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Entry
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- *602290 - TRIPARTITE MOTIF-CONTAINING PROTEIN 32; TRIM32
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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">*602290</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#cytogenetics">Cytogenetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<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/602290">Table View</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000119401;t=ENST00000450136" 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=22954" 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=602290" 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 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=ENSG00000119401;t=ENST00000450136" 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_001099679,NM_001379048,NM_001379049,NM_001379050,NM_012210" 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_012210" 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=602290" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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</a>
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</span>
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</span>
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</div>
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<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://hprd.org/summary?hprd_id=03797&isoform_id=03797_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/TRIM32" 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/758423,13111963,20178303,32693498,119607852,119607853,153791514,153792582,226881028,227905396,1822188068,1822188083,1822188099,2500092253" 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/Q13049" 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=22954" 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=ENSG00000119401;t=ENST00000450136" 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=TRIM32" 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=TRIM32" 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+22954" 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/TRIM32" 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:22954" 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/22954" 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=chr9&hgg_gene=ENST00000450136.2&hgg_start=116687305&hgg_end=116701299&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:16380" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:16380" 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=602290[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=602290[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000119401" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=TRIM32" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=TRIM32" 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=TRIM32" 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="http://www.LOVD.nl/TRIM32" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=TRIM32&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/PA38130" 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:16380" 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://www.mousephenotype.org/data/genes/MGI:1917057" 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/TRIM32#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:1917057" 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/22954/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=22954" 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-060428-1" 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">
|
|
<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:22954" 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=TRIM32&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> 240064008, 43226001<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>
|
|
602290
|
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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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TRIPARTITE MOTIF-CONTAINING PROTEIN 32; TRIM32
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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>
|
|
</span>
|
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</p>
|
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</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TAT-INTERACTING PROTEIN, 72-KD<br />
|
|
HT2A<br />
|
|
BBS11 GENE; BBS11
|
|
</span>
|
|
</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">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TRIM32" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TRIM32</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>
|
|
<span class="mim-text-font">
|
|
<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/9/453?start=-3&limit=10&highlight=453">9q33.1</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr9:116687305-116701299&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'})">9:116,687,305-116,701,299</a> </span>
|
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</em>
|
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</strong>
|
|
<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>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=615988,254110" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
|
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/9/453?start=-3&limit=10&highlight=453">
|
|
9q33.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
?Bardet-Biedl syndrome 11
|
|
|
|
<span class="mim-tip-hint" title="A question mark (?) indicates that the relationship between the phenotype and gene is provisional">
|
|
<span class="glyphicon glyphicon-question-sign" aria-hidden="true"></span>
|
|
</span>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/615988"> 615988 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<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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<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
Muscular dystrophy, limb-girdle, autosomal recessive 8
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/254110"> 254110 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
|
|
|
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|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
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<p>Members of the tripartite motif (TRIM) protein family, such as TRIM32, contain RING, BBOX, and coiled-coil domains, as well as variable C-terminal domains. TRIM32 functions as an E3 ubiquitin ligase in the ubiquitin-proteasome system, which is responsible for protein degradation (summary by <a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" 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>Transcriptional activation of HIV-1 gene expression by the viral Tat protein requires the interaction of a cellular cofactor with the Tat activation domain. This domain consists of the cysteine-rich and core motifs of HIV-1 Tat and is functionally conserved in the distantly related Tat proteins of HIV-2 and EIAV. <a href="#3" class="mim-tip-reference" title="Fridell, R. A., Harding, L. S., Bogerd, H. P., Cullen, B. R. <strong>Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.</strong> Virology 209: 347-357, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778269</a>] [<a href="https://doi.org/10.1006/viro.1995.1266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7778269">Fridell et al. (1995)</a> used the yeast 2-hybrid system to identify TRIM32, which they called HT2A, a protein that specifically and precisely binds the activation domain of HIV-1 Tat and that can interact with the HIV-2 and EIAV Tat proteins in vivo. <a href="#3" class="mim-tip-reference" title="Fridell, R. A., Harding, L. S., Bogerd, H. P., Cullen, B. R. <strong>Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.</strong> Virology 209: 347-357, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778269</a>] [<a href="https://doi.org/10.1006/viro.1995.1266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7778269">Fridell et al. (1995)</a> demonstrated that the interaction between HT2A and the activation domain of HIV-1 Tat can be readily detected in the mammalian cell nucleus. They isolated the HT2A cDNA from a HeLa cell cDNA library and found that it contains an open reading frame encoding a predicted 653-amino acid protein of 72 kD. Using Northern blot analysis, they detected a major, approximately 3.7-kb HT2A transcript and a minor, approximately 2.7-kb HT2A transcript in all examined tissues. HT2A contains an N-terminal C3HC4 zinc finger motif, indicating that it is a member of the ring finger family (see RING1, <a href="/entry/602045">602045</a>) which includes transcription factors, nucleic acid binding proteins, and oncogenes. HT2A is most similar to the ring finger subfamily that includes RFP (<a href="/entry/602165">602165</a>), PML (<a href="/entry/102578">102578</a>), T18, RPT1, and Ro autoantigen (<a href="/entry/600063">600063</a>) since it contains a cysteine/histidine cluster and a heptad repeat of hydrophobic residues that is predicted to form a coiled-coil structure. The unique C-terminal region of HT2A is necessary and sufficient for binding to Tat. <a href="#3" class="mim-tip-reference" title="Fridell, R. A., Harding, L. S., Bogerd, H. P., Cullen, B. R. <strong>Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.</strong> Virology 209: 347-357, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778269</a>] [<a href="https://doi.org/10.1006/viro.1995.1266" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7778269">Fridell et al. (1995)</a> suggested that HT2A may play a significant role in mediating the biologic activity of the HIV-1 Tat protein in vivo. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7778269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> stated that the TRIM32 protein contains a RING zinc finger domain, BBOX domain, BBC domain, and 6 C-terminal NHL domains. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong> Am. J. Hum. Genet. 70: 663-672, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822024">Frosk et al. (2002)</a> reported that the TRIM32 gene contains 2 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong> Am. J. Hum. Genet. 70: 663-672, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822024">Frosk et al. (2002)</a> determined that the TRIM32 gene maps to chromosome 9q31-q33, between markers D9S1126 and D9S737. TRIM32 overlaps with intron 12 of the ASTN2 gene (<a href="/entry/612856">612856</a>) on the opposite strand. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822024" 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>Using short tandem repeat polymorphism (STRP) and single-nucleotide polymorphism (SNP) microarray genotyping, <a href="#1" class="mim-tip-reference" title="Chiang, A. P., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K.-Y. A., Huang, J., Elbedour, K., Carmi, R., Slusarski, D. C., Casavant, T. L., Stone, E. M., Sheffield, V. C. <strong>Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).</strong> Proc. Nat. Acad. Sci. 103: 6287-6292, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16606853[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/10.1073/pnas.0600158103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606853">Chiang et al. (2006)</a> identified the TRIM32 gene within a 2.4-Mb region on chromosome 9q33.1 linked to the Bardet-Biedl syndrome (<a href="/entry/209900">209900</a>) phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> showed that TRIM32 is a widely expressed ubiquitin ligase that is localized to the Z-line in skeletal muscle. TRIM32 bound and ubiquitinated dysbindin, augmenting its degradation. Knockdown of TRIM32 in myoblasts resulted in elevated levels of dysbindin (DTNBP1; <a href="/entry/607145">607145</a>). The D487N (<a href="#0001">602290.0001</a>) and R394H (<a href="#0004">602290.0004</a>) mutant proteins impaired ubiquitin ligase activity towards dysbindin and were mislocalized in heterologous cells. The D487N mutant could bind to both dysbindin and its ubiquitin-conjugating E2 enzyme but was defective in monoubiquitination. <a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> concluded that TRIM32 is a regulator of dysbindin and that TRIM32 mutations may impair substrate ubiquitination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" 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 an approach that combined screening of candidate genes with a CGH array and massively parallel sequencing, <a href="#11" class="mim-tip-reference" title="Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J. A., Penisson-Besnier, I., Nadaj-Pakleza, A., Roudaut, C., Criqui, A., Orhant, L., Peyroulan, D., Ben Yaou, R., and 11 others. <strong>Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing.</strong> Europ. J. Hum. Genet. 23: 929-934, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25351777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25351777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25351777[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25351777">Nectoux et al. (2015)</a> identified 2 patients with LGMDR8 with homozygous or compound heterozygous mutations in the TRIM32 gene. In the first patient, one allele had a frameshift mutation (<a href="#0006">602290.0006</a>), confirmed by Sanger sequencing, and the other allele had a 124.4-kb deletion that included the entire TRIM32 gene. The second patient, born to nonconsanguineous parents, had a homozygous 336-kb deletion including the TRIM32 gene. The deletions in both patients, which were confirmed by quantitative PCR, included part of the ASTN2 gene (<a href="/entry/612856">612856</a>). Analysis of the breakpoints showed that the 5-prime boundaries of both deletions were located within regions enriched with genomic repeats, possibly making rearrangements and deletions more likely to occur. Parents were not available for study for either patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25351777" 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><strong><em>Limb-Girdle Muscular Dystrophy, Autosomal Recessive 8</em></strong></p><p>
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Autosomal recessive limb-girdle muscular dystrophy-8 (LGMDR8; <a href="/entry/254110">254110</a>), previously symbolized LGMD2H, is a mild autosomal recessive myopathy that was first described in the Hutterite population of Manitoba, Canada. <a href="#5" class="mim-tip-reference" title="Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong> Am. J. Hum. Genet. 70: 663-672, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822024">Frosk et al. (2002)</a> narrowed the map assignment of the gene to a region of 560 kb on 9q and found that the region contains 4 known genes, including the TRIM32 gene. All affected individuals were homozygous for an asp487-to-asn (D487N; <a href="#0001">602290.0001</a>) mutation in TRIM32. The mutation occurred in an NHL (named after the proteins NCL1, HT2A, and LIN-41) domain at a position that is highly conserved. NHL domains are involved in protein-protein interactions. The domain structure of the TRIM32 protein suggested that it may be an E3-ubiquitin ligase. This may represent a novel pathogenic mechanism for muscular dystrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822024" 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="#13" class="mim-tip-reference" title="Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V. <strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong> Hum. Mutat. 29: 240-247, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>] [<a href="https://doi.org/10.1002/humu.20633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994549">Saccone et al. (2008)</a> identified homozygous mutations in the TRIM32 gene (see, e.g., <a href="#0003">602290.0003</a>; <a href="#0004">602290.0004</a>) in non-Hutterite patients with LGMD2H. Both mutations occurred in the NHL domain. In vitro functional expression studies showed that these mutations abrogated TRIM32 self-interaction and UBE2N (<a href="/entry/603679">603679</a>) binding, indicating a dramatic effect on protein folding. In contrast, in vitro studies showed that the BBS P130S mutation retained the ability to self-interact, suggesting a different pathogenic mechanism in BBS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" 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>Using comparative genomic hybridization (CGH) and sequencing of the TRIM32 gene in a 35-year-old woman with LGMDR8, <a href="#12" class="mim-tip-reference" title="Neri, M., Selvatici, R., Scotton, C., Trabanelli, C., Armaroli, A., De Grandis, D., Levy, N., Gualandi, F., Ferlini, A. <strong>A patient with limb girdle muscular dystrophy carries a TRIM32 deletion, detected by a novel CGH array, in compound heterozygosis with a nonsense mutation.</strong> Neuromusc. Disord. 23: 478-482, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23541687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23541687</a>] [<a href="https://doi.org/10.1016/j.nmd.2013.02.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23541687">Neri et al. (2013)</a> identified compound heterozygous mutations: a nonsense mutation (R316X; <a href="#0005">602290.0005</a>) in the C-terminal NHL domain of TRIM32 on one allele and a deletion including the entire TRIM32 gene on the other allele. The precise breakpoints of the deletion could not be defined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23541687" 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>Using an approach that combined screening of candidate genes with a CGH array and massively parallel sequencing, <a href="#11" class="mim-tip-reference" title="Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J. A., Penisson-Besnier, I., Nadaj-Pakleza, A., Roudaut, C., Criqui, A., Orhant, L., Peyroulan, D., Ben Yaou, R., and 11 others. <strong>Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing.</strong> Europ. J. Hum. Genet. 23: 929-934, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25351777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25351777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25351777[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25351777">Nectoux et al. (2015)</a> identified a patient with LGMDR8 who had a frameshift mutation in the TRIM32 gene (c.160delC; <a href="#0006">602290.0006</a>), confirmed by Sanger sequencing, and a 124.4-kb deletion that included the entire TRIM32 gene and part of the ASTN2 gene (<a href="/entry/612856">612856</a>); see CYTOGENETICS. The deletion was confirmed by quantitative PCR. The parents were not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25351777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Bardet-Biedl Syndrome 11</em></strong></p><p>
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Bardet-Biedl syndrome (BBS; see <a href="/entry/209900">209900</a>) is a pleiotropic autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal abnormalities, learning disabilities, and hypogenitalism. The disorder displays extensive genetic heterogeneity. <a href="#1" class="mim-tip-reference" title="Chiang, A. P., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K.-Y. A., Huang, J., Elbedour, K., Carmi, R., Slusarski, D. C., Casavant, T. L., Stone, E. M., Sheffield, V. C. <strong>Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).</strong> Proc. Nat. Acad. Sci. 103: 6287-6292, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16606853[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/10.1073/pnas.0600158103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606853">Chiang et al. (2006)</a> used high density SNP genotyping to identify the disease-causing gene in a single small consanguineous Israeli Bedouin BBS family (BBS11; <a href="/entry/615988">615988</a>) in which linkage studies failed to identify a disease locus. SNP genotyping revealed a homozygous candidate region. Mutation analysis in the region of homozygosity identified a homozygous missense mutation in a conserved B-box domain of TRIM32 (P130S; <a href="#0002">602290.0002</a>). Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci dataset demonstrated that TRIM32 is a BBS gene. This study showed the value of high density SNP genotyping for homozygosity mapping and the use of expression correlation data for evaluation of candidate genes, and identified the involvement of the proteasome degradation pathway in BBS. The ubiquitin/proteasome system had not been implicated in this disorder. Another TRIM32 variant, a missense mutation associated with autosomal recessive limb girdle muscular dystrophy (D487N; <a href="#0001">602290.0001</a>), does not affect the E3 ubiquitin ligase activity, whereas disruption of the TRIM32 coiled-coil domain, as in the P130S mutation, reduces the binding affinity to myosin (<a href="#7" class="mim-tip-reference" title="Kudryashova, E., Kudryashov, D., Kramerova, I., Spencer, M. J. <strong>Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin.</strong> J. Molec. Biol. 354: 413-424, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16243356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16243356</a>] [<a href="https://doi.org/10.1016/j.jmb.2005.09.068" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16243356">Kudryashova et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16606853+16243356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#8" class="mim-tip-reference" title="Kudryashova, E., Wu, J., Havton, L. A., Spencer, M. J. <strong>Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component.</strong> Hum. Molec. Genet. 18: 1353-1367, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19155210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19155210</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19155210[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19155210">Kudryashova et al. (2009)</a> generated a Trim32-null mouse model of human muscular dystrophy phenotypes. Histologic analysis of Trim32-null skeletal muscles revealed mild myopathic changes. Electron microscopy showed areas with Z-line streaming and a dilated sarcotubular system with vacuoles, replicating the phenotypes of LGMD2H and sarcotubular myopathy. The level of Trim32 expression in normal mouse brain exceeded that observed in skeletal muscle by more than 100-fold. Analysis of Trim32-null neural tissue revealed a decreased concentration of neurofilaments and a reduction in myelinated motor axon diameters. The axonal changes suggested a shift toward a slower motor unit type. Trim32-null soleus muscle expressed an elevated type I slow myosin isotype with a concomitant reduction in the type II fast myosin. <a href="#8" class="mim-tip-reference" title="Kudryashova, E., Wu, J., Havton, L. A., Spencer, M. J. <strong>Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component.</strong> Hum. Molec. Genet. 18: 1353-1367, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19155210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19155210</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19155210[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp036" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19155210">Kudryashova et al. (2009)</a> suggested that muscular dystrophy due to TRIM32 mutation may involve both neurogenic and myogenic characteristics. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19155210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong> Am. J. Hum. Genet. 70: 663-672, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822024">Frosk et al. (2002)</a> found homozygosity for an asp487-to-asn (D487N) missense mutation in the TRIM32 gene as a causative mutation in the mild autosomal recessive myopathy observed in Manitoba Hutterites (LGMDR8; <a href="/entry/254110">254110</a>). <a href="#5" class="mim-tip-reference" title="Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K. <strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong> Am. J. Hum. Genet. 70: 663-672, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/339083" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11822024">Frosk et al. (2002)</a> stated that of 60 cases of LGMD studied in Manitoba Hutterites, most were caused by the D487N mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11822024" 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="#14" class="mim-tip-reference" title="Schoser, B. G. H., Frosk, P., Engel, A. G., Klutzny, U., Lochmuller, H., Wrogemann, K. <strong>Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H.</strong> Ann. Neurol. 57: 591-595, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786463</a>] [<a href="https://doi.org/10.1002/ana.20441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15786463">Schoser et al. (2005)</a> identified the homozygous D487N mutation in the patients reported by <a href="#6" class="mim-tip-reference" title="Jerusalem, F., Engel, A. G., Gomez, M. R. <strong>Sarcotubular myopathy.</strong> Neurology 23: 897-906, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4269389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4269389</a>] [<a href="https://doi.org/10.1212/wnl.23.9.897" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4269389">Jerusalem et al. (1973)</a> and <a href="#10" class="mim-tip-reference" title="Muller-Felber, W., Schlotter, B., Topfer, M., Ketelsen, U.-P., Muller-Hocker, J., Pongratz, D. <strong>Phenotypic variability in two brothers with sarcotubular myopathy. (Letter)</strong> J. Neurol. 246: 408-411, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10399877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10399877</a>] [<a href="https://doi.org/10.1007/s004150050374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10399877">Muller-Felber et al. (1999)</a>, confirming that they had LGMDR8. In addition, haplotype analysis showed that all LGMDR8 patients shared the same haplotype, suggesting that the mutation arose before the emergence of the Hutterite religion in central Europe in the 16th century. <a href="#14" class="mim-tip-reference" title="Schoser, B. G. H., Frosk, P., Engel, A. G., Klutzny, U., Lochmuller, H., Wrogemann, K. <strong>Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H.</strong> Ann. Neurol. 57: 591-595, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786463</a>] [<a href="https://doi.org/10.1002/ana.20441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15786463">Schoser et al. (2005)</a> noted the phenotypic variability caused by the same mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4269389+15786463+10399877" 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="#4" class="mim-tip-reference" title="Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R. <strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong> Europ. J. Hum. Genet. 13: 978-982, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15886712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15886712</a>] [<a href="https://doi.org/10.1038/sj.ejhg.5201436" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15886712">Frosk et al. (2005)</a> reported a Hutterite family in which 2 boys, aged 7 and 10 years, were homozygous for both the D487N mutation and an LGMD2I (LGMDR9; <a href="/entry/607155">607155</a>)-related FKRP mutation (L276I; <a href="/entry/606596#0004">606596.0004</a>). Although they presented at an early age with exercise intolerance and increased serum creatine kinase, the clinical phenotype was not significantly more severe than that of patients with isolated LGMD2H or LGMD2I. Both parents and 3 other sibs were homozygous for the D487N mutation, with highly variable phenotypic expression. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15886712" 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 vitro functional expression studies by <a href="#13" class="mim-tip-reference" title="Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V. <strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong> Hum. Mutat. 29: 240-247, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>] [<a href="https://doi.org/10.1002/humu.20633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994549">Saccone et al. (2008)</a> demonstrated that D487N-mutant protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (<a href="/entry/603679">603679</a>). The consequences of this mutation were similar to complete deletion of the coiled coil-NHL domains, suggesting a dramatic effect on protein folding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> showed that D487N-mutant protein impaired TRIM32 ubiquitin ligase activity towards dysbindin (DTNBP1; <a href="/entry/607145">607145</a>) and mislocalized in heterologous cells. The D487N mutant could bind to both dysbindin and its ubiquitin-conjugating E2 enzyme but was defective in monoubiquitination. <a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> suggest that D487N mutation may impair substrate ubiquitination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" 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>Among 1,493 Schmiedeleut (S-leut) Hutterites from the United States, <a href="#2" class="mim-tip-reference" title="Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C. <strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong> Am. J. Hum. Genet. 91: 608-620, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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/10.1016/j.ajhg.2012.08.007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22981120">Chong et al. (2012)</a> found 228 heterozygotes and 9 homozygotes for the D487N mutation in the TRIM32 gene, for a frequency of 0.153, or 1 in 6.5. The carrier frequency in other populations was unknown, with only 2 non-Hutterite cases having been reported (<a href="#14" class="mim-tip-reference" title="Schoser, B. G. H., Frosk, P., Engel, A. G., Klutzny, U., Lochmuller, H., Wrogemann, K. <strong>Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H.</strong> Ann. Neurol. 57: 591-595, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786463</a>] [<a href="https://doi.org/10.1002/ana.20441" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15786463">Schoser et al., 2005</a>). The 9 homozygous individuals ranged in age from 10 to 42 years, and were unaware of their status. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22981120+15786463" 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> rs111033571 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs111033571;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/rs111033571?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=rs111033571" 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=rs111033571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>By homozygosity mapping using high-density SNP genotyping, <a href="#1" class="mim-tip-reference" title="Chiang, A. P., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K.-Y. A., Huang, J., Elbedour, K., Carmi, R., Slusarski, D. C., Casavant, T. L., Stone, E. M., Sheffield, V. C. <strong>Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).</strong> Proc. Nat. Acad. Sci. 103: 6287-6292, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16606853[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/10.1073/pnas.0600158103" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16606853">Chiang et al. (2006)</a> identified the TRIM32 gene as the site of mutations causing Bardet-Biedl syndrome (BBS11; <a href="/entry/615988">615988</a>) in a small consanguineous Israeli Bedouin family. The specific mutation was a change of codon 130 from CCT (pro) to TCT (ser). The substitution was present in homozygous state in the affected individuals. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16606853" 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 vitro functional expression studies by <a href="#13" class="mim-tip-reference" title="Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V. <strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong> Hum. Mutat. 29: 240-247, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>] [<a href="https://doi.org/10.1002/humu.20633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994549">Saccone et al. (2008)</a> demonstrated that the P130S-mutant protein maintained self-interaction ability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" 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">rs1588218453 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1588218453;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=rs1588218453" 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=rs1588218453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a 44-year-old Croatian woman with limb-girdle muscular dystrophy type 2H (LGMDR8; <a href="/entry/254110">254110</a>), <a href="#13" class="mim-tip-reference" title="Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V. <strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong> Hum. Mutat. 29: 240-247, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>] [<a href="https://doi.org/10.1002/humu.20633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994549">Saccone et al. (2008)</a> identified a homozygous 1-bp deletion (1559delC) in the TRIM32 gene within a conserved region of the NHL domain, resulting in frameshift and premature termination. The patient had slowly progressive proximal muscle weakness and wasting, respiratory weakness, and chronic keratitis. In vitro functional expression studies showed that truncated protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (<a href="/entry/603679">603679</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" 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> rs121434447 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121434447;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/rs121434447?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=rs121434447" 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=rs121434447" 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=RCV000007778 OR RCV000362326 OR RCV000638363 OR RCV001334685 OR RCV004748510 OR RCV005042010" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000007778, RCV000362326, RCV000638363, RCV001334685, RCV004748510, RCV005042010" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000007778...</a>
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<p>In a man with limb-girdle muscular dystrophy type 2H (LGMDR8; <a href="/entry/254110">254110</a>), <a href="#13" class="mim-tip-reference" title="Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V. <strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong> Hum. Mutat. 29: 240-247, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>] [<a href="https://doi.org/10.1002/humu.20633" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17994549">Saccone et al. (2008)</a> identified a homozygous 1180G-A transition in the TRIM32 gene, resulting in an arg394-to-his (R394H) substitution in a conserved residue of an NHL domain. Disease onset was in the third decade with weakness and paresthesias. He had marked proximal weakness and atrophy, as well as respiratory weakness, and lost the ability to walk at age 64 after prolonged immobility for other causes. A second patient was found to be heterozygous for the R394H mutation. He was 73 years old and had mild symptoms with no respiratory involvement. In vitro functional expression studies showed that R394H-mutant protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (<a href="/entry/603679">603679</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J. <strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong> Hum. Molec. Genet. 18: 2344-2358, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19349376">Locke et al. (2009)</a> showed that R394H-mutant protein impaired TRIM32 ubiquitin ligase activity towards dysbindin and mislocalized in heterologous cells, but was able to self-associate. Coexpression of wildtype and R394H-mutant TRIM32 reduced the level of dysbindin monoubiquitination, possibly indicating that R394H may compromise function of the wildtype protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19349376" 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 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</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> rs199664043 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs199664043;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/rs199664043?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=rs199664043" 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=rs199664043" 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=RCV001350863 OR RCV002221274 OR RCV003135986 OR RCV003405557 OR RCV005040192" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001350863, RCV002221274, RCV003135986, RCV003405557, RCV005040192" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001350863...</a>
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<p>By sequencing of the TRIM32 gene in a 35-year-old Italian woman with autosomal recessive limb-girdle muscular dystrophy (LGMDR8; <a href="/entry/254110">254110</a>), <a href="#12" class="mim-tip-reference" title="Neri, M., Selvatici, R., Scotton, C., Trabanelli, C., Armaroli, A., De Grandis, D., Levy, N., Gualandi, F., Ferlini, A. <strong>A patient with limb girdle muscular dystrophy carries a TRIM32 deletion, detected by a novel CGH array, in compound heterozygosis with a nonsense mutation.</strong> Neuromusc. Disord. 23: 478-482, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23541687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23541687</a>] [<a href="https://doi.org/10.1016/j.nmd.2013.02.003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23541687">Neri et al. (2013)</a> identified a heterozygous c.1837C-T transition, resulting in an arg316-to-ter (R316X) in the C-terminal NHL domain. The mutation was found in compound heterozygosity with a deletion of the entire TRIM32 gene, identified by a custom comparative genomic hybridization (CGH) array. The breakpoints of the deletion could not be defined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23541687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</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">rs2132075382 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs2132075382;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=rs2132075382" 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=rs2132075382" 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=RCV001844801" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001844801" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001844801</a>
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<p>Using a combined approach of comparative genomic hybridization array and massively parallel sequencing, <a href="#11" class="mim-tip-reference" title="Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J. A., Penisson-Besnier, I., Nadaj-Pakleza, A., Roudaut, C., Criqui, A., Orhant, L., Peyroulan, D., Ben Yaou, R., and 11 others. <strong>Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing.</strong> Europ. J. Hum. Genet. 23: 929-934, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25351777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25351777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25351777[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/ejhg.2014.223" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25351777">Nectoux et al. (2015)</a> identified a patient with autosomal recessive limb-girdle muscular dystrophy (LGMDR8; <a href="/entry/254110">254110</a>) who was compound heterozygous for a 1-bp deletion (c.1603delC, NM_012210.3) in the TRIM32 gene, resulting in a frameshift (Leu535SerfsTer21), and a 124.4-kb deletion including the entire TRIM32 gene and part of the ASTN2 gene (<a href="/entry/612856">612856</a>). The patient had a mild phenotype of progressive limb-girdle muscular dystrophy as typically seen in patients with LGMDR8. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25351777" 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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Chiang, A. P., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K.-Y. A., Huang, J., Elbedour, K., Carmi, R., Slusarski, D. C., Casavant, T. L., Stone, E. M., Sheffield, V. C.
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<strong>Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).</strong>
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Proc. Nat. Acad. Sci. 103: 6287-6292, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16606853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16606853</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16606853[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=16606853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.0600158103" target="_blank">Full Text</a>]
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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<strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong>
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Am. J. Hum. Genet. 91: 608-620, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22981120/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22981120</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22981120[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=22981120" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ajhg.2012.08.007" target="_blank">Full Text</a>]
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Fridell, R. A., Harding, L. S., Bogerd, H. P., Cullen, B. R.
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<strong>Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.</strong>
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Virology 209: 347-357, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7778269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7778269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7778269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/viro.1995.1266" target="_blank">Full Text</a>]
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Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R.
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<strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong>
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Europ. J. Hum. Genet. 13: 978-982, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15886712/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15886712</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15886712" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/sj.ejhg.5201436" target="_blank">Full Text</a>]
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Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K.
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<strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong>
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Am. J. Hum. Genet. 70: 663-672, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11822024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11822024</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11822024[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=11822024" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/339083" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Jerusalem1973" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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|
Jerusalem, F., Engel, A. G., Gomez, M. R.
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|
<strong>Sarcotubular myopathy.</strong>
|
|
Neurology 23: 897-906, 1973.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4269389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4269389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4269389" 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/10.1212/wnl.23.9.897" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="7" class="mim-anchor"></a>
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<a id="Kudryashova2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kudryashova, E., Kudryashov, D., Kramerova, I., Spencer, M. J.
|
|
<strong>Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin.</strong>
|
|
J. Molec. Biol. 354: 413-424, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16243356/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16243356</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16243356" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.jmb.2005.09.068" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Kudryashova2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kudryashova, E., Wu, J., Havton, L. A., Spencer, M. J.
|
|
<strong>Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component.</strong>
|
|
Hum. Molec. Genet. 18: 1353-1367, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19155210/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19155210</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19155210[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=19155210" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp036" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="9" class="mim-anchor"></a>
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<a id="Locke2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J.
|
|
<strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong>
|
|
Hum. Molec. Genet. 18: 2344-2358, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19349376/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19349376</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19349376[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=19349376" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/ddp167" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Muller-Felber1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Muller-Felber, W., Schlotter, B., Topfer, M., Ketelsen, U.-P., Muller-Hocker, J., Pongratz, D.
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<strong>Phenotypic variability in two brothers with sarcotubular myopathy. (Letter)</strong>
|
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J. Neurol. 246: 408-411, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10399877/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10399877</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10399877" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s004150050374" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="11" class="mim-anchor"></a>
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<a id="Nectoux2015" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J. A., Penisson-Besnier, I., Nadaj-Pakleza, A., Roudaut, C., Criqui, A., Orhant, L., Peyroulan, D., Ben Yaou, R., and 11 others.
|
|
<strong>Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing.</strong>
|
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Europ. J. Hum. Genet. 23: 929-934, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25351777/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25351777</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25351777[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=25351777" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ejhg.2014.223" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Neri2013" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Neri, M., Selvatici, R., Scotton, C., Trabanelli, C., Armaroli, A., De Grandis, D., Levy, N., Gualandi, F., Ferlini, A.
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<strong>A patient with limb girdle muscular dystrophy carries a TRIM32 deletion, detected by a novel CGH array, in compound heterozygosis with a nonsense mutation.</strong>
|
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Neuromusc. Disord. 23: 478-482, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23541687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23541687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23541687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.nmd.2013.02.003" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Saccone2008" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V.
|
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<strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong>
|
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Hum. Mutat. 29: 240-247, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17994549/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17994549</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17994549" 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/humu.20633" target="_blank">Full Text</a>]
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Schoser2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Schoser, B. G. H., Frosk, P., Engel, A. G., Klutzny, U., Lochmuller, H., Wrogemann, K.
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<strong>Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H.</strong>
|
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Ann. Neurol. 57: 591-595, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15786463/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15786463</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15786463" 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/ana.20441" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Sonja A. Rasmussen - updated : 03/10/2022
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Matthew B. Gross - updated : 07/14/2016<br>Ada Hamosh - updated : 2/7/2013<br>George E. Tiller - updated : 3/30/2010<br>George E. Tiller - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Victor A. McKusick - updated : 6/8/2006<br>Cassandra L. Kniffin - updated : 2/10/2006<br>Cassandra L. Kniffin - updated : 4/27/2005<br>Victor A. McKusick - updated : 3/21/2002
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</span>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patti M. Sherman : 1/28/1998
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/29/2024
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/10/2022<br>carol : 09/25/2018<br>mgross : 07/14/2016<br>alopez : 7/23/2015<br>carol : 10/24/2014<br>alopez : 10/16/2014<br>carol : 9/16/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>wwang : 11/10/2009<br>terry : 10/27/2009<br>wwang : 3/12/2008<br>ckniffin : 3/6/2008<br>terry : 11/3/2006<br>alopez : 6/12/2006<br>alopez : 6/12/2006<br>terry : 6/8/2006<br>wwang : 2/20/2006<br>ckniffin : 2/10/2006<br>tkritzer : 5/9/2005<br>ckniffin : 4/27/2005<br>carol : 3/29/2005<br>carol : 2/16/2005<br>carol : 7/11/2002<br>alopez : 3/27/2002<br>terry : 3/21/2002<br>joanna : 3/11/2002<br>mgross : 2/8/2001<br>psherman : 6/10/1998<br>dholmes : 1/28/1998
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 602290
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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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TRIPARTITE MOTIF-CONTAINING PROTEIN 32; TRIM32
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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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<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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TAT-INTERACTING PROTEIN, 72-KD<br />
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HT2A<br />
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BBS11 GENE; BBS11
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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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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TRIM32</em></strong>
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</span>
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</p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 240064008, 43226001;
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</span>
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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: 9q33.1
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Genomic coordinates <span class="small">(GRCh38)</span> : 9:116,687,305-116,701,299 </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="2">
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<span class="mim-font">
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9q33.1
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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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?Bardet-Biedl syndrome 11
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</span>
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</td>
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<td>
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<span class="mim-font">
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615988
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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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<tr>
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<td>
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<span class="mim-font">
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Muscular dystrophy, limb-girdle, autosomal recessive 8
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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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254110
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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>Members of the tripartite motif (TRIM) protein family, such as TRIM32, contain RING, BBOX, and coiled-coil domains, as well as variable C-terminal domains. TRIM32 functions as an E3 ubiquitin ligase in the ubiquitin-proteasome system, which is responsible for protein degradation (summary by Locke et al., 2009). </p>
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</span>
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<div>
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<br />
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</div>
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<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>Transcriptional activation of HIV-1 gene expression by the viral Tat protein requires the interaction of a cellular cofactor with the Tat activation domain. This domain consists of the cysteine-rich and core motifs of HIV-1 Tat and is functionally conserved in the distantly related Tat proteins of HIV-2 and EIAV. Fridell et al. (1995) used the yeast 2-hybrid system to identify TRIM32, which they called HT2A, a protein that specifically and precisely binds the activation domain of HIV-1 Tat and that can interact with the HIV-2 and EIAV Tat proteins in vivo. Fridell et al. (1995) demonstrated that the interaction between HT2A and the activation domain of HIV-1 Tat can be readily detected in the mammalian cell nucleus. They isolated the HT2A cDNA from a HeLa cell cDNA library and found that it contains an open reading frame encoding a predicted 653-amino acid protein of 72 kD. Using Northern blot analysis, they detected a major, approximately 3.7-kb HT2A transcript and a minor, approximately 2.7-kb HT2A transcript in all examined tissues. HT2A contains an N-terminal C3HC4 zinc finger motif, indicating that it is a member of the ring finger family (see RING1, 602045) which includes transcription factors, nucleic acid binding proteins, and oncogenes. HT2A is most similar to the ring finger subfamily that includes RFP (602165), PML (102578), T18, RPT1, and Ro autoantigen (600063) since it contains a cysteine/histidine cluster and a heptad repeat of hydrophobic residues that is predicted to form a coiled-coil structure. The unique C-terminal region of HT2A is necessary and sufficient for binding to Tat. Fridell et al. (1995) suggested that HT2A may play a significant role in mediating the biologic activity of the HIV-1 Tat protein in vivo. </p><p>Locke et al. (2009) stated that the TRIM32 protein contains a RING zinc finger domain, BBOX domain, BBC domain, and 6 C-terminal NHL domains. </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 Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Frosk et al. (2002) reported that the TRIM32 gene contains 2 exons. </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>Frosk et al. (2002) determined that the TRIM32 gene maps to chromosome 9q31-q33, between markers D9S1126 and D9S737. TRIM32 overlaps with intron 12 of the ASTN2 gene (612856) on the opposite strand. </p><p>Using short tandem repeat polymorphism (STRP) and single-nucleotide polymorphism (SNP) microarray genotyping, Chiang et al. (2006) identified the TRIM32 gene within a 2.4-Mb region on chromosome 9q33.1 linked to the Bardet-Biedl syndrome (209900) phenotype. </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>Locke et al. (2009) showed that TRIM32 is a widely expressed ubiquitin ligase that is localized to the Z-line in skeletal muscle. TRIM32 bound and ubiquitinated dysbindin, augmenting its degradation. Knockdown of TRIM32 in myoblasts resulted in elevated levels of dysbindin (DTNBP1; 607145). The D487N (602290.0001) and R394H (602290.0004) mutant proteins impaired ubiquitin ligase activity towards dysbindin and were mislocalized in heterologous cells. The D487N mutant could bind to both dysbindin and its ubiquitin-conjugating E2 enzyme but was defective in monoubiquitination. Locke et al. (2009) concluded that TRIM32 is a regulator of dysbindin and that TRIM32 mutations may impair substrate ubiquitination. </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>Cytogenetics</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 an approach that combined screening of candidate genes with a CGH array and massively parallel sequencing, Nectoux et al. (2015) identified 2 patients with LGMDR8 with homozygous or compound heterozygous mutations in the TRIM32 gene. In the first patient, one allele had a frameshift mutation (602290.0006), confirmed by Sanger sequencing, and the other allele had a 124.4-kb deletion that included the entire TRIM32 gene. The second patient, born to nonconsanguineous parents, had a homozygous 336-kb deletion including the TRIM32 gene. The deletions in both patients, which were confirmed by quantitative PCR, included part of the ASTN2 gene (612856). Analysis of the breakpoints showed that the 5-prime boundaries of both deletions were located within regions enriched with genomic repeats, possibly making rearrangements and deletions more likely to occur. Parents were not available for study for either patient. </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><strong><em>Limb-Girdle Muscular Dystrophy, Autosomal Recessive 8</em></strong></p><p>
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Autosomal recessive limb-girdle muscular dystrophy-8 (LGMDR8; 254110), previously symbolized LGMD2H, is a mild autosomal recessive myopathy that was first described in the Hutterite population of Manitoba, Canada. Frosk et al. (2002) narrowed the map assignment of the gene to a region of 560 kb on 9q and found that the region contains 4 known genes, including the TRIM32 gene. All affected individuals were homozygous for an asp487-to-asn (D487N; 602290.0001) mutation in TRIM32. The mutation occurred in an NHL (named after the proteins NCL1, HT2A, and LIN-41) domain at a position that is highly conserved. NHL domains are involved in protein-protein interactions. The domain structure of the TRIM32 protein suggested that it may be an E3-ubiquitin ligase. This may represent a novel pathogenic mechanism for muscular dystrophy. </p><p>Saccone et al. (2008) identified homozygous mutations in the TRIM32 gene (see, e.g., 602290.0003; 602290.0004) in non-Hutterite patients with LGMD2H. Both mutations occurred in the NHL domain. In vitro functional expression studies showed that these mutations abrogated TRIM32 self-interaction and UBE2N (603679) binding, indicating a dramatic effect on protein folding. In contrast, in vitro studies showed that the BBS P130S mutation retained the ability to self-interact, suggesting a different pathogenic mechanism in BBS. </p><p>Using comparative genomic hybridization (CGH) and sequencing of the TRIM32 gene in a 35-year-old woman with LGMDR8, Neri et al. (2013) identified compound heterozygous mutations: a nonsense mutation (R316X; 602290.0005) in the C-terminal NHL domain of TRIM32 on one allele and a deletion including the entire TRIM32 gene on the other allele. The precise breakpoints of the deletion could not be defined. </p><p>Using an approach that combined screening of candidate genes with a CGH array and massively parallel sequencing, Nectoux et al. (2015) identified a patient with LGMDR8 who had a frameshift mutation in the TRIM32 gene (c.160delC; 602290.0006), confirmed by Sanger sequencing, and a 124.4-kb deletion that included the entire TRIM32 gene and part of the ASTN2 gene (612856); see CYTOGENETICS. The deletion was confirmed by quantitative PCR. The parents were not available for study. </p><p><strong><em>Bardet-Biedl Syndrome 11</em></strong></p><p>
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Bardet-Biedl syndrome (BBS; see 209900) is a pleiotropic autosomal recessive disorder characterized by obesity, pigmentary retinopathy, polydactyly, renal abnormalities, learning disabilities, and hypogenitalism. The disorder displays extensive genetic heterogeneity. Chiang et al. (2006) used high density SNP genotyping to identify the disease-causing gene in a single small consanguineous Israeli Bedouin BBS family (BBS11; 615988) in which linkage studies failed to identify a disease locus. SNP genotyping revealed a homozygous candidate region. Mutation analysis in the region of homozygosity identified a homozygous missense mutation in a conserved B-box domain of TRIM32 (P130S; 602290.0002). Functional analysis of this gene in zebrafish and expression correlation analyses among other BBS genes in an expression quantitative trait loci dataset demonstrated that TRIM32 is a BBS gene. This study showed the value of high density SNP genotyping for homozygosity mapping and the use of expression correlation data for evaluation of candidate genes, and identified the involvement of the proteasome degradation pathway in BBS. The ubiquitin/proteasome system had not been implicated in this disorder. Another TRIM32 variant, a missense mutation associated with autosomal recessive limb girdle muscular dystrophy (D487N; 602290.0001), does not affect the E3 ubiquitin ligase activity, whereas disruption of the TRIM32 coiled-coil domain, as in the P130S mutation, reduces the binding affinity to myosin (Kudryashova et al., 2005). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kudryashova et al. (2009) generated a Trim32-null mouse model of human muscular dystrophy phenotypes. Histologic analysis of Trim32-null skeletal muscles revealed mild myopathic changes. Electron microscopy showed areas with Z-line streaming and a dilated sarcotubular system with vacuoles, replicating the phenotypes of LGMD2H and sarcotubular myopathy. The level of Trim32 expression in normal mouse brain exceeded that observed in skeletal muscle by more than 100-fold. Analysis of Trim32-null neural tissue revealed a decreased concentration of neurofilaments and a reduction in myelinated motor axon diameters. The axonal changes suggested a shift toward a slower motor unit type. Trim32-null soleus muscle expressed an elevated type I slow myosin isotype with a concomitant reduction in the type II fast myosin. Kudryashova et al. (2009) suggested that muscular dystrophy due to TRIM32 mutation may involve both neurogenic and myogenic characteristics. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</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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TRIM32, ASP487ASN ({dbSNP rs111033570})
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<br />
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SNP: rs111033570,
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gnomAD: rs111033570,
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ClinVar: RCV000007775, RCV000414917, RCV000538874, RCV001198489, RCV001781203, RCV004748509, RCV004814854
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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>Frosk et al. (2002) found homozygosity for an asp487-to-asn (D487N) missense mutation in the TRIM32 gene as a causative mutation in the mild autosomal recessive myopathy observed in Manitoba Hutterites (LGMDR8; 254110). Frosk et al. (2002) stated that of 60 cases of LGMD studied in Manitoba Hutterites, most were caused by the D487N mutation. </p><p>Schoser et al. (2005) identified the homozygous D487N mutation in the patients reported by Jerusalem et al. (1973) and Muller-Felber et al. (1999), confirming that they had LGMDR8. In addition, haplotype analysis showed that all LGMDR8 patients shared the same haplotype, suggesting that the mutation arose before the emergence of the Hutterite religion in central Europe in the 16th century. Schoser et al. (2005) noted the phenotypic variability caused by the same mutation. </p><p>Frosk et al. (2005) reported a Hutterite family in which 2 boys, aged 7 and 10 years, were homozygous for both the D487N mutation and an LGMD2I (LGMDR9; 607155)-related FKRP mutation (L276I; 606596.0004). Although they presented at an early age with exercise intolerance and increased serum creatine kinase, the clinical phenotype was not significantly more severe than that of patients with isolated LGMD2H or LGMD2I. Both parents and 3 other sibs were homozygous for the D487N mutation, with highly variable phenotypic expression. </p><p>In vitro functional expression studies by Saccone et al. (2008) demonstrated that D487N-mutant protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (603679). The consequences of this mutation were similar to complete deletion of the coiled coil-NHL domains, suggesting a dramatic effect on protein folding. </p><p>Locke et al. (2009) showed that D487N-mutant protein impaired TRIM32 ubiquitin ligase activity towards dysbindin (DTNBP1; 607145) and mislocalized in heterologous cells. The D487N mutant could bind to both dysbindin and its ubiquitin-conjugating E2 enzyme but was defective in monoubiquitination. Locke et al. (2009) suggest that D487N mutation may impair substrate ubiquitination. </p><p>Among 1,493 Schmiedeleut (S-leut) Hutterites from the United States, Chong et al. (2012) found 228 heterozygotes and 9 homozygotes for the D487N mutation in the TRIM32 gene, for a frequency of 0.153, or 1 in 6.5. The carrier frequency in other populations was unknown, with only 2 non-Hutterite cases having been reported (Schoser et al., 2005). The 9 homozygous individuals ranged in age from 10 to 42 years, and were unaware of their status. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 BARDET-BIEDL SYNDROME 11 (1 family)</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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TRIM32, PRO130SER
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<br />
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SNP: rs111033571,
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gnomAD: rs111033571,
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ClinVar: RCV000007776, RCV000199127, RCV003488330, RCV003904817
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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>By homozygosity mapping using high-density SNP genotyping, Chiang et al. (2006) identified the TRIM32 gene as the site of mutations causing Bardet-Biedl syndrome (BBS11; 615988) in a small consanguineous Israeli Bedouin family. The specific mutation was a change of codon 130 from CCT (pro) to TCT (ser). The substitution was present in homozygous state in the affected individuals. </p><p>In vitro functional expression studies by Saccone et al. (2008) demonstrated that the P130S-mutant protein maintained self-interaction ability. </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 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</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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TRIM32, 1-BP DEL, 1559C
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<br />
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SNP: rs1588218453,
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ClinVar: RCV000007777, RCV001198484, RCV001781204, RCV002504765, RCV003522918
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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 44-year-old Croatian woman with limb-girdle muscular dystrophy type 2H (LGMDR8; 254110), Saccone et al. (2008) identified a homozygous 1-bp deletion (1559delC) in the TRIM32 gene within a conserved region of the NHL domain, resulting in frameshift and premature termination. The patient had slowly progressive proximal muscle weakness and wasting, respiratory weakness, and chronic keratitis. In vitro functional expression studies showed that truncated protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (603679). </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 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</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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TRIM32, ARG394HIS
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<br />
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SNP: rs121434447,
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gnomAD: rs121434447,
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ClinVar: RCV000007778, RCV000362326, RCV000638363, RCV001334685, RCV004748510, RCV005042010
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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 man with limb-girdle muscular dystrophy type 2H (LGMDR8; 254110), Saccone et al. (2008) identified a homozygous 1180G-A transition in the TRIM32 gene, resulting in an arg394-to-his (R394H) substitution in a conserved residue of an NHL domain. Disease onset was in the third decade with weakness and paresthesias. He had marked proximal weakness and atrophy, as well as respiratory weakness, and lost the ability to walk at age 64 after prolonged immobility for other causes. A second patient was found to be heterozygous for the R394H mutation. He was 73 years old and had mild symptoms with no respiratory involvement. In vitro functional expression studies showed that R394H-mutant protein lost the ability to homodimerize and showed inhibited binding to full-length UBE2N (603679). </p><p>Locke et al. (2009) showed that R394H-mutant protein impaired TRIM32 ubiquitin ligase activity towards dysbindin and mislocalized in heterologous cells, but was able to self-associate. Coexpression of wildtype and R394H-mutant TRIM32 reduced the level of dysbindin monoubiquitination, possibly indicating that R394H may compromise function of the wildtype protein. </p>
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<strong>.0005 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</strong>
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TRIM32, ARG316TER
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SNP: rs199664043,
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gnomAD: rs199664043,
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ClinVar: RCV001350863, RCV002221274, RCV003135986, RCV003405557, RCV005040192
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<p>By sequencing of the TRIM32 gene in a 35-year-old Italian woman with autosomal recessive limb-girdle muscular dystrophy (LGMDR8; 254110), Neri et al. (2013) identified a heterozygous c.1837C-T transition, resulting in an arg316-to-ter (R316X) in the C-terminal NHL domain. The mutation was found in compound heterozygosity with a deletion of the entire TRIM32 gene, identified by a custom comparative genomic hybridization (CGH) array. The breakpoints of the deletion could not be defined. </p>
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<strong>.0006 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8</strong>
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TRIM32, 1-BP DEL, 1603C
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SNP: rs2132075382,
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ClinVar: RCV001844801
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<p>Using a combined approach of comparative genomic hybridization array and massively parallel sequencing, Nectoux et al. (2015) identified a patient with autosomal recessive limb-girdle muscular dystrophy (LGMDR8; 254110) who was compound heterozygous for a 1-bp deletion (c.1603delC, NM_012210.3) in the TRIM32 gene, resulting in a frameshift (Leu535SerfsTer21), and a 124.4-kb deletion including the entire TRIM32 gene and part of the ASTN2 gene (612856). The patient had a mild phenotype of progressive limb-girdle muscular dystrophy as typically seen in patients with LGMDR8. </p>
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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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Chiang, A. P., Beck, J. S., Yen, H.-J., Tayeh, M. K., Scheetz, T. E., Swiderski, R. E., Nishimura, D. Y., Braun, T. A., Kim, K.-Y. A., Huang, J., Elbedour, K., Carmi, R., Slusarski, D. C., Casavant, T. L., Stone, E. M., Sheffield, V. C.
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<strong>Homozygosity mapping with SNP arrays identifies TRIM32, an E3 ubiquitin ligase, as a Bardet-Biedl syndrome gene (BBS11).</strong>
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Proc. Nat. Acad. Sci. 103: 6287-6292, 2006.
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[PubMed: 16606853]
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Chong, J. X., Ouwenga, R., Anderson, R. L., Waggoner, D. J., Ober, C.
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<strong>A population-based study of autosomal-recessive disease-causing mutations in a founder population.</strong>
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<p class="mim-text-font">
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Fridell, R. A., Harding, L. S., Bogerd, H. P., Cullen, B. R.
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<strong>Identification of a novel human zinc finger protein that specifically interacts with the activation domain of lentiviral Tat proteins.</strong>
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Virology 209: 347-357, 1995.
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<p class="mim-text-font">
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Frosk, P., Del Bigio, M. R., Wrogemann, K., Greenberg, C. R.
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<strong>Hutterite brothers both affected with two forms of limb girdle muscular dystrophy: LGMD2H and LGMD2I.</strong>
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Europ. J. Hum. Genet. 13: 978-982, 2005.
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[PubMed: 15886712]
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[Full Text: https://doi.org/10.1038/sj.ejhg.5201436]
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Frosk, P., Weiler, T., Nylen, E., Sudha, T., Greenberg, C. R., Morgan, K., Fujiwara, T. M., Wrogemann, K.
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<strong>Limb-girdle muscular dystrophy type 2H associated with mutation in TRIM32, a putative E3-ubiquitin-ligase gene.</strong>
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Am. J. Hum. Genet. 70: 663-672, 2002.
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[PubMed: 11822024]
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[Full Text: https://doi.org/10.1086/339083]
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<p class="mim-text-font">
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Jerusalem, F., Engel, A. G., Gomez, M. R.
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<strong>Sarcotubular myopathy.</strong>
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Neurology 23: 897-906, 1973.
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[PubMed: 4269389]
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[Full Text: https://doi.org/10.1212/wnl.23.9.897]
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<li>
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<p class="mim-text-font">
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Kudryashova, E., Kudryashov, D., Kramerova, I., Spencer, M. J.
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<strong>Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2H that binds to skeletal muscle myosin and ubiquitinates actin.</strong>
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J. Molec. Biol. 354: 413-424, 2005.
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[PubMed: 16243356]
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[Full Text: https://doi.org/10.1016/j.jmb.2005.09.068]
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</p>
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<p class="mim-text-font">
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Kudryashova, E., Wu, J., Havton, L. A., Spencer, M. J.
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<strong>Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component.</strong>
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Hum. Molec. Genet. 18: 1353-1367, 2009.
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[PubMed: 19155210]
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[Full Text: https://doi.org/10.1093/hmg/ddp036]
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<p class="mim-text-font">
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Locke, M., Tinsley, C. L., Benson, M. A., Blake, D. J.
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<strong>TRIM32 is an E3 ubiquitin ligase for dysbindin.</strong>
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Hum. Molec. Genet. 18: 2344-2358, 2009.
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[PubMed: 19349376]
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[Full Text: https://doi.org/10.1093/hmg/ddp167]
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Muller-Felber, W., Schlotter, B., Topfer, M., Ketelsen, U.-P., Muller-Hocker, J., Pongratz, D.
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<strong>Phenotypic variability in two brothers with sarcotubular myopathy. (Letter)</strong>
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J. Neurol. 246: 408-411, 1999.
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[PubMed: 10399877]
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[Full Text: https://doi.org/10.1007/s004150050374]
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</li>
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<li>
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<p class="mim-text-font">
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Nectoux, J., de Cid, R., Baulande, S., Leturcq, F., Urtizberea, J. A., Penisson-Besnier, I., Nadaj-Pakleza, A., Roudaut, C., Criqui, A., Orhant, L., Peyroulan, D., Ben Yaou, R., and 11 others.
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<strong>Detection of TRIM32 deletions in LGMD patients analyzed by a combined strategy of CGH array and massively parallel sequencing.</strong>
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Europ. J. Hum. Genet. 23: 929-934, 2015.
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[PubMed: 25351777]
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[Full Text: https://doi.org/10.1038/ejhg.2014.223]
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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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Neri, M., Selvatici, R., Scotton, C., Trabanelli, C., Armaroli, A., De Grandis, D., Levy, N., Gualandi, F., Ferlini, A.
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<strong>A patient with limb girdle muscular dystrophy carries a TRIM32 deletion, detected by a novel CGH array, in compound heterozygosis with a nonsense mutation.</strong>
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Neuromusc. Disord. 23: 478-482, 2013.
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[PubMed: 23541687]
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[Full Text: https://doi.org/10.1016/j.nmd.2013.02.003]
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Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., Nigro, V.
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<strong>Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H.</strong>
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Hum. Mutat. 29: 240-247, 2008.
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[PubMed: 17994549]
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[Full Text: https://doi.org/10.1002/humu.20633]
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<p class="mim-text-font">
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Schoser, B. G. H., Frosk, P., Engel, A. G., Klutzny, U., Lochmuller, H., Wrogemann, K.
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<strong>Commonality of TRIM32 mutation in causing sarcotubular myopathy and LGMD2H.</strong>
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Ann. Neurol. 57: 591-595, 2005.
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[PubMed: 15786463]
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[Full Text: https://doi.org/10.1002/ana.20441]
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Sonja A. Rasmussen - updated : 03/10/2022<br>Matthew B. Gross - updated : 07/14/2016<br>Ada Hamosh - updated : 2/7/2013<br>George E. Tiller - updated : 3/30/2010<br>George E. Tiller - updated : 10/27/2009<br>Cassandra L. Kniffin - updated : 3/6/2008<br>Victor A. McKusick - updated : 6/8/2006<br>Cassandra L. Kniffin - updated : 2/10/2006<br>Cassandra L. Kniffin - updated : 4/27/2005<br>Victor A. McKusick - updated : 3/21/2002
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carol : 02/29/2024<br>carol : 03/10/2022<br>carol : 09/25/2018<br>mgross : 07/14/2016<br>alopez : 7/23/2015<br>carol : 10/24/2014<br>alopez : 10/16/2014<br>carol : 9/16/2013<br>alopez : 2/13/2013<br>terry : 2/7/2013<br>wwang : 3/31/2010<br>terry : 3/30/2010<br>wwang : 11/10/2009<br>terry : 10/27/2009<br>wwang : 3/12/2008<br>ckniffin : 3/6/2008<br>terry : 11/3/2006<br>alopez : 6/12/2006<br>alopez : 6/12/2006<br>terry : 6/8/2006<br>wwang : 2/20/2006<br>ckniffin : 2/10/2006<br>tkritzer : 5/9/2005<br>ckniffin : 4/27/2005<br>carol : 3/29/2005<br>carol : 2/16/2005<br>carol : 7/11/2002<br>alopez : 3/27/2002<br>terry : 3/21/2002<br>joanna : 3/11/2002<br>mgross : 2/8/2001<br>psherman : 6/10/1998<br>dholmes : 1/28/1998
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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