% of 120 Lehrerleut controls. It was not present in 500 Schmiedeleut controls. The disorder was characterized by delayed development, moderate intellectual disability, and dysmorphic facial features. Variable developmental anomalies, such as cardiac and renal defects, were also present. In HeLa cells, wildtype THOC6 showed a speckled nuclear localization, whereas mutant G46R THOC6 was confined to the cytoplasm, indicating that the mutation caused impaired intracellular localization. Knockdown of THOC6 in HeLa cells by siRNA resulted in increased apoptosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23621916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
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THOC6, ARG87TER
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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> rs763344375 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs763344375;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/rs763344375?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=rs763344375" 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=rs763344375" 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=RCV000624090 OR RCV000680235" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000624090, RCV000680235" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000624090...</a>
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<p>In a 4-year-old Saudi boy with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), born to first cousins once removed, <a href="#3" class="mim-tip-reference" title="Anazi, S., Alshammari, M., Moneis, D., Abouelhoda, M., Ibrahim, N., Alkuraya, F. S. <strong>Confirming the candidacy of THOC6 in the etiology of intellectual disability. (Letter)</strong> Am. J. Med. Genet. 170A: 1367-1369, 2016.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26739162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26739162</a>] [<a href="https://doi.org/10.1002/ajmg.a.37549" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26739162">Anazi et al. (2016)</a> identified homozygosity for a c.259C-T transition (c.259C-T, NM_001142350.2) in the THOC6, resulting in an arg87-to-ter (R87X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26739162" 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 an 18-year-old woman from the U.S. with BBIS, who was born to nonconsanguineous parents, <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a> identified compound heterozygous mutations in the THOC6 gene: R87X and a thr250-to-pro (T250P; <a href="#0006">615403.0006</a>) substitution. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 BEAULIEU-BOYCOTT-INNES SYNDROME</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">rs1567416845 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1567416845;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=rs1567416845" 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=rs1567416845" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000680236" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680236" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680236</a>
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<p>In a 7-year-old boy, born to consanguineous Iranian parents, with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a> identified homozygosity for a c.611A-C transversion (c.611A-C, NM_024339.3) in the THOC6 gene, resulting in a gln204-to-pro (Q204P) substitution. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not present in the ExAC database. Protein modeling suggested that the mutation interrupts the normal structure and function of THOC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
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THOC6, TYR45TER
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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> rs772533643 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs772533643;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/rs772533643?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=rs772533643" 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=rs772533643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000680237" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680237" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680237</a>
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<p>In a 6-year-old French boy, born to nonconsanguineous parents, with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a> identified compound heterozygous mutations in the THOC6 gene: a c.135C-A transversion (c.135C-A, NM_024339.3), resulting in a tyr45-to-ter (Y45X) substitution, and a c.569G-A transition, resulting in gly190-to-glu (G190E; <a href="#0005">615403.0005</a>) substitution. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The parents were each heterozygous for one of the mutations, which were present at low frequency in the ExAC database. Protein modeling suggested that the missense mutation interrupts the normal structure and function of THOC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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 BEAULIEU-BOYCOTT-INNES SYNDROME</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> rs199795381 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199795381;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/rs199795381?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=rs199795381" 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=rs199795381" 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=RCV000680238 OR RCV001528676 OR RCV003403573" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000680238, RCV001528676, RCV003403573" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000680238...</a>
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<p>For discussion of the c.569G-A transition (c.569G-A, NM_024339.3) in the THOC6 gene, resulting in a gly190-to-glu (G190E) substitution, that was found in compound heterozygous state in a patient with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>) by <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a>, see <a href="#0004">615403.0004</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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 female patient with BBIS, <a href="#7" class="mim-tip-reference" title="Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A. <strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong> Hum. Molec. Genet. 28: 952-960, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476144</a>] [<a href="https://doi.org/10.1093/hmg/ddy391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30476144">Mattioli et al. (2019)</a> identified compound heterozygosity for mutations in the THOC6 gene: the G190E mutation inherited from her father, and a rare haplotype that included 3 amino acid changes (W100R, V234L, G275D; <a href="#0009">615403.0009</a>) inherited from her mother. Both the triple mutant and G190E variants changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (<a href="/entry/606930">606930</a>) and THOC5 (<a href="/entry/612733">612733</a>). Two of the amino acid changes (W100R and G275D) from the 3-variant haplotype were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476144" 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">rs1555498821 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1555498821;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=rs1555498821" 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=rs1555498821" 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=RCV000623020 OR RCV000680239" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000623020, RCV000680239" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000623020...</a>
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<p>In an 18-year-old woman from the U.S. with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), who was born to nonconsanguineous parents, <a href="#2" class="mim-tip-reference" title="Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium. <strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong> Clin. Genet. 91: 92-99, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>] [<a href="https://doi.org/10.1111/cge.12793" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27102954">Amos et al. (2017)</a> identified compound heterozygous mutations in the THOC6 gene: a c.748A-C transition (c.748A-C, NM_024339.3), resulting in a thr250-to-pro (T250P) substitution, and the previously identified R87X mutation (<a href="#0002">615403.0002</a>). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The nonsense mutation was inherited from the unaffected mother; the father could not be tested and the T250P mutation was presumed to be paternal or de novo. The T250P mutation was not found in the ExAC database, and protein modeling suggested that it interrupts the normal structure and function of THOC6. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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> rs1194408714 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1194408714;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/rs1194408714?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=rs1194408714" 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=rs1194408714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an Italian girl with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), <a href="#1" class="mim-tip-reference" title="Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., Allegri, A. M. E., Mancardi, M. M., Maghnie, M., Severino, M., Telethon Undiagnosed Diseases Program, Nigro, V., Capra, V. <strong>Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome.</strong> Am. J. Med. Genet. 176A: 2835-2840, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30238602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30238602</a>] [<a href="https://doi.org/10.1002/ajmg.a.40534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30238602">Accogli et al. (2018)</a> identified compound heterozygous mutations in the THOC6 gene: a c.577C-T transition (c.577C-T, NM_024339) in exon 8, resulting in an arg193-to-ter (R193X) substitution, inherited from her mother, and a 2-bp deletion (c.792_793delCA; <a href="#0008">615403.0008</a>) in exon 11, resulting in a frameshift and a premature termination codon (Val264ValfsTer48), inherited from her father. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. The R193X mutation was not found in any public databases. The 2-bp deletion was found in 1 of 246,156 alleles in the gnomAD database, with a frequency of .4062x10(-5). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30238602" 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> rs773022351 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs773022351;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/rs773022351?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=rs773022351" 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=rs773022351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 2-bp deletion (c.792_793delCA, NM_024339) in the THOC6 gene that was found in compound heterozygous state in an Italian girl with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>) by <a href="#1" class="mim-tip-reference" title="Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., Allegri, A. M. E., Mancardi, M. M., Maghnie, M., Severino, M., Telethon Undiagnosed Diseases Program, Nigro, V., Capra, V. <strong>Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome.</strong> Am. J. Med. Genet. 176A: 2835-2840, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30238602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30238602</a>] [<a href="https://doi.org/10.1002/ajmg.a.40534" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30238602">Accogli et al. (2018)</a>, see <a href="#0007">615403.0007</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30238602" 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> rs138632121 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs138632121;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/rs138632121?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=rs138632121" 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=rs138632121" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs150940923 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs150940923;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/rs150940923?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=rs150940923" 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=rs150940923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div> <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> rs200426926 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200426926;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/rs200426926?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=rs200426926" 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=rs200426926" 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=RCV000622420 OR RCV000623380 OR RCV000624518 OR RCV000850494 OR RCV000850495 OR RCV000850496 OR RCV001263559 OR RCV001541157 OR RCV001553458 OR RCV001591401" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000622420, RCV000623380, RCV000624518, RCV000850494, RCV000850495, RCV000850496, RCV001263559, RCV001541157, RCV001553458, RCV001591401" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000622420...</a>
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<p>In a boy with Beaulieu-Boycott-Innes syndrome (BBIS; <a href="/entry/613680">613680</a>), <a href="#7" class="mim-tip-reference" title="Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A. <strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong> Hum. Molec. Genet. 28: 952-960, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476144</a>] [<a href="https://doi.org/10.1093/hmg/ddy391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30476144">Mattioli et al. (2019)</a> identified homozygosity for a rare haplotype including 3 amino acid changes (W100R, V234L, G275D) in the THOC6 gene due to maternal uniparental disomy of chromosome 16. The mutation was found by trio exome sequencing. The triple mutant changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (<a href="/entry/606930">606930</a>) and THOC5 (<a href="/entry/612733">612733</a>). Two of the amino acid changes (W100R and G275D) were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. Another patient reported by <a href="#7" class="mim-tip-reference" title="Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A. <strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong> Hum. Molec. Genet. 28: 952-960, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476144</a>] [<a href="https://doi.org/10.1093/hmg/ddy391" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30476144">Mattioli et al. (2019)</a> was compound heterozygous for the 3-amino acid haplotype and a missense mutation (G190E; <a href="#0005">615403.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476144" 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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Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., Allegri, A. M. E., Mancardi, M. M., Maghnie, M., Severino, M., Telethon Undiagnosed Diseases Program, Nigro, V., Capra, V.
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<strong>Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30238602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30238602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30238602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.40534" target="_blank">Full Text</a>]
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Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium.
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<strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong>
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Clin. Genet. 91: 92-99, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27102954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27102954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27102954" 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/cge.12793" target="_blank">Full Text</a>]
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Anazi, S., Alshammari, M., Moneis, D., Abouelhoda, M., Ibrahim, N., Alkuraya, F. S.
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<strong>Confirming the candidacy of THOC6 in the etiology of intellectual disability. (Letter)</strong>
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Am. J. Med. Genet. 170A: 1367-1369, 2016.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26739162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26739162</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26739162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.37549" target="_blank">Full Text</a>]
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Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M.
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<strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong>
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Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23621916/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23621916</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23621916[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=23621916" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1186/1750-1172-8-62" target="_blank">Full Text</a>]
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Baltimore, Md. 9/6/2013.
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Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R.
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<strong>Recruitment of the human TREX complex to mRNA during splicing.</strong>
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Genes Dev. 19: 1512-1517, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15998806/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15998806</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15998806[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=15998806" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A.
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<strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong>
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Hum. Molec. Genet. 28: 952-960, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30476144/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30476144</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30476144" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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carol : 09/23/2024<br>carol : 11/07/2020<br>carol : 11/06/2020<br>carol : 10/22/2020<br>alopez : 02/12/2020<br>carol : 09/14/2018<br>carol : 09/12/2013<br>carol : 9/11/2013<br>tpirozzi : 9/9/2013<br>ckniffin : 9/9/2013<br>mgross : 9/6/2013
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<span class="mim-font">
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<strong>*</strong> 615403
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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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THO COMPLEX, SUBUNIT 6; THOC6
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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FUNCTIONAL SPLICEOSOME-ASSOCIATED PROTEIN, 35-KD; FSAP35
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: THOC6</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> 773554009;
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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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<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: 16p13.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 16:3,024,035-3,027,750 </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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16p13.3
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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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Beaulieu-Boycott-Innes syndrome
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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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613680
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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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<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>The THOC6 gene encodes a subunit of the THO complex, which is involved in coordinating mRNA processing with export. The THO complex is a component of the TREX (transcription/export) complex (summary by Beaulieu et al., 2013). </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 mass spectrometric analysis of proteins that coimmunoprecipitated with UAP56 (DDX39B; 142560) from HeLa cell nuclear extracts, followed by PCR, Masuda et al. (2005) cloned THOC6, which they designated FSAP35. The deduced protein contains a WD40 repeat domain. THOC6 had an apparent molecular mass of 35 kD by SDS-PAGE. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using immunoprecipitation and mass spectrometric analysis of HeLa cell nuclear extracts, Masuda et al. (2005) found that the human TREX complex contained THO2 (THOC2; 300395), FSAP79 (THOC5; 612733), HPR1 (THOC1; 606930), UAP56, TEX1 (THOC3; 606929), FSAP35, ALY (THOC4; 604171), and FSAP24 (THOC7; 611965). Immunodepletion and gel-filtration analyses revealed that THO2, HPR1, FSAP79, FSAP35, and FSAP24 were tightly associated in the THO complex, whereas UAP56, ALY, and TEX1 were more loosely associated. Immunoprecipitation of any TREX component efficiently immunoprecipitated spliced mRNA and cDNA transcripts, but not unspliced pre-mRNAs. Immunodepletion of any component had no effect on spliceosome assembly, splicing, or RNA stability. The TREX complex assembled on every mRNA examined. Mutation analysis showed that the C terminus of ALY was required for binding of both UAP56 and the THO complex. The C terminus of UAP56 was sufficient for ALY binding. The N terminus of UAP56 interacted weakly with the THO complex and TEX1, suggesting that other regions of UAP56 are required for maximal binding. Masuda et al. (2005) concluded that recruitment of the human TREX complex is not directly coupled to transcription, as in yeast. </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>Hartz (2013) mapped the THOC6 gene to chromosome 16p13.3 based on an alignment of the THOC6 sequence (GenBank BC003118) with the genomic sequence (GRCh37).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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<p>In 2 sets of sisters from related Dariusleut Hutterite families with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), a neurodevelopmental disorder, Beaulieu et al. (2013) identified a homozygous missense mutation in the THOC6 gene (G46R; 615403.0001). The mutation, which was found by Sanger sequencing followed by exome sequencing, segregated with the disorder in the family and was not found in the NHLBI Exome Variant Server and dbSNP databases, in 435 control exomes, or in 150 controls from the general population. The variant was seen in the heterozygous state in 3% of 92 Dariusleut controls and in 2% of 120 Lehrerleut controls. It was not present in 500 Schmiedeleut controls. In vitro functional expression studies showed that the mutation caused abnormal intracellular localization; knockdown of THOC6 in HeLa cells caused an increase in apoptosis. No THOC6 mutations were found in 140 female patients with intellectual disability and microcephaly. </p><p>In a 4-year old Saudi boy with BBIS, born to first cousins once removed, Anazi et al. (2016) identified a homozygous nonsense mutation in the THOC6 gene (R87X; 615403.0002). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. </p><p>In 3 unrelated patients from France, Iran, and the U.S. with BBIS, Amos et al. (2017) identified homozygous or compound heterozygous mutations in the THOC6 gene (615403.0002-615403.0006). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. </p><p>In an Italian girl with BBIS, Accogli et al. (2018) identified compound heterozygosity for 2 loss-of-function mutations in the THOC6 gene (615403.0007-615403.0008). The mutations were found by trio exome sequencing and confirmed by Sanger sequence. Each parent was heterozygous for one of the mutations. </p><p>Mattioli et al. (2019) used trio exome sequencing to evaluate 2 patients with BBIS. In the first patient, the authors identified homozygosity for a rare haplotype that included 3 amino acid changes (W100R, V234L, G275D; 615403.0009) in the THOC6 gene due to maternal uniparental disomy of chromosome 16, and in the second patient, they identified compound heterozygosity for the same haplotype, inherited from the mother, and a previously reported missense mutation (G190E; 615403.0005), inherited from the father. Both the triple mutant and G190E variants changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (606930) and THOC5 (612733). Two of the amino acid changes (W100R and G275D) from the 3-variant haplotype were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. </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>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
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<p>In zebrafish, Beaulieu et al. (2013) found that the Thoc6 ortholog was present during embryonic neurodevelopment. The gene was highly expressed in the developing midbrain and the eyes at 24 hours postfertilization, and later became restricted to the posterior part of the midbrain and the midbrain-hindbrain boundary. </p>
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</span>
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<div>
|
|
<br />
|
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</div>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>9 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
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|
<div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
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THOC6, GLY46ARG
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<br />
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|
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SNP: rs587777030,
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gnomAD: rs587777030,
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ClinVar: RCV000054832
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In 2 sets of sisters from related Dariusleut Hutterite families with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), Beaulieu et al. (2013) identified a homozygous c.136G-A transition in the THOC6 gene, resulting in a gly46-to-arg (G46R) substitution at a highly conserved residue. The mutation, which was found by Sanger sequencing followed by exome sequencing, segregated with the disorder in the family and was not found in the NHLBI Exome Variant Server and dbSNP databases, in 435 control exomes, or in 150 controls from the general population. The variant was seen in heterozygous state in 3% of 92 Dariusleut controls and in 2% of 120 Lehrerleut controls. It was not present in 500 Schmiedeleut controls. The disorder was characterized by delayed development, moderate intellectual disability, and dysmorphic facial features. Variable developmental anomalies, such as cardiac and renal defects, were also present. In HeLa cells, wildtype THOC6 showed a speckled nuclear localization, whereas mutant G46R THOC6 was confined to the cytoplasm, indicating that the mutation caused impaired intracellular localization. Knockdown of THOC6 in HeLa cells by siRNA resulted in increased apoptosis. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
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<span class="mim-text-font">
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THOC6, ARG87TER
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<br />
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SNP: rs763344375,
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gnomAD: rs763344375,
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ClinVar: RCV000624090, RCV000680235
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</span>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 4-year-old Saudi boy with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), born to first cousins once removed, Anazi et al. (2016) identified homozygosity for a c.259C-T transition (c.259C-T, NM_001142350.2) in the THOC6, resulting in an arg87-to-ter (R87X) substitution. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. </p><p>In an 18-year-old woman from the U.S. with BBIS, who was born to nonconsanguineous parents, Amos et al. (2017) identified compound heterozygous mutations in the THOC6 gene: R87X and a thr250-to-pro (T250P; 615403.0006) substitution. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. </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 BEAULIEU-BOYCOTT-INNES SYNDROME</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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THOC6, GLN204PRO
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<br />
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SNP: rs1567416845,
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ClinVar: RCV000680236
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In a 7-year-old boy, born to consanguineous Iranian parents, with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), Amos et al. (2017) identified homozygosity for a c.611A-C transversion (c.611A-C, NM_024339.3) in the THOC6 gene, resulting in a gln204-to-pro (Q204P) substitution. The variant, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family and was not present in the ExAC database. Protein modeling suggested that the mutation interrupts the normal structure and function of THOC6. </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 BEAULIEU-BOYCOTT-INNES SYNDROME</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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THOC6, TYR45TER
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<br />
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SNP: rs772533643,
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gnomAD: rs772533643,
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ClinVar: RCV000680237
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</span>
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
<p>In a 6-year-old French boy, born to nonconsanguineous parents, with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), Amos et al. (2017) identified compound heterozygous mutations in the THOC6 gene: a c.135C-A transversion (c.135C-A, NM_024339.3), resulting in a tyr45-to-ter (Y45X) substitution, and a c.569G-A transition, resulting in gly190-to-glu (G190E; 615403.0005) substitution. The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The parents were each heterozygous for one of the mutations, which were present at low frequency in the ExAC database. Protein modeling suggested that the missense mutation interrupts the normal structure and function of THOC6. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<strong>.0005 BEAULIEU-BOYCOTT-INNES SYNDROME</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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THOC6, GLY190GLU
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<br />
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SNP: rs199795381,
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gnomAD: rs199795381,
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ClinVar: RCV000680238, RCV001528676, RCV003403573
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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 c.569G-A transition (c.569G-A, NM_024339.3) in the THOC6 gene, resulting in a gly190-to-glu (G190E) substitution, that was found in compound heterozygous state in a patient with Beaulieu-Boycott-Innes syndrome (BBIS; 613680) by Amos et al. (2017), see 615403.0004. </p><p>In a female patient with BBIS, Mattioli et al. (2019) identified compound heterozygosity for mutations in the THOC6 gene: the G190E mutation inherited from her father, and a rare haplotype that included 3 amino acid changes (W100R, V234L, G275D; 615403.0009) inherited from her mother. Both the triple mutant and G190E variants changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (606930) and THOC5 (612733). Two of the amino acid changes (W100R and G275D) from the 3-variant haplotype were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. </p>
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<span class="mim-font">
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<strong>.0006 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
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THOC6, THR250PRO
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<br />
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SNP: rs1555498821,
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ClinVar: RCV000623020, RCV000680239
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<p>In an 18-year-old woman from the U.S. with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), who was born to nonconsanguineous parents, Amos et al. (2017) identified compound heterozygous mutations in the THOC6 gene: a c.748A-C transition (c.748A-C, NM_024339.3), resulting in a thr250-to-pro (T250P) substitution, and the previously identified R87X mutation (615403.0002). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. The nonsense mutation was inherited from the unaffected mother; the father could not be tested and the T250P mutation was presumed to be paternal or de novo. The T250P mutation was not found in the ExAC database, and protein modeling suggested that it interrupts the normal structure and function of THOC6. </p>
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<span class="mim-font">
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<strong>.0007 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
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THOC6, ARG193TER
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<br />
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SNP: rs1194408714,
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gnomAD: rs1194408714,
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ClinVar: RCV001261871
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<p>In an Italian girl with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), Accogli et al. (2018) identified compound heterozygous mutations in the THOC6 gene: a c.577C-T transition (c.577C-T, NM_024339) in exon 8, resulting in an arg193-to-ter (R193X) substitution, inherited from her mother, and a 2-bp deletion (c.792_793delCA; 615403.0008) in exon 11, resulting in a frameshift and a premature termination codon (Val264ValfsTer48), inherited from her father. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. The R193X mutation was not found in any public databases. The 2-bp deletion was found in 1 of 246,156 alleles in the gnomAD database, with a frequency of .4062x10(-5). </p>
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<span class="mim-font">
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<strong>.0008 BEAULIEU-BOYCOTT-INNES SYNDROME</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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THOC6, 2-BP DEL, 792CA ({dbSNP rs543984154})
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<br />
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SNP: rs773022351,
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gnomAD: rs773022351,
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ClinVar: RCV001261872
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<div>
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<span class="mim-text-font">
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<p>For discussion of the 2-bp deletion (c.792_793delCA, NM_024339) in the THOC6 gene that was found in compound heterozygous state in an Italian girl with Beaulieu-Boycott-Innes syndrome (BBIS; 613680) by Accogli et al. (2018), see 615403.0007. </p>
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</span>
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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>.0009 BEAULIEU-BOYCOTT-INNES SYNDROME</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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THOC6, HAPLOTYPE, TRP100ARG, VAL234LEU, GLY275ASP
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<br />
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SNP: rs138632121, rs150940923, rs200426926,
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gnomAD: rs138632121, rs150940923, rs200426926,
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ClinVar: RCV000622420, RCV000623380, RCV000624518, RCV000850494, RCV000850495, RCV000850496, RCV001263559, RCV001541157, RCV001553458, RCV001591401
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<div>
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<span class="mim-text-font">
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<p>In a boy with Beaulieu-Boycott-Innes syndrome (BBIS; 613680), Mattioli et al. (2019) identified homozygosity for a rare haplotype including 3 amino acid changes (W100R, V234L, G275D) in the THOC6 gene due to maternal uniparental disomy of chromosome 16. The mutation was found by trio exome sequencing. The triple mutant changed the physiologic localization of the THOC6 protein from its normal nuclear location to an abnormal cytosolic localization as well as its interaction with 2 THO subunits, THOC1 (606930) and THOC5 (612733). Two of the amino acid changes (W100R and G275D) were predicted on their own to be deleterious according to most programs used, possibly resulting in pathogenicity of the haplotype. The W100R variant was predicted to be most pathogenic because it alters a tryptophan located in a WD-repeat domain, which is usually implicated in multiprotein assembly and interaction. The W100R variant was the only one of the 3 in the haplotype that on its own affected the nuclear localization of THOC6. Another patient reported by Mattioli et al. (2019) was compound heterozygous for the 3-amino acid haplotype and a missense mutation (G190E; 615403.0005). </p>
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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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<ol>
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<li>
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<p class="mim-text-font">
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Accogli, A., Scala, M., Calcagno, A., Castello, R., Torella, A., Musacchia, F., Allegri, A. M. E., Mancardi, M. M., Maghnie, M., Severino, M., Telethon Undiagnosed Diseases Program, Nigro, V., Capra, V.
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<strong>Novel CNS malformations and skeletal anomalies in a patient with Beaulieu-Boycott-Innes syndrome.</strong>
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Am. J. Med. Genet. 176A: 2835-2840, 2018.
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[PubMed: 30238602]
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[Full Text: https://doi.org/10.1002/ajmg.a.40534]
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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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Amos, J. S., Huang, L., Thevenon, J., Kariminedjad, A., Beaulieu, C. L., Masurel-Paulet, A., Najmabadi, H., Fattahi, Z., Beheshtian, M., Tonekaboni, S. H., Tang, S., Helbig, K. L., Alcaraz, W., Riviere, J.-B., Faivre, L., Innes, A. M., Lebel, R. R., Boycott, K. M., Care4Rare Canada Consortium.
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<strong>Autosomal recessive mutations in THOC6 cause intellectual disability: syndrome delineation requiring forward and reverse phenotyping.</strong>
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Clin. Genet. 91: 92-99, 2017.
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[PubMed: 27102954]
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[Full Text: https://doi.org/10.1111/cge.12793]
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</li>
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<li>
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<p class="mim-text-font">
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Anazi, S., Alshammari, M., Moneis, D., Abouelhoda, M., Ibrahim, N., Alkuraya, F. S.
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<strong>Confirming the candidacy of THOC6 in the etiology of intellectual disability. (Letter)</strong>
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Am. J. Med. Genet. 170A: 1367-1369, 2016.
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[PubMed: 26739162]
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[Full Text: https://doi.org/10.1002/ajmg.a.37549]
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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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Beaulieu, C. L., Huang, L., Innes, A. M., Akimenko, M.-A., Puffenberger, E. G., Schwartz, C., Jerry, P., Ober, C., Hegele, R. A., McLeod, D. R., Schwartzentruber, J., Majewski, J., Bulman, D. E., Parboosingh, J. S., Boycott, K. M.
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<strong>Intellectual disability associated with a homozygous missense mutation in THOC6.</strong>
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Orphanet J. Rare Dis. 8: 62, 2013. Note: Electronic Article.
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[PubMed: 23621916]
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[Full Text: https://doi.org/10.1186/1750-1172-8-62]
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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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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 9/6/2013.
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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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Masuda, S., Das, R., Cheng, H., Hurt, E., Dorman, N., Reed, R.
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<strong>Recruitment of the human TREX complex to mRNA during splicing.</strong>
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Genes Dev. 19: 1512-1517, 2005.
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[PubMed: 15998806]
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[Full Text: https://doi.org/10.1101/gad.1302205]
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<li>
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<p class="mim-text-font">
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Mattioli, F., Isidor, B., Abdul-Rahman, O., Gunter, A., Huang, L., Kumar, R., Beaulieu, C., Gecz, J., Innes, M., Mandel, J.-L., Piton, A.
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<strong>Clinical and functional characterization of recurrent missense variants implicated in THOC6-related intellectual disability.</strong>
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Hum. Molec. Genet. 28: 952-960, 2019.
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[PubMed: 30476144]
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[Full Text: https://doi.org/10.1093/hmg/ddy391]
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Contributors:
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 10/22/2020<br>Sonja A. Rasmussen - updated : 09/14/2018<br>Cassandra L. Kniffin - updated : 9/9/2013
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</span>
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<span class="mim-text-font">
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Patricia A. Hartz : 9/6/2013
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carol : 09/24/2024<br>carol : 09/23/2024<br>carol : 11/07/2020<br>carol : 11/06/2020<br>carol : 10/22/2020<br>alopez : 02/12/2020<br>carol : 09/14/2018<br>carol : 09/12/2013<br>carol : 9/11/2013<br>tpirozzi : 9/9/2013<br>ckniffin : 9/9/2013<br>mgross : 9/6/2013
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<div class="modal-footer">
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<button type="button" id="mimDonationPopupDonate" class="btn btn-success btn-block" data-dismiss="modal"> Donate To OMIM! </button>
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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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</body>
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</html>
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