BCKDHA

Chr 19AR

branched chain keto acid dehydrogenase E1 subunit alpha

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

NCBI Gene: 593ENSG00000248098UniProt: P12694OMIM: 608348

This gene encodes the alpha subunit of the E1 component of the branched-chain alpha-keto acid dehydrogenase complex, which catalyzes the second step in the catabolism of leucine, isoleucine, and valine in mitochondria. Mutations cause maple syrup urine disease type IA through autosomal recessive inheritance. The pathogenic mechanism involves loss of function, leading to accumulation of branched-chain amino acids and their toxic metabolites.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 1.031 OMIM phenotype
Clinical Summary— BCKDHA
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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.
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ClinVar Variants
59 unique Pathogenic / Likely Pathogenic· 86 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →
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GeneReview available — BCKDHA
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBCKDHA-related maple syrup urine diseaseLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7033th %ile
GOF
0.6150th %ile
LOF
0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic41
VUS86
Likely Benign125
Benign13
Conflicting9
18
Pathogenic
41
Likely Pathogenic
86
VUS
125
Likely Benign
13
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
1
3
0
18
Likely Pathogenic
28
13
0
0
41
VUS
1
75
5
5
86
Likely Benign
0
1
46
78
125
Benign
0
0
13
0
13
Conflicting
—9
Total43906783292

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BCKDHA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The pyruvate dehydrogenase kinase inhibitor dichloroacetate mitigates alcohol-induced hepatic inflammation and metabolic disturbances in mice.
Wu J et al.·Hepatol Commun
2024
Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.
Yang J et al.·J Pediatr Endocrinol Metab
2021
Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease.
Zeynalzadeh M et al.·J Pediatr Endocrinol Metab
2018Cohort
Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.
Margutti AVB et al.·Orphanet J Rare Dis
2020Cohort
Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases.
Li X et al.·Eur J Med Genet
2015Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
IDH3A Deficiency Compromises Adaptive Thermogenesis and Exacerbates Obesity-Induced Metabolic Dysfunction via Impaired BCKDHA-Dependent BCAA Catabolism.
Lu X et al.·Diabetes
2026Open Access
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
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