BCKDHA

Chr 19AR

branched chain keto acid dehydrogenase E1 subunit alpha

Also known as: BCKDE1A, MSU, MSUD1, MSUD1A, OVD1A

NCBI Gene: 593ENSG00000248098UniProt: P12694

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]

Primary Disease Associations & Inheritance

Maple syrup urine disease, type IaMIM #248600
AR
0
Active trials
0
Pathogenic / LP
0
ClinVar variants
20
Pubs (1 yr)
0.7
Missense Z
1.03
LOEUF
Clinical Summary— BCKDHA
🧬
Gene-Disease Validity (ClinGen)
maple syrup urine disease type 1A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.03LOEUF
pLI 0.000
Z-score 1.44
OE 0.68 (0.46–1.03)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.68Z-score
OE missense 0.89 (0.80–0.98)
256 obs / 288.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.68 (0.46–1.03)
0≤0.351.4
Missense OE0.89 (0.80–0.98)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 16 / 23.5Missense obs/exp: 256 / 288.7Syn Z: 0.07
DN
DN
0.7033th %ile
GOF
0.6150th %ile
LOF
0.3065th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

BCKDHA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

BCKDHA-related maple syrup urine disease

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Integrated Amino Acid Profiling and 4D-DIA Proteomics Reveal Protein Quality Divergence and Metabolic Adaptation in Cordyceps Species
Tang C et al.·J Fungi (Basel)
2025
PPM1K mediates metabolic disorder of branched-chain amino acid and regulates cerebral ischemia-reperfusion injury by activating ferroptosis in neurons
Li T et al.·Cell Death Dis
2023
The mitochondrial BCKD complex interacts with hepatic apolipoprotein E in cultured cells in vitro and mouse livers in vivo
Rueter J et al.·Cell Mol Life Sci
2023Functional
Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts BCKDHA : A case report
Yokoi K et al.·JIMD Rep
2022Case report
Branched-chain amino acid catabolic defect promotes alpha-cell proliferation via activating mTOR signaling.
Yang Y et al.·Mol Cell Endocrinol
2023
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PRSS55 regulates BCAA metabolism and interacts with BCKDK and BCKDHA in mouse testes and sperm.
Ge H et al.·Cell Biosci
2025Open AccessFunctional
BCKDHA-BCKDHB digenic gene therapy restores metabolic homeostasis in two mouse models and a calf with classic maple syrup urine disease.
Wang J et al.·Sci Transl Med
2025Functional
Dephosphorylation of branched-chain α-keto acid dehydrogenase E1α (BCKDHA) promotes branched-chain amino acid catabolism and renders cancer cells resistant to X-rays by mitigating DNA damage.
Bo T et al.·Biochem Biophys Res Commun
2025
BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA.
Zhou F et al.·Cell Death Dis
2024Open Access
BCKDHA contributes to melanoma progression by promoting the expressions of lipogenic enzymes FASN and ACLY.
Tian Y et al.·Exp Dermatol
2023
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients