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BCKDHA branched chain keto acid dehydrogenase E1 subunit alpha [ Homo sapiens (human) ]

Gene ID: 593, updated on 11-Apr-2024

Summary

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Official Symbol
BCKDHAprovided by HGNC
Official Full Name
branched chain keto acid dehydrogenase E1 subunit alphaprovided by HGNC
Primary source
HGNC:HGNC:986
See related
Ensembl:ENSG00000248098 MIM:608348; AllianceGenome:HGNC:986
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
MSU; MSUD1; OVD1A; MSUD1A; BCKDE1A
Summary
The branched-chain alpha-keto acid (BCAA) dehydrogenase (BCKD) complex is an innter mitochondrial enzyme complex that catalyzes the second major step in the catabolism of the branched-chain amino acids leucine, isoleucine, and valine. The BCKD complex consists of three catalytic components: a heterotetrameric (alpha2-beta2) branched-chain alpha-keto acid decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a dihydrolipoamide dehydrogenase (E3). This gene encodes the alpha subunit of the decarboxylase (E1) component. Mutations in this gene result in maple syrup urine disease, type IA. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]
Expression
Ubiquitous expression in heart (RPKM 29.4), kidney (RPKM 27.9) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
19q13.2
Exon count:
9
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (41397818..41425002)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (44219041..44246226)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (41903723..41930907)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14679 Neighboring gene B9 domain containing 2 Neighboring gene transmembrane protein 91 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10665 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:41885758-41885931 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41889835-41890334 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:41892254-41892432 Neighboring gene exosome component 5 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:41903234-41903906 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:41903907-41904578 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41912476-41913430 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:41913431-41914386 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14681 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10666 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10667 Neighboring gene VISTA enhancer hs1948 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14682 Neighboring gene distal membrane arm assembly component 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing. Fernández-Lainez C, et al. Clin Chim Acta, 2018 Aug. PMID 29673582
  2. Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease. You Y, et al. Genet Med, 2014 Aug. PMID 24603436
  3. Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease. Ali EZ, et al. J Pediatr Endocrinol Metab, 2013. PMID 23729548
  4. Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene. Park HD, et al. Ann Clin Lab Sci, 2011 Spring. PMID 21844576
  5. Functional characterization of the novel intronic nucleotide change c.288+9C>T within the BCKDHA gene: understanding a variant presentation of maple syrup urine disease. Fernández-Guerra P, et al. J Inherit Metab Dis, 2010 Dec. PMID 20431954

See all (99) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.
    Title: Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.
  2. Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.
    Title: Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.
  3. Six different novel genetic variants were validated in BCKDHB gene and BCKDHA gene, including c.523 T > C, c.659delA, c.550delT, c.863G > A and two gross deletions
    Title: Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease.
  4. pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease
    Title: In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing.
  5. Data suggest that the following genetic modifications are involved in patients with maple syrup urine disease in Iran: (1) mutation in BCKDHA (branched chain keto acid dehydrogenase E1 alpha); (2) mutation in BCKDHB (branched chain keto acid dehydrogenase E1 subunit beta); (3) mutation in DBT (dihydrolipoamide branched chain transacylase E2; one patient).
    Title: Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease.
  6. we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants
    Title: Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.
  7. Five novel mutations in BCKDHA were identified in MSUD patients.
    Title: Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases.
  8. The novel DBT mutation c.650-651insT was more prevalent than the deleted 4.7-kb heterozygote in the Amis population. The reported 4.7-kb deletion indicating a possible founder mutation may be preserved.
    Title: Different gene preferences of maple syrup urine disease in the aboriginal tribes of Taiwan.
  9. Targeted parallel sequencing revealed novel mutations in the gene BCKDHA for prenatal testing of maple syrup urine disease.
    Title: Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.
  10. Data from infant/her heterozygous parents (first cousins) suggest homozygous mutation (S144I) in BCKDHA can result in maple syrup urine disease (IA); molecular modeling suggests this missense mutation in exon 4 affects protein stability. [CASE STUDY]
    Title: Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease.
Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Potential readthrough

Included gene: TMEM91

Homology

Clone Names

  • FLJ45695

Gene Ontology Provided by GOA

Function Evidence Code Pubs
contributes_to 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity IDA
Inferred from Direct Assay
more info
 PubMed 
contributes_to branched-chain alpha-keto acid dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables carboxy-lyase activity TAS
Traceable Author Statement
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in branched-chain amino acid catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in branched-chain amino acid catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in branched-chain amino acid catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
part_of branched-chain alpha-ketoacid dehydrogenase complex IDA
Inferred from Direct Assay
more info
 PubMed 
located_in mitochondrial matrix NAS
Non-traceable Author Statement
more info
 PubMed 
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HDA PubMed 
located_in mitochondrion TAS
Traceable Author Statement
more info
 PubMed 
part_of oxoglutarate dehydrogenase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of oxoglutarate dehydrogenase complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
Names
2-oxoisovalerate dehydrogenase (lipoamide)
BCKDH E1-alpha
branched chain keto acid dehydrogenase E1 alpha protein
branched chain keto acid dehydrogenase E1, alpha polypeptide
branched-chain alpha-keto acid dehydrogenase E1 component alpha chain
NP_000700.1
NP_001158255.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_013004.1 RefSeqGene

    Range
    5030..32214
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000709.4 → NP_000700.1  2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_000700.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AK298188, BC023983, BQ018849
    Consensus CDS
    CCDS12581.1
    UniProtKB/Swiss-Prot
    B4DP47, E7EW46, P12694, Q16034, Q16472
    UniProtKB/TrEMBL
    B2R8A9
    Related
    ENSP00000269980.2, ENST00000269980.7
    Conserved Domains (2) summary
    PLN02374
    Location:17 → 413
    PLN02374; pyruvate dehydrogenase (acetyl-transferring)
    pfam00676
    Location:106 → 405
    E1_dh; Dehydrogenase E1 component

  2. NM_001164783.2 → NP_001158255.1  2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 2 precursor

    See identical proteins and their annotated locations for NP_001158255.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (2) lacks one internal amino acid, compared to isoform 1.
    Source sequence(s)
    AB209828, AK298188, BI910860, BQ018849
    UniProtKB/TrEMBL
    B2R8A9, Q59EI3
    Conserved Domains (2) summary
    PLN02374
    Location:17 → 412
    PLN02374; pyruvate dehydrogenase (acetyl-transferring)
    pfam00676
    Location:106 → 404
    E1_dh; Dehydrogenase E1 component

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    41397818..41425002
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    44219041..44246226
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P12694.2 GenPept UniProtKB/Swiss-Prot:P12694

Gene LinkOut

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