BCKDK

Chr 16p11.2

branched chain keto acid dehydrogenase kinase

MANE:: ENST00000219794.11

OMIM: 614901 ↗NCBI: 10295 ↗Ensembl ↗

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Predicted protein structure

AlphaFold predicted structure

BCKDK · O14874

v62025-08-01

Predicted Aligned Error matrix for BCKDK — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

83.2/ 100

Confident

412 residues

Confidence breakdown

Very high(≥ 90)67%
Confident(70–90)12%
Low(50–70)7%
Very low(< 50)14%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Intellectual disability
BIALLELIC, autosomal or pseudoautosomal
Likely inborn error of metabolism
BIALLELIC, autosomal or pseudoautosomal
Undiagnosed metabolic disorders
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder

Disease associations (Open Targets)

branched-chain keto acid dehydrogenase kinase deficiency
0.75
Intellectual disability
0.44
maple syrup urine disease type 1A
0.27
autoimmune disorder of central nervous system
0.22
hereditary disease
0.19
metabolic syndrome
0.12
maple syrup urine disease, mild variant
0.12
neoplasm
0.10
breast cancer
0.10
breast carcinoma
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Branched-chain alpha-ketoacid dehydrogenase kinase

Serine/threonine-protein kinase component of macronutrients metabolism. Forms a functional kinase and phosphatase pair with PPM1K, serving as a metabolic regulatory node that coordinates branched-chain amino acids (BCAAs) with glucose and lipid metabolism via two distinct phosphoprotein targets: mitochondrial BCKDHA subunit of the branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex and cytosolic ACLY, a lipogenic enzyme of Krebs cycle (PubMed:24449431, PubMed:29779826, PubMed:37558654). Phosphorylates and inactivates mitochondrial BCKDH complex a multisubunit complex consisting of three multimeric components each involved in different steps of BCAA catabolism: E1 composed of BCKDHA and BCKDHB, E2 core composed of DBT monomers, and E3 composed of DLD monomers. Associates with the E2 component of BCKDH complex and phosphorylates BCKDHA on Ser-337, leading to conformational changes that interrupt substrate channeling between E1 and E2 and inactivates the BCKDH complex (PubMed:29779826, PubMed:37558654). Phosphorylates ACLY on Ser-455 in response to changes in cellular carbohydrate abundance such as occurs during fasting to feeding metabolic transition. Refeeding stimulates MLXIPL/ChREBP transcription factor, leading to increased BCKDK to PPM1K expression ratio, phosphorylation and activation of ACLY that ultimately results in the generation of malonyl-CoA and oxaloacetate immediate substrates of de novo lipogenesis and glucogenesis, respectively (PubMed:29779826). Recognizes phosphosites having SxxE/D canonical motif (PubMed:29779826)