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Entry
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- *143450 - HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, BETA SUBUNIT; HADHB
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- OMIM
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<div id="mimSearch" class="hidden-print">
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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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<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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Advanced Search
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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 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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<a href="/history"> Search History </a>
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</form>
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<div class="row">
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<p />
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<div class="row">
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*143450</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<li role="presentation">
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<a href="#title"><strong>Title</strong></a>
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<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 role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<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="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</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/143450">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=ENSG00000138029;t=ENST00000317799" 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=3032" 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=143450" 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=ENSG00000138029;t=ENST00000317799" 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_000183,NM_001281512,NM_001281513,XM_011532803" 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_000183" 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=143450" 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=00887&isoform_id=00887_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/HADHB" 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/862458,2662397,4504327,11640566,15778991,17068370,21410078,44890770,62822075,116241345,119621105,119621106,119621107,189069397,194375490,194379384,194385794,528281411,528281413,767914416,2462572350" 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/P55084" 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=3032" 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=ENSG00000138029;t=ENST00000317799" 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=HADHB" 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=HADHB" 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+3032" 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/HADHB" 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:3032" 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/3032" 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=chr2&hgg_gene=ENST00000317799.10&hgg_start=26244939&hgg_end=26290465&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:4803" 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/hadhb" 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=143450[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><a href="https://www.possumcore.com/nuxeo/nxdoc/default/e86e3558-e421-4f8d-a5c3-254b9408a8eb/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</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=143450[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/HADHB/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/ENSG00000138029" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.gwascentral.org/search?q=HADHB" 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=HADHB" 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=HADHB&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/PA29177" 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:4803" 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/FBgn0025352.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:2136381" 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/HADHB#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:2136381" 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/3032/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://omia.org/OMIA002480/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3032" 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=WBGene00015125;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-030131-8550" 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="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</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="mimCellLinesLinksFold" 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://catalog.coriell.org/Search?q=OmimNum:143450" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3032" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HADHB&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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143450
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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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HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, BETA SUBUNIT; HADHB
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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TRIFUNCTIONAL PROTEIN, BETA SUBUNIT<br />
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MITOCHONDRIAL TRIFUNCTIONAL PROTEIN, BETA SUBUNIT<br />
|
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ECHB
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HADHB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HADHB</a></em></strong>
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Cytogenetic location: <a href="/geneMap/2/104?start=-3&limit=10&highlight=104">2p23.3</a>
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Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:26244939-26290465&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'})">2:26,244,939-26,290,465</a> </span>
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<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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<span class="mim-font">
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Mitochondrial trifunctional protein deficiency 2
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<span class="mim-font">
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<a href="/entry/620300"> 620300 </a>
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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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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
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PheneGene Graphics <span class="caret"></span>
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</button>
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<ul class="dropdown-menu" style="width: 17em;">
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<li><a href="/graph/linear/143450" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/143450" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>The HADHA (<a href="/entry/600890">600890</a>) and HADHB genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in the beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase step. The beta subunit harbors the 3-ketoacyl-CoA thiolase activity (<a href="https://enzyme.expasy.org/EC/2.3.1.16" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.3.1.16</a>) (<a href="#5" class="mim-tip-reference" title="Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong> J. Clin. Invest. 93: 1740-1747, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163672</a>] [<a href="https://doi.org/10.1172/JCI117158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8163672">Kamijo et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong> J. Clin. Invest. 93: 1740-1747, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163672</a>] [<a href="https://doi.org/10.1172/JCI117158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8163672">Kamijo et al. (1994)</a> identified cDNAs for the genes encoding the alpha and beta subunits of the holoenzyme. The beta subunit cDNA encodes a 51.293-kD precursor, which ultimately becomes the 47.484-kD mature subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Orii, K. E., Orii, K. O., Souri, M., Orii, T., Kondo, N., Hashimoto, T., Aoyama, T. <strong>Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.</strong> J. Biol. Chem. 274: 8077-8084, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10075708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10075708</a>] [<a href="https://doi.org/10.1074/jbc.274.12.8077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10075708">Orii et al. (1999)</a> determined that the HADHA and HADHB genes are linked in a head-to-head arrangement on opposite strands and that they have in common a 350-bp 5-prime flanking region. This region has bidirectional promoter activity with 2 critical cis elements that are activated by transcription factor SP1 (<a href="/entry/189906">189906</a>) binding. The authors concluded that expression of trifunctional protein subunits is probably coordinately regulated by a common promoter and by SP1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10075708" 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="#12" class="mim-tip-reference" title="Uchida, Y., Izai, K., Orii, T., Hashimoto, T. <strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein.</strong> J. Biol. Chem. 267: 1034-1041, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1730633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1730633</a>]" pmid="1730633">Uchida et al. (1992)</a> and <a href="#1" class="mim-tip-reference" title="Carpenter, K., Pollitt, R. J., Middleton, B. <strong>Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.</strong> Biochem. Biophys. Res. Commun. 183: 443-448, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1550553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1550553</a>] [<a href="https://doi.org/10.1016/0006-291x(92)90501-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1550553">Carpenter et al. (1992)</a> demonstrated that long-chain 3-hydroxyacyl-CoA dehydrogenase is in fact a trifunctional protein which also has enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activity. <a href="#1" class="mim-tip-reference" title="Carpenter, K., Pollitt, R. J., Middleton, B. <strong>Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.</strong> Biochem. Biophys. Res. Commun. 183: 443-448, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1550553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1550553</a>] [<a href="https://doi.org/10.1016/0006-291x(92)90501-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1550553">Carpenter et al. (1992)</a> and <a href="#12" class="mim-tip-reference" title="Uchida, Y., Izai, K., Orii, T., Hashimoto, T. <strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein.</strong> J. Biol. Chem. 267: 1034-1041, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1730633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1730633</a>]" pmid="1730633">Uchida et al. (1992)</a> worked with human and rat liver, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1730633+1550553" 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="#5" class="mim-tip-reference" title="Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong> J. Clin. Invest. 93: 1740-1747, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163672</a>] [<a href="https://doi.org/10.1172/JCI117158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8163672">Kamijo et al. (1994)</a> examined the biosynthesis of the human trifunctional protein in cultured skin fibroblasts from 2 patients with LCHAD deficiency. The cells from 1 patient indicated a content of the protein that was less than 10% of that in control cells, due to very rapid degradation of protein newly synthesized in the mitochondria. Diminution of the protein was associated with a decrease in all 3 enzymatic activities. In cells from the second patient, the rate of degradation of newly synthesized protein was faster than in control cells, giving rise to a trifunctional protein 60% of control levels. The 3-hydroxyacyl-CoA dehydrogenase activity with medium-chain to long-chain substrates was decreased drastically, with minor changes in activities of the 2 other enzymes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163672" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#7" class="mim-tip-reference" title="Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T. <strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong> Hum. Molec. Genet. 6: 1215-1224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259266">Orii et al. (1997)</a> determined that the HADHB gene has 16 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259266" 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 somatic cell hybrid studies, <a href="#2" class="mim-tip-reference" title="Craig, I., Tolley, E., Bobrow, M. <strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong> Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976."None>Craig et al. (1976)</a> tentatively assigned the structural gene for this enzyme to chromosome 7. However, studies by fluorescence in situ hybridization reported 20 years later indicated that both the HADHB and HADHA genes are located on 2p23 (<a href="#14" class="mim-tip-reference" title="Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R. <strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong> Genomics 37: 141-143, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921383</a>] [<a href="https://doi.org/10.1006/geno.1996.0533" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921383">Yang et al., 1996</a>). By fluorescence in situ hybridization, <a href="#7" class="mim-tip-reference" title="Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T. <strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong> Hum. Molec. Genet. 6: 1215-1224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259266">Orii et al. (1997)</a> confirmed the mapping of the HADHB gene to 2p23. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9259266+8921383" 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>Studies on the defects in the mitochondrial trifunctional enzyme in patients with trifunctional protein deficiency (MTPD1, <a href="/entry/609015">609015</a>; MTPD2, <a href="/entry/620300">620300</a>) suggested to <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a> that there are 2 types of defects: patients in group 1 have normal amounts of crossreacting material by immunoblot and lack only long-chain 3-hydroxyacyl-CoA dehydrogenase activity, whereas patients in group 2 have a trace amount of crossreacting material, with all 3 activities being low. <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a> identified 3 patients in group 2 and made analyses at the cDNA level. In 1 patient, there was a heterozygous 71-bp deletion at position 110-180 in the alpha subunit. In the other 2 patients, there was an abnormal beta subunit; 1 patient was homozygous for an A-to-G transition at nucleotide 788 (<a href="#0001">143450.0001</a>), whereas the other patient was compound heterozygous for a 182G-A (<a href="#0002">143450.0002</a>) and a 740G-A (<a href="#0003">143450.0003</a>) mutation. This was the first demonstration of disease-causing mutations in the beta subunit. Using a vaccinia virus system and gel filtration analysis for cDNA expression experiments in patients' fibroblasts, <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a> found that both normal alpha and beta subunits, and possibly their association, are important for stabilizing the trifunctional protein. They commented that the 788A-G mutation on the beta subunit seemed to interfere with the association, the result being rapid decomposition of the trifunctional protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T. <strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong> Hum. Molec. Genet. 6: 1215-1224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259266">Orii et al. (1997)</a> identified 2 Japanese patients in whom the 3 enzyme activities of the trifunctional protein were undetectable in fibroblasts. One of the patients had compound heterozygous mutations in the HADHB gene, including an exonic single T insertion that created a new cryptic 5-prime splice site (<a href="#0005">143450.0005</a>) and a 1331G-A transition that resulted in an arg411-to-lys amino acid substitution (<a href="#0004">143450.0004</a>). The second patient was homozygous for the 1331G-A transition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259266" 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="#10" class="mim-tip-reference" title="Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S. <strong>Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.</strong> Molec. Genet. Metab. 98: 372-377, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19699128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19699128</a>] [<a href="https://doi.org/10.1016/j.ymgme.2009.07.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19699128">Purevsuren et al. (2009)</a> reported 5 Japanese patients, including 3 who had previously been reported, with mitochondrial trifunctional protein deficiency due to homozygous or compound heterozygous mutations in the HADHB gene (see, e.g., <a href="#0004">143450.0004</a> and <a href="#0006">143450.0006</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19699128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
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For discussion of a possible association between variation in the HADHB gene and early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, <a href="/entry/118210">118210</a>), see <a href="#0010">143450.0010</a>.</p>
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<p><a href="#11" class="mim-tip-reference" title="Spiekerkoetter, U., Sun, B., Khuchua, Z., Bennett, M. J., Strauss, A. W. <strong>Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.</strong> Hum. Mutat. 21: 598-607, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754706</a>] [<a href="https://doi.org/10.1002/humu.10211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754706">Spiekerkoetter et al. (2003)</a> characterized 15 patients from 13 families with beta-subunit mutations of the mitochondrial trifunctional protein. Three clinical phenotypes were apparent: 4 patients had a severe neonatal presentation with cardiomyopathy, Reye-like symptoms, and early death; 2 patients had a hepatic form with recurrent hypoketotic hypoglycemia; and 9 patients had a milder, later-onset neuromyopathic phenotype with episodic myoglobinuria. Maternal HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurred in 2 mothers independently of the fetal phenotype. Mutation analysis revealed 16 different mutations, 12 of which were missense mutations. Based on homology to yeast thiolase, which had been characterized structurally, <a href="#11" class="mim-tip-reference" title="Spiekerkoetter, U., Sun, B., Khuchua, Z., Bennett, M. J., Strauss, A. W. <strong>Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.</strong> Hum. Mutat. 21: 598-607, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754706</a>] [<a href="https://doi.org/10.1002/humu.10211" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12754706">Spiekerkoetter et al. (2003)</a> found that the location of the mutation within the protein correlated with the clinical phenotype. Outer loop mutations that were expected to alter protein stability were present only in milder forms. The degree of reduction in thiolase antigen also correlated with the severity of clinical presentation. Thus, although TFP deficiency is highly heterogeneous, some genotype-phenotype correlation could be established. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In vitro functional expression studies of HADHB gene mutations in 5 Japanese patients with MTPD2 by <a href="#10" class="mim-tip-reference" title="Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S. <strong>Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.</strong> Molec. Genet. Metab. 98: 372-377, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19699128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19699128</a>] [<a href="https://doi.org/10.1016/j.ymgme.2009.07.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19699128">Purevsuren et al. (2009)</a> indicated a genotype/phenotype correlation: patients whose mutations resulted in no residual protein activity had a more severe phenotype than those whose mutations had residual activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19699128" 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="Dagher, R., Massie, R., Gentil, B. J. <strong>MTP deficiency caused by HADHB mutations: pathophysiology and clinical manifestations.</strong> Molec. Genet. Metab. 133: 1-7, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33744096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33744096</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.03.010" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33744096">Dagher et al. (2021)</a> reviewed pathophysiology, clinical phenotype, and molecular findings in MTP deficiency caused by biallelic mutations in the HADHB gene. The authors noted that mutations in the HADHB gene often lead to deficiency of all 3 enzymatic functions of the mitochondrial trifunctional protein because the mutations frequently affect amino acid residues located at the interface of the dimerization domains between HADHB and HADHA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33744096" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913131 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913131;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=rs121913131" 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=rs121913131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with mitochondrial trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>), <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a> found probable homozygosity for an A-to-G transition at nucleotide 788 of the HADHB gene, predicted to cause a substitution of glycine for aspartic acid-263 (D263G). The patient was previously reported by <a href="#5" class="mim-tip-reference" title="Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong> J. Clin. Invest. 93: 1740-1747, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163672</a>] [<a href="https://doi.org/10.1172/JCI117158" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8163672">Kamijo et al. (1994)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8163672+8651282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs121913132 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913132;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/rs121913132?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=rs121913132" 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=rs121913132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a male Caucasian patient who presented with hypoglycemia, hyperammonemia, mild liver dysfunction, and 3-hydroxydicarboxylic aciduria (MTPD2; <a href="/entry/620300">620300</a>) at 4 months of age, <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a> described compound heterozygosity for an arg61-to-his (R61H) mutation and an arg247-to-his (R247H; <a href="#0003">143450.0003</a>) mutation in the HADHB gene. These were due to nucleotide substitutions 182G-A and 740G-A, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651282" 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 TRIFUNCTIONAL PROTEIN DEFICIENCY 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> rs121913133 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913133;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/rs121913133?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=rs121913133" 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=rs121913133" 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=RCV000481427 OR RCV003156216 OR RCV003460481 OR RCV004566745" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000481427, RCV003156216, RCV003460481, RCV004566745" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000481427...</a>
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<p>For discussion of the arg247-to-his (R247H) mutation in the HADHB gene that was found in compound heterozygous state in a patient with hypoglycemia, hyperammonemia, mild liver dysfunction, and 3-hydroxydicarboxylic aciduria (MTPD2; <a href="/entry/620300">620300</a>) by <a href="#13" class="mim-tip-reference" title="Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T. <strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong> Am. J. Hum. Genet. 58: 979-988, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>]" pmid="8651282">Ushikubo et al. (1996)</a>, see <a href="#0002">143450.0002</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651282" 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 TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
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HADHB, ARG411LYS
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121913134 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121913134;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=rs121913134" 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=rs121913134" 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=RCV003156217" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003156217" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003156217</a>
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<p>In a Japanese patient with mitochondrial trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>), <a href="#7" class="mim-tip-reference" title="Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T. <strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong> Hum. Molec. Genet. 6: 1215-1224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259266">Orii et al. (1997)</a> found homozygosity for a 1331G-A transition, resulting in an arg411-to-lys (R411K) amino acid substitution. The patient had onset at age 15 years of muscle pain and weakness associated with rhabdomyolysis. Development was normal. In another Japanese patient, the R411K mutation was present in compound heterozygous state with an exonic single T insertion, creating a new cryptic 5-prime splice site (<a href="#0005">143450.0005</a>). This patient had a more severe phenotype, with onset at 13 months of age of lethargy, hypotonia, and recurrent respiratory infections. He had cardiac arrest, liver dysfunction, and delayed psychomotor development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259266" 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 in vitro functional expression studies, <a href="#10" class="mim-tip-reference" title="Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S. <strong>Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.</strong> Molec. Genet. Metab. 98: 372-377, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19699128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19699128</a>] [<a href="https://doi.org/10.1016/j.ymgme.2009.07.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19699128">Purevsuren et al. (2009)</a> demonstrated that the R411K mutant had 14% residual enzyme activity at 37 degrees C and faint expression of alpha- and beta-subunit proteins. However, residual activity at 30 degrees C increased significantly to more than 50% of wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19699128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0005" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0005 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
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HADHB, 1-BP INS, 36-BP DEL
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003156218" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003156218" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003156218</a>
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<p>In a Japanese patient with mitochondrial trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>), <a href="#7" class="mim-tip-reference" title="Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T. <strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong> Hum. Molec. Genet. 6: 1215-1224, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>] [<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9259266">Orii et al. (1997)</a> found a 36-bp deletion at position 776-811 of the HADHB gene. The deletion was caused by a single T insertion at nucleotide position 777, which is 36 bp upstream from the 5-prime splice of intron 9. The insertion caused the deletion by creating a new cryptic 5-prime splice site. The patient was compound heterozygous for an R411K substitution (<a href="#0004">143450.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0006" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0006 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
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HADHB, VAL422GLY
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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> rs267606859 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs267606859;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/rs267606859?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=rs267606859" 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=rs267606859" 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=RCV000015974 OR RCV003125832 OR RCV005025060" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015974, RCV003125832, RCV005025060" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015974...</a>
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<p>In a Japanese male infant, born of consanguineous parents, with trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>), <a href="#10" class="mim-tip-reference" title="Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S. <strong>Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.</strong> Molec. Genet. Metab. 98: 372-377, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19699128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19699128</a>] [<a href="https://doi.org/10.1016/j.ymgme.2009.07.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19699128">Purevsuren et al. (2009)</a> identified a homozygous 1364T-G transversion in the HADHB gene, resulting in a val422-to-gly (V422G) substitution. He presented on the fifth day of life with dyspnea, cyanosis, lactic acidosis, hyperammonemia, and liver dysfunction. He died of cardiac arrest at age 3 months. In vitro functional expression assays showed no apparent residual enzyme activity at 37 degrees C, and Western blot showed no alpha or beta subunits. However, there was some residual enzyme activity at 30 degrees C. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19699128" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0007" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0007 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2 WITH MYOPATHY AND NEUROPATHY</strong>
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HADHB, ALA392VAL
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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> rs764623179 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs764623179;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/rs764623179?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=rs764623179" 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=rs764623179" 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=RCV000170518 OR RCV003156229" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000170518, RCV003156229" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000170518...</a>
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<p>In a pair of dizygotic Japanese twins, born of consanguineous parents, with mitochondrial trifunctional protein deficiency (see <a href="/entry/620300">620300</a>), <a href="#6" class="mim-tip-reference" title="Naiki, M., Ochi, N., Kato, Y. S., Purevsuren, J., Yamada, K., Kimura, R., Fukushi, D., Hara, S., Yamada, Y., Kumagai, T., Yamaguchi, S., Wakamatsu, N. <strong>Mutations in HADHB, which encodes the beta-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.</strong> Am. J. Med. Genet. 164A: 1180-1187, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24664533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24664533</a>] [<a href="https://doi.org/10.1002/ajmg.a.36434" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24664533">Naiki et al. (2014)</a> identified a homozygous c.1175C-T transition (c.1175C-T, NM_000183) in exon 14 of the HADHB gene, resulting in an ala392-to-val (A392V) substitution near the active site of the protein. Each unaffected parent was heterozygous for the mutation, which was not found in 200 normal alleles. Western blot analysis of patient cells showed decreased or absent levels of the alpha and beta subunits of the mitochondrial trifunctional protein. The mutant HADHB protein failed to form an active hetero-octamer with the wildtype alpha subunit (HADHA; <a href="/entry/600890">600890</a>). The patients had infantile onset of hypoparathyroidism, episodic rhabdomyolysis, and a progressive polyneuropathy, consistent with a neuromyopathic phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24664533" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0008" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0008 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 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">rs886037844 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs886037844;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=rs886037844" 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=rs886037844" 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=RCV003156238" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003156238" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003156238</a>
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<p>In a Korean infant with fatal mitochondrial trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>), <a href="#9" class="mim-tip-reference" title="Park, H.-D., Kim, S. R., Ki, C.-S., Lee, S.-Y., Chang, Y. S., Jin, D.-K., Park, W. S. <strong>Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency.</strong> Ann. Clin. Lab. Sci. 39: 399-404, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19880769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19880769</a>]" pmid="19880769">Park et al. (2009)</a> identified compound heterozygous mutations in the HADHB gene: a 1-bp duplication (c.358dupT, NM_000183.2) in exon 7, resulting in a frameshift and premature termination (Ala120CysfsTer8), and a c.1364T-G transversion in exon 15, resulting in a val455-to-gly (V455G; <a href="#0009">143450.0009</a>) substitution. Each unaffected parent was heterozygous for 1 of the mutations, which were not found in 100 Korean control alleles. Functional studies of the variants were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19880769" 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>.0009 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000015974 OR RCV003125832 OR RCV005025060" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000015974, RCV003125832, RCV005025060" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000015974...</a>
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<p>For discussion of the c.1364T-G transversion (c.1364T-G, NM_000183.2) in exon 15 of the HADHB gene, resulting in a val455-to-gly (V455G) substitution, that was found in compound heterozygous state in a Korean infant with fatal mitochondrial trifunctional protein deficiency (MTPD2; <a href="/entry/620300">620300</a>) by <a href="#9" class="mim-tip-reference" title="Park, H.-D., Kim, S. R., Ki, C.-S., Lee, S.-Y., Chang, Y. S., Jin, D.-K., Park, W. S. <strong>Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency.</strong> Ann. Clin. Lab. Sci. 39: 399-404, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19880769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19880769</a>]" pmid="19880769">Park et al. (2009)</a>, see <a href="#0008">143450.0008</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19880769" 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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HADHB, IVS4AS, G-C, -1
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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> rs200777054 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200777054;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/rs200777054?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=rs200777054" 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=rs200777054" 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=RCV000239550 OR RCV000789677" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239550, RCV000789677" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239550...</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to an early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, <a href="/entry/118210">118210</a>) has not been confirmed.</p><p>In 2 sibs, born of unrelated Korean parents, with early-onset axonal sensorimotor neuropathy, <a href="#4" class="mim-tip-reference" title="Hong, Y. B., Lee, J. H., Park, J.-M., Choi, Y.-R., Hyun, Y. S., Yoon, B. R., Yoo, J. H., Koo, H., Jung, S.-C., Chung, K. W., Choi, B.-O. <strong>A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-Tooth disease.</strong> BMC Med. Genet. 14: 125, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24314034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24314034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24314034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1471-2350-14-125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24314034">Hong et al. (2013)</a> identified compound heterozygous variants in the HADHB gene: a G-to-C transversion (c.210-1G-C, NM_000183) in intron 4, resulting in the deletion of exon 5, and a c.686G-T transversion, resulting in an arg229-to-leu (R229L; <a href="#0011">143450.0011</a>) substitution at a highly conserved residue in the thiolase N domain. The variants, which were found by whole-exome sequencing, were filtered against the dbSNP (build 135) and 1000 Genomes Project databases, and segregated with the disorder in the family. Western blot analysis of patient fibroblasts showed decreased levels of HADHB compared to controls, and expression of the mutations in HEK293 cells confirmed that the mutations resulted in unstable mutant proteins. However, additional functional studies of the variants were not performed, and enzyme activity in patient cells was not determined. The patients developed distal limb weakness resulting in gait difficulties and foot drop at about 5 years of age. The disorder was progressive, and both required a walker in their teens. In their mid-thirties, both patients had distal muscle weakness and atrophy affecting the upper and lower limbs, associated with distal sensory impairment and loss of deep tendon reflexes. Electrophysiologic studies showed slightly decreased motor nerve conduction velocities and absence of most of the sensory nerve action potentials. Sural nerve biopsy of 1 patient showed absence of large myelinated fibers, occasional regenerating axonal clusters, pseudo-onion bulb formation, regenerating clusters, axons with swelling and vacuolization of the axoplasm, and abnormal mitochondria. The findings were consistent with a length-dependent axonal neuropathy. Neither patient had additional findings of mitochondrial trifunctional protein deficiency, such as myopathy, rhabdomyolysis, cardiomyopathy, or liver dysfunction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24314034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="0011" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>.0011 VARIANT OF UNKNOWN SIGNIFICANCE</strong>
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HADHB, ARG229LEU
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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> rs375654005 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs375654005;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/rs375654005?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=rs375654005" 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=rs375654005" 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=RCV000239502" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000239502" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000239502</a>
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<p>This variant is classified as a variant of unknown significance because its contribution to an early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, <a href="/entry/118210">118210</a>) has not been confirmed.</p><p>For discussion of the c.686G-T transversion (c.686G-T, NM_000183) in the HADHB gene, resulting in an arg229-to-leu (R229L) substitution, that was found in compound heterozygous state in Korean sibs with early-onset axonal neuropathy by <a href="#4" class="mim-tip-reference" title="Hong, Y. B., Lee, J. H., Park, J.-M., Choi, Y.-R., Hyun, Y. S., Yoon, B. R., Yoo, J. H., Koo, H., Jung, S.-C., Chung, K. W., Choi, B.-O. <strong>A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-Tooth disease.</strong> BMC Med. Genet. 14: 125, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24314034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24314034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24314034[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1186/1471-2350-14-125" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24314034">Hong et al. (2013)</a>, see <a href="#0010">143450.0010</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24314034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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<a id="Carpenter1992" class="mim-anchor"></a>
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Carpenter, K., Pollitt, R. J., Middleton, B.
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<strong>Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.</strong>
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Biochem. Biophys. Res. Commun. 183: 443-448, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1550553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1550553</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1550553" 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/10.1016/0006-291x(92)90501-b" target="_blank">Full Text</a>]
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<a id="Craig1976" class="mim-anchor"></a>
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Craig, I., Tolley, E., Bobrow, M.
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<strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong>
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Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976.
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Dagher, R., Massie, R., Gentil, B. J.
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<strong>MTP deficiency caused by HADHB mutations: pathophysiology and clinical manifestations.</strong>
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Molec. Genet. Metab. 133: 1-7, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33744096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33744096</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33744096" 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.2021.03.010" target="_blank">Full Text</a>]
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<a id="Hong2013" class="mim-anchor"></a>
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Hong, Y. B., Lee, J. H., Park, J.-M., Choi, Y.-R., Hyun, Y. S., Yoon, B. R., Yoo, J. H., Koo, H., Jung, S.-C., Chung, K. W., Choi, B.-O.
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<strong>A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-Tooth disease.</strong>
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BMC Med. Genet. 14: 125, 2013. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24314034/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24314034</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24314034[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=24314034" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1186/1471-2350-14-125" target="_blank">Full Text</a>]
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<div class="">
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<p class="mim-text-font">
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Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T.
|
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<strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong>
|
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J. Clin. Invest. 93: 1740-1747, 1994.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8163672/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8163672</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8163672" 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/10.1172/JCI117158" target="_blank">Full Text</a>]
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<a id="6" class="mim-anchor"></a>
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<a id="Naiki2014" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Naiki, M., Ochi, N., Kato, Y. S., Purevsuren, J., Yamada, K., Kimura, R., Fukushi, D., Hara, S., Yamada, Y., Kumagai, T., Yamaguchi, S., Wakamatsu, N.
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|
<strong>Mutations in HADHB, which encodes the beta-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.</strong>
|
|
Am. J. Med. Genet. 164A: 1180-1187, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24664533/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24664533</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24664533" 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.36434" target="_blank">Full Text</a>]
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</p>
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<a id="7" class="mim-anchor"></a>
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<a id="Orii1997" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T.
|
|
<strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong>
|
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Hum. Molec. Genet. 6: 1215-1224, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259266</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.8.1215" target="_blank">Full Text</a>]
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<li>
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<a id="8" class="mim-anchor"></a>
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<a id="Orii1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Orii, K. E., Orii, K. O., Souri, M., Orii, T., Kondo, N., Hashimoto, T., Aoyama, T.
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<strong>Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.</strong>
|
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J. Biol. Chem. 274: 8077-8084, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10075708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10075708</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10075708" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1074/jbc.274.12.8077" target="_blank">Full Text</a>]
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<a id="9" class="mim-anchor"></a>
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<a id="Park2009" class="mim-anchor"></a>
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<p class="mim-text-font">
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Park, H.-D., Kim, S. R., Ki, C.-S., Lee, S.-Y., Chang, Y. S., Jin, D.-K., Park, W. S.
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<strong>Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency.</strong>
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Ann. Clin. Lab. Sci. 39: 399-404, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19880769/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19880769</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19880769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="10" class="mim-anchor"></a>
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<a id="Purevsuren2009" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S.
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<strong>Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.</strong>
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Molec. Genet. Metab. 98: 372-377, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19699128/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19699128</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19699128" 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.2009.07.011" target="_blank">Full Text</a>]
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<a id="11" class="mim-anchor"></a>
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<a id="Spiekerkoetter2003" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Spiekerkoetter, U., Sun, B., Khuchua, Z., Bennett, M. J., Strauss, A. W.
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<strong>Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.</strong>
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Hum. Mutat. 21: 598-607, 2003.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12754706/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12754706</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12754706" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.10211" target="_blank">Full Text</a>]
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<li>
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<a id="12" class="mim-anchor"></a>
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<a id="Uchida1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Uchida, Y., Izai, K., Orii, T., Hashimoto, T.
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<strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein.</strong>
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J. Biol. Chem. 267: 1034-1041, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1730633/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1730633</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1730633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<li>
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<a id="13" class="mim-anchor"></a>
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<a id="Ushikubo1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T.
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<strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong>
|
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Am. J. Hum. Genet. 58: 979-988, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651282/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651282</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651282" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Yang1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R.
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<strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong>
|
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Genomics 37: 141-143, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8921383" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1006/geno.1996.0533" target="_blank">Full Text</a>]
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</p>
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</ol>
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<div>
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<br />
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</div>
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<a id="contributors" class="mim-anchor"></a>
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<span class="mim-text-font">
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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</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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Hilary J. Vernon - updated : 05/13/2021
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</span>
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/15/2016<br>Cassandra L. Kniffin - updated : 5/13/2015<br>Cassandra L. Kniffin - updated : 7/20/2010<br>Ada Hamosh - reorganized : 11/10/2004<br>Victor A. McKusick - updated : 7/11/2003<br>Patricia A. Hartz - updated : 11/4/2002<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 8/22/1997
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</span>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 03/27/2023
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</span>
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 02/13/2023<br>carol : 05/13/2021<br>carol : 08/16/2016<br>ckniffin : 08/15/2016<br>alopez : 05/18/2015<br>mcolton : 5/13/2015<br>ckniffin : 5/13/2015<br>wwang : 11/10/2010<br>wwang : 7/27/2010<br>ckniffin : 7/20/2010<br>carol : 12/14/2007<br>carol : 7/17/2006<br>carol : 7/17/2006<br>carol : 7/14/2005<br>carol : 11/16/2004<br>carol : 11/12/2004<br>carol : 11/10/2004<br>carol : 11/10/2004<br>cwells : 7/16/2003<br>terry : 7/11/2003<br>carol : 5/23/2003<br>mgross : 11/4/2002<br>mgross : 11/4/2002<br>ckniffin : 6/13/2002<br>carol : 4/30/2002<br>carol : 11/23/1998<br>terry : 10/6/1998<br>terry : 8/25/1997<br>terry : 8/22/1997<br>alopez : 6/4/1997<br>mark : 10/17/1996<br>terry : 10/10/1996<br>terry : 5/3/1996<br>terry : 4/29/1996<br>mark : 10/25/1995<br>carol : 2/15/1995<br>mimadm : 9/24/1994<br>carol : 1/6/1993<br>supermim : 3/16/1992<br>carol : 5/24/1991
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</span>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 143450
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, BETA SUBUNIT; HADHB
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</span>
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</h3>
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</div>
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<div>
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<br />
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<div>
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<div >
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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TRIFUNCTIONAL PROTEIN, BETA SUBUNIT<br />
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MITOCHONDRIAL TRIFUNCTIONAL PROTEIN, BETA SUBUNIT<br />
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ECHB
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HADHB</em></strong>
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</span>
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</p>
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</div>
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<p>
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<span class="mim-text-font">
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<strong>
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<em>
|
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Cytogenetic location: 2p23.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:26,244,939-26,290,465 </span>
|
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</em>
|
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</strong>
|
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Gene-Phenotype Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
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</th>
|
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</tr>
|
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</thead>
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<tbody>
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<tr>
|
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<td rowspan="1">
|
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<span class="mim-font">
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2p23.3
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</span>
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</td>
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<td>
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<span class="mim-font">
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|
Mitochondrial trifunctional protein deficiency 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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|
620300
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
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">
|
|
3
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>TEXT</strong>
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</span>
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</h4>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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|
<p>The HADHA (600890) and HADHB genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in the beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase step. The beta subunit harbors the 3-ketoacyl-CoA thiolase activity (EC 2.3.1.16) (Kamijo et al., 1994). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>Cloning and Expression</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kamijo et al. (1994) identified cDNAs for the genes encoding the alpha and beta subunits of the holoenzyme. The beta subunit cDNA encodes a 51.293-kD precursor, which ultimately becomes the 47.484-kD mature subunit. </p><p>Orii et al. (1999) determined that the HADHA and HADHB genes are linked in a head-to-head arrangement on opposite strands and that they have in common a 350-bp 5-prime flanking region. This region has bidirectional promoter activity with 2 critical cis elements that are activated by transcription factor SP1 (189906) binding. The authors concluded that expression of trifunctional protein subunits is probably coordinately regulated by a common promoter and by SP1. </p><p>Uchida et al. (1992) and Carpenter et al. (1992) demonstrated that long-chain 3-hydroxyacyl-CoA dehydrogenase is in fact a trifunctional protein which also has enoyl-CoA hydratase and 3-ketoacyl-CoA thiolase activity. Carpenter et al. (1992) and Uchida et al. (1992) worked with human and rat liver, respectively. </p><p>Kamijo et al. (1994) examined the biosynthesis of the human trifunctional protein in cultured skin fibroblasts from 2 patients with LCHAD deficiency. The cells from 1 patient indicated a content of the protein that was less than 10% of that in control cells, due to very rapid degradation of protein newly synthesized in the mitochondria. Diminution of the protein was associated with a decrease in all 3 enzymatic activities. In cells from the second patient, the rate of degradation of newly synthesized protein was faster than in control cells, giving rise to a trifunctional protein 60% of control levels. The 3-hydroxyacyl-CoA dehydrogenase activity with medium-chain to long-chain substrates was decreased drastically, with minor changes in activities of the 2 other enzymes. </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>
|
|
<span class="mim-font">
|
|
<strong>Gene Structure</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Orii et al. (1997) determined that the HADHB gene has 16 exons. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<p>By somatic cell hybrid studies, Craig et al. (1976) tentatively assigned the structural gene for this enzyme to chromosome 7. However, studies by fluorescence in situ hybridization reported 20 years later indicated that both the HADHB and HADHA genes are located on 2p23 (Yang et al., 1996). By fluorescence in situ hybridization, Orii et al. (1997) confirmed the mapping of the HADHB gene to 2p23. </p>
|
|
</span>
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<div>
|
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<br />
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</div>
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<div>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
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</span>
|
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</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Studies on the defects in the mitochondrial trifunctional enzyme in patients with trifunctional protein deficiency (MTPD1, 609015; MTPD2, 620300) suggested to Ushikubo et al. (1996) that there are 2 types of defects: patients in group 1 have normal amounts of crossreacting material by immunoblot and lack only long-chain 3-hydroxyacyl-CoA dehydrogenase activity, whereas patients in group 2 have a trace amount of crossreacting material, with all 3 activities being low. Ushikubo et al. (1996) identified 3 patients in group 2 and made analyses at the cDNA level. In 1 patient, there was a heterozygous 71-bp deletion at position 110-180 in the alpha subunit. In the other 2 patients, there was an abnormal beta subunit; 1 patient was homozygous for an A-to-G transition at nucleotide 788 (143450.0001), whereas the other patient was compound heterozygous for a 182G-A (143450.0002) and a 740G-A (143450.0003) mutation. This was the first demonstration of disease-causing mutations in the beta subunit. Using a vaccinia virus system and gel filtration analysis for cDNA expression experiments in patients' fibroblasts, Ushikubo et al. (1996) found that both normal alpha and beta subunits, and possibly their association, are important for stabilizing the trifunctional protein. They commented that the 788A-G mutation on the beta subunit seemed to interfere with the association, the result being rapid decomposition of the trifunctional protein. </p><p>Orii et al. (1997) identified 2 Japanese patients in whom the 3 enzyme activities of the trifunctional protein were undetectable in fibroblasts. One of the patients had compound heterozygous mutations in the HADHB gene, including an exonic single T insertion that created a new cryptic 5-prime splice site (143450.0005) and a 1331G-A transition that resulted in an arg411-to-lys amino acid substitution (143450.0004). The second patient was homozygous for the 1331G-A transition. </p><p>Purevsuren et al. (2009) reported 5 Japanese patients, including 3 who had previously been reported, with mitochondrial trifunctional protein deficiency due to homozygous or compound heterozygous mutations in the HADHB gene (see, e.g., 143450.0004 and 143450.0006). </p><p><strong><em>Associations Pending Confirmation</em></strong></p><p>
|
|
For discussion of a possible association between variation in the HADHB gene and early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, 118210), see 143450.0010.</p>
|
|
</span>
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<div>
|
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<br />
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</div>
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Genotype/Phenotype Correlations</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Spiekerkoetter et al. (2003) characterized 15 patients from 13 families with beta-subunit mutations of the mitochondrial trifunctional protein. Three clinical phenotypes were apparent: 4 patients had a severe neonatal presentation with cardiomyopathy, Reye-like symptoms, and early death; 2 patients had a hepatic form with recurrent hypoketotic hypoglycemia; and 9 patients had a milder, later-onset neuromyopathic phenotype with episodic myoglobinuria. Maternal HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurred in 2 mothers independently of the fetal phenotype. Mutation analysis revealed 16 different mutations, 12 of which were missense mutations. Based on homology to yeast thiolase, which had been characterized structurally, Spiekerkoetter et al. (2003) found that the location of the mutation within the protein correlated with the clinical phenotype. Outer loop mutations that were expected to alter protein stability were present only in milder forms. The degree of reduction in thiolase antigen also correlated with the severity of clinical presentation. Thus, although TFP deficiency is highly heterogeneous, some genotype-phenotype correlation could be established. </p><p>In vitro functional expression studies of HADHB gene mutations in 5 Japanese patients with MTPD2 by Purevsuren et al. (2009) indicated a genotype/phenotype correlation: patients whose mutations resulted in no residual protein activity had a more severe phenotype than those whose mutations had residual activity. </p><p>Dagher et al. (2021) reviewed pathophysiology, clinical phenotype, and molecular findings in MTP deficiency caused by biallelic mutations in the HADHB gene. The authors noted that mutations in the HADHB gene often lead to deficiency of all 3 enzymatic functions of the mitochondrial trifunctional protein because the mutations frequently affect amino acid residues located at the interface of the dimerization domains between HADHB and HADHA. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
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</div>
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>ALLELIC VARIANTS</strong>
|
|
</span>
|
|
<strong>11 Selected Examples):</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0001 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, ASP263GLY
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|
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|
|
|
<br />
|
|
|
|
SNP: rs121913131,
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|
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|
|
|
|
|
ClinVar: RCV003156214
|
|
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|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a patient with mitochondrial trifunctional protein deficiency (MTPD2; 620300), Ushikubo et al. (1996) found probable homozygosity for an A-to-G transition at nucleotide 788 of the HADHB gene, predicted to cause a substitution of glycine for aspartic acid-263 (D263G). The patient was previously reported by Kamijo et al. (1994). </p>
|
|
</span>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
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|
|
</div>
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|
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0002 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, ARG61HIS
|
|
|
|
|
|
<br />
|
|
|
|
SNP: rs121913132,
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|
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|
|
|
gnomAD: rs121913132,
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|
|
|
|
|
ClinVar: RCV000015970, RCV000520375, RCV003156215, RCV004566744
|
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|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a male Caucasian patient who presented with hypoglycemia, hyperammonemia, mild liver dysfunction, and 3-hydroxydicarboxylic aciduria (MTPD2; 620300) at 4 months of age, Ushikubo et al. (1996) described compound heterozygosity for an arg61-to-his (R61H) mutation and an arg247-to-his (R247H; 143450.0003) mutation in the HADHB gene. These were due to nucleotide substitutions 182G-A and 740G-A, respectively. </p>
|
|
</span>
|
|
</div>
|
|
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|
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<div>
|
|
<br />
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|
</div>
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</div>
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|
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0003 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, ARG247HIS
|
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|
<br />
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|
|
SNP: rs121913133,
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|
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gnomAD: rs121913133,
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|
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|
|
|
ClinVar: RCV000481427, RCV003156216, RCV003460481, RCV004566745
|
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|
|
|
|
</span>
|
|
</div>
|
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|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>For discussion of the arg247-to-his (R247H) mutation in the HADHB gene that was found in compound heterozygous state in a patient with hypoglycemia, hyperammonemia, mild liver dysfunction, and 3-hydroxydicarboxylic aciduria (MTPD2; 620300) by Ushikubo et al. (1996), see 143450.0002. </p>
|
|
</span>
|
|
</div>
|
|
|
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|
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<div>
|
|
<br />
|
|
</div>
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</div>
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|
|
<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0004 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, ARG411LYS
|
|
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|
|
|
<br />
|
|
|
|
SNP: rs121913134,
|
|
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|
|
|
|
|
ClinVar: RCV003156217
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with mitochondrial trifunctional protein deficiency (MTPD2; 620300), Orii et al. (1997) found homozygosity for a 1331G-A transition, resulting in an arg411-to-lys (R411K) amino acid substitution. The patient had onset at age 15 years of muscle pain and weakness associated with rhabdomyolysis. Development was normal. In another Japanese patient, the R411K mutation was present in compound heterozygous state with an exonic single T insertion, creating a new cryptic 5-prime splice site (143450.0005). This patient had a more severe phenotype, with onset at 13 months of age of lethargy, hypotonia, and recurrent respiratory infections. He had cardiac arrest, liver dysfunction, and delayed psychomotor development. </p><p>By in vitro functional expression studies, Purevsuren et al. (2009) demonstrated that the R411K mutant had 14% residual enzyme activity at 37 degrees C and faint expression of alpha- and beta-subunit proteins. However, residual activity at 30 degrees C increased significantly to more than 50% of wildtype. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
|
<br />
|
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</div>
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</div>
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|
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<div>
|
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|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0005 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, 1-BP INS, 36-BP DEL
|
|
|
|
|
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<br />
|
|
|
|
|
|
|
|
ClinVar: RCV003156218
|
|
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese patient with mitochondrial trifunctional protein deficiency (MTPD2; 620300), Orii et al. (1997) found a 36-bp deletion at position 776-811 of the HADHB gene. The deletion was caused by a single T insertion at nucleotide position 777, which is 36 bp upstream from the 5-prime splice of intron 9. The insertion caused the deletion by creating a new cryptic 5-prime splice site. The patient was compound heterozygous for an R411K substitution (143450.0004). </p>
|
|
</span>
|
|
</div>
|
|
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|
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|
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<div>
|
|
<br />
|
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</div>
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</div>
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|
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|
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<div>
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0006 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
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|
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, VAL422GLY
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|
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|
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<br />
|
|
|
|
SNP: rs267606859,
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|
|
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gnomAD: rs267606859,
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|
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ClinVar: RCV000015974, RCV003125832, RCV005025060
|
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|
|
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</span>
|
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</div>
|
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|
|
|
|
<div>
|
|
<span class="mim-text-font">
|
|
<p>In a Japanese male infant, born of consanguineous parents, with trifunctional protein deficiency (MTPD2; 620300), Purevsuren et al. (2009) identified a homozygous 1364T-G transversion in the HADHB gene, resulting in a val422-to-gly (V422G) substitution. He presented on the fifth day of life with dyspnea, cyanosis, lactic acidosis, hyperammonemia, and liver dysfunction. He died of cardiac arrest at age 3 months. In vitro functional expression assays showed no apparent residual enzyme activity at 37 degrees C, and Western blot showed no alpha or beta subunits. However, there was some residual enzyme activity at 30 degrees C. </p>
|
|
</span>
|
|
</div>
|
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0007 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2 WITH MYOPATHY AND NEUROPATHY</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<div>
|
|
<span class="mim-text-font">
|
|
|
|
HADHB, ALA392VAL
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<br />
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|
|
SNP: rs764623179,
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|
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gnomAD: rs764623179,
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|
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ClinVar: RCV000170518, RCV003156229
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|
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</span>
|
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</div>
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<div>
|
|
<span class="mim-text-font">
|
|
<p>In a pair of dizygotic Japanese twins, born of consanguineous parents, with mitochondrial trifunctional protein deficiency (see 620300), Naiki et al. (2014) identified a homozygous c.1175C-T transition (c.1175C-T, NM_000183) in exon 14 of the HADHB gene, resulting in an ala392-to-val (A392V) substitution near the active site of the protein. Each unaffected parent was heterozygous for the mutation, which was not found in 200 normal alleles. Western blot analysis of patient cells showed decreased or absent levels of the alpha and beta subunits of the mitochondrial trifunctional protein. The mutant HADHB protein failed to form an active hetero-octamer with the wildtype alpha subunit (HADHA; 600890). The patients had infantile onset of hypoparathyroidism, episodic rhabdomyolysis, and a progressive polyneuropathy, consistent with a neuromyopathic phenotype. </p>
|
|
</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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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>.0008 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 2</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
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<div>
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<span class="mim-text-font">
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HADHB, 1-BP DUP, 358T
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<br />
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SNP: rs886037844,
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ClinVar: RCV003156238
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a Korean infant with fatal mitochondrial trifunctional protein deficiency (MTPD2; 620300), Park et al. (2009) identified compound heterozygous mutations in the HADHB gene: a 1-bp duplication (c.358dupT, NM_000183.2) in exon 7, resulting in a frameshift and premature termination (Ala120CysfsTer8), and a c.1364T-G transversion in exon 15, resulting in a val455-to-gly (V455G; 143450.0009) substitution. Each unaffected parent was heterozygous for 1 of the mutations, which were not found in 100 Korean control alleles. Functional studies of the variants were not performed. </p>
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</span>
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<div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0009 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 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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HADHB, VAL455GLY
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<br />
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ClinVar: RCV000015974, RCV003125832, RCV005025060
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</span>
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<span class="mim-text-font">
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<p>For discussion of the c.1364T-G transversion (c.1364T-G, NM_000183.2) in exon 15 of the HADHB gene, resulting in a val455-to-gly (V455G) substitution, that was found in compound heterozygous state in a Korean infant with fatal mitochondrial trifunctional protein deficiency (MTPD2; 620300) by Park et al. (2009), see 143450.0008. </p>
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</span>
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</div>
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 VARIANT OF UNKNOWN SIGNIFICANCE</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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HADHB, IVS4AS, G-C, -1
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<br />
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SNP: rs200777054,
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gnomAD: rs200777054,
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ClinVar: RCV000239550, RCV000789677
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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>This variant is classified as a variant of unknown significance because its contribution to an early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, 118210) has not been confirmed.</p><p>In 2 sibs, born of unrelated Korean parents, with early-onset axonal sensorimotor neuropathy, Hong et al. (2013) identified compound heterozygous variants in the HADHB gene: a G-to-C transversion (c.210-1G-C, NM_000183) in intron 4, resulting in the deletion of exon 5, and a c.686G-T transversion, resulting in an arg229-to-leu (R229L; 143450.0011) substitution at a highly conserved residue in the thiolase N domain. The variants, which were found by whole-exome sequencing, were filtered against the dbSNP (build 135) and 1000 Genomes Project databases, and segregated with the disorder in the family. Western blot analysis of patient fibroblasts showed decreased levels of HADHB compared to controls, and expression of the mutations in HEK293 cells confirmed that the mutations resulted in unstable mutant proteins. However, additional functional studies of the variants were not performed, and enzyme activity in patient cells was not determined. The patients developed distal limb weakness resulting in gait difficulties and foot drop at about 5 years of age. The disorder was progressive, and both required a walker in their teens. In their mid-thirties, both patients had distal muscle weakness and atrophy affecting the upper and lower limbs, associated with distal sensory impairment and loss of deep tendon reflexes. Electrophysiologic studies showed slightly decreased motor nerve conduction velocities and absence of most of the sensory nerve action potentials. Sural nerve biopsy of 1 patient showed absence of large myelinated fibers, occasional regenerating axonal clusters, pseudo-onion bulb formation, regenerating clusters, axons with swelling and vacuolization of the axoplasm, and abnormal mitochondria. The findings were consistent with a length-dependent axonal neuropathy. Neither patient had additional findings of mitochondrial trifunctional protein deficiency, such as myopathy, rhabdomyolysis, cardiomyopathy, or liver dysfunction. </p>
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</span>
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</div>
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<div>
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</div>
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</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>.0011 VARIANT OF UNKNOWN SIGNIFICANCE</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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HADHB, ARG229LEU
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<br />
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SNP: rs375654005,
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gnomAD: rs375654005,
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ClinVar: RCV000239502
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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>This variant is classified as a variant of unknown significance because its contribution to an early-onset peripheral neuropathy resembling axonal Charcot-Marie-Tooth disease (see, e.g., CMT2A1, 118210) has not been confirmed.</p><p>For discussion of the c.686G-T transversion (c.686G-T, NM_000183) in the HADHB gene, resulting in an arg229-to-leu (R229L) substitution, that was found in compound heterozygous state in Korean sibs with early-onset axonal neuropathy by Hong et al. (2013), see 143450.0010. </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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<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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Carpenter, K., Pollitt, R. J., Middleton, B.
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<strong>Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria.</strong>
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Biochem. Biophys. Res. Commun. 183: 443-448, 1992.
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Craig, I., Tolley, E., Bobrow, M.
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<strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong>
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Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976.
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<p class="mim-text-font">
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Dagher, R., Massie, R., Gentil, B. J.
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<strong>MTP deficiency caused by HADHB mutations: pathophysiology and clinical manifestations.</strong>
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Molec. Genet. Metab. 133: 1-7, 2021.
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[PubMed: 33744096]
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[Full Text: https://doi.org/10.1016/j.ymgme.2021.03.010]
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Hong, Y. B., Lee, J. H., Park, J.-M., Choi, Y.-R., Hyun, Y. S., Yoon, B. R., Yoo, J. H., Koo, H., Jung, S.-C., Chung, K. W., Choi, B.-O.
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<strong>A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-Tooth disease.</strong>
|
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BMC Med. Genet. 14: 125, 2013. Note: Electronic Article.
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<p class="mim-text-font">
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Kamijo, T., Wanders, R. J. A., Saudubray, J.-M., Aoyama, T., Komiyama, A., Hashimoto, T.
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<strong>Mitochondrial trifunctional protein deficiency: catalytic heterogeneity of the mutant enzyme in two patients.</strong>
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[PubMed: 8163672]
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Naiki, M., Ochi, N., Kato, Y. S., Purevsuren, J., Yamada, K., Kimura, R., Fukushi, D., Hara, S., Yamada, Y., Kumagai, T., Yamaguchi, S., Wakamatsu, N.
|
|
<strong>Mutations in HADHB, which encodes the beta-subunit of mitochondrial trifunctional protein, cause infantile onset hypoparathyroidism and peripheral polyneuropathy.</strong>
|
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Am. J. Med. Genet. 164A: 1180-1187, 2014.
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[PubMed: 24664533]
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[Full Text: https://doi.org/10.1002/ajmg.a.36434]
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<li>
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<p class="mim-text-font">
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Orii, K. E., Aoyama, T., Wakui, K., Fukushima, Y., Miyajima, H., Yamaguchi, S., Orii, T., Kondo, N., Hashimoto, T.
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<strong>Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.</strong>
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Hum. Molec. Genet. 6: 1215-1224, 1997.
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[PubMed: 9259266]
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[Full Text: https://doi.org/10.1093/hmg/6.8.1215]
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<li>
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<p class="mim-text-font">
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Orii, K. E., Orii, K. O., Souri, M., Orii, T., Kondo, N., Hashimoto, T., Aoyama, T.
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<strong>Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.</strong>
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J. Biol. Chem. 274: 8077-8084, 1999.
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[PubMed: 10075708]
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[Full Text: https://doi.org/10.1074/jbc.274.12.8077]
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<li>
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<p class="mim-text-font">
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Park, H.-D., Kim, S. R., Ki, C.-S., Lee, S.-Y., Chang, Y. S., Jin, D.-K., Park, W. S.
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<strong>Two novel HADHB gene mutations in a Korean patient with mitochondrial trifunctional protein deficiency.</strong>
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Ann. Clin. Lab. Sci. 39: 399-404, 2009.
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[PubMed: 19880769]
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<p class="mim-text-font">
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Purevsuren, J., Fukao, T., Hasegawa, Y., Kobayashi, H., Li, H., Mushimoto, Y., Fukuda, S., Yamaguchi, S.
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Spiekerkoetter, U., Sun, B., Khuchua, Z., Bennett, M. J., Strauss, A. W.
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<strong>Molecular and phenotypic heterogeneity in mitochondrial trifunctional protein deficiency due to beta-subunit mutations.</strong>
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Uchida, Y., Izai, K., Orii, T., Hashimoto, T.
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<strong>Novel fatty acid beta-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein.</strong>
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[PubMed: 1730633]
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<p class="mim-text-font">
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Ushikubo, S., Aoyama, T., Kamijo, T., Wanders, R. J. A., Rinaldo, P., Vockley, J., Hashimoto, T.
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<strong>Molecular characterization of mitochondrial trifunctional protein deficiency: formation of the enzyme complex is important for stabilization of both alpha- and beta-subunits.</strong>
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Am. J. Hum. Genet. 58: 979-988, 1996.
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[PubMed: 8651282]
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<p class="mim-text-font">
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Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R.
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<strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong>
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Genomics 37: 141-143, 1996.
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[PubMed: 8921383]
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[Full Text: https://doi.org/10.1006/geno.1996.0533]
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<span class="text-nowrap mim-text-font">
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 05/13/2021<br>Cassandra L. Kniffin - updated : 08/15/2016<br>Cassandra L. Kniffin - updated : 5/13/2015<br>Cassandra L. Kniffin - updated : 7/20/2010<br>Ada Hamosh - reorganized : 11/10/2004<br>Victor A. McKusick - updated : 7/11/2003<br>Patricia A. Hartz - updated : 11/4/2002<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 8/22/1997
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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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Victor A. McKusick : 6/4/1986
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carol : 03/27/2023<br>carol : 02/13/2023<br>carol : 05/13/2021<br>carol : 08/16/2016<br>ckniffin : 08/15/2016<br>alopez : 05/18/2015<br>mcolton : 5/13/2015<br>ckniffin : 5/13/2015<br>wwang : 11/10/2010<br>wwang : 7/27/2010<br>ckniffin : 7/20/2010<br>carol : 12/14/2007<br>carol : 7/17/2006<br>carol : 7/17/2006<br>carol : 7/14/2005<br>carol : 11/16/2004<br>carol : 11/12/2004<br>carol : 11/10/2004<br>carol : 11/10/2004<br>cwells : 7/16/2003<br>terry : 7/11/2003<br>carol : 5/23/2003<br>mgross : 11/4/2002<br>mgross : 11/4/2002<br>ckniffin : 6/13/2002<br>carol : 4/30/2002<br>carol : 11/23/1998<br>terry : 10/6/1998<br>terry : 8/25/1997<br>terry : 8/22/1997<br>alopez : 6/4/1997<br>mark : 10/17/1996<br>terry : 10/10/1996<br>terry : 5/3/1996<br>terry : 4/29/1996<br>mark : 10/25/1995<br>carol : 2/15/1995<br>mimadm : 9/24/1994<br>carol : 1/6/1993<br>supermim : 3/16/1992<br>carol : 5/24/1991
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