nih-gov/www.ncbi.nlm.nih.gov/omim/248611

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<title>
Entry
- *248611 - BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, BETA POLYPEPTIDE; BCKDHB
- OMIM
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<span class="h4">*248611</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#description">Description</a>
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<a href="#cloning">Cloning and Expression</a>
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<a href="#geneStructure">Gene Structure</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_183050" 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>
<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=248611" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimProtein">
<span class="panel-title">
<span class="small">
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9658;</span> Protein
</a>
</span>
</span>
</div>
<div id="mimProteinLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://hprd.org/summary?hprd_id=02011&isoform_id=02011_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>
<div><a href="https://www.proteinatlas.org/search/BCKDHB" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/protein/129034,179362,219493,747713,1256395,1256397,1480477,4557353,25304054,34101272,54696988,71297038,119569081,119569082,119569083,158260977,194385640,221040270,332368119,530383218,922312244,974987472,2037090365,2037090367,2037090369,2037090371,2037090373,2037090375,2037090377,2217362620,2217362628,2217362631,2217362633,2217362635,2217362638,2462609933,2462609940,2462609948,2462609952,2571858808,2571858816,2571858821,2571858834,2571858838,2571858840,2571858851,2571858858,2571858882,2571858895,2571858915" 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>
<div><a href="https://www.uniprot.org/uniprotkb/P21953" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimGeneInfo">
<span class="panel-title">
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<div id="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Gene Info</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimGeneInfoLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="http://biogps.org/#goto=genereport&id=594" 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>
<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000083123;t=ENST00000320393" 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>
<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=BCKDHB" 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>
<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=BCKDHB" 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>
<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+594" 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>
<dd><a href="http://v1.marrvel.org/search/gene/BCKDHB" 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>
<dd><a href="https://monarchinitiative.org/NCBIGene:594" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
<div><a href="https://www.ncbi.nlm.nih.gov/gene/594" 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>
<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr6&hgg_gene=ENST00000656173.1&hgg_start=80106610&hgg_end=80466676&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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
<span class="panel-title">
<span class="small">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Clinical Resources</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
<div class="panel-body small mim-panel-body">
<div><a href="https://search.clinicalgenome.org/kb/gene-dosage/HGNC:987" class="mim-tip-hint" title="A ClinGen curated resource of genes and regions of the genome that are dosage sensitive and should be targeted on a cytogenomic array." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Dosage', 'domain': 'dosage.clinicalgenome.org'})">ClinGen Dosage</a></div>
<div><a href="https://search.clinicalgenome.org/kb/genes/HGNC:987" 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>
<div><a href="https://medlineplus.gov/genetics/gene/bckdhb" 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>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=248611[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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
<span class="panel-title">
<span class="small">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">&#9660;</span> Variation
</a>
</span>
</span>
</div>
<div id="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=248611[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>
<div><a href="https://www.deciphergenomics.org/gene/BCKDHB/overview/clinical-info" class="mim-tip-hint" title="DECIPHER" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'DECIPHER', 'domain': 'DECIPHER'})">DECIPHER</a></div>
<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000083123" 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>
<div><a href="https://www.ebi.ac.uk/gwas/search?query=BCKDHB" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog&nbsp;</a></div>
<div><a href="https://www.gwascentral.org/search?q=BCKDHB" 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&nbsp;</a></div>
<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=BCKDHB" 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>
<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=BCKDHB&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>
<div><a href="https://www.pharmgkb.org/gene/PA25298" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/gene/HGNC:987" 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>
<div><a href="https://flybase.org/reports/FBgn0039993.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>
<div><a href="https://www.mousephenotype.org/data/genes/MGI:88137" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
<div><a href="http://v1.marrvel.org/search/gene/BCKDHB#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>
<div><a href="http://www.informatics.jax.org/marker/MGI:88137" 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>
<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>
<div><a href="https://www.ncbi.nlm.nih.gov/gene/594/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>
<div><a href="https://www.orthodb.org/?ncbi=594" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
<div><a href="https://wormbase.org/db/gene/gene?name=WBGene00006518;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>
<div><a href="https://zfin.org/ZDB-GENE-030124-2" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:248611" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellularPathways">
<span class="panel-title">
<span class="small">
<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cellular Pathways</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellularPathwaysLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:594" 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>
<div><a href="https://reactome.org/content/query?q=BCKDHB&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>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<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.">
&nbsp;
</span>
</span>
</div>
<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">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
&nbsp;
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Gene description">
<span class="text-danger"><strong>*</strong></span>
248611
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, BETA POLYPEPTIDE; BCKDHB
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
E1B
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="approvedGeneSymbols" class="mim-anchor"></a>
<p>
<span class="mim-text-font">
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=BCKDHB" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">BCKDHB</a></em></strong>
</span>
</p>
</div>
<div>
<a id="cytogeneticLocation" class="mim-anchor"></a>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: <a href="/geneMap/6/669?start=-3&limit=10&highlight=669">6q14.1</a>
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr6:80106610-80466676&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'})">6:80,106,610-80,466,676</a> </span>
</em>
</strong>
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<a id="geneMap" class="mim-anchor"></a>
<div style="margin-bottom: 10px;">
<span class="h4 mim-font">
<strong>Gene-Phenotype Relationships</strong>
</span>
</div>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="1">
<span class="mim-font">
<a href="/geneMap/6/669?start=-3&limit=10&highlight=669">
6q14.1
</a>
</span>
</td>
<td>
<span class="mim-font">
Maple syrup urine disease, type Ib
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620698"> 620698 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known">3</abbr>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
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<li><a href="/graph/linear/248611" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </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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<strong>TEXT</strong>
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>The second major step in the catabolism of the branched-chain amino acids, isoleucine, leucine, and valine, is catalyzed by the branched-chain alpha-keto acid dehydrogenase complex (BCKD; <a href="https://enzyme.expasy.org/EC/1.2.4.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.2.4.4</a>), an inner-mitochondrial enzyme complex that consists of 3 catalytic components: a heterotetrameric (alpha2, beta2) branched-chain alpha-keto acid decarboxylase (E1), a homo-24-meric dihydrolipoyl transacylase (E2; <a href="/entry/248610">248610</a>), and a homodimeric dihydrolipoamide dehydrogenase (E3; <a href="/entry/238331">238331</a>). The reaction is irreversible and constitutes the first committed step in BCAA oxidation. The complex also contains 2 regulatory enzymes, a kinase and a phosphorylase.</p><p>The BCKDHB gene encodes the beta subunit of E1, and the BCKDHA gene (<a href="/entry/608348">608348</a>) encodes the alpha subunit of E1.</p>
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<a id="cloning" class="mim-anchor"></a>
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<strong>Cloning and Expression</strong>
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<p><a href="#7" class="mim-tip-reference" title="Nobukuni, Y., Mitsubuchi, H., Endo, F., Akaboshi, I., Asaka, J., Matsuda, I. &lt;strong&gt;Maple syrup urine disease: complete primary structure of the E1-beta subunit of human branched-chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease.&lt;/strong&gt; J. Clin. Invest. 86: 242-247, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2365818/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2365818&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI114690&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2365818">Nobukuni et al. (1990)</a> isolated and characterized a cDNA clone corresponding to the entire precursor of the BCKDHB gene from a human placental cDNA library. The cDNA encodes a mature 342-amino acid subunit with a molecular mass of 37.6 kD. The beta subunit is synthesized as a precursor with a leader sequence of 50 amino acids. Its primary structure shows strong homology to the structure of the bovine enzyme and to that of the E1-beta subunit of the human PDH complex (<a href="/entry/179060">179060</a>). By Northern blot analysis, <a href="#1" class="mim-tip-reference" title="Chuang, J. L., Cox, R. P., Chuang, D. T. &lt;strong&gt;Molecular cloning of the mature E1b-beta subunit of human branched-chain alpha-keto acid dehydrogenase complex.&lt;/strong&gt; FEBS Lett. 262: 305-309, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2335211/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2335211&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0014-5793(90)80215-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2335211">Chuang et al. (1990)</a> detected a 1.4-kb mRNA transcript for the E1-beta subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2365818+2335211" 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="geneStructure" class="mim-anchor"></a>
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<strong>Gene Structure</strong>
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<p><a href="#5" class="mim-tip-reference" title="Mitsubuchi, H., Nobukuni, Y., Endo, F., Matsuda, I. &lt;strong&gt;Structural organization and chromosomal localization of the gene for the E1-beta subunit of human branched chain alpha-keto acid dehydrogenase.&lt;/strong&gt; J. Biol. Chem. 266: 14686-14691, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1860867/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1860867&lt;/a&gt;]" pmid="1860867">Mitsubuchi et al. (1991)</a> found that the BCKDHB gene contains 10 exons. <a href="#2" class="mim-tip-reference" title="Chuang, J. L., Cox, R. P., Chuang, D. T. &lt;strong&gt;Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3-prime UTR in one of the two E1-beta mRNAs arises from intronic sequences.&lt;/strong&gt; Am. J. Hum. Genet. 58: 1373-1377, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8651316/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8651316&lt;/a&gt;]" pmid="8651316">Chuang et al. (1996)</a> determined that the BCKDHB gene contains 11 exons. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1860867+8651316" 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="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMappingToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Mapping</strong>
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<p>By analysis of somatic cell hybrids, <a href="#5" class="mim-tip-reference" title="Mitsubuchi, H., Nobukuni, Y., Endo, F., Matsuda, I. &lt;strong&gt;Structural organization and chromosomal localization of the gene for the E1-beta subunit of human branched chain alpha-keto acid dehydrogenase.&lt;/strong&gt; J. Biol. Chem. 266: 14686-14691, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1860867/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1860867&lt;/a&gt;]" pmid="1860867">Mitsubuchi et al. (1991)</a> mapped the BCKDHB gene to chromosome 6. By in situ hybridization, <a href="#9" class="mim-tip-reference" title="Zneimer, S. M., Lau, K. S., Eddy, R. L., Shows, T. B., Chuang, J. L., Chuang, D. T., Cox, R. P. &lt;strong&gt;Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1-beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31.&lt;/strong&gt; Genomics 10: 740-747, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1889817/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1889817&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0888-7543(91)90458-q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1889817">Zneimer et al. (1991)</a> localized the BCKDHB gene to 6p22-p21. Based on sequence analysis, <a href="#4" class="mim-tip-reference" title="Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C., Snyderman, S. E., Diaz, G. A. &lt;strong&gt;Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.&lt;/strong&gt; Am. J. Hum. Genet. 69: 863-868, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11509994/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11509994&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11509994[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/323677&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11509994">Edelmann et al. (2001)</a> localized the BCKDHB gene to 6q14. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11509994+1860867+1889817" 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="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>In a patient with classic maple syrup urine disease (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#6" class="mim-tip-reference" title="Nobukuni, Y., Mitsubuchi, H., Akaboshi, I., Indo, Y., Endo, F., Yoshioka, A., Matsuda, I. &lt;strong&gt;Maple syrup urine disease: complete defect of the E1-beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease.&lt;/strong&gt; J. Clin. Invest. 87: 1862-1866, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2022752/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2022752&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI115209&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2022752">Nobukuni et al. (1991)</a> identified a homozygous 11-bp deletion in exon 1 of the E1-beta gene (<a href="#0001">248611.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022752" 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="Patel, M. S., Harris, R. A. &lt;strong&gt;Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.&lt;/strong&gt; FASEB J. 9: 1164-1172, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7672509/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7672509&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1096/fasebj.9.12.7672509&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7672509">Patel and Harris (1995)</a> provided a diagram of 2 point mutations, 2 small deletions, and 1 small insertion that had been reported in the BCKDHB gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7672509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C., Snyderman, S. E., Diaz, G. A. &lt;strong&gt;Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.&lt;/strong&gt; Am. J. Hum. Genet. 69: 863-868, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11509994/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11509994&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11509994[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/323677&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11509994">Edelmann et al. (2001)</a> noted that approximately 33% (10 of 34) of families with MSUD followed in their clinic in New York were of Ashkenazi Jewish descent, leading them to search for a common mutation within this group. Three novel mutations in the BCKDHB gene were identified in 7 unrelated affected Ashkenazi Jewish patients. Six of the 7 had the same mutation (R183P; <a href="#0002">248611.0002</a>). The locations of the affected residues in the crystal structure of the E1-beta subunit suggested possible mechanisms for the deleterious effects of these mutations. Large-scale population screening of Ashkenazi Jewish individuals for the R183P mutation revealed that the carrier frequency of the mutant allele was approximately 1 in 113 persons; the 1 patient not carrying R183P had a previously described homozygous mutation in the gene encoding the E2 subunit (<a href="/entry/248610#0009">248610.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11509994" 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 3 unrelated Israeli patients with classic MSUD, <a href="#3" class="mim-tip-reference" title="Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T. &lt;strong&gt;Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.&lt;/strong&gt; J. Biol. Chem. 279: 17792-17800, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14742428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14742428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M313879200&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14742428">Chuang et al. (2004)</a> identified homozygous or compound heterozygous mutations in the BCKDHB gene (<a href="#0003">248611.0003</a>-<a href="#0006">248611.0006</a>). Functional expression studies in E. coli showed that the different mutations had variable expression but no residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" 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="allelicVariants" class="mim-anchor"></a>
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<strong>ALLELIC VARIANTS (<a href="/help/faq#1_4"></strong>
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<strong>6 Selected Examples</a>):</strong>
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</h4>
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<a href="/allelicVariants/248611" class="btn btn-default" role="button"> Table View </a>
&nbsp;&nbsp;<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=248611[MIM]" class="btn btn-default mim-tip-hint" role="button" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a>
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<a id="0001" class="mim-anchor"></a>
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<strong>.0001&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, 11-BP DEL
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<p>In a patient with classic maple syrup urine disease type IB (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#6" class="mim-tip-reference" title="Nobukuni, Y., Mitsubuchi, H., Akaboshi, I., Indo, Y., Endo, F., Yoshioka, A., Matsuda, I. &lt;strong&gt;Maple syrup urine disease: complete defect of the E1-beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease.&lt;/strong&gt; J. Clin. Invest. 87: 1862-1866, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2022752/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2022752&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI115209&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2022752">Nobukuni et al. (1991)</a> identified a homozygous 11-bp deletion in exon 1 of the E1-beta gene, within the mitochondrial targeting peptide. Both parents were heterozygous for the mutation, whereas an affected brother and a sister were homozygous. The absence of the E1-beta subunit resulted in instability of the E1-alpha subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0002&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, ARG183PRO
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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">&#x25cf;</span> rs79761867 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs79761867;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/rs79761867?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs79761867" 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=rs79761867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
<span class="mim-text-font">
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000056008 OR RCV000082754 OR RCV000589206 OR RCV002512989 OR RCV004566721" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000056008, RCV000082754, RCV000589206, RCV002512989, RCV004566721" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000056008...</a>
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<p>In Ashkenazi Jewish patients with classic maple syrup urine disease type IB (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#4" class="mim-tip-reference" title="Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C., Snyderman, S. E., Diaz, G. A. &lt;strong&gt;Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.&lt;/strong&gt; Am. J. Hum. Genet. 69: 863-868, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11509994/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11509994&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=11509994[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/323677&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11509994">Edelmann et al. (2001)</a> identified homozygosity for a 538G-C change in exon 5 of the BCKDHB gene, resulting in an arg183-to-pro (R183P) substitution. the mutation was detected in 10 of 12 chromosomes screened. The mutation is predicted to induce a structural change in the protein and impair proper folding. Two other Ashkenazi Jewish patients were compound heterozygous for the R183P mutation and another BCKDHB mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11509994" 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&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, HIS156TYR
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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">&#x25cf;</span> rs121965004 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965004;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/rs121965004?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">&#x25cf;</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs121965004" 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=rs121965004" 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=RCV003460460 OR RCV003534309" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003460460, RCV003534309" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003460460...</a>
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<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#3" class="mim-tip-reference" title="Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T. &lt;strong&gt;Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.&lt;/strong&gt; J. Biol. Chem. 279: 17792-17800, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14742428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14742428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M313879200&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14742428">Chuang et al. (2004)</a> identified a homozygous C-to-T transition in the BCKDHB gene, resulting in a his156-to-tyr (H156Y) substitution. Expression studies of the mutant protein in E. coli showed that the H156Y protein was expressed at much lower levels compared to control (18%) and formed multiple species ranging from heterodimers to heterotetramers, reflecting an assembly defect. There was no residual enzyme activity and severely reduced affinity for the thiamine cofactor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" 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&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, VAL69GLY
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs121965005 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs121965005;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=rs121965005" 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=rs121965005" 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=RCV003534310" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003534310" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003534310</a>
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<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#3" class="mim-tip-reference" title="Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T. &lt;strong&gt;Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.&lt;/strong&gt; J. Biol. Chem. 279: 17792-17800, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14742428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14742428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M313879200&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14742428">Chuang et al. (2004)</a> identified a homozygous T-to-G transversion in the BCKDHB gene, resulting in a val69-to-gly (V69G) substitution. Functional expression studies in E. coli showed that the V69G mutant protein was not expressed, likely due to protein misfolding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, 4-BP DEL, IVS9
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1562242135 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1562242135;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=rs1562242135" 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=rs1562242135" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
<span class="mim-text-font">
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003460461 OR RCV003534311" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003460461, RCV003534311" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003460461...</a>
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<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; <a href="/entry/620698">620698</a>), <a href="#3" class="mim-tip-reference" title="Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T. &lt;strong&gt;Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.&lt;/strong&gt; J. Biol. Chem. 279: 17792-17800, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14742428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14742428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M313879200&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14742428">Chuang et al. (2004)</a> identified compound heterozygosity for 2 mutations in the BCKDHB gene: a 4-bp deletion in intron 9 resulting in the deletion of exon 10, and an 8-bp insertion in exon 10 (<a href="#0006">248611.0006</a>) resulting in a frameshift. There was no residual enzyme activity for either mutant protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006&nbsp;MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
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BCKDHB, 8-BP INS, NT1109
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<span class="mim-text-font">
<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV003534312" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV003534312" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV003534312</a>
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<p>For discussion of the 8-bp insertion in the BCKDHB gene that was found in compound heterozygous state in a patient with classic maple syrup urine disease (MSUD1B; <a href="/entry/620698">620698</a>) by <a href="#3" class="mim-tip-reference" title="Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T. &lt;strong&gt;Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.&lt;/strong&gt; J. Biol. Chem. 279: 17792-17800, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14742428/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14742428&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M313879200&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14742428">Chuang et al. (2004)</a>, see <a href="#0005">248611.0005</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" 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>REFERENCES</strong>
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<a id="Chuang1990" class="mim-anchor"></a>
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Chuang, J. L., Cox, R. P., Chuang, D. T.
<strong>Molecular cloning of the mature E1b-beta subunit of human branched-chain alpha-keto acid dehydrogenase complex.</strong>
FEBS Lett. 262: 305-309, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2335211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2335211</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2335211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0014-5793(90)80215-5" target="_blank">Full Text</a>]
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Chuang, J. L., Cox, R. P., Chuang, D. T.
<strong>Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3-prime UTR in one of the two E1-beta mRNAs arises from intronic sequences.</strong>
Am. J. Hum. Genet. 58: 1373-1377, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8651316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8651316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8651316" 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="Chuang2004" class="mim-anchor"></a>
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Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T.
<strong>Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.</strong>
J. Biol. Chem. 279: 17792-17800, 2004.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14742428/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14742428</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14742428" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1074/jbc.M313879200" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Edelmann2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C., Snyderman, S. E., Diaz, G. A.
<strong>Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.</strong>
Am. J. Hum. Genet. 69: 863-868, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11509994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11509994</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11509994[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=11509994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/323677" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Mitsubuchi1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Mitsubuchi, H., Nobukuni, Y., Endo, F., Matsuda, I.
<strong>Structural organization and chromosomal localization of the gene for the E1-beta subunit of human branched chain alpha-keto acid dehydrogenase.</strong>
J. Biol. Chem. 266: 14686-14691, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1860867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1860867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1860867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Nobukuni1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nobukuni, Y., Mitsubuchi, H., Akaboshi, I., Indo, Y., Endo, F., Yoshioka, A., Matsuda, I.
<strong>Maple syrup urine disease: complete defect of the E1-beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease.</strong>
J. Clin. Invest. 87: 1862-1866, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2022752/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2022752</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2022752" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI115209" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Nobukuni1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nobukuni, Y., Mitsubuchi, H., Endo, F., Akaboshi, I., Asaka, J., Matsuda, I.
<strong>Maple syrup urine disease: complete primary structure of the E1-beta subunit of human branched-chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease.</strong>
J. Clin. Invest. 86: 242-247, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2365818/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2365818</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2365818" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI114690" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Patel1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Patel, M. S., Harris, R. A.
<strong>Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.</strong>
FASEB J. 9: 1164-1172, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7672509/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7672509</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7672509" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1096/fasebj.9.12.7672509" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Zneimer1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Zneimer, S. M., Lau, K. S., Eddy, R. L., Shows, T. B., Chuang, J. L., Chuang, D. T., Cox, R. P.
<strong>Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1-beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31.</strong>
Genomics 10: 740-747, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1889817/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1889817</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1889817" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0888-7543(91)90458-q" target="_blank">Full Text</a>]
</p>
</div>
</li>
</ol>
<div>
<br />
</div>
</div>
</div>
<div>
<a id="contributors" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="mim-text-font">
<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Cassandra L. Kniffin - updated : 6/14/2007
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseContributors">
<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">
<span class="mim-text-font">
Cassandra L. Kniffin - reorganized : 1/28/2004<br>Cassandra L. Kniffin - updated : 12/29/2003<br>Carol A. Bocchini - updated : 10/19/2001<br>Victor A. McKusick - updated : 10/17/2001
</span>
</div>
</div>
</div>
<div>
<a id="creationDate" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
Creation Date:
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 11/9/1990
</span>
</div>
</div>
</div>
<div>
<a id="editHistory" class="mim-anchor"></a>
<div class="row">
<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
<span class="text-nowrap mim-text-font">
<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
</span>
</div>
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
carol : 02/09/2024
</span>
</div>
</div>
<div class="row collapse" id="mimCollapseEditHistory">
<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">
<span class="mim-text-font">
carol : 02/09/2024<br>carol : 04/29/2015<br>wwang : 6/28/2007<br>ckniffin : 6/14/2007<br>joanna : 10/30/2006<br>terry : 9/27/2005<br>alopez : 6/13/2005<br>ckniffin : 8/24/2004<br>carol : 1/28/2004<br>ckniffin : 12/29/2003<br>carol : 10/19/2001<br>carol : 10/19/2001<br>terry : 10/17/2001<br>carol : 6/19/1998<br>carol : 4/24/1998<br>mark : 10/31/1995<br>mimadm : 2/19/1994<br>supermim : 3/17/1992<br>carol : 1/16/1992<br>carol : 10/7/1991<br>carol : 9/20/1991
</span>
</div>
</div>
</div>
</div>
</div>
</div>
<div class="container visible-print-block">
<div class="row">
<div class="col-md-8 col-md-offset-1">
<div>
<div>
<h3>
<span class="mim-font">
<strong>*</strong> 248611
</span>
</h3>
</div>
<div>
<h3>
<span class="mim-font">
BRANCHED-CHAIN KETO ACID DEHYDROGENASE E1, BETA POLYPEPTIDE; BCKDHB
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<div >
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
E1B
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
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<div>
<p>
<span class="mim-text-font">
<strong><em>HGNC Approved Gene Symbol: BCKDHB</em></strong>
</span>
</p>
</div>
<div>
<p>
<span class="mim-text-font">
<strong>
<em>
Cytogenetic location: 6q14.1
&nbsp;
Genomic coordinates <span class="small">(GRCh38)</span> : 6:80,106,610-80,466,676 </span>
</em>
</strong>
<span class="small">(from NCBI)</span>
</span>
</p>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene-Phenotype Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
</tr>
</thead>
<tbody>
<tr>
<td rowspan="1">
<span class="mim-font">
6q14.1
</span>
</td>
<td>
<span class="mim-font">
Maple syrup urine disease, type Ib
</span>
</td>
<td>
<span class="mim-font">
620698
</span>
</td>
<td>
<span class="mim-font">
Autosomal recessive
</span>
</td>
<td>
<span class="mim-font">
3
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>TEXT</strong>
</span>
</h4>
<div>
<h4>
<span class="mim-font">
<strong>Description</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The second major step in the catabolism of the branched-chain amino acids, isoleucine, leucine, and valine, is catalyzed by the branched-chain alpha-keto acid dehydrogenase complex (BCKD; EC 1.2.4.4), an inner-mitochondrial enzyme complex that consists of 3 catalytic components: a heterotetrameric (alpha2, beta2) branched-chain alpha-keto acid decarboxylase (E1), a homo-24-meric dihydrolipoyl transacylase (E2; 248610), and a homodimeric dihydrolipoamide dehydrogenase (E3; 238331). The reaction is irreversible and constitutes the first committed step in BCAA oxidation. The complex also contains 2 regulatory enzymes, a kinase and a phosphorylase.</p><p>The BCKDHB gene encodes the beta subunit of E1, and the BCKDHA gene (608348) encodes the alpha subunit of E1.</p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Cloning and Expression</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Nobukuni et al. (1990) isolated and characterized a cDNA clone corresponding to the entire precursor of the BCKDHB gene from a human placental cDNA library. The cDNA encodes a mature 342-amino acid subunit with a molecular mass of 37.6 kD. The beta subunit is synthesized as a precursor with a leader sequence of 50 amino acids. Its primary structure shows strong homology to the structure of the bovine enzyme and to that of the E1-beta subunit of the human PDH complex (179060). By Northern blot analysis, Chuang et al. (1990) detected a 1.4-kb mRNA transcript for the E1-beta subunit. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Gene Structure</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Mitsubuchi et al. (1991) found that the BCKDHB gene contains 10 exons. Chuang et al. (1996) determined that the BCKDHB gene contains 11 exons. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Mapping</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>By analysis of somatic cell hybrids, Mitsubuchi et al. (1991) mapped the BCKDHB gene to chromosome 6. By in situ hybridization, Zneimer et al. (1991) localized the BCKDHB gene to 6p22-p21. Based on sequence analysis, Edelmann et al. (2001) localized the BCKDHB gene to 6q14. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In a patient with classic maple syrup urine disease (MSUD1B; 620698), Nobukuni et al. (1991) identified a homozygous 11-bp deletion in exon 1 of the E1-beta gene (248611.0001). </p><p>Patel and Harris (1995) provided a diagram of 2 point mutations, 2 small deletions, and 1 small insertion that had been reported in the BCKDHB gene. </p><p>Edelmann et al. (2001) noted that approximately 33% (10 of 34) of families with MSUD followed in their clinic in New York were of Ashkenazi Jewish descent, leading them to search for a common mutation within this group. Three novel mutations in the BCKDHB gene were identified in 7 unrelated affected Ashkenazi Jewish patients. Six of the 7 had the same mutation (R183P; 248611.0002). The locations of the affected residues in the crystal structure of the E1-beta subunit suggested possible mechanisms for the deleterious effects of these mutations. Large-scale population screening of Ashkenazi Jewish individuals for the R183P mutation revealed that the carrier frequency of the mutant allele was approximately 1 in 113 persons; the 1 patient not carrying R183P had a previously described homozygous mutation in the gene encoding the E2 subunit (248610.0009). </p><p>In 3 unrelated Israeli patients with classic MSUD, Chuang et al. (2004) identified homozygous or compound heterozygous mutations in the BCKDHB gene (248611.0003-248611.0006). Functional expression studies in E. coli showed that the different mutations had variable expression but no residual enzyme activity. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>ALLELIC VARIANTS</strong>
</span>
<strong>6 Selected Examples):</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0001 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, 11-BP DEL
<br />
SNP: rs398124601,
ClinVar: RCV000173586, RCV000780961, RCV001390112, RCV004566972
</span>
</div>
<div>
<span class="mim-text-font">
<p>In a patient with classic maple syrup urine disease type IB (MSUD1B; 620698), Nobukuni et al. (1991) identified a homozygous 11-bp deletion in exon 1 of the E1-beta gene, within the mitochondrial targeting peptide. Both parents were heterozygous for the mutation, whereas an affected brother and a sister were homozygous. The absence of the E1-beta subunit resulted in instability of the E1-alpha subunit. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0002 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, ARG183PRO
<br />
SNP: rs79761867,
gnomAD: rs79761867,
ClinVar: RCV000056008, RCV000082754, RCV000589206, RCV002512989, RCV004566721
</span>
</div>
<div>
<span class="mim-text-font">
<p>In Ashkenazi Jewish patients with classic maple syrup urine disease type IB (MSUD1B; 620698), Edelmann et al. (2001) identified homozygosity for a 538G-C change in exon 5 of the BCKDHB gene, resulting in an arg183-to-pro (R183P) substitution. the mutation was detected in 10 of 12 chromosomes screened. The mutation is predicted to induce a structural change in the protein and impair proper folding. Two other Ashkenazi Jewish patients were compound heterozygous for the R183P mutation and another BCKDHB mutation. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0003 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, HIS156TYR
<br />
SNP: rs121965004,
gnomAD: rs121965004,
ClinVar: RCV003460460, RCV003534309
</span>
</div>
<div>
<span class="mim-text-font">
<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; 620698), Chuang et al. (2004) identified a homozygous C-to-T transition in the BCKDHB gene, resulting in a his156-to-tyr (H156Y) substitution. Expression studies of the mutant protein in E. coli showed that the H156Y protein was expressed at much lower levels compared to control (18%) and formed multiple species ranging from heterodimers to heterotetramers, reflecting an assembly defect. There was no residual enzyme activity and severely reduced affinity for the thiamine cofactor. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0004 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, VAL69GLY
<br />
SNP: rs121965005,
ClinVar: RCV003534310
</span>
</div>
<div>
<span class="mim-text-font">
<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; 620698), Chuang et al. (2004) identified a homozygous T-to-G transversion in the BCKDHB gene, resulting in a val69-to-gly (V69G) substitution. Functional expression studies in E. coli showed that the V69G mutant protein was not expressed, likely due to protein misfolding. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0005 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, 4-BP DEL, IVS9
<br />
SNP: rs1562242135,
ClinVar: RCV003460461, RCV003534311
</span>
</div>
<div>
<span class="mim-text-font">
<p>In an Israeli patient with classic maple syrup urine disease (MSUD1B; 620698), Chuang et al. (2004) identified compound heterozygosity for 2 mutations in the BCKDHB gene: a 4-bp deletion in intron 9 resulting in the deletion of exon 10, and an 8-bp insertion in exon 10 (248611.0006) resulting in a frameshift. There was no residual enzyme activity for either mutant protein. </p>
</span>
</div>
<div>
<br />
</div>
</div>
<div>
<div>
<h4>
<span class="mim-font">
<strong>.0006 &nbsp; MAPLE SYRUP URINE DISEASE, TYPE IB</strong>
</span>
</h4>
</div>
<div>
<span class="mim-text-font">
BCKDHB, 8-BP INS, NT1109
<br />
ClinVar: RCV003534312
</span>
</div>
<div>
<span class="mim-text-font">
<p>For discussion of the 8-bp insertion in the BCKDHB gene that was found in compound heterozygous state in a patient with classic maple syrup urine disease (MSUD1B; 620698) by Chuang et al. (2004), see 248611.0005. </p>
</span>
</div>
<div>
<br />
</div>
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Chuang, J. L., Cox, R. P., Chuang, D. T.
<strong>Molecular cloning of the mature E1b-beta subunit of human branched-chain alpha-keto acid dehydrogenase complex.</strong>
FEBS Lett. 262: 305-309, 1990.
[PubMed: 2335211]
[Full Text: https://doi.org/10.1016/0014-5793(90)80215-5]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, J. L., Cox, R. P., Chuang, D. T.
<strong>Maple syrup urine disease: the E1beta gene of human branched-chain alpha-ketoacid dehydrogenase complex has 11 rather than 10 exons, and the 3-prime UTR in one of the two E1-beta mRNAs arises from intronic sequences.</strong>
Am. J. Hum. Genet. 58: 1373-1377, 1996.
[PubMed: 8651316]
</p>
</li>
<li>
<p class="mim-text-font">
Chuang, J. L., Wynn, R. M., Moss, C. C., Song, J., Li, J., Awad, N., Mandel, H., Chuang, D. T.
<strong>Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients.</strong>
J. Biol. Chem. 279: 17792-17800, 2004.
[PubMed: 14742428]
[Full Text: https://doi.org/10.1074/jbc.M313879200]
</p>
</li>
<li>
<p class="mim-text-font">
Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C., Snyderman, S. E., Diaz, G. A.
<strong>Maple syrup urine disease: identification and carrier-frequency determination of a novel founder mutation in the Ashkenazi Jewish population.</strong>
Am. J. Hum. Genet. 69: 863-868, 2001.
[PubMed: 11509994]
[Full Text: https://doi.org/10.1086/323677]
</p>
</li>
<li>
<p class="mim-text-font">
Mitsubuchi, H., Nobukuni, Y., Endo, F., Matsuda, I.
<strong>Structural organization and chromosomal localization of the gene for the E1-beta subunit of human branched chain alpha-keto acid dehydrogenase.</strong>
J. Biol. Chem. 266: 14686-14691, 1991.
[PubMed: 1860867]
</p>
</li>
<li>
<p class="mim-text-font">
Nobukuni, Y., Mitsubuchi, H., Akaboshi, I., Indo, Y., Endo, F., Yoshioka, A., Matsuda, I.
<strong>Maple syrup urine disease: complete defect of the E1-beta subunit of the branched chain alpha-ketoacid dehydrogenase complex due to a deletion of an 11-bp repeat sequence which encodes a mitochondrial targeting leader peptide in a family with the disease.</strong>
J. Clin. Invest. 87: 1862-1866, 1991.
[PubMed: 2022752]
[Full Text: https://doi.org/10.1172/JCI115209]
</p>
</li>
<li>
<p class="mim-text-font">
Nobukuni, Y., Mitsubuchi, H., Endo, F., Akaboshi, I., Asaka, J., Matsuda, I.
<strong>Maple syrup urine disease: complete primary structure of the E1-beta subunit of human branched-chain alpha-ketoacid dehydrogenase complex deduced from the nucleotide sequence and a gene analysis of patients with this disease.</strong>
J. Clin. Invest. 86: 242-247, 1990.
[PubMed: 2365818]
[Full Text: https://doi.org/10.1172/JCI114690]
</p>
</li>
<li>
<p class="mim-text-font">
Patel, M. S., Harris, R. A.
<strong>Mammalian alpha-keto acid dehydrogenase complexes: gene regulation and genetic defects.</strong>
FASEB J. 9: 1164-1172, 1995.
[PubMed: 7672509]
[Full Text: https://doi.org/10.1096/fasebj.9.12.7672509]
</p>
</li>
<li>
<p class="mim-text-font">
Zneimer, S. M., Lau, K. S., Eddy, R. L., Shows, T. B., Chuang, J. L., Chuang, D. T., Cox, R. P.
<strong>Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1-beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31.</strong>
Genomics 10: 740-747, 1991.
[PubMed: 1889817]
[Full Text: https://doi.org/10.1016/0888-7543(91)90458-q]
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