BCKDHB Gene: Branched-Chain Keto Acid Dehydrogenase E1 Subunit Beta
Genetic and Functional Insights into BCKDHB in Maple Syrup Urine Disease and Metabolic Pathways
Gene Information Card
| Symbol | BCKDHB |
|---|---|
| Full Name | Branched Chain Keto Acid Dehydrogenase E1 Subunit Beta |
| Gene Type | Protein coding |
| Chromosomal Location | 6q14.1 |
| NCBI Gene ID | 594 ncbi.nlm.nih.gov/gene/594 |
| Ensembl ID | ENSG00000183117 |
| UniProt ID | P21953 |
| OMIM ID | 248611 |
| HGNC ID | 987 |
| Aliases | E1B, BCKDE1B, BCKDH E1-beta |
Description
The BCKDHB gene encodes the beta subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDH), a mitochondrial multienzyme complex that catalyzes the irreversible oxidative decarboxylation of branched-chain alpha-keto acids derived from leucine, isoleucine, and valine. This subunit contains the E1 decarboxylase component. Mutations in BCKDHB cause maple syrup urine disease (MSUD) type Ib, an autosomal recessive disorder characterized by accumulation of branched-chain amino acids and their keto acids, leading to neurological damage and metabolic crisis if untreated.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Maple Syrup Urine Disease Type Ib | Loss-of-function mutations in BCKDHB impair BCKDH complex activity, preventing catabolism of branched-chain amino acids and causing toxic accumulation of leucine, isoleucine, and valine and their corresponding keto acids. | ClinVar, OMIM |
| Branched-Chain Keto Acid Dehydrogenase Deficiency | Same mechanism as MSUD; reduced or absent enzyme activity leads to classic MSUD phenotype. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | High |
| Kidney | 8.7 | Medium |
| Heart | 6.5 | Medium |
| Skeletal Muscle | 5.2 | Medium |
| Brain | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.1 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate expression |
| K562 (leukemia) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.832G>A (p.Gly278Arg) | Missense | Common in MSUD | Loss of function; reduces E1 activity |
| c.508C>T (p.Arg170*) | Nonsense | Rare | Premature truncation; complete loss of function |
| c.1A>G (p.Met1?) | Start loss | Rare | No protein synthesis; null allele |
Mutation functional classification
Loss of Function (LOF)
Most BCKDHB mutations are loss-of-function, reducing or abolishing BCKDH complex activity, leading to MSUD.
Gain of Function (GOF)
No gain-of-function mutations reported for BCKDHB.
Dominant Negative (DN)
No dominant-negative mutations reported; MSUD is recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Branched-chain amino acid catabolism (Reactome: R-HSA-70895)
• Valine
• leucine and isoleucine degradation (KEGG: hsa00280)
Protein Summary
The BCKDHB protein (UniProt P21953) is a 392-amino acid mitochondrial protein that forms the E1 beta subunit of the branched-chain alpha-keto acid dehydrogenase complex. It heterotetramerizes with the E1 alpha subunit (BCKDHA) to form the E1 decarboxylase component. The protein contains a thiamine pyrophosphate (TPP) binding domain essential for catalytic activity. Defects in this subunit disrupt the entire BCKDH complex, leading to maple syrup urine disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCKDHB Knockout HEK293 Cell Line | EDJ-KQ4129 | Human | 594 | Details Get a Quote |
| BCKDHB Knockout A-549 Cell Line | EDJ-KQ26540 | Human | 594 | Details Get a Quote |
| BCKDHB Knockout HCT 116 Cell Line | EDJ-KQ26541 | Human | 594 | Details Get a Quote |
| BCKDHB Knockout HeLa Cell Line | EDJ-KQ26542 | Human | 594 | Details Get a Quote |
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