BCKDHB

Chr 6AR

branched chain keto acid dehydrogenase E1 subunit beta

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

NCBI Gene: 594 ENSG00000083123 UniProt: P21953 OMIM: 248611

The E1 beta subunit of branched-chain keto acid dehydrogenase catalyzes the catabolism of branched-chain amino acids in the mitochondrial matrix. Autosomal recessive mutations cause maple syrup urine disease type 1B, characterized by maple syrup-scented urine, intellectual disability, developmental delays, and feeding difficulties. Loss of enzymatic function leads to toxic accumulation of branched-chain amino acids and their metabolites.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 1.101 OMIM phenotype

Clinical Summary— BCKDHB

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Gene-Disease Validity (ClinGen)

maple syrup urine disease type 1B · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

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

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ClinVar Variants

247 unique Pathogenic / Likely Pathogenic· 201 VUS of 876 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — BCKDHB

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?

1.10LOEUF

pLI 0.000

Z-score 1.19

OE 0.73 (0.49–1.10)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.18Z-score

OE missense 1.03 (0.93–1.15)

226 obs / 218.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.73 (0.49–1.10)

0≤0.351.4

Missense OE?1.03 (0.93–1.15)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 16 / 22.0Missense obs/exp: 226 / 218.7Syn Z: -0.77

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveBCKDHB-related maple syrup urine diseaseLOFAR

This gene — mechanism propensity

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

0.6551th %ile

GOF

0.5758th %ile

LOF

0.3647th %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

876 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90

Likely Pathogenic157

VUS201

Likely Benign325

Benign61

Conflicting29

Pathogenic

157

Likely Pathogenic

201

VUS

325

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	60	11	19	0	90
Likely Pathogenic	95	57	5	0	157
VUS	1	157	40	3	201
Likely Benign	0	4	136	185	325
Benign	0	1	60	0	61
Conflicting	—				29
Total	156	230	260	188	863

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap BCKDHB — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →