3481 lines
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Entry
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- *610230 - tRNA 5-METHYLAMINOMETHYL-2-THIOURIDYLATE METHYLTRANSFERASE; TRMU
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- OMIM
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<p>
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<span class="h4">*610230</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#geneFunction">Gene Function</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/610230">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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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="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 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=ENSG00000100416;t=ENST00000645190" 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=55687" 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=610230" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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</a>
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</span>
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</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=ENSG00000100416;t=ENST00000645190" 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_001282782,NM_001282783,NM_001282784,NM_001282785,NM_018006,NR_104240,NR_104241,XM_011530272,XM_011530273,XM_047441444,XM_047441445,XM_047441446" 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_018006" 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=610230" 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=15571&isoform_id=15571_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/TRMU" 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/7022010,8134740,17149283,17432490,31542641,47678421,51593662,54633233,83776736,83776738,83776740,116283770,119593828,119593829,119593830,119593831,119593832,158254860,194379662,194381158,544346331,544346333,544346335,544346337,768025317,768025321,2217339946,2217339948,2217339950,2462585204,2462585206,2462585208,2462585210,2462585212" 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/O75648" 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=55687" 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=ENSG00000100416;t=ENST00000645190" 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=TRMU" 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=TRMU" 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+55687" 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/TRMU" 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:55687" 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/55687" 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=chr22&hgg_gene=ENST00000645190.1&hgg_start=46335714&hgg_end=46357340&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:25481" 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:25481" 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=610230[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=610230[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/TRMU/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000100416" 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=TRMU" 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=TRMU" 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=TRMU" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=TRMU&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/PA142670701" 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:25481" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="https://flybase.org/reports/FBgn0040337.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:1919276" 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/TRMU#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:1919276" 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/55687/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=55687" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00007114;class=Gene" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name'{'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">Wormbase Gene</a></div>
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<div><a href="https://zfin.org/ZDB-GENE-050522-540" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
|
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=TRMU&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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610230
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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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tRNA 5-METHYLAMINOMETHYL-2-THIOURIDYLATE METHYLTRANSFERASE; TRMU
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</span>
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</h3>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
TRNT1<br />
|
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MTO2, S. CEREVISIAE, HOMOLOG OF; MTO2
|
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</span>
|
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</h4>
|
|
</div>
|
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</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TRMU" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TRMU</a></em></strong>
|
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
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<strong>
|
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<em>
|
|
Cytogenetic location: <a href="/geneMap/22/388?start=-3&limit=10&highlight=388">22q13.31</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr22:46335714-46357340&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'})">22:46,335,714-46,357,340</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>
|
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<div style="margin-bottom: 10px;">
|
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<span class="h4 mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
|
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</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
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Location
|
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</th>
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<th>
|
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Phenotype
|
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<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=580000,613070" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
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</a>
|
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</span>
|
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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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|
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<tr>
|
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<td rowspan="2">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/22/388?start=-3&limit=10&highlight=388">
|
|
22q13.31
|
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</a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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{Deafness, mitochondrial, modifier of}
|
|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/580000"> 580000 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Mitochondrial">Mi</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<tr>
|
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<td>
|
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<span class="mim-font">
|
|
Liver failure, transient infantile
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
|
|
<a href="/entry/613070"> 613070 </a>
|
|
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
|
<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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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group">
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<p>TRMU is an evolutionarily conserved protein involved in mitochondrial tRNA modification, and is thus important for mitochondrial translation (<a href="#9" class="mim-tip-reference" title="Yan, Q., Li, X., Faye, G., Guan, M.-X. <strong>Mutations in MTO2 related to tRNA modification impair mitochondrial gene expression and protein synthesis in the presence of a paromomycin resistance mutation in mitochondrial 15 S rRNA.</strong> J. Biol. Chem. 280: 29151-29157, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944150[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/10.1074/jbc.M504247200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944150">Yan et al., 2005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By searching a database for sequences similar to yeast Mto2, followed by RT-PCR of a human osteosarcoma cell line cDNA library, <a href="#9" class="mim-tip-reference" title="Yan, Q., Li, X., Faye, G., Guan, M.-X. <strong>Mutations in MTO2 related to tRNA modification impair mitochondrial gene expression and protein synthesis in the presence of a paromomycin resistance mutation in mitochondrial 15 S rRNA.</strong> J. Biol. Chem. 280: 29151-29157, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944150[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/10.1074/jbc.M504247200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944150">Yan et al. (2005)</a> cloned TRMU, which they designated MTO2. Fluorescence-tagged MTO2 localized to mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944150" 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>By 5-prime and 3-prime RACE, <a href="#7" class="mim-tip-reference" title="Yan, Q., Bykhovskaya, Y., Li, R., Mengesha, E., Shohat, M., Estivill, X., Fischel-Ghodsian, N., Guan, M.-X. <strong>Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.</strong> Biochem. Biophys. Res. Commun. 342: 1130-1136, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.02.078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16513084">Yan et al. (2006)</a> identified several TRMU splice variants. The full-length 421-amino acid protein has a calculated molecular mass of 47.7 kD. The other transcripts lack exon 3 and encode a deduced 99-amino acid protein. Northern blot analysis detected high expression of a 1.9-kb TRMU transcript in heart, skeletal muscle, and kidney. Intermediate expression was detected in brain, placenta, spleen, and small intestine, and low expression was detected in liver, colon, lung, thymus, and leukocytes. Expression was nearly uniform in 8 brain regions examined. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Yan, Q., Guan, M.-X. <strong>Identification and characterization of mouse TRMU gene encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase.</strong> Biochim. Biophys. Acta 1676: 119-126, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14746906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14746906</a>] [<a href="https://doi.org/10.1016/j.bbaexp.2003.11.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14746906">Yan and Guan (2004)</a> cloned mouse Trmu. The deduced 417-amino acid protein contains a typical mitochondrial target sequence and shares 91% identity with human TRMU. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14746906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Yan, Q., Bykhovskaya, Y., Li, R., Mengesha, E., Shohat, M., Estivill, X., Fischel-Ghodsian, N., Guan, M.-X. <strong>Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.</strong> Biochem. Biophys. Res. Commun. 342: 1130-1136, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.02.078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16513084">Yan et al. (2006)</a> determined that the TRMU gene contains 11 exons and spans about 22 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#7" class="mim-tip-reference" title="Yan, Q., Bykhovskaya, Y., Li, R., Mengesha, E., Shohat, M., Estivill, X., Fischel-Ghodsian, N., Guan, M.-X. <strong>Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.</strong> Biochem. Biophys. Res. Commun. 342: 1130-1136, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.02.078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16513084">Yan et al. (2006)</a> mapped the TRMU gene to chromosome 22q13. <a href="#8" class="mim-tip-reference" title="Yan, Q., Guan, M.-X. <strong>Identification and characterization of mouse TRMU gene encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase.</strong> Biochim. Biophys. Acta 1676: 119-126, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14746906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14746906</a>] [<a href="https://doi.org/10.1016/j.bbaexp.2003.11.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14746906">Yan and Guan (2004)</a> mapped the mouse Trmu gene to chromosome 15. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=16513084+14746906" 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="Yan, Q., Li, X., Faye, G., Guan, M.-X. <strong>Mutations in MTO2 related to tRNA modification impair mitochondrial gene expression and protein synthesis in the presence of a paromomycin resistance mutation in mitochondrial 15 S rRNA.</strong> J. Biol. Chem. 280: 29151-29157, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944150[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/10.1074/jbc.M504247200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15944150">Yan et al. (2005)</a> demonstrated that human MTO2 could partially restore the respiratory-deficient phenotype of Mto2-null yeast carrying a mutation in 15S ribosomal RNA (rRNA), 1409C-G, associated with aminoglycoside resistance. The yeast 1409C-G mutation in 15S rRNA corresponds to the deafness-associated 1494C-T mutation (<a href="/entry/561000#0004">561000.0004</a>) in human 12S rRNA (MTRNR1; <a href="/entry/561000">561000</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15944150" 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 families with the deafness-associated 12S rRNA 1555A-G mutation (<a href="/entry/561000#0001">561000.0001</a>), <a href="#7" class="mim-tip-reference" title="Yan, Q., Bykhovskaya, Y., Li, R., Mengesha, E., Shohat, M., Estivill, X., Fischel-Ghodsian, N., Guan, M.-X. <strong>Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.</strong> Biochem. Biophys. Res. Commun. 342: 1130-1136, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513084</a>] [<a href="https://doi.org/10.1016/j.bbrc.2006.02.078" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16513084">Yan et al. (2006)</a> found suggestive linkage and linkage disequilibrium between microsatellite markers adjacent to TRMU and the presence of deafness. They hypothesized that TRMU may modulate the phenotypic manifestation of deafness-associated mitochondrial 12S rRNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Guan, M.-X., Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, E., Suzuki, T., del Castillo, I., and 10 others. <strong>Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.</strong> Am. J. Hum. Genet. 79: 291-302, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16826519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16826519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16826519[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/10.1086/506389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16826519">Guan et al. (2006)</a> noted that TRMU is responsible for the 2-thiolation of hypermodified nucleoside 5-methyl-aminomethy-2-thio-uridine. This modified nucleotide, found in the wobble position of several bacterial and human mitochondrial tRNAs (mt tRNAs) specific for glutamate, lysine, and glutamine, has a pivotal role in the structure and function of tRNAs, including structural stabilization, aminoacylation, and codon recognition at the decoding site of small rRNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16826519" 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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The 1555A-G mutation of mitochondrial 12S rRNA (<a href="/entry/561000#0001">561000.0001</a>) is associated with aminoglycoside-induced and nonsyndromic deafness in many families worldwide (<a href="#5" class="mim-tip-reference" title="Prezant, T. R., Agapian, J. V., Bohlman, M. C., Bu, X., Oztas, S., Qiu, W.-Q., Arnos, K. S., Cortopassi, G. A., Jaber, L., Rotter, J. I., Shohat, M., Fischel-Ghodsian, N. <strong>Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.</strong> Nature Genet. 4: 289-294, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7689389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7689389</a>] [<a href="https://doi.org/10.1038/ng0793-289" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7689389">Prezant et al., 1993</a>). Studies of Guan et al. (<a href="#2" class="mim-tip-reference" title="Guan, M.-X., Fischel-Ghodsian, N., Attardi, G. <strong>Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation.</strong> Hum. Molec. Genet. 5: 963-971, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817331</a>] [<a href="https://doi.org/10.1093/hmg/5.7.963" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8817331">1996</a>, <a href="#1" class="mim-tip-reference" title="Guan, M. X., Fischel-Ghodsian, N., Attardi, G. <strong>Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation.</strong> Hum. Molec. Genet. 10: 573-580, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230176</a>] [<a href="https://doi.org/10.1093/hmg/10.6.573" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11230176">2001</a>) revealed that the 1555A-G mutation, although a primary factor underlying the development of deafness, is not alone sufficient to produce a deafness phenotype. Nuclear modifier genes have been proposed as modulators of the phenotypic manifestations of the mitochondrial mutation. <a href="#3" class="mim-tip-reference" title="Guan, M.-X., Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, E., Suzuki, T., del Castillo, I., and 10 others. <strong>Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.</strong> Am. J. Hum. Genet. 79: 291-302, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16826519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16826519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16826519[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/10.1086/506389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16826519">Guan et al. (2006)</a> identified the nuclear modifier gene TRMU, which encodes a highly conserved mitochondrial protein related to transfer RNA (tRNA) modification. Studies in a large Arab Israeli kindred, in an Italian family, and in 6 Spanish families carrying the 1555A-G or the 1494C-T (<a href="/entry/561000#0004">561000.0004</a>) mutation revealed a missense mutation (<a href="#0001">610230.0001</a>) altering an invariant amino acid residue (A10S) in the evolutionarily conserved N-terminal region of the TRMU protein. All members of the Arab Israeli, Italian, and Spanish families carrying both the TRMU A10S and the 12S rRNA 1555A-G mutations exhibited prelingual profound deafness. Functional analysis showed that the A10S mutation did not affect importation of TRMU precursors into mitochondria. However, the homozygous A10S mutation led to a marked failure in mitochondrial tRNA metabolisms, specifically reducing the steady-state levels of mitochondrial tRNA. As a consequence, these defects contributed to the impairment of mitochondrial protein synthesis. These findings indicated that the mutated TRMU, acting as a modifier factor, modulates the phenotypic manifestation of the deafness-associated 12S rRNA mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11230176+7689389+16826519+8817331" 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>Transient Infantile Liver Failure</em></strong></p><p>
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By linkage analysis, followed by candidate gene sequencing, <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> identified homozygous and compound heterozygous mutations in the TRMU gene (see, e.g., <a href="#0002">610230.0002</a>-<a href="#0005">610230.0005</a>) in patients with transient infantile liver failure (LFIT; <a href="/entry/613070">613070</a>). Seven patients of Yemenite Jewish origin had the same Y77H mutation (<a href="#0002">610230.0002</a>), indicating a founder effect. Overall, 9 mutations were identified in 13 patients. Those who survived the initial acute episode showed clinical and biochemical resolution of liver failure and had no further episodes. A study of tRNAs in cells derived from 3 of the patients showed a severe reduction of thio-modified mitochondrial tRNAs, whereas the pattern of hybridization obtained for the cytosolic tRNA-lys, modified by another enzyme, was similar to controls. The findings suggested that the mitochondrial translation defect resulted from reduced modification of several mitochondrial tRNAs. Noting that the availability of cysteine in the neonatal period is limited, <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> proposed that there is a window of time during 1 to 4 months of age during which patients with TRMU mutations are at an increased risk of developing liver failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19732863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=610230[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<strong>.0001 DEAFNESS, MITOCHONDRIAL, MODIFIER OF</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> rs11090865 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs11090865;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/rs11090865?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=rs11090865" 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=rs11090865" 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 large Arab Israeli kindred, in an Italian family, and in 6 Spanish families with sensorineural deafness carrying the 1555A-G (<a href="/entry/561000#0001">561000.0001</a>) or the 1494C-T (<a href="/entry/561000#0004">561000.0004</a>) mutation in mitochondrial 12S ribosomal RNA (rRNA), <a href="#3" class="mim-tip-reference" title="Guan, M.-X., Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, E., Suzuki, T., del Castillo, I., and 10 others. <strong>Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.</strong> Am. J. Hum. Genet. 79: 291-302, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16826519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16826519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16826519[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/10.1086/506389" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16826519">Guan et al. (2006)</a> found that a 28G-T transversion in exon 1 of the TRMU gene, resulting in an ala10-to-ser substitution (A10S), modified the phenotypic expression of the 12S rRNA mutation. All members of the Arab-Israeli and Italian-Spanish families carrying both the TRMU A10S and the 12S rRNA 1555A-G mutations exhibited prelingual profound deafness. The A10S mutation resulted in a defect in 2-thio modification in mitochondrial tRNAs, which led to decreases of the steady-state level of mitochondrial tRNAs, subsequently causing impairment of mitochondrial translation. Resultant biochemical defects aggravated the mitochondrial dysfunction below the threshold for normal cell function, thereby expressing the deafness phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16826519" 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 molecular dynamic simulations, <a href="#4" class="mim-tip-reference" title="Meng, F., Cang, X., Peng, Y., Li, R., Zhang, Z., Li, F., Fan, Q., Guan, A. S., Fischel-Ghosian, N., Zhao, X., Guan, M.-X. <strong>Biochemical evidence for a nuclear modifier allele (A10S) in TRMU (methylaminomethyl-2-thiouridylate-methyltransferase) related to mitochondrial tRNA modification in the phenotypic manifestation of deafness-associated 12S rRNA mutation.</strong> J. Biol. Chem. 292: 2881-2892, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28049726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28049726</a>] [<a href="https://doi.org/10.1074/jbc.M116.749374" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28049726">Meng et al. (2017)</a> showed that the A10S mutation introduced a ser10 dynamic electrostatic interaction with lys106 in helix-4 of the TRMU catalytic domain. Western blot analysis revealed reduced levels of TRMU in cells with the A10S mutation, and thermal shift analysis showed that the Tm value of the mutant TRMU protein was lower than wildtype. The A10S mutation also caused marked decreases in 2-thiouridine modification of U34 in tRNAs for lys (MTTK; <a href="/entry/590060">590060</a>), glu (MTTE; <a href="/entry/590025">590025</a>), and gln (MTTQ; <a href="/entry/590030">590030</a>), while mildly increasing the aminoacylated efficiency of the tRNAs. The altered 2-thiouridine modification worsened the impairment of mitochondrial translocation associated with the MTRNR1 1555A-G mutation. Defective translation resulted in reduced activity in mitochondrial respiration chains, leading to reduction of mitochondrial ATP production and elevated production of reactive oxidative species. Thus, the A10S mutation in TRMU worsened the mitochondrial dysfunction associated with the 1555A-G mutation, exceeding the threshold for expressing the deafness phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28049726" 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> rs118203990 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118203990;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/rs118203990?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=rs118203990" 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=rs118203990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 5 Yemenite Jewish patients with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> identified a homozygous 232T-C transition in the TRMU gene, resulting in a tyr77-to-his (Y77H) substitution. Another Yemenite Jewish patient was compound heterozygous for Y77H and a splice site mutation (<a href="#0003">610230.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19732863" 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> rs778799889 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs778799889;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/rs778799889?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=rs778799889" 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=rs778799889" 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=RCV001390441 OR RCV001801250" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001390441, RCV001801250" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001390441...</a>
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<p>In a Yemenite Jewish patient with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> identified compound heterozygosity for 2 mutations in the TRMU gene: a G-to-A transition, resulting in the skipping of exon 3, and the Y77H mutation (<a href="#0002">610230.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19732863" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In an Arab patient with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> identified a homozygous 815G-A transition in the TRMU gene, resulting in a gly272-to-asp (G272D) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19732863" 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 LIVER FAILURE, INFANTILE, TRANSIENT</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> rs118203992 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs118203992;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/rs118203992?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=rs118203992" 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=rs118203992" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 2 Algerian patients with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#10" class="mim-tip-reference" title="Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O. <strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong> Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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.2009.08.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19732863">Zeharia et al. (2009)</a> identified a homozygous 2T-A transversion in the TRMU gene, resulting in a met1-to-lys (M1K) substitution in the initiation codon. The infants presented at ages 1 and 2 days, respectively, and died at ages 3 and 4 months, respectively. The mutation was not identified in 106 individuals of North African origin. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19732863" 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 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
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TRMU, VAL279MET
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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> rs387907022 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907022;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/rs387907022?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=rs387907022" 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=rs387907022" 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=RCV000023804 OR RCV000442392 OR RCV000623265 OR RCV002496439 OR RCV003473122" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023804, RCV000442392, RCV000623265, RCV002496439, RCV003473122" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023804...</a>
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<p>In a 4-year-old Irish girl with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#6" class="mim-tip-reference" title="Uusimaa, J., Jungbluth, H., Fratter, C., Crisponi, G., Feng, L., Zeviani, M., Hughes, I., Treacy, E. P., Birks, J., Brown, G. K., Sewry, C. A., McDermott, M., Muntoni, F., Poulton, J. <strong>Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease.</strong> J. Med. Genet. 48: 660-668, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21931168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21931168</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21931168[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/10.1136/jmg.2011.089995" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21931168">Uusimaa et al. (2011)</a> identified compound heterozygosity for 2 mutations in the TRMU gene: an 835G-A transition resulting in a val279-to-met (V279M) substitution in a highly conserved residue, and a splice site mutation (<a href="#0007">610230.0007</a>). Each unaffected parent was heterozygous for 1 of the mutations. The patient presented in infancy with acute liver failure and lactic acidosis with profound cytochrome c oxidase deficiency in muscle and liver samples. Brain MRI showed abnormal high signal in the right thalamus, which disappeared by age 1 year. She also had feeding difficulties and hypotonia in early infancy. Although she recovered, she had mildly delayed walking, axial weakness, and bulbar involvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21931168" 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> rs753039116 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs753039116;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/rs753039116?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=rs753039116" 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=rs753039116" 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=RCV000489397 OR RCV001274268 OR RCV003476176" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000489397, RCV001274268, RCV003476176" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000489397...</a>
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<p>In a girl with transient infantile liver failure (<a href="/entry/613070">613070</a>), <a href="#6" class="mim-tip-reference" title="Uusimaa, J., Jungbluth, H., Fratter, C., Crisponi, G., Feng, L., Zeviani, M., Hughes, I., Treacy, E. P., Birks, J., Brown, G. K., Sewry, C. A., McDermott, M., Muntoni, F., Poulton, J. <strong>Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease.</strong> J. Med. Genet. 48: 660-668, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21931168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21931168</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21931168[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/10.1136/jmg.2011.089995" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21931168">Uusimaa et al. (2011)</a> identified compound heterozygosity for 2 mutations in the TRMU gene: a C-to-G transversion in intron 11, causing a splice site mutation, and V279M (<a href="#0006">610230.0006</a>). The splice site mutation resulted in 50% aberrantly spliced transcript, which generated a frameshift and premature termination. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21931168" 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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Guan, M. X., Fischel-Ghodsian, N., Attardi, G.
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Hum. Molec. Genet. 10: 573-580, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11230176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11230176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11230176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="2" class="mim-anchor"></a>
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<a id="Guan1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Guan, M.-X., Fischel-Ghodsian, N., Attardi, G.
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<strong>Biochemical evidence for nuclear gene involvement in phenotype of non-syndromic deafness associated with mitochondrial 12S rRNA mutation.</strong>
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Hum. Molec. Genet. 5: 963-971, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8817331/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8817331</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8817331" 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/5.7.963" target="_blank">Full Text</a>]
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</p>
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<a id="3" class="mim-anchor"></a>
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<a id="Guan2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Guan, M.-X., Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, E., Suzuki, T., del Castillo, I., and 10 others.
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<strong>Mutation in TRMU related to transfer RNA modification modulates the phenotypic expression of the deafness-associated mitochondrial 12S ribosomal RNA mutations.</strong>
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Am. J. Hum. Genet. 79: 291-302, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16826519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16826519</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=16826519[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=16826519" 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/10.1086/506389" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="4" class="mim-anchor"></a>
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<a id="Meng2017" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Meng, F., Cang, X., Peng, Y., Li, R., Zhang, Z., Li, F., Fan, Q., Guan, A. S., Fischel-Ghosian, N., Zhao, X., Guan, M.-X.
|
|
<strong>Biochemical evidence for a nuclear modifier allele (A10S) in TRMU (methylaminomethyl-2-thiouridylate-methyltransferase) related to mitochondrial tRNA modification in the phenotypic manifestation of deafness-associated 12S rRNA mutation.</strong>
|
|
J. Biol. Chem. 292: 2881-2892, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28049726/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28049726</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28049726" 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/10.1074/jbc.M116.749374" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="5" class="mim-anchor"></a>
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<a id="Prezant1993" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Prezant, T. R., Agapian, J. V., Bohlman, M. C., Bu, X., Oztas, S., Qiu, W.-Q., Arnos, K. S., Cortopassi, G. A., Jaber, L., Rotter, J. I., Shohat, M., Fischel-Ghodsian, N.
|
|
<strong>Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness.</strong>
|
|
Nature Genet. 4: 289-294, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7689389/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7689389</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7689389" 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/ng0793-289" target="_blank">Full Text</a>]
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<li>
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<a id="6" class="mim-anchor"></a>
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<a id="Uusimaa2011" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Uusimaa, J., Jungbluth, H., Fratter, C., Crisponi, G., Feng, L., Zeviani, M., Hughes, I., Treacy, E. P., Birks, J., Brown, G. K., Sewry, C. A., McDermott, M., Muntoni, F., Poulton, J.
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<strong>Reversible infantile respiratory chain deficiency is a unique, genetically heterogenous mitochondrial disease.</strong>
|
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J. Med. Genet. 48: 660-668, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21931168/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21931168</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=21931168[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=21931168" 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/10.1136/jmg.2011.089995" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
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<a id="Yan2006" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yan, Q., Bykhovskaya, Y., Li, R., Mengesha, E., Shohat, M., Estivill, X., Fischel-Ghodsian, N., Guan, M.-X.
|
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<strong>Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations.</strong>
|
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Biochem. Biophys. Res. Commun. 342: 1130-1136, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16513084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16513084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16513084" 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.bbrc.2006.02.078" target="_blank">Full Text</a>]
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Yan2004" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yan, Q., Guan, M.-X.
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<strong>Identification and characterization of mouse TRMU gene encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase.</strong>
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Biochim. Biophys. Acta 1676: 119-126, 2004.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14746906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14746906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14746906" 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.bbaexp.2003.11.010" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Yan2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yan, Q., Li, X., Faye, G., Guan, M.-X.
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<strong>Mutations in MTO2 related to tRNA modification impair mitochondrial gene expression and protein synthesis in the presence of a paromomycin resistance mutation in mitochondrial 15 S rRNA.</strong>
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J. Biol. Chem. 280: 29151-29157, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15944150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15944150</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15944150[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=15944150" 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/10.1074/jbc.M504247200" target="_blank">Full Text</a>]
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<li>
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<a id="10" class="mim-anchor"></a>
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<a id="Zeharia2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O.
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<strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong>
|
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Am. J. Hum. Genet. 85: 401-407, 2009. Note: Erratum: Am. J. Hum. Genet. 86: 295 only, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19732863/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19732863</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19732863[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=19732863" 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.2009.08.004" target="_blank">Full Text</a>]
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</ol>
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<br />
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div 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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Paul J. Converse - updated : 08/23/2017
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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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Cassandra L. Kniffin - updated : 10/27/2011<br>Cassandra L. Kniffin - updated : 10/6/2009<br>Victor A. McKusick - updated : 7/10/2006
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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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Patricia A. Hartz : 7/5/2006
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 08/23/2017
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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 : 09/24/2013<br>carol : 10/27/2011<br>ckniffin : 10/27/2011<br>carol : 3/19/2010<br>wwang : 10/8/2009<br>ckniffin : 10/6/2009<br>alopez : 7/18/2006<br>alopez : 7/17/2006<br>terry : 7/10/2006<br>mgross : 7/5/2006
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<h3>
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<span class="mim-font">
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<strong>*</strong> 610230
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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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tRNA 5-METHYLAMINOMETHYL-2-THIOURIDYLATE METHYLTRANSFERASE; TRMU
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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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<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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TRNT1<br />
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MTO2, S. CEREVISIAE, HOMOLOG OF; MTO2
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TRMU</em></strong>
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</span>
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</p>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 22q13.31
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Genomic coordinates <span class="small">(GRCh38)</span> : 22:46,335,714-46,357,340 </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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<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>
|
|
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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22q13.31
|
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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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{Deafness, mitochondrial, modifier of}
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
580000
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
Mitochondrial
|
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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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Liver failure, transient infantile
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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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613070
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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>TRMU is an evolutionarily conserved protein involved in mitochondrial tRNA modification, and is thus important for mitochondrial translation (Yan 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>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By searching a database for sequences similar to yeast Mto2, followed by RT-PCR of a human osteosarcoma cell line cDNA library, Yan et al. (2005) cloned TRMU, which they designated MTO2. Fluorescence-tagged MTO2 localized to mitochondria. </p><p>By 5-prime and 3-prime RACE, Yan et al. (2006) identified several TRMU splice variants. The full-length 421-amino acid protein has a calculated molecular mass of 47.7 kD. The other transcripts lack exon 3 and encode a deduced 99-amino acid protein. Northern blot analysis detected high expression of a 1.9-kb TRMU transcript in heart, skeletal muscle, and kidney. Intermediate expression was detected in brain, placenta, spleen, and small intestine, and low expression was detected in liver, colon, lung, thymus, and leukocytes. Expression was nearly uniform in 8 brain regions examined. </p><p>Yan and Guan (2004) cloned mouse Trmu. The deduced 417-amino acid protein contains a typical mitochondrial target sequence and shares 91% identity with human TRMU. </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>Yan et al. (2006) determined that the TRMU gene contains 11 exons and spans about 22 kb. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Yan et al. (2006) mapped the TRMU gene to chromosome 22q13. Yan and Guan (2004) mapped the mouse Trmu gene to chromosome 15. </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>Yan et al. (2005) demonstrated that human MTO2 could partially restore the respiratory-deficient phenotype of Mto2-null yeast carrying a mutation in 15S ribosomal RNA (rRNA), 1409C-G, associated with aminoglycoside resistance. The yeast 1409C-G mutation in 15S rRNA corresponds to the deafness-associated 1494C-T mutation (561000.0004) in human 12S rRNA (MTRNR1; 561000). </p><p>In families with the deafness-associated 12S rRNA 1555A-G mutation (561000.0001), Yan et al. (2006) found suggestive linkage and linkage disequilibrium between microsatellite markers adjacent to TRMU and the presence of deafness. They hypothesized that TRMU may modulate the phenotypic manifestation of deafness-associated mitochondrial 12S rRNA mutations. </p><p>Guan et al. (2006) noted that TRMU is responsible for the 2-thiolation of hypermodified nucleoside 5-methyl-aminomethy-2-thio-uridine. This modified nucleotide, found in the wobble position of several bacterial and human mitochondrial tRNAs (mt tRNAs) specific for glutamate, lysine, and glutamine, has a pivotal role in the structure and function of tRNAs, including structural stabilization, aminoacylation, and codon recognition at the decoding site of small rRNA. </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">
|
|
<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>Deafness Modification</em></strong></p><p>
|
|
The 1555A-G mutation of mitochondrial 12S rRNA (561000.0001) is associated with aminoglycoside-induced and nonsyndromic deafness in many families worldwide (Prezant et al., 1993). Studies of Guan et al. (1996, 2001) revealed that the 1555A-G mutation, although a primary factor underlying the development of deafness, is not alone sufficient to produce a deafness phenotype. Nuclear modifier genes have been proposed as modulators of the phenotypic manifestations of the mitochondrial mutation. Guan et al. (2006) identified the nuclear modifier gene TRMU, which encodes a highly conserved mitochondrial protein related to transfer RNA (tRNA) modification. Studies in a large Arab Israeli kindred, in an Italian family, and in 6 Spanish families carrying the 1555A-G or the 1494C-T (561000.0004) mutation revealed a missense mutation (610230.0001) altering an invariant amino acid residue (A10S) in the evolutionarily conserved N-terminal region of the TRMU protein. All members of the Arab Israeli, Italian, and Spanish families carrying both the TRMU A10S and the 12S rRNA 1555A-G mutations exhibited prelingual profound deafness. Functional analysis showed that the A10S mutation did not affect importation of TRMU precursors into mitochondria. However, the homozygous A10S mutation led to a marked failure in mitochondrial tRNA metabolisms, specifically reducing the steady-state levels of mitochondrial tRNA. As a consequence, these defects contributed to the impairment of mitochondrial protein synthesis. These findings indicated that the mutated TRMU, acting as a modifier factor, modulates the phenotypic manifestation of the deafness-associated 12S rRNA mutations. </p><p><strong><em>Transient Infantile Liver Failure</em></strong></p><p>
|
|
By linkage analysis, followed by candidate gene sequencing, Zeharia et al. (2009) identified homozygous and compound heterozygous mutations in the TRMU gene (see, e.g., 610230.0002-610230.0005) in patients with transient infantile liver failure (LFIT; 613070). Seven patients of Yemenite Jewish origin had the same Y77H mutation (610230.0002), indicating a founder effect. Overall, 9 mutations were identified in 13 patients. Those who survived the initial acute episode showed clinical and biochemical resolution of liver failure and had no further episodes. A study of tRNAs in cells derived from 3 of the patients showed a severe reduction of thio-modified mitochondrial tRNAs, whereas the pattern of hybridization obtained for the cytosolic tRNA-lys, modified by another enzyme, was similar to controls. The findings suggested that the mitochondrial translation defect resulted from reduced modification of several mitochondrial tRNAs. Noting that the availability of cysteine in the neonatal period is limited, Zeharia et al. (2009) proposed that there is a window of time during 1 to 4 months of age during which patients with TRMU mutations are at an increased risk of developing liver failure. </p>
|
|
</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>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>7 Selected Examples):</strong>
|
|
</span>
|
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</h4>
|
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<div>
|
|
<p />
|
|
</div>
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<div>
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|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 DEAFNESS, MITOCHONDRIAL, MODIFIER OF</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
TRMU, 28G-T, ALA10SER
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|
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<br />
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|
|
SNP: rs11090865,
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|
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gnomAD: rs11090865,
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|
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ClinVar: RCV000001353, RCV000173461, RCV000295210, RCV000676757, RCV002496227
|
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|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a large Arab Israeli kindred, in an Italian family, and in 6 Spanish families with sensorineural deafness carrying the 1555A-G (561000.0001) or the 1494C-T (561000.0004) mutation in mitochondrial 12S ribosomal RNA (rRNA), Guan et al. (2006) found that a 28G-T transversion in exon 1 of the TRMU gene, resulting in an ala10-to-ser substitution (A10S), modified the phenotypic expression of the 12S rRNA mutation. All members of the Arab-Israeli and Italian-Spanish families carrying both the TRMU A10S and the 12S rRNA 1555A-G mutations exhibited prelingual profound deafness. The A10S mutation resulted in a defect in 2-thio modification in mitochondrial tRNAs, which led to decreases of the steady-state level of mitochondrial tRNAs, subsequently causing impairment of mitochondrial translation. Resultant biochemical defects aggravated the mitochondrial dysfunction below the threshold for normal cell function, thereby expressing the deafness phenotype. </p><p>Using molecular dynamic simulations, Meng et al. (2017) showed that the A10S mutation introduced a ser10 dynamic electrostatic interaction with lys106 in helix-4 of the TRMU catalytic domain. Western blot analysis revealed reduced levels of TRMU in cells with the A10S mutation, and thermal shift analysis showed that the Tm value of the mutant TRMU protein was lower than wildtype. The A10S mutation also caused marked decreases in 2-thiouridine modification of U34 in tRNAs for lys (MTTK; 590060), glu (MTTE; 590025), and gln (MTTQ; 590030), while mildly increasing the aminoacylated efficiency of the tRNAs. The altered 2-thiouridine modification worsened the impairment of mitochondrial translocation associated with the MTRNR1 1555A-G mutation. Defective translation resulted in reduced activity in mitochondrial respiration chains, leading to reduction of mitochondrial ATP production and elevated production of reactive oxidative species. Thus, the A10S mutation in TRMU worsened the mitochondrial dysfunction associated with the 1555A-G mutation, exceeding the threshold for expressing the deafness phenotype. </p>
|
|
</span>
|
|
</div>
|
|
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|
|
<div>
|
|
<br />
|
|
</div>
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|
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</div>
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
TRMU, TYR77HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs118203990,
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|
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|
|
|
gnomAD: rs118203990,
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|
|
|
|
|
ClinVar: RCV000001354, RCV001851536, RCV003472956, RCV003944789, RCV005024985
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 5 Yemenite Jewish patients with transient infantile liver failure (613070), Zeharia et al. (2009) identified a homozygous 232T-C transition in the TRMU gene, resulting in a tyr77-to-his (Y77H) substitution. Another Yemenite Jewish patient was compound heterozygous for Y77H and a splice site mutation (610230.0003). </p>
|
|
</span>
|
|
</div>
|
|
|
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|
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|
|
<div>
|
|
<br />
|
|
</div>
|
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|
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</div>
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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TRMU, IVS3AS, G-A, -1
|
|
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|
|
|
<br />
|
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|
|
SNP: rs778799889,
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|
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|
|
gnomAD: rs778799889,
|
|
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|
|
|
ClinVar: RCV001390441, RCV001801250
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Yemenite Jewish patient with transient infantile liver failure (613070), Zeharia et al. (2009) identified compound heterozygosity for 2 mutations in the TRMU gene: a G-to-A transition, resulting in the skipping of exon 3, and the Y77H mutation (610230.0002). </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TRMU, GLY272ASP
|
|
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|
|
<br />
|
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|
|
SNP: rs118203991,
|
|
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|
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|
|
ClinVar: RCV000001356
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In an Arab patient with transient infantile liver failure (613070), Zeharia et al. (2009) identified a homozygous 815G-A transition in the TRMU gene, resulting in a gly272-to-asp (G272D) substitution. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
TRMU, MET1LYS
|
|
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|
|
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<br />
|
|
|
|
SNP: rs118203992,
|
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|
|
|
gnomAD: rs118203992,
|
|
|
|
|
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ClinVar: RCV000001357, RCV004018052
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In 2 Algerian patients with transient infantile liver failure (613070), Zeharia et al. (2009) identified a homozygous 2T-A transversion in the TRMU gene, resulting in a met1-to-lys (M1K) substitution in the initiation codon. The infants presented at ages 1 and 2 days, respectively, and died at ages 3 and 4 months, respectively. The mutation was not identified in 106 individuals of North African origin. </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
|
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|
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</div>
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|
|
|
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
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</div>
|
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<div>
|
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<span class="mim-text-font">
|
|
|
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TRMU, VAL279MET
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<br />
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|
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SNP: rs387907022,
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|
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gnomAD: rs387907022,
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|
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ClinVar: RCV000023804, RCV000442392, RCV000623265, RCV002496439, RCV003473122
|
|
|
|
|
|
</span>
|
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</div>
|
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|
|
|
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a 4-year-old Irish girl with transient infantile liver failure (613070), Uusimaa et al. (2011) identified compound heterozygosity for 2 mutations in the TRMU gene: an 835G-A transition resulting in a val279-to-met (V279M) substitution in a highly conserved residue, and a splice site mutation (610230.0007). Each unaffected parent was heterozygous for 1 of the mutations. The patient presented in infancy with acute liver failure and lactic acidosis with profound cytochrome c oxidase deficiency in muscle and liver samples. Brain MRI showed abnormal high signal in the right thalamus, which disappeared by age 1 year. She also had feeding difficulties and hypotonia in early infancy. Although she recovered, she had mildly delayed walking, axial weakness, and bulbar involvement. </p>
|
|
</span>
|
|
</div>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 LIVER FAILURE, INFANTILE, TRANSIENT</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
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<span class="mim-text-font">
|
|
|
|
TRMU, IVS11AS, C-G, -3
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<br />
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|
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SNP: rs753039116,
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|
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gnomAD: rs753039116,
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ClinVar: RCV000489397, RCV001274268, RCV003476176
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a girl with transient infantile liver failure (613070), Uusimaa et al. (2011) identified compound heterozygosity for 2 mutations in the TRMU gene: a C-to-G transversion in intron 11, causing a splice site mutation, and V279M (610230.0006). The splice site mutation resulted in 50% aberrantly spliced transcript, which generated a frameshift and premature termination. </p>
|
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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</div>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
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</span>
|
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</h4>
|
|
<div>
|
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<p />
|
|
</div>
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<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Guan, M. X., Fischel-Ghodsian, N., Attardi, G.
|
|
<strong>Nuclear background determines biochemical phenotype in the deafness-associated mitochondrial 12S rRNA mutation.</strong>
|
|
Hum. Molec. Genet. 10: 573-580, 2001.
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|
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|
|
[PubMed: 11230176]
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Zeharia, A., Shaag, A., Pappo, O., Mager-Heckel, A.-M., Saada, A., Beinat, M., Karicheva, O., Mandel, H., Ofek, N., Segel, R., Marom, D., Rotig, A., Tarassov, I., Elpeleg, O.
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<strong>Acute infantile liver failure due to mutations in the TRMU gene.</strong>
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