BCKDHB

Chr 6AR

branched chain keto acid dehydrogenase E1 subunit beta

Also known as: BCKDE1B, BCKDH E1-beta, E1B, MSUD1B, OVD1B

NCBI Gene: 594ENSG00000083123UniProt: P21953

This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]

Primary Disease Associations & Inheritance

Maple syrup urine disease, type IbMIM #620698
AR
487
ClinVar variants
128
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— BCKDHB
🧬
Gene-Disease Validity (ClinGen)
maple syrup urine disease type 1B · 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.
📋
ClinVar Variants
128 Pathogenic / Likely Pathogenic· 139 VUS of 487 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.10LOEUF
pLI 0.000
Z-score 1.19
OE 0.73 (0.49–1.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.18Z-score
OE missense 1.03 (0.93–1.15)
226 obs / 218.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.49–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.93–1.15)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 16 / 22.0Missense obs/exp: 226 / 218.7Syn Z: -0.77

ClinVar Variant Classifications

487 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic71
VUS139
Likely Benign202
Benign8
Conflicting10
57
Pathogenic
71
Likely Pathogenic
139
VUS
202
Likely Benign
8
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
3
34
0
57
Likely Pathogenic
42
17
12
0
71
VUS
1
103
33
2
139
Likely Benign
0
3
85
114
202
Benign
0
0
8
0
8
Conflicting
—10
Total63126172116487

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

View in ClinVar →

Protein Context — Lollipop Plot

BCKDHB · protein map & ClinVar variants

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

Gene2Phenotype Curations

BCKDHB-related maple syrup urine disease

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Maple syrup urine disease, type Ib

MIM #620698

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — BCKDHB
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Neonatal maple syrup urine disease in China: two novel mutations in the BCKDHB gene and literature review.
Jiang HH et al.·J Pediatr Endocrinol Metab
2021Review
Successful treatment of severe MSUD in Bckdhb(-/-) mice with neonatal AAV gene therapy.
Pontoizeau C et al.·J Inherit Metab Dis
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
Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease.
Nguyen TTN et al.·Mol Genet Genomic Med
2020Case report
Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.
Margutti AVB et al.·Orphanet J Rare Dis
2020Cohort
Maple syrup urine disease diagnosis in Brazilian patients by massive parallel sequencing.
Tresbach RH et al.·Mol Genet Metab
2024Cohort
Expanding the Genetic Spectrum of PPM1K-Related Maple Syrup Urine Disease: A Novel Mutation.
Kılıç M et al.·Am J Med Genet A
2025Case report
Two novel mutations in the BCKDHB gene that cause maple syrup urine disease.
Han B et al.·Pediatr Neonatol
2018Case report
Molecular basis of various forms of maple syrup urine disease in Chilean patients.
Campanholi DRR et al.·Mol Genet Genomic Med
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools