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<title>
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Entry
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- *612418 - TRANSMEMBRANE PROTEIN 70; TMEM70
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- OMIM
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</ul>
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<div id="mimSearch" class="hidden-print">
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<div class="container">
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<form method="get" action="/search" id="mimEntrySearchForm" name="entrySearchForm" class="form-horizontal">
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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="hidden" id="mimSearchSort" name="sort" value="score desc, prefix_sort desc" />
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<div class="col-lg-8 col-md-8 col-sm-8 col-xs-8">
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<div class="input-group">
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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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<div class="input-group-btn">
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<button type="submit" id="mimEntrySearchSubmit" class="btn btn-default" style="width: 5em;"><span class="glyphicon glyphicon-search"></span></button>
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<button type="button" class="btn btn-default dropdown-toggle" data-toggle="dropdown"> Options <span class="caret"></span></button>
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<ul class="dropdown-menu dropdown-menu-right">
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<li class="dropdown-header">
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Advanced Search
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</li>
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<li style="margin-left: 0.5em;">
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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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</li>
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<li style="margin-left: 0.5em;">
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<a href="/search/advanced/geneMap"> Gene Map </a>
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<li role="separator" class="divider"></li>
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<a href="/history"> Search History </a>
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</form>
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<p />
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<div id="mimAlertBanner">
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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">*612418</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 role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneFunction">Gene Function</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<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/612418">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=ENSG00000175606;t=ENST00000312184" 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=54968" 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=612418" 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=ENSG00000175606;t=ENST00000312184" 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_001040613,NM_017866,NR_033334" 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_017866" 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=612418" 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=07923&isoform_id=07923_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/TMEM70" 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/7020704,33988025,34147498,74733203,95007020,119607428,119607429,440576055" 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/Q9BUB7" 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=54968" 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=ENSG00000175606;t=ENST00000312184" 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=TMEM70" 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=TMEM70" 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+54968" 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/TMEM70" 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:54968" 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/54968" 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=chr8&hgg_gene=ENST00000312184.6&hgg_start=73976195&hgg_end=73982783&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:26050" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/tmem70" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=612418[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=612418[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://www.deciphergenomics.org/gene/TMEM70/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000175606" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=TMEM70" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=TMEM70" 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=TMEM70" 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=TMEM70&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/PA142670783" 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:26050" 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/FBgn0035805.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:1915068" 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/TMEM70#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:1915068" 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/54968/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=54968" 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=WBGene00009330;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-070912-593" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
|
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://reactome.org/content/query?q=TMEM70&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
|
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<div class="text-right">
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Gene description">
|
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<span class="text-danger"><strong>*</strong></span>
|
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612418
|
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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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TRANSMEMBRANE PROTEIN 70; TMEM70
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=TMEM70" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">TMEM70</a></em></strong>
|
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</span>
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</p>
|
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/8/348?start=-3&limit=10&highlight=348">8q21.11</a>
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|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr8:73976195-73982783&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'})">8:73,976,195-73,982,783</a> </span>
|
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</em>
|
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</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
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</div>
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<div>
|
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<br />
|
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</div>
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<div>
|
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<a id="geneMap" class="mim-anchor"></a>
|
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<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
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<tr class="active">
|
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<th>
|
|
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>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="1">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/8/348?start=-3&limit=10&highlight=348">
|
|
8q21.11
|
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</a>
|
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</span>
|
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</td>
|
|
|
|
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<td>
|
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<span class="mim-font">
|
|
Mitochondrial complex V (ATP synthase) deficiency, nuclear type 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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|
<a href="/entry/614052"> 614052 </a>
|
|
|
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</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
|
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</span>
|
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</td>
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</tr>
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<p>TMEM70 is a mitochondrial protein required for the assembly of complex I (see <a href="/entry/602694">602694</a>) and complex V (see <a href="/entry/102910">102910</a>) in the oxidative phosphorylation system (OXPHOS) (<a href="#6" class="mim-tip-reference" title="Sanchez-Caballero, L., Elurbe, D. M., Baertling, F., Guerrero-Castillo, S., van den Brand, M., van Strien, J., van Dam, T. J. P., Rodenburg, R., Brandt, U., Huynen, M. A., Nijtmans, L. G. J. <strong>TMEM70 functions in the assembly of complexes I and V.</strong> Biochim. Biophys. Acta Bioenerg. 1861: 148202, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275929</a>] [<a href="https://doi.org/10.1016/j.bbabio.2020.148202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275929">Sanchez-Caballero et al., 2020</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Using a computational approach to identify genes encoding putative mitochondrial proteins, <a href="#1" class="mim-tip-reference" title="Calvo, S., Jain, M., Xie, X., Sheth, S. A., Chang, B., Goldberger, O. A., Spinazzola, A., Zeviani, M., Carr, S. A., Mootha, V. K. <strong>Systematic identification of human mitochondrial disease genes through integrative genomics.</strong> Nature Genet. 38: 576-582, 2006.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582907</a>] [<a href="https://doi.org/10.1038/ng1776" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16582907">Calvo et al. (2006)</a> identified full-length TMEM70 and subsequently cloned the corresponding cDNA. Fluorescence-tagged TMEM70 colocalized with a mitochondrial marker in transfected HeLa cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a> identified TMEM70 within a region of chromosome 8 associated with a form of mitochondrial ATP synthase deficiency (<a href="/entry/614052">614052</a>). The deduced protein contains a conserved DUF1301 domain and 2 putative transmembrane regions. RT-PCR detected TMEM70 in all tissues examined, which included liver, muscle, kidney, and pancreas, as well as in fibroblasts. Phylogenetic analysis revealed TMEM70 orthologs in multicellular eukaryotes and plants, but not in yeast and fungi. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" 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 phylogenetic analysis, <a href="#6" class="mim-tip-reference" title="Sanchez-Caballero, L., Elurbe, D. M., Baertling, F., Guerrero-Castillo, S., van den Brand, M., van Strien, J., van Dam, T. J. P., Rodenburg, R., Brandt, U., Huynen, M. A., Nijtmans, L. G. J. <strong>TMEM70 functions in the assembly of complexes I and V.</strong> Biochim. Biophys. Acta Bioenerg. 1861: 148202, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275929</a>] [<a href="https://doi.org/10.1016/j.bbabio.2020.148202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275929">Sanchez-Caballero et al. (2020)</a> identified human TMEM223 (<a href="/entry/620434">620434</a>) and TMEM186 (<a href="/entry/620433">620433</a>) as paralogs of TMEM70, even though TMEM70 shares only 9% and 14% amino acid identity with TMEM223 and TMEM186, respectively. Fractionation and immunofluorescence assays showed that TMEM70, TMEM223, and TMEM186 were mitochondrial proteins. In silico analysis suggested that TMEM70, TMEM223, and TMEM186 share a similar asymmetric hairpin topology, with a short N-terminal sequence located in the mitochondrial matrix followed by an in/out and an out/in transmembrane helix and a longer C-terminal sequence. All 3 proteins are phylogenetically widespread and are present in the last eukaryotic common ancestor. As a mitochondrial protein family, all 3 coevolved with the oxidative phosphorylation system (OXPHOS) and only occur in species with OXPHOS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By genomic sequence analysis, <a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a> mapped the TMEM10 gene to chromosome 8. <a href="#5" class="mim-tip-reference" title="Hartz, P. A. <strong>Personal Communication.</strong> Baltimore, Md. 11/18/2008."None>Hartz (2008)</a> mapped the TMEM70 gene to chromosome 8q21.11 based on an alignment of the TMEM70 sequence (GenBank <a href="https://www.ncbi.nlm.nih.gov/search/all/?term=AK000540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'GENBANK\', \'domain\': \'ncbi.nlm.nih.gov\'})">AK000540</a>) with the genomic sequence (build 36.1). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" 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>Following transfection of wildtype TMEM70 into skin fibroblasts obtained from individuals with isolated mitochondrial ATP synthase deficiency due to mutations in the TMEM70 gene, <a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a> observed increased amounts of F1 and Fo structural subunits of ATP synthase and production of normal concentrations of full size, assembled ATP synthase complex. Consequently, TMEM70 restored oligomycin-sensitive ATP hydrolysis, ADP-stimulated respiration, mitochondrial ATP synthesis, and ADP-induced decrease of mitochondrial membrane potential. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using biotin-labeled TMEM70, <a href="#6" class="mim-tip-reference" title="Sanchez-Caballero, L., Elurbe, D. M., Baertling, F., Guerrero-Castillo, S., van den Brand, M., van Strien, J., van Dam, T. J. P., Rodenburg, R., Brandt, U., Huynen, M. A., Nijtmans, L. G. J. <strong>TMEM70 functions in the assembly of complexes I and V.</strong> Biochim. Biophys. Acta Bioenerg. 1861: 148202, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275929</a>] [<a href="https://doi.org/10.1016/j.bbabio.2020.148202" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32275929">Sanchez-Caballero et al. (2020)</a> showed that TMEM70 was associated with OXPHOS complex I, complex V, and the small subunit of the ribosome in HEK293 cells. TMEM70 knockout analysis confirmed interaction of TMEM70 with complex I and complex V, as loss of TMEM70 resulted in decreased abundance of the subunits of complex I and complex V and decreased activities of complex I and complex V. Further analysis confirmed that assembly of complexes I and V was impaired in the absence of TMEM70, as loss of TMEM70 resulted in accumulation of an assembly intermediate followed by a reduction of the next assembly intermediate in the pathway. Despite TMEM70 interaction with the small subunit of the ribosome, the assembly process of ribosomes and translation efficiency in mitochondria were not affected by TMEM70 knockout, suggesting that TMEM70 did not play a significant role in assembly or functioning of the ribosome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275929" 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="Carroll, J., He, J., Ding, S., Fearnley, I. M., Walker, J. E. <strong>TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.</strong> Proc. Nat. Acad. Sci. 118: e2100558118, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33753518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33753518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33753518[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1073/pnas.2100558118" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33753518">Carroll et al. (2021)</a> identified TMEM70 and TMEM242 (<a href="/entry/620721">620721</a>) as assembly factors associated with subunit c (see <a href="/entry/602736">602736</a>) of ATP synthase in HEK293 cells. Knockout of TMEM242 or TMEM70 in HAP1 cells altered but did not eliminate assembly of ATP synthase and, to a lesser degree, respiratory enzyme complexes I, III (see <a href="/entry/516020">516020</a>), and IV (see <a href="/entry/516030">516030</a>). Deletion of both TMEM70 and TMEM242 prevented assembly of ATP synthase and enhanced the effects on complex I resulting from deletion of TMEM242 or TMEM70. Removal of TMEM242, but not of TMEM70, also affected introduction of subunits ATP6 (MTATP6; <a href="/entry/516060">516060</a>), ATP8 (MTATP8; <a href="/entry/516070">516070</a>), j (ATP5MJ), and k (ATP5MK) into ATP synthase. Further analysis revealed that TMEM70 and TMEM242 also interacted with the mitochondrial complex I assembly (MCIA) complex, which supports assembly of the membrane arm of complex I. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33753518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected individuals from 6 Romani families with neonatal mitochondrial encephalocardiomyopathy associated with complex V (ATP synthase) deficiency (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a> identified a homozygous mutation in the TMEM70 gene (<a href="#0001">612418.0001</a>). The same homozygous mutation was identified in 23 additional patients. Cooccurrence of cases with severe and milder phenotypes with the same mutation was thought to represent varying quality and functionality of individual nonsense-mediated RNA decay systems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" 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 6 patients from 4 unrelated consanguineous Arab-Muslim families with MC5DN2, <a href="#7" class="mim-tip-reference" title="Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I. <strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong> J. Med. Genet. 48: 177-182, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21147908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21147908</a>] [<a href="https://doi.org/10.1136/jmg.2010.084608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21147908">Spiegel et al. (2011)</a> identified 4 different homozygous mutations in the TMEM70 gene (see, e.g., <a href="#0003">612418.0003</a>-<a href="#0005">612418.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21147908" 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 2 Bedouin sibs, born to consanguineous parents, with MC5DN2, <a href="#8" class="mim-tip-reference" title="Staretz-Chacham, O., Wormser, O., Manor, E., Birk, O. S., Ferreira, C. R. <strong>TMEM70 deficiency: novel mutation and hypercitrullinemia during metabolic decompensation.</strong> Am. J. Med. Genet. 179A: 1293-1298, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30950220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30950220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30950220[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/10.1002/ajmg.a.61138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30950220">Staretz-Chacham et al. (2019)</a> identified a homozygous frameshift mutation in the TMEM70 gene (<a href="#0006">612418.0006</a>). The mutation was found by homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing. Family segregation studies were not performed. The variant was not found in the dbSNP (build 150) or ExAC databases but was present at a low frequency (0.0009248%) in the gnomAD database. It was not found in 153 ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30950220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=612418[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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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> rs183973249 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs183973249;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/rs183973249?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=rs183973249" 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=rs183973249" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In affected members of 6 families with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a> identified a homozygous A-to-G transition in intron 2 of the TMEM70 gene (c.317-2A-G), resulting in aberrant splicing and loss of the mRNA transcript. The same homozygous mutation was identified in 23 additional patients. One patient was compound heterozygous for this mutation and a 2-bp insertion (118_119insGT; <a href="#0002">612418.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Catteruccia, M., Verrigni, D., Martinelli, D., Torraco, A., Agovino, T., Bonafe, L., D'Amico, A., Donati, M. A., Adorisio, R., Santorelli, F. M., Carrozzo, R., Bertini, E., Dionisi-Vici, C. <strong>Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.</strong> Molec. Genet. Metab. 111: 353-359, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24485043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24485043</a>] [<a href="https://doi.org/10.1016/j.ymgme.2014.01.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24485043">Catteruccia et al. (2014)</a> identified a homozygous c.317-2A-G mutation in 6 of 9 patients with MC5DN2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24485043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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">rs796052056 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs796052056;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=rs796052056" 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=rs796052056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>For discussion of the 2-bp insertion in the TMEM70 gene (118_119insGT) that was found in compound heterozygous state in a patient with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>) by <a href="#4" class="mim-tip-reference" title="Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others. <strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong> Nature Genet. 40: 1288-1290, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>] [<a href="https://doi.org/10.1038/ng.246" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18953340">Cizkova et al. (2008)</a>, see <a href="#0001">612418.0001</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0003 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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">rs1586636643 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1586636643;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=rs1586636643" 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=rs1586636643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In an 11-month-old boy, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#7" class="mim-tip-reference" title="Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I. <strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong> J. Med. Genet. 48: 177-182, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21147908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21147908</a>] [<a href="https://doi.org/10.1136/jmg.2010.084608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21147908">Spiegel et al. (2011)</a> identified a homozygous 366A-T transversion in exon 2 of the TMEM70 gene, resulting in a tyr112-to-ter (Y112X) substitution. The patient had hypertrophic cardiomyopathy, lactic acidosis, mild psychomotor retardation, hypospadias, and facial dysmorphism. Skeletal muscle complex V activity was 16% of controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21147908" 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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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> rs387907070 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs387907070;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/rs387907070?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=rs387907070" 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=rs387907070" 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=RCV000023948 OR RCV001539609 OR RCV002513212" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000023948, RCV001539609, RCV002513212" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000023948...</a>
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<p>In a female infant, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#7" class="mim-tip-reference" title="Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I. <strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong> J. Med. Genet. 48: 177-182, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21147908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21147908</a>] [<a href="https://doi.org/10.1136/jmg.2010.084608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21147908">Spiegel et al. (2011)</a> identified a homozygous 238C-T transition in exon 2 of the TMEM70 gene, resulting in an arg80-to-ter (R80X) substitution. At birth, the patient showed respiratory insufficiency and hypotonia, and soon developed severe lactic acidosis and impaired liver function, followed by death from multiorgan failure at age 7 days. Skeletal muscle complex V activity was 4% of controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21147908" 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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</strong>
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TMEM70, 2-BP DEL, 578CA
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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> rs777501387 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs777501387;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/rs777501387?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=rs777501387" 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=rs777501387" 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=RCV000484311 OR RCV001050497" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000484311, RCV001050497" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000484311...</a>
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<p>In 2 sibs, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#7" class="mim-tip-reference" title="Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I. <strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong> J. Med. Genet. 48: 177-182, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21147908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21147908</a>] [<a href="https://doi.org/10.1136/jmg.2010.084608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21147908">Spiegel et al. (2011)</a> identified a homozygous 2-bp deletion (578delCA) in exon 3 of the TMEM70 gene, resulting in a truncated 197-residue protein. One brother was alive at age 26 years, and the other died at age 3. Both had hypotonia, hypertrophic cardiomyopathy, recurrent encephalopathic episodes, lactic acidosis, 3-methylglutaconic aciduria, and severe psychomotor retardation. Other features included infantile cataract and delayed gastric emptying. Skeletal muscle complex V activity was undetectable in the surviving patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21147908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</strong>
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TMEM70, 1-BP DUP, 105T
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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> rs1411381518 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1411381518;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/rs1411381518?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=rs1411381518" 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=rs1411381518" 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=RCV000995903" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000995903" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000995903</a>
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<p>In 2 Bedouin sibs, born to consanguineous parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; <a href="/entry/614052">614052</a>), <a href="#8" class="mim-tip-reference" title="Staretz-Chacham, O., Wormser, O., Manor, E., Birk, O. S., Ferreira, C. R. <strong>TMEM70 deficiency: novel mutation and hypercitrullinemia during metabolic decompensation.</strong> Am. J. Med. Genet. 179A: 1293-1298, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30950220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30950220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30950220[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/10.1002/ajmg.a.61138" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30950220">Staretz-Chacham et al. (2019)</a> identified a homozygous 1-bp duplication (c.105dupT, NM_017866.5) in exon 1 of the TMEM70 gene, resulting in a frameshift and a premature termination codon (Val36CysfsTer52). The mutation was predicted to result in loss of function of the protein. The mutation was found by homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing. Family segregation studies were not performed. The variant was not found in the dbSNP (build 150) or ExAC databases but was present at a low frequency (0.0009248%) in the gnomAD database. It was not found in 153 ethnically matched controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30950220" 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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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>REFERENCES</strong>
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<a id="Calvo2006" class="mim-anchor"></a>
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Calvo, S., Jain, M., Xie, X., Sheth, S. A., Chang, B., Goldberger, O. A., Spinazzola, A., Zeviani, M., Carr, S. A., Mootha, V. K.
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<strong>Systematic identification of human mitochondrial disease genes through integrative genomics.</strong>
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Nature Genet. 38: 576-582, 2006.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16582907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16582907</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16582907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng1776" target="_blank">Full Text</a>]
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Carroll, J., He, J., Ding, S., Fearnley, I. M., Walker, J. E.
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<strong>TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.</strong>
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Proc. Nat. Acad. Sci. 118: e2100558118, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33753518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33753518</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33753518[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=33753518" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.2100558118" target="_blank">Full Text</a>]
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<a id="Catteruccia2014" class="mim-anchor"></a>
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Catteruccia, M., Verrigni, D., Martinelli, D., Torraco, A., Agovino, T., Bonafe, L., D'Amico, A., Donati, M. A., Adorisio, R., Santorelli, F. M., Carrozzo, R., Bertini, E., Dionisi-Vici, C.
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<strong>Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.</strong>
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Molec. Genet. Metab. 111: 353-359, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24485043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24485043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24485043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2014.01.001" target="_blank">Full Text</a>]
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<a id="Cizkova2008" class="mim-anchor"></a>
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Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others.
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<strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong>
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Nature Genet. 40: 1288-1290, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18953340/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18953340</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18953340" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng.246" target="_blank">Full Text</a>]
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<a id="Hartz2008" class="mim-anchor"></a>
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 11/18/2008.
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Sanchez-Caballero, L., Elurbe, D. M., Baertling, F., Guerrero-Castillo, S., van den Brand, M., van Strien, J., van Dam, T. J. P., Rodenburg, R., Brandt, U., Huynen, M. A., Nijtmans, L. G. J.
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<strong>TMEM70 functions in the assembly of complexes I and V.</strong>
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Biochim. Biophys. Acta Bioenerg. 1861: 148202, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32275929/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32275929</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32275929" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.bbabio.2020.148202" target="_blank">Full Text</a>]
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Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I.
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<strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong>
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J. Med. Genet. 48: 177-182, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21147908/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21147908</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21147908" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1136/jmg.2010.084608" target="_blank">Full Text</a>]
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Staretz-Chacham, O., Wormser, O., Manor, E., Birk, O. S., Ferreira, C. R.
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<strong>TMEM70 deficiency: novel mutation and hypercitrullinemia during metabolic decompensation.</strong>
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Am. J. Med. Genet. 179A: 1293-1298, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30950220/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30950220</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30950220[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=30950220" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61138" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Bao Lige - updated : 02/15/2024
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Bao Lige - updated : 06/26/2023<br>Hilary J. Vernon - updated : 08/11/2020<br>Cassandra L. Kniffin - updated : 7/1/2014<br>Cassandra L. Kniffin - updated : 12/1/2011<br>Cassandra L. Kniffin - updated : 11/19/2008
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Patricia A. Hartz : 11/19/2008
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</span>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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mgross : 02/15/2024
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<span class="mim-text-font">
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mgross : 06/26/2023<br>carol : 08/13/2020<br>carol : 08/12/2020<br>carol : 08/11/2020<br>carol : 05/21/2015<br>mcolton : 5/15/2015<br>carol : 7/2/2014<br>ckniffin : 7/1/2014<br>carol : 12/5/2011<br>ckniffin : 12/1/2011<br>carol : 6/23/2011<br>carol : 6/13/2011<br>alopez : 11/21/2008<br>ckniffin : 11/19/2008<br>carol : 11/19/2008<br>carol : 11/19/2008
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<span class="mim-font">
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<strong>*</strong> 612418
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<h3>
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<span class="mim-font">
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TRANSMEMBRANE PROTEIN 70; TMEM70
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</span>
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</h3>
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<br />
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: TMEM70</em></strong>
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</span>
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</p>
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<span class="mim-text-font">
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<strong>
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<em>
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Cytogenetic location: 8q21.11
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Genomic coordinates <span class="small">(GRCh38)</span> : 8:73,976,195-73,982,783 </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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<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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<td rowspan="1">
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<span class="mim-font">
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8q21.11
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</span>
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</td>
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<td>
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<span class="mim-font">
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Mitochondrial complex V (ATP synthase) deficiency, nuclear type 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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614052
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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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</tbody>
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</table>
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<div>
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>TMEM70 is a mitochondrial protein required for the assembly of complex I (see 602694) and complex V (see 102910) in the oxidative phosphorylation system (OXPHOS) (Sanchez-Caballero et al., 2020). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>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>Using a computational approach to identify genes encoding putative mitochondrial proteins, Calvo et al. (2006) identified full-length TMEM70 and subsequently cloned the corresponding cDNA. Fluorescence-tagged TMEM70 colocalized with a mitochondrial marker in transfected HeLa cells. </p><p>Cizkova et al. (2008) identified TMEM70 within a region of chromosome 8 associated with a form of mitochondrial ATP synthase deficiency (614052). The deduced protein contains a conserved DUF1301 domain and 2 putative transmembrane regions. RT-PCR detected TMEM70 in all tissues examined, which included liver, muscle, kidney, and pancreas, as well as in fibroblasts. Phylogenetic analysis revealed TMEM70 orthologs in multicellular eukaryotes and plants, but not in yeast and fungi. </p><p>By phylogenetic analysis, Sanchez-Caballero et al. (2020) identified human TMEM223 (620434) and TMEM186 (620433) as paralogs of TMEM70, even though TMEM70 shares only 9% and 14% amino acid identity with TMEM223 and TMEM186, respectively. Fractionation and immunofluorescence assays showed that TMEM70, TMEM223, and TMEM186 were mitochondrial proteins. In silico analysis suggested that TMEM70, TMEM223, and TMEM186 share a similar asymmetric hairpin topology, with a short N-terminal sequence located in the mitochondrial matrix followed by an in/out and an out/in transmembrane helix and a longer C-terminal sequence. All 3 proteins are phylogenetically widespread and are present in the last eukaryotic common ancestor. As a mitochondrial protein family, all 3 coevolved with the oxidative phosphorylation system (OXPHOS) and only occur in species with OXPHOS. </p>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>By genomic sequence analysis, Cizkova et al. (2008) mapped the TMEM10 gene to chromosome 8. Hartz (2008) mapped the TMEM70 gene to chromosome 8q21.11 based on an alignment of the TMEM70 sequence (GenBank AK000540) with the genomic sequence (build 36.1). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Gene Function</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Following transfection of wildtype TMEM70 into skin fibroblasts obtained from individuals with isolated mitochondrial ATP synthase deficiency due to mutations in the TMEM70 gene, Cizkova et al. (2008) observed increased amounts of F1 and Fo structural subunits of ATP synthase and production of normal concentrations of full size, assembled ATP synthase complex. Consequently, TMEM70 restored oligomycin-sensitive ATP hydrolysis, ADP-stimulated respiration, mitochondrial ATP synthesis, and ADP-induced decrease of mitochondrial membrane potential. </p><p>Using biotin-labeled TMEM70, Sanchez-Caballero et al. (2020) showed that TMEM70 was associated with OXPHOS complex I, complex V, and the small subunit of the ribosome in HEK293 cells. TMEM70 knockout analysis confirmed interaction of TMEM70 with complex I and complex V, as loss of TMEM70 resulted in decreased abundance of the subunits of complex I and complex V and decreased activities of complex I and complex V. Further analysis confirmed that assembly of complexes I and V was impaired in the absence of TMEM70, as loss of TMEM70 resulted in accumulation of an assembly intermediate followed by a reduction of the next assembly intermediate in the pathway. Despite TMEM70 interaction with the small subunit of the ribosome, the assembly process of ribosomes and translation efficiency in mitochondria were not affected by TMEM70 knockout, suggesting that TMEM70 did not play a significant role in assembly or functioning of the ribosome. </p><p>Carroll et al. (2021) identified TMEM70 and TMEM242 (620721) as assembly factors associated with subunit c (see 602736) of ATP synthase in HEK293 cells. Knockout of TMEM242 or TMEM70 in HAP1 cells altered but did not eliminate assembly of ATP synthase and, to a lesser degree, respiratory enzyme complexes I, III (see 516020), and IV (see 516030). Deletion of both TMEM70 and TMEM242 prevented assembly of ATP synthase and enhanced the effects on complex I resulting from deletion of TMEM242 or TMEM70. Removal of TMEM242, but not of TMEM70, also affected introduction of subunits ATP6 (MTATP6; 516060), ATP8 (MTATP8; 516070), j (ATP5MJ), and k (ATP5MK) into ATP synthase. Further analysis revealed that TMEM70 and TMEM242 also interacted with the mitochondrial complex I assembly (MCIA) complex, which supports assembly of the membrane arm of complex I. </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 affected individuals from 6 Romani families with neonatal mitochondrial encephalocardiomyopathy associated with complex V (ATP synthase) deficiency (MC5DN2; 614052), Cizkova et al. (2008) identified a homozygous mutation in the TMEM70 gene (612418.0001). The same homozygous mutation was identified in 23 additional patients. Cooccurrence of cases with severe and milder phenotypes with the same mutation was thought to represent varying quality and functionality of individual nonsense-mediated RNA decay systems. </p><p>In 6 patients from 4 unrelated consanguineous Arab-Muslim families with MC5DN2, Spiegel et al. (2011) identified 4 different homozygous mutations in the TMEM70 gene (see, e.g., 612418.0003-612418.0005). </p><p>In 2 Bedouin sibs, born to consanguineous parents, with MC5DN2, Staretz-Chacham et al. (2019) identified a homozygous frameshift mutation in the TMEM70 gene (612418.0006). The mutation was found by homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing. Family segregation studies were not performed. The variant was not found in the dbSNP (build 150) or ExAC databases but was present at a low frequency (0.0009248%) in the gnomAD database. It was not found in 153 ethnically matched controls. </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>
|
|
<span class="mim-font">
|
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<strong>ALLELIC VARIANTS</strong>
|
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</span>
|
|
<strong>6 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<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">
|
|
<strong>.0001 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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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TMEM70, IVS2AS, A-G, -2
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<br />
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SNP: rs183973249,
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gnomAD: rs183973249,
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ClinVar: RCV000000570, RCV000390940, RCV003128385, RCV003389034, RCV003415606
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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 affected members of 6 families with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052), Cizkova et al. (2008) identified a homozygous A-to-G transition in intron 2 of the TMEM70 gene (c.317-2A-G), resulting in aberrant splicing and loss of the mRNA transcript. The same homozygous mutation was identified in 23 additional patients. One patient was compound heterozygous for this mutation and a 2-bp insertion (118_119insGT; 612418.0002). </p><p>Catteruccia et al. (2014) identified a homozygous c.317-2A-G mutation in 6 of 9 patients with MC5DN2. </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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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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TMEM70, 2-BP INS, 118GT
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<br />
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SNP: rs796052056,
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ClinVar: RCV000186214, RCV000678391, RCV000825576
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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 2-bp insertion in the TMEM70 gene (118_119insGT) that was found in compound heterozygous state in a patient with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052) by Cizkova et al. (2008), see 612418.0001. </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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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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TMEM70, TYR112TER
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<br />
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SNP: rs1586636643,
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ClinVar: RCV000023947
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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 11-month-old boy, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052), Spiegel et al. (2011) identified a homozygous 366A-T transversion in exon 2 of the TMEM70 gene, resulting in a tyr112-to-ter (Y112X) substitution. The patient had hypertrophic cardiomyopathy, lactic acidosis, mild psychomotor retardation, hypospadias, and facial dysmorphism. Skeletal muscle complex V activity was 16% of controls. </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 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</strong>
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</span>
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</h4>
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</div>
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TMEM70, ARG80TER
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<br />
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SNP: rs387907070,
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gnomAD: rs387907070,
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ClinVar: RCV000023948, RCV001539609, RCV002513212
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<p>In a female infant, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052), Spiegel et al. (2011) identified a homozygous 238C-T transition in exon 2 of the TMEM70 gene, resulting in an arg80-to-ter (R80X) substitution. At birth, the patient showed respiratory insufficiency and hypotonia, and soon developed severe lactic acidosis and impaired liver function, followed by death from multiorgan failure at age 7 days. Skeletal muscle complex V activity was 4% of controls. </p>
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<span class="mim-font">
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<strong>.0005 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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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TMEM70, 2-BP DEL, 578CA
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<br />
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SNP: rs777501387,
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gnomAD: rs777501387,
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ClinVar: RCV000484311, RCV001050497
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<span class="mim-text-font">
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<p>In 2 sibs, born of consanguineous Arab Muslim parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052), Spiegel et al. (2011) identified a homozygous 2-bp deletion (578delCA) in exon 3 of the TMEM70 gene, resulting in a truncated 197-residue protein. One brother was alive at age 26 years, and the other died at age 3. Both had hypotonia, hypertrophic cardiomyopathy, recurrent encephalopathic episodes, lactic acidosis, 3-methylglutaconic aciduria, and severe psychomotor retardation. Other features included infantile cataract and delayed gastric emptying. Skeletal muscle complex V activity was undetectable in the surviving patient. </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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<h4>
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<span class="mim-font">
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<strong>.0006 MITOCHONDRIAL COMPLEX V (ATP SYNTHASE) DEFICIENCY, NUCLEAR TYPE 2</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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TMEM70, 1-BP DUP, 105T
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<br />
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SNP: rs1411381518,
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gnomAD: rs1411381518,
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ClinVar: RCV000995903
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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 Bedouin sibs, born to consanguineous parents, with mitochondrial complex V deficiency nuclear type 2 (MC5DN2; 614052), Staretz-Chacham et al. (2019) identified a homozygous 1-bp duplication (c.105dupT, NM_017866.5) in exon 1 of the TMEM70 gene, resulting in a frameshift and a premature termination codon (Val36CysfsTer52). The mutation was predicted to result in loss of function of the protein. The mutation was found by homozygosity mapping and whole-exome sequencing and confirmed by Sanger sequencing. Family segregation studies were not performed. The variant was not found in the dbSNP (build 150) or ExAC databases but was present at a low frequency (0.0009248%) in the gnomAD database. It was not found in 153 ethnically matched controls. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Calvo, S., Jain, M., Xie, X., Sheth, S. A., Chang, B., Goldberger, O. A., Spinazzola, A., Zeviani, M., Carr, S. A., Mootha, V. K.
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<strong>Systematic identification of human mitochondrial disease genes through integrative genomics.</strong>
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Nature Genet. 38: 576-582, 2006.
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[PubMed: 16582907]
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[Full Text: https://doi.org/10.1038/ng1776]
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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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Carroll, J., He, J., Ding, S., Fearnley, I. M., Walker, J. E.
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<strong>TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.</strong>
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Proc. Nat. Acad. Sci. 118: e2100558118, 2021.
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[PubMed: 33753518]
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[Full Text: https://doi.org/10.1073/pnas.2100558118]
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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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Catteruccia, M., Verrigni, D., Martinelli, D., Torraco, A., Agovino, T., Bonafe, L., D'Amico, A., Donati, M. A., Adorisio, R., Santorelli, F. M., Carrozzo, R., Bertini, E., Dionisi-Vici, C.
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<strong>Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.</strong>
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Molec. Genet. Metab. 111: 353-359, 2014.
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[PubMed: 24485043]
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[Full Text: https://doi.org/10.1016/j.ymgme.2014.01.001]
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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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Cizkova, A., Stranecky, V., Mayr, J. A., Tesarova, M., Havlickova, V., Paul, J., Ivanek, R., Kuss, A. W., Hansikova, H., Kaplanova, V., Vrbacky, M., Hartmannova, H., and 9 others.
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<strong>TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.</strong>
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Nature Genet. 40: 1288-1290, 2008.
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[PubMed: 18953340]
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[Full Text: https://doi.org/10.1038/ng.246]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Hartz, P. A.
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<strong>Personal Communication.</strong>
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Baltimore, Md. 11/18/2008.
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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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Sanchez-Caballero, L., Elurbe, D. M., Baertling, F., Guerrero-Castillo, S., van den Brand, M., van Strien, J., van Dam, T. J. P., Rodenburg, R., Brandt, U., Huynen, M. A., Nijtmans, L. G. J.
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<strong>TMEM70 functions in the assembly of complexes I and V.</strong>
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Biochim. Biophys. Acta Bioenerg. 1861: 148202, 2020.
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[PubMed: 32275929]
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[Full Text: https://doi.org/10.1016/j.bbabio.2020.148202]
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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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Spiegel, R., Khayat, M., Shalev, S. A., Horovitz, Y., Mandel, H., Hershkovitz, E., Barghuti, F., Shaag, A., Saada, A., Korman, S. H., Elpeleg, O., Yatsiv, I.
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<strong>TMEM70 mutations are a common cause of nuclear encoded ATP synthase assembly defect: further delineation of a new syndrome.</strong>
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J. Med. Genet. 48: 177-182, 2011.
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[PubMed: 21147908]
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[Full Text: https://doi.org/10.1136/jmg.2010.084608]
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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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Staretz-Chacham, O., Wormser, O., Manor, E., Birk, O. S., Ferreira, C. R.
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<strong>TMEM70 deficiency: novel mutation and hypercitrullinemia during metabolic decompensation.</strong>
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Am. J. Med. Genet. 179A: 1293-1298, 2019.
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[PubMed: 30950220]
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[Full Text: https://doi.org/10.1002/ajmg.a.61138]
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</p>
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</ol>
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Bao Lige - updated : 02/15/2024<br>Bao Lige - updated : 06/26/2023<br>Hilary J. Vernon - updated : 08/11/2020<br>Cassandra L. Kniffin - updated : 7/1/2014<br>Cassandra L. Kniffin - updated : 12/1/2011<br>Cassandra L. Kniffin - updated : 11/19/2008
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