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<title>
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Entry
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- *607381 - TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50; TIMM50
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- OMIM
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<div id="mimSearch" class="hidden-print">
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<input type="hidden" id="mimSearchIndex" name="index" value="entry" />
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<input type="hidden" id="mimSearchStart" name="start" value="1" />
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<input type="hidden" id="mimSearchLimit" name="limit" value="10" />
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<input type="search" id="mimEntrySearch" name="search" class="form-control" value="" placeholder="Search OMIM..." maxlength="5000" autocomplete="off" autocorrect="off" autocapitalize="none" spellcheck="false" autofocus />
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Advanced Search
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<a href="/search/advanced/entry"> OMIM </a>
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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/clinicalSynopsis"> Clinical Synopses </a>
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<a href="/search/advanced/geneMap"> Gene Map </a>
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</form>
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*607381</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<ul id="mimFloatingTocMenuItems" class="nav nav-pills nav-stacked mim-floating-toc-padding">
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<li role="presentation">
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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>
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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>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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</li>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/607381">Table View</a>
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</li>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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</li>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
|
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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</a>
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</span>
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</span>
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</div>
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<div id="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000105197;t=ENST00000607714" 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=92609" 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=607381" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
|
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</a>
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</span>
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</span>
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</div>
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<div id="mimDnaLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000105197;t=ENST00000607714" 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_001001563,NM_001329559,XM_011527491,XM_047439681" 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_001001563" 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=607381" 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=12118&isoform_id=12118_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/TIMM50" 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/14290586,14789599,45594397,46561982,73909141,83305924,111306454,111309241,119577305,119577306,119577307,768012048,1044635741,1480771479,2217323853,2462568662,2462568664" 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/Q3ZCQ8" 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=92609" 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=ENSG00000105197;t=ENST00000607714" 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=TIMM50" 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=TIMM50" 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+92609" 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/TIMM50" 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:92609" 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/92609" 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=chr19&hgg_gene=ENST00000607714.6&hgg_start=39480838&hgg_end=39493779&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
|
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
|
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:23656" 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=607381[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=607381[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000105197" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=TIMM50" 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=TIMM50" 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=TIMM50&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/PA134902846" 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:23656" 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/FBgn0032971.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:1913775" 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/TIMM50#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:1913775" 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/92609/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=92609" 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=WBGene00011897;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-040426-1618" 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">
|
|
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
|
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
|
<div style="display: table-row">
|
|
<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=TIMM50&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
|
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 1222672002<br />
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">ICD+</a>
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</div>
|
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<div>
|
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
|
607381
|
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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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|
|
TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50; TIMM50
|
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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>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50, YEAST, HOMOLOG OF; TIM50
|
|
</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>
|
|
<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TIMM50" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TIMM50</a></em></strong>
|
|
</span>
|
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</p>
|
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</div>
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<div>
|
|
<a id="cytogeneticLocation" class="mim-anchor"></a>
|
|
<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/19/684?start=-3&limit=10&highlight=684">19q13.2</a>
|
|
|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr19:39480838-39493779&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'})">19:39,480,838-39,493,779</a> </span>
|
|
</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
|
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|
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|
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</span>
|
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</p>
|
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</div>
|
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<div>
|
|
<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
|
</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
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|
</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/19/684?start=-3&limit=10&highlight=684">
|
|
19q13.2
|
|
</a>
|
|
</span>
|
|
</td>
|
|
|
|
|
|
<td>
|
|
<span class="mim-font">
|
|
3-methylglutaconic aciduria, type IX
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/entry/617698"> 617698 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
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<span class="mim-font">
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<p>The TIMM50 gene encodes a subunit of the mitochondrial presequence import machinery called the TIM23 complex. TIMM50 serves as a major receptor in the intermembrane space that binds to proteins on their way to cross the mitochondrial inner membrane (summary by <a href="#5" class="mim-tip-reference" title="Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. <strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong> Clin. Genet. 91: 690-696, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1111/cge.12855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27573165">Shahrour et al., 2017</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27573165" 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="Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T. <strong>Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes.</strong> Cell 111: 519-528, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12437925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12437925</a>] [<a href="https://doi.org/10.1016/s0092-8674(02)01053-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12437925">Yamamoto et al. (2002)</a> identified Tim50, a component of the yeast Tim23 (<a href="/entry/605034">605034</a>) import machinery, which mediates translocation of presequence-containing proteins across the mitochondrial inner membrane. By searching sequence databases, they identified open reading frames encoding proteins with similarity to Tim50 and with a putative mitochondrial presequence in the genomes of evolutionarily distant organisms, including human. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437925" 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="Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T. <strong>Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes.</strong> Cell 111: 519-528, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12437925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12437925</a>] [<a href="https://doi.org/10.1016/s0092-8674(02)01053-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12437925">Yamamoto et al. (2002)</a> determined that yeast Tim50 is anchored to the inner mitochondrial membrane, exposing the C-terminal domain to the intermembrane space. Tim50 was found to interact with the N-terminal intermembrane space domain of Tim23. Functional defects of Tim50 either by depletion of the protein or addition of anti-Tim50 antibodies blocked the protein translocation across the inner membrane. A translocation intermediate accumulated at the translocator of the outer mitochondrial membrane (TOM) complex was cross-linked to Tim50. The authors concluded that Tim50, in cooperation with Tim23, facilitates transfer of the translocating protein from the TOM complex to the Tim23 complex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437925" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P. <strong>Tim50 maintains the permeability barrier of the mitochondrial inner membrane.</strong> Science 312: 1523-1526, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16763150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16763150</a>] [<a href="https://doi.org/10.1126/science.1127628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16763150">Meinecke et al. (2006)</a> found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, <a href="#2" class="mim-tip-reference" title="Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P. <strong>Tim50 maintains the permeability barrier of the mitochondrial inner membrane.</strong> Science 312: 1523-1526, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16763150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16763150</a>] [<a href="https://doi.org/10.1126/science.1127628" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16763150">Meinecke et al. (2006)</a> concluded that the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16763150" 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="#1" class="mim-tip-reference" title="Gross, M. B. <strong>Personal Communication.</strong> Baltimore, Md. 5/29/2014."None>Gross (2014)</a> mapped the TIMM50 gene to chromosome 19q13.2 based on an alignment of the TIMM50 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AY444561" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AY444561</a>) with the genomic sequence (GRCh37).</p>
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<p>In 4 patients from 2 unrelated consanguineous families with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), <a href="#5" class="mim-tip-reference" title="Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. <strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong> Clin. Genet. 91: 690-696, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1111/cge.12855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27573165">Shahrour et al. (2017)</a> identified homozygous missense mutations in the TIMM50 gene (T252M, <a href="#0001">607381.0001</a> and R217W, <a href="#0002">607381.0002</a>). The mutations, which were found by exome sequencing, segregated with the disorder in the family. The human homolog of TIMM50 failed to rescue a Tim50-null growth defect in yeast, and expression of the homologous substitution for R217W (R159W) in yeast resulted in normal growth and did not impair the import function of Tim50. These findings indicated that this substitution is tolerated in yeast, but not in humans. Although <a href="#5" class="mim-tip-reference" title="Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. <strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong> Clin. Genet. 91: 690-696, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1111/cge.12855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27573165">Shahrour et al. (2017)</a> could not demonstrate the pathogenicity of the mutations in a yeast-based system, they concluded that they are disease-causing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27573165" 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 whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, <a href="#3" class="mim-tip-reference" title="Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S. <strong>Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter)</strong> Clin. Genet. 98: 102-103, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32369862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32369862</a>] [<a href="https://doi.org/10.1111/cge.13763" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32369862">Mir et al. (2020)</a> identified homozygosity for the T252M mutation in the TIMM50 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32369862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a child with MGCA9, <a href="#4" class="mim-tip-reference" title="Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M. <strong>Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.</strong> EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30190335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30190335</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30190335[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/10.15252/emmm.201708698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30190335">Reyes et al. (2018)</a> identified compound heterozygous mutations in the TIMM50 gene (S112X, <a href="#0003">607381.0003</a> and G190A, <a href="#0004">607381.0004</a>). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. Patient fibroblasts had reduced mitochondrial membrane potential, impaired TIM23-dependent protein import, and reduced steady state levels of tested subunits of respiratory chain complexes I, II, and IV. Introduction of wildtype TIMM50 into patient fibroblasts remediated these defects. When patient fibroblasts were grown in galactose-containing media (which is dependent on oxidative phosphorylation) compared to glucose containing media (which is reliant on glycolytic metabolism), improvement in expression of members of the TIM23 transport complex, levels of subunits of respiratory chain complexes, and ATP-dependent respiration was seen, although apoptosis was increased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30190335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 17-year-old boy with MGCA9, <a href="#6" class="mim-tip-reference" title="Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others. <strong>Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.</strong> Hum. Mutat. 40: 1700-1712, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31058414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31058414</a>] [<a href="https://doi.org/10.1002/humu.23779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31058414">Tort et al. (2019)</a> identified compound heterozygous mutations in the TIMM50 gene (R114Q, <a href="#0005">607381.0005</a>; G269S, <a href="#0006">607381.0006</a>). Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. In patient fibroblasts, expression of 10 subunits of the mitochondrial respiratory chain and localization of 6 subunits of the respiratory chain in the mitochondrial inner membrane were normal, indicating that the TIMM50 mutations did not disrupt mitochondrial protein expression or localization. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes, and respirometry demonstrated decreased maximal respiratory capacity. The studies indicated a role for TIMM50 in cristae maintenance and assembly of OXPHOS complexes and supercomplexes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31058414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=607381[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 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</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> rs1244226820 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1244226820;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/rs1244226820?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=rs1244226820" 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=rs1244226820" 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=RCV000509024 OR RCV005091152" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000509024, RCV005091152" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000509024...</a>
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<p>In 2 sibs, born of consanguineous Bedouin parents (family A), with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), <a href="#5" class="mim-tip-reference" title="Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. <strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong> Clin. Genet. 91: 690-696, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1111/cge.12855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27573165">Shahrour et al. (2017)</a> identified a homozygous c.755C-T transition (c.755C-T, NM_001001563.1) in the TIMM50 gene, resulting in a thr252-to-met (T252M) substitution at a highly conserved residue in the mitochondrial intermembrane space. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. A fetus was also found to be homozygous for the mutation. The mutation was not present in large cohorts of control exome analyses or in an ethnic-specific exome cohort. Functional studies of the variant were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27573165" 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 whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, <a href="#3" class="mim-tip-reference" title="Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S. <strong>Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter)</strong> Clin. Genet. 98: 102-103, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32369862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32369862</a>] [<a href="https://doi.org/10.1111/cge.13763" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32369862">Mir et al. (2020)</a> identified homozygosity for the T252M mutation in the TIMM50 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32369862" 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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<span class="mim-font">
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<strong>.0002 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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TIMM50, ARG217TRP
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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> rs1300848445 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1300848445;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/rs1300848445?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=rs1300848445" 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=rs1300848445" 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=RCV000509033 OR RCV001367110" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000509033, RCV001367110" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000509033...</a>
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<p>In 2 sibs, born of consanguineous Muslim parents (family B), with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), <a href="#5" class="mim-tip-reference" title="Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others. <strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong> Clin. Genet. 91: 690-696, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1111/cge.12855" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27573165">Shahrour et al. (2017)</a> identified a homozygous c.649C-T transition (c.649C-T, NM_001001563.1) in the TIMM50 gene, resulting in an arg217-to-trp (R217W) substitution at a conserved residue in the mitochondrial intermembrane space. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database or in 700 in-house control exomes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27573165" 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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<span class="mim-font">
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<strong>.0003 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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TIMM50, SER112TER
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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> rs35135520 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs35135520;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/rs35135520?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=rs35135520" 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=rs35135520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000677434 OR RCV001328000" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000677434, RCV001328000" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000677434...</a>
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<p>In an Italian child with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), <a href="#4" class="mim-tip-reference" title="Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M. <strong>Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.</strong> EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30190335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30190335</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30190335[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/10.15252/emmm.201708698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30190335">Reyes et al. (2018)</a> identified compound heterozygous mutations in the TIMM50 gene: a c.335C-A transversion (c.335C-A, NM_001001563) in exon 1, resulting in a ser112-to-ter (S112X) substitution, and a c.569G-C transversion in exon 3, resulting in a gly190-to-ala (G190A; 607381.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be carriers. The S112X mutation was not present in the ExAC database, and the G190A mutation was present in ExAC in only 1 of approximately 200,000 alleles. TIMM50 protein expression, as well as protein expression of other members of the mitochondrial TIM23 transport complex, was reduced in patient fibroblasts. Import of TFAM (<a href="/entry/600438">600438</a>) into mitochondria via the TIM23 complex was severely impaired in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30190335" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0004 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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TIMM50, GLY190ALA (<a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs776019250;toggle_HGVS_names=open" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'dbSNP\', \'domain\': \'ensembl.org\'})">rs776019250</a>)
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs776019250 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs776019250;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/rs776019250?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=rs776019250" 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=rs776019250" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<span class="mim-text-font">
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000677433 OR RCV001328001" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000677433, RCV001328001" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000677433...</a>
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<span class="mim-text-font">
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<p>For discussion of the c.569G-C transversion (c.569G-C, NM_001001563) in the TIMM50 gene, resulting in a gly190-to-ala (G190A) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), by <a href="#4" class="mim-tip-reference" title="Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M. <strong>Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.</strong> EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30190335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30190335</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30190335[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/10.15252/emmm.201708698" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30190335">Reyes et al. (2018)</a>, see <a href="#0003">607381.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30190335" 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 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</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> rs778355943 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs778355943;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/rs778355943?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=rs778355943" 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=rs778355943" 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=RCV001812628 OR RCV003120700" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV001812628, RCV003120700" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV001812628...</a>
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<p>In a 17-year-old patient with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>), <a href="#6" class="mim-tip-reference" title="Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others. <strong>Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.</strong> Hum. Mutat. 40: 1700-1712, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31058414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31058414</a>] [<a href="https://doi.org/10.1002/humu.23779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31058414">Tort et al. (2019)</a> identified compound heterozygous mutations in the TIMM50 gene: a c.341G-A transition (c.341G-A, NM_001001563.5), resulting in an arg114-to-gln (R114Q) substitution, inherited from the mother, and a c.805G-A transition, resulting in a gly269-to-ser (G269S; <a href="#0006">607381.0006</a>) substitution, inherited from the father. Both mutations occurred at highly conserved residues. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31058414" 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">rs797044891 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs797044891;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs797044891" 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=rs797044891" 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=RCV000190713 OR RCV001812182" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000190713, RCV001812182" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000190713...</a>
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<p>For discussion of the c.805G-A transition (c.805G-A, NM_001001563.5) in the TIMM50 gene, resulting in a gly269-to-ser (G269S) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; <a href="/entry/617698">617698</a>) by <a href="#6" class="mim-tip-reference" title="Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others. <strong>Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.</strong> Hum. Mutat. 40: 1700-1712, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31058414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31058414</a>] [<a href="https://doi.org/10.1002/humu.23779" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31058414">Tort et al. (2019)</a>, see <a href="#0005">607381.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31058414" 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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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 5/29/2014.
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Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P.
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<strong>Tim50 maintains the permeability barrier of the mitochondrial inner membrane.</strong>
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Science 312: 1523-1526, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16763150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16763150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16763150" 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/10.1126/science.1127628" target="_blank">Full Text</a>]
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Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S.
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<strong>Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter)</strong>
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Clin. Genet. 98: 102-103, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32369862/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32369862</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32369862" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/cge.13763" target="_blank">Full Text</a>]
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Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M.
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<strong>Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.</strong>
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EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30190335/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30190335</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30190335[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=30190335" 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/10.15252/emmm.201708698" target="_blank">Full Text</a>]
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Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others.
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<strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong>
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Clin. Genet. 91: 690-696, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27573165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27573165</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=27573165[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=27573165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others.
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<strong>Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.</strong>
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Hum. Mutat. 40: 1700-1712, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31058414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31058414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31058414" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T.
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<strong>Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes.</strong>
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Cell 111: 519-528, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12437925/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12437925</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12437925" 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/s0092-8674(02)01053-x" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 01/14/2022
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Hilary J. Vernon - updated : 03/15/2021<br>Hilary J. Vernon - updated : 02/01/2021<br>Cassandra L. Kniffin - updated : 10/03/2017<br>Matthew B. Gross - updated : 05/29/2014<br>Ada Hamosh - updated : 7/24/2006
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carol : 03/16/2021<br>carol : 03/15/2021<br>carol : 02/11/2021<br>carol : 02/01/2021<br>mgross : 05/04/2020<br>carol : 12/18/2019<br>alopez : 10/03/2017<br>ckniffin : 10/03/2017<br>mgross : 05/29/2014<br>terry : 7/24/2006<br>alopez : 12/1/2004<br>mgross : 11/25/2002
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<h3>
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<span class="mim-font">
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<strong>*</strong> 607381
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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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TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50; TIMM50
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</h3>
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</div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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TRANSLOCASE OF INNER MITOCHONDRIAL MEMBRANE 50, YEAST, HOMOLOG OF; TIM50
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</span>
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</h4>
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</div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TIMM50</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 1222672002;
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</p>
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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: 19q13.2
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Genomic coordinates <span class="small">(GRCh38)</span> : 19:39,480,838-39,493,779 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td rowspan="1">
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<span class="mim-font">
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19q13.2
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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-methylglutaconic aciduria, type IX
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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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617698
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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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<br />
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The TIMM50 gene encodes a subunit of the mitochondrial presequence import machinery called the TIM23 complex. TIMM50 serves as a major receptor in the intermembrane space that binds to proteins on their way to cross the mitochondrial inner membrane (summary by Shahrour et al., 2017). </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>Yamamoto et al. (2002) identified Tim50, a component of the yeast Tim23 (605034) import machinery, which mediates translocation of presequence-containing proteins across the mitochondrial inner membrane. By searching sequence databases, they identified open reading frames encoding proteins with similarity to Tim50 and with a putative mitochondrial presequence in the genomes of evolutionarily distant organisms, including human. </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Yamamoto et al. (2002) determined that yeast Tim50 is anchored to the inner mitochondrial membrane, exposing the C-terminal domain to the intermembrane space. Tim50 was found to interact with the N-terminal intermembrane space domain of Tim23. Functional defects of Tim50 either by depletion of the protein or addition of anti-Tim50 antibodies blocked the protein translocation across the inner membrane. A translocation intermediate accumulated at the translocator of the outer mitochondrial membrane (TOM) complex was cross-linked to Tim50. The authors concluded that Tim50, in cooperation with Tim23, facilitates transfer of the translocating protein from the TOM complex to the Tim23 complex. </p><p>Meinecke et al. (2006) found that the intermembrane space domain of Tim50 induced the Tim23 channel to close. Presequences overcame this effect and activated the channel for translocation. Thus, Meinecke et al. (2006) concluded that the hydrophilic cis domain of Tim50 maintains the permeability barrier of mitochondria by closing the translocation pore in a presequence-regulated manner. </p>
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</span>
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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>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>Gross (2014) mapped the TIMM50 gene to chromosome 19q13.2 based on an alignment of the TIMM50 sequence (GenBank AY444561) with the genomic sequence (GRCh37).</p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 4 patients from 2 unrelated consanguineous families with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified homozygous missense mutations in the TIMM50 gene (T252M, 607381.0001 and R217W, 607381.0002). The mutations, which were found by exome sequencing, segregated with the disorder in the family. The human homolog of TIMM50 failed to rescue a Tim50-null growth defect in yeast, and expression of the homologous substitution for R217W (R159W) in yeast resulted in normal growth and did not impair the import function of Tim50. These findings indicated that this substitution is tolerated in yeast, but not in humans. Although Shahrour et al. (2017) could not demonstrate the pathogenicity of the mutations in a yeast-based system, they concluded that they are disease-causing. </p><p>By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene. </p><p>In a child with MGCA9, Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene (S112X, 607381.0003 and G190A, 607381.0004). The mutations were found by whole-exome sequencing and confirmed by Sanger sequencing. Each parent was heterozygous for one of the mutations. Patient fibroblasts had reduced mitochondrial membrane potential, impaired TIM23-dependent protein import, and reduced steady state levels of tested subunits of respiratory chain complexes I, II, and IV. Introduction of wildtype TIMM50 into patient fibroblasts remediated these defects. When patient fibroblasts were grown in galactose-containing media (which is dependent on oxidative phosphorylation) compared to glucose containing media (which is reliant on glycolytic metabolism), improvement in expression of members of the TIM23 transport complex, levels of subunits of respiratory chain complexes, and ATP-dependent respiration was seen, although apoptosis was increased. </p><p>In a 17-year-old boy with MGCA9, Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene (R114Q, 607381.0005; G269S, 607381.0006). Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. In patient fibroblasts, expression of 10 subunits of the mitochondrial respiratory chain and localization of 6 subunits of the respiratory chain in the mitochondrial inner membrane were normal, indicating that the TIMM50 mutations did not disrupt mitochondrial protein expression or localization. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes, and respirometry demonstrated decreased maximal respiratory capacity. The studies indicated a role for TIMM50 in cristae maintenance and assembly of OXPHOS complexes and supercomplexes. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>ALLELIC VARIANTS</strong>
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</span>
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<strong>6 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, THR252MET
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<br />
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SNP: rs1244226820,
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gnomAD: rs1244226820,
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ClinVar: RCV000509024, RCV005091152
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs, born of consanguineous Bedouin parents (family A), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.755C-T transition (c.755C-T, NM_001001563.1) in the TIMM50 gene, resulting in a thr252-to-met (T252M) substitution at a highly conserved residue in the mitochondrial intermembrane space. The mutation, which was found by a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family. A fetus was also found to be homozygous for the mutation. The mutation was not present in large cohorts of control exome analyses or in an ethnic-specific exome cohort. Functional studies of the variant were not performed. </p><p>By whole-exome sequencing in a 20-month-old girl, born to consanguineous Saudi parents, with MGCA9, Mir et al. (2020) identified homozygosity for the T252M mutation in the TIMM50 gene. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, ARG217TRP
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<br />
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SNP: rs1300848445,
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gnomAD: rs1300848445,
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ClinVar: RCV000509033, RCV001367110
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 sibs, born of consanguineous Muslim parents (family B), with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Shahrour et al. (2017) identified a homozygous c.649C-T transition (c.649C-T, NM_001001563.1) in the TIMM50 gene, resulting in an arg217-to-trp (R217W) substitution at a conserved residue in the mitochondrial intermembrane space. The mutation, which was found by exome sequencing, segregated with the disorder in the family. It was not found in the ExAC database or in 700 in-house control exomes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0003 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, SER112TER
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<br />
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SNP: rs35135520,
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gnomAD: rs35135520,
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ClinVar: RCV000677434, RCV001328000
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In an Italian child with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Reyes et al. (2018) identified compound heterozygous mutations in the TIMM50 gene: a c.335C-A transversion (c.335C-A, NM_001001563) in exon 1, resulting in a ser112-to-ter (S112X) substitution, and a c.569G-C transversion in exon 3, resulting in a gly190-to-ala (G190A; 607381.0004) substitution. The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The parents were shown to be carriers. The S112X mutation was not present in the ExAC database, and the G190A mutation was present in ExAC in only 1 of approximately 200,000 alleles. TIMM50 protein expression, as well as protein expression of other members of the mitochondrial TIM23 transport complex, was reduced in patient fibroblasts. Import of TFAM (600438) into mitochondria via the TIM23 complex was severely impaired in patient fibroblasts. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0004 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, GLY190ALA ({dbSNP rs776019250})
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<br />
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SNP: rs776019250,
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gnomAD: rs776019250,
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ClinVar: RCV000677433, RCV001328001
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.569G-C transversion (c.569G-C, NM_001001563) in the TIMM50 gene, resulting in a gly190-to-ala (G190A) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), by Reyes et al. (2018), see 607381.0003. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0005 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, ARG114GLN
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<br />
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SNP: rs778355943,
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gnomAD: rs778355943,
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ClinVar: RCV001812628, RCV003120700
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a 17-year-old patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698), Tort et al. (2019) identified compound heterozygous mutations in the TIMM50 gene: a c.341G-A transition (c.341G-A, NM_001001563.5), resulting in an arg114-to-gln (R114Q) substitution, inherited from the mother, and a c.805G-A transition, resulting in a gly269-to-ser (G269S; 607381.0006) substitution, inherited from the father. Both mutations occurred at highly conserved residues. The mutations were identified by trio exome sequencing and confirmed by Sanger sequencing. Testing in patient fibroblasts demonstrated normal TIMM50 mRNA levels and reduced protein levels, indicating that the mutations may affect protein stability. Microscopy in patient fibroblasts showed abnormal mitochondrial cristae structure. BN-PAGE analysis in patient fibroblasts showed reduced mitochondrial respiratory chain complexes I, II, IV, and V and reduced levels of respiratory supercomplexes. </p>
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</span>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0006 3-@METHYLGLUTACONIC ACIDURIA, TYPE IX</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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TIMM50, GLY269SER
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<br />
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SNP: rs797044891,
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ClinVar: RCV000190713, RCV001812182
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</span>
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<p>For discussion of the c.805G-A transition (c.805G-A, NM_001001563.5) in the TIMM50 gene, resulting in a gly269-to-ser (G269S) substitution, that was found in compound heterozygous state in a patient with 3-methylglutaconic aciduria type IX (MGCA9; 617698) by Tort et al. (2019), see 607381.0005. </p>
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</div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Gross, M. B.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 5/29/2014.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Meinecke, M., Wagner, R., Kovermann, P., Guiard, B., Mick, D. U., Hutu, D. P., Voos, W., Truscott, K. N., Chacinska, A., Pfanner, N., Rehling, P.
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<strong>Tim50 maintains the permeability barrier of the mitochondrial inner membrane.</strong>
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Science 312: 1523-1526, 2006.
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[PubMed: 16763150]
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[Full Text: https://doi.org/10.1126/science.1127628]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Mir, A., Hadab, S., Sammak, M., Alhazmi, R., Housawi, Y., Bashir, S.
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<strong>Complete resolution of epileptic spasms with vigabatrin in a patient with 3-methylglutaconic aciduria caused by TIMM50 gene mutation. (Letter)</strong>
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Clin. Genet. 98: 102-103, 2020.
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[PubMed: 32369862]
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[Full Text: https://doi.org/10.1111/cge.13763]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Reyes, A., Melchionda, L., Burlina, A., Robinson, A. J., Ghezzi, D., Zeviani, M.
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<strong>Mutations in TIMM50 compromise cell survival in OxPhos-dependent metabolic conditions.</strong>
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EMBO Molec. Med. 10: e8698, 2018. Note: Electronic Article.
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[PubMed: 30190335]
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[Full Text: https://doi.org/10.15252/emmm.201708698]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Shahrour, M. A., Staretz-Chacham , O., Dayan, D., Stephen, J., Weech, A., Damseh, N., Pri Chen, H., Edvardson, S., Mazaheri, S., Saada, A., NISC Intramural Sequencing, Hershkovitz, E., and 9 others.
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<strong>Mitochondrial epileptic encephalopathy, 3-methylglutaconic aciduria and variable complex V deficiency associated with TIMM50 mutations.</strong>
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Clin. Genet. 91: 690-696, 2017.
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[PubMed: 27573165]
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[Full Text: https://doi.org/10.1111/cge.12855]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Tort, F., Ugarteburu, O., Texido, L., Gea-Sorli, S., Garcia-Villoria, J., Ferrer-Cortes, X., Arias, A., Matalonga, L., Gort, L., Ferrer, I., Guitart-Mampel, M., Garrabou, G., and 9 others.
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<strong>Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.</strong>
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Hum. Mutat. 40: 1700-1712, 2019.
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[PubMed: 31058414]
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[Full Text: https://doi.org/10.1002/humu.23779]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Yamamoto, H., Esaki, M., Kanamori, T., Tamura, Y., Nishikawa, S., Endo, T.
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<strong>Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes.</strong>
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Cell 111: 519-528, 2002.
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[PubMed: 12437925]
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[Full Text: https://doi.org/10.1016/s0092-8674(02)01053-x]
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</p>
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</li>
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</ol>
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<div>
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<br />
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Contributors:
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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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Hilary J. Vernon - updated : 01/14/2022<br>Hilary J. Vernon - updated : 03/15/2021<br>Hilary J. Vernon - updated : 02/01/2021<br>Cassandra L. Kniffin - updated : 10/03/2017<br>Matthew B. Gross - updated : 05/29/2014<br>Ada Hamosh - updated : 7/24/2006
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</span>
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<span class="mim-text-font">
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Stylianos E. Antonarakis : 11/25/2002
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carol : 01/14/2022<br>carol : 03/16/2021<br>carol : 03/15/2021<br>carol : 02/11/2021<br>carol : 02/01/2021<br>mgross : 05/04/2020<br>carol : 12/18/2019<br>alopez : 10/03/2017<br>ckniffin : 10/03/2017<br>mgross : 05/29/2014<br>terry : 7/24/2006<br>alopez : 12/1/2004<br>mgross : 11/25/2002
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