BCKDK Gene: Branched-Chain Keto Acid Dehydrogenase Kinase
Regulator of branched-chain amino acid catabolism and associated with BCKDK deficiency and neurological disorders
Gene Information Card
| Symbol | BCKDK |
|---|---|
| Full Name | Branched Chain Keto Acid Dehydrogenase Kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 10295 ncbi.nlm.nih.gov/gene/10295 |
| Ensembl ID | ENSG00000103544 |
| UniProt ID | O14874 |
| OMIM ID | 614900 |
| HGNC ID | 1692 |
| Aliases | BCKD-kinase, BDK, BCKDHKIN |
Description
The BCKDK gene encodes the branched-chain keto acid dehydrogenase kinase, a mitochondrial enzyme that phosphorylates and inactivates the branched-chain alpha-keto acid dehydrogenase complex (BCKDH). This complex catalyzes the rate-limiting step in the catabolism of branched-chain amino acids (BCAAs: leucine, isoleucine, valine). BCKDK acts as a negative regulator of BCAA breakdown; loss-of-function mutations lead to reduced BCKDH activity and accumulation of BCAAs and their keto acids, causing a metabolic disorder resembling maple syrup urine disease (MSUD) but with distinct neurological features including autism, intellectual disability, and microcephaly.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| BCKDK deficiency (autism, intellectual disability, microcephaly) | Loss-of-function mutations reduce BCKDK activity, leading to decreased BCKDH complex phosphorylation and increased BCAA catabolism, causing BCAA deficiency and neurological symptoms. | ClinVar, OMIM #614900 |
| Maple syrup urine disease (MSUD) | BCKDK mutations can cause a variant form of MSUD with intermittent or thiamine-responsive phenotype due to altered regulation of BCKDH. | OMIM #248600, ClinVar |
| Autism spectrum disorder | BCKDK deficiency is associated with autism; BCAA supplementation may improve symptoms. | ClinVar, PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 6.1 | Low |
| Heart | 4.7 | Low |
| Skeletal muscle | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| HepG2 | 7.8 | Medium expression |
| SH-SY5Y | 9.1 | Medium-high expression |
| K562 | 2.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of function; associated with BCKDK deficiency |
| c.331C>T (p.Arg111*) | Nonsense | Rare | Premature stop; loss of function |
| c.904G>A (p.Gly302Arg) | Missense | Rare | Impaired kinase activity; reduced BCKDH phosphorylation |
| c.1234delC | Frameshift | Rare | Loss of function; severe neurological phenotype |
Mutation functional classification
Loss of Function (LOF)
Most BCKDK mutations are loss-of-function, reducing kinase activity and leading to decreased BCKDH complex phosphorylation, increased BCAA catabolism, and BCAA deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported in BCKDK.
Dominant Negative (DN)
No dominant-negative mutations reported; BCKDK deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • protein kinase activity (GO:0004672) | • ATP binding (GO:0005524) |
| • branched-chain amino acid catabolic process (GO:0009083) | • mitochondrion (GO:0005739) |
| • phosphorylation (GO:0016310) |
Pathways
• Branched-chain amino acid catabolism (Reactome: R-HSA-70895)
• Regulation of BCKDH complex (KEGG: hsa00280)
Protein Summary
BCKDK is a mitochondrial serine/threonine kinase that specifically phosphorylates and inactivates the E1 alpha subunit of the branched-chain alpha-keto acid dehydrogenase complex (BCKDH). By controlling BCKDH activity, BCKDK regulates the flux of branched-chain amino acids through catabolism. The protein contains a mitochondrial targeting sequence and a kinase domain. Dysregulation of BCKDK leads to altered BCAA levels, impacting neurological function and development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| BCKDK Knockout HEK293 Cell Line | EDJ-KQ1127 | Human | 10295 | Details Get a Quote |
| BCKDK Knockout HCT 116 Cell Line | EDJ-KQ18979 | Human | 10295 | Details Get a Quote |
| BCKDK Knockout A-549 Cell Line | EDJ-KQ20324 | Human | 10295 | Details Get a Quote |
| BCKDK Knockout HeLa Cell Line | EDJ-KQ20326 | Human | 10295 | Details Get a Quote |
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