BCKDK (branched chain keto acid dehydrogenase kinase)

Gene

• Entrez ID: 10295
• Gene name: Branched chain keto acid dehydrogenase kinase
• Gene symbol: BCKDK
• Synonyms (NCBI Gene): BCKDKD, BDK
• Chromosome: 16
• Chromosome location: 16p11.2
• Summary: The branched-chain alpha-ketoacid dehydrogenase complex (BCKD) is an important regulator of the valine, leucine, and isoleucine catabolic pathways. The protein encoded by this gene is found in the mitochondrion, where it phosphorylates and inactivates BCK

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs142542453	A>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs145180240	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, 3 prime UTR variant, intron variant, synonymous variant
rs147210405	G>A,C	Pathogenic	Coding sequence variant, missense variant
rs369521689	C>A,G,T	Likely-pathogenic	Stop gained, coding sequence variant, synonymous variant
rs374121679	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs397514573	C>A,G,T	Uncertain-significance, pathogenic	Missense variant, synonymous variant, coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025739	hsa-miR-7-5p	Microarray	19073608
MIRT027050	hsa-miR-103a-3p	Sequencing	20371350
MIRT047623	hsa-miR-10a-5p	CLASH	23622248
MIRT046097	hsa-miR-125b-5p	CLASH	23622248
MIRT040528	hsa-miR-92b-3p	CLASH	23622248
MIRT040213	hsa-miR-615-3p	CLASH	23622248
MIRT040213	hsa-miR-615-3p	CLASH	23622248
MIRT524776	hsa-miR-6771-3p	PAR-CLIP	23446348
MIRT524775	hsa-miR-3675-3p	PAR-CLIP	23446348
MIRT524774	hsa-miR-6849-3p	PAR-CLIP	23446348
MIRT524773	hsa-miR-3190-5p	PAR-CLIP	23446348
MIRT524772	hsa-miR-3926	PAR-CLIP	23446348
MIRT524771	hsa-miR-4684-5p	PAR-CLIP	23446348
MIRT524770	hsa-miR-548s	PAR-CLIP	23446348
MIRT524776	hsa-miR-6771-3p	PAR-CLIP	23446348
MIRT524775	hsa-miR-3675-3p	PAR-CLIP	23446348
MIRT524774	hsa-miR-6849-3p	PAR-CLIP	23446348
MIRT524773	hsa-miR-3190-5p	PAR-CLIP	23446348
MIRT524772	hsa-miR-3926	PAR-CLIP	23446348
MIRT524771	hsa-miR-4684-5p	PAR-CLIP	23446348
MIRT524770	hsa-miR-548s	PAR-CLIP	23446348
MIRT818091	hsa-miR-18a	CLIP-seq
MIRT818092	hsa-miR-18b	CLIP-seq
MIRT818093	hsa-miR-1972	CLIP-seq
MIRT818094	hsa-miR-3149	CLIP-seq
MIRT818095	hsa-miR-3151	CLIP-seq
MIRT818096	hsa-miR-4447	CLIP-seq
MIRT818097	hsa-miR-4468	CLIP-seq
MIRT818098	hsa-miR-4472	CLIP-seq
MIRT818099	hsa-miR-4690-5p	CLIP-seq
MIRT818100	hsa-miR-4735-3p	CLIP-seq
MIRT818101	hsa-miR-4792	CLIP-seq
MIRT818102	hsa-miR-491-5p	CLIP-seq
MIRT818103	hsa-miR-568	CLIP-seq
MIRT1941824	hsa-miR-1266	CLIP-seq
MIRT1941825	hsa-miR-3155	CLIP-seq
MIRT1941826	hsa-miR-3155b	CLIP-seq
MIRT1941827	hsa-miR-3664-3p	CLIP-seq
MIRT1941828	hsa-miR-4286	CLIP-seq
MIRT1941829	hsa-miR-4290	CLIP-seq
MIRT1941830	hsa-miR-4518	CLIP-seq
MIRT1941831	hsa-miR-4755-3p	CLIP-seq
MIRT1941832	hsa-miR-484	CLIP-seq
MIRT1941828	hsa-miR-4286	CLIP-seq
MIRT1941829	hsa-miR-4290	CLIP-seq
MIRT2180692	hsa-miR-602	CLIP-seq
MIRT1941828	hsa-miR-4286	CLIP-seq
MIRT1941829	hsa-miR-4290	CLIP-seq
MIRT2180692	hsa-miR-602	CLIP-seq
MIRT2484117	hsa-miR-103a	CLIP-seq
MIRT2484118	hsa-miR-107	CLIP-seq
MIRT2484119	hsa-miR-1205	CLIP-seq
MIRT2484120	hsa-miR-147	CLIP-seq
MIRT2484121	hsa-miR-1909	CLIP-seq
MIRT2484122	hsa-miR-3911	CLIP-seq
MIRT2484123	hsa-miR-4302	CLIP-seq
MIRT818097	hsa-miR-4468	CLIP-seq
MIRT2484124	hsa-miR-4519	CLIP-seq
MIRT818099	hsa-miR-4690-5p	CLIP-seq
MIRT2484125	hsa-miR-4786-5p	CLIP-seq
MIRT818101	hsa-miR-4792	CLIP-seq
MIRT2484126	hsa-miR-644	CLIP-seq
MIRT2484127	hsa-miR-769-5p	CLIP-seq
MIRT2484119	hsa-miR-1205	CLIP-seq
MIRT2484121	hsa-miR-1909	CLIP-seq
MIRT818093	hsa-miR-1972	CLIP-seq
MIRT818097	hsa-miR-4468	CLIP-seq
MIRT818099	hsa-miR-4690-5p	CLIP-seq
MIRT818101	hsa-miR-4792	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004672	Function	Protein kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	IEA
GO:0004674	Function	Protein serine/threonine kinase activity	ISS
GO:0004722	Function	Protein serine/threonine phosphatase activity	IDA	29779826
GO:0004740	Function	Pyruvate dehydrogenase (acetyl-transferring) kinase activity	IBA
GO:0005515	Function	Protein binding	IPI	18985028, 21988832, 28514442, 32296183, 32814053, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	ISS
GO:0005739	Component	Mitochondrion	HDA	20833797
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	11839747
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006550	Process	L-isoleucine catabolic process	IEA
GO:0006552	Process	L-leucine catabolic process	IEA
GO:0006574	Process	L-valine catabolic process	IEA
GO:0007283	Process	Spermatogenesis	IEA
GO:0008610	Process	Lipid biosynthetic process	IMP	29779826
GO:0009063	Process	Amino acid catabolic process	NAS	2403034
GO:0009083	Process	Branched-chain amino acid catabolic process	IEA
GO:0009083	Process	Branched-chain amino acid catabolic process	ISS
GO:0009083	Process	Branched-chain amino acid catabolic process	TAS	11839747
GO:0010510	Process	Regulation of pyruvate decarboxylation to acetyl-CoA	IBA
GO:0010906	Process	Regulation of glucose metabolic process	IBA
GO:0016301	Function	Kinase activity	IEA
GO:0016301	Function	Kinase activity	TAS	11839747
GO:0016740	Function	Transferase activity	IEA
GO:0016772	Function	Transferase activity, transferring phosphorus-containing groups	IEA
GO:0045252	Component	Oxoglutarate dehydrogenase complex	IEA
GO:0045252	Component	Oxoglutarate dehydrogenase complex	ISS
GO:0045252	Component	Oxoglutarate dehydrogenase complex	TAS	11839747
GO:0047323	Function	[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity	IEA
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0140096	Function	Catalytic activity, acting on a protein	IEA

Other IDs

• MIM: 614901
• HGNC: 16902
• e!Ensembl: ENSG00000103507

Protein

• UniProt ID: O14874
• Protein name: Branched-chain alpha-ketoacid dehydrogenase kinase (BCKDH kinase) (BCKDHKIN) (BDK) (EC 2.7.11.1) ([3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial) (EC 2.7.11.4)
• Protein function: 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
• PDB: 8F5F, 8F5J, 8F5S, 9DI9
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10436	BCDHK_Adom3	69 → 222	Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase	Family
  PF02518	HATPase_c	265 → 403	Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous.
• Sequence:

  MILASVLRSGPGGGLPLRPLLGPALALRARSTSATDTHHVEMARERSKTVTSFYNQSAID
  AAAEKPSVRLTPTMMLYAGRSQDGSHLLKSARYLQQELPVRIAHRIKGFRCLPFIIGCNP
  TILHVHELYIRAFQKLTDFPPIKDQADEAQYCQLVRQLLDDHKDVVTLLAEGLRESRKHI
  EDEKLVRYFLDKTLTSRLGIRMLATHHLALHEDKPDFVGIICTRLSPKKIIEKWVDFARR
  LCEHKYGNAPRVRINGHVAARFPFIPMPLDYILPELLKNAMRATMESHLDTPYNVPDVVI
  TIANNDVDLIIRISDRGGGIAHKDLDRVMDYHFTTAEASTQDPRISPLFGHLDMHSGAQS
  GPMHGFGFGLPTSRAYAEYLGGSLQLQSLQGIGTDVYLRLRHIDGREESFRI

• Sequence length: 412

Pathways

Reactome:

Branched-chain amino acid catabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Branched-chain keto acid dehydrogenase kinase deficiency	Pathogenic; Likely pathogenic	rs2143936992, rs1035318937, rs377423130, rs2544145079, rs369521689, rs397514573, rs2057392733, rs147210405	RCV001706906 RCV002267564 RCV003388178 RCV003487268 RCV000503689 RCV000032959 RCV000032960 RCV000032961	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Intellectual disability	Likely pathogenic	rs2057404166	RCV001291529	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM EPILEPSY SYNDROME DUE TO BRANCHED CHAIN KETOACID DEHYDROGENASE KINASE DEFICIENCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM-EPILEPSY SYNDROME DUE TO BRANCHED CHAIN KETOACID DEHYDROGENASE KINASE DEFICIENCY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BCKDK-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Maple syrup urine disease, mild variant	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Papillary renal cell carcinoma type 1	-	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSON DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer Disease	Alzheimer disease	Pubtator	29777097	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	29777097		★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorder	Autism	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Autism-epilepsy syndrome due to branched chain ketoacid dehydrogenase kinase deficiency	Autism-Epilepsy Syndrome	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic Disorder	Autism	BEFREE	22956686, 26809120		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	26809120	Associate	★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	CLINGEN_DG	16875466, 22956686, 24449431, 26809120, 27472223, 8064409		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	ORPHANET_DG	22956686		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	UNIPROT_DG	22956686, 24449431		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	GENOMICS_ENGLAND_DG	24449431, 27604308		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
BRANCHED-CHAIN KETO ACID DEHYDROGENASE KINASE DEFICIENCY	Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Breast Neoplasms	Breast neoplasm	Pubtator	37460470	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	37715534	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	22956686		★☆☆☆☆ Found in Text Mining only
Epileptic Encephalopathy Early Infantile 3	Developmental and epileptic encephalopathy	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty liver	Pubtator	35797133	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	38054015	Associate	★☆☆☆☆ Found in Text Mining only
Hyperkinesis	Hyperkinesia	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	22956686		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	24449431		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Kidney Neoplasms	Kidney neoplasm	Pubtator	37715534	Associate	★☆☆☆☆ Found in Text Mining only
Lafora Disease	Lafora Disease	BEFREE	28917824		★☆☆☆☆ Found in Text Mining only
Lewy Body Disease	Lewy body disease	Pubtator	28917824	Associate	★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	28051178		★☆☆☆☆ Found in Text Mining only
Maple Syrup Urine Disease	Maple syrup urine disease	Pubtator	26809120, 35205278	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic syndrome	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	35216372	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	26809120	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	29777097	Associate	★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	GWASCAT_DG	25064009, 28892059		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	BEFREE	28917824, 30880162		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Parkinson Disease	Parkinson disease	Pubtator	28917824, 33436766, 35332097	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polycystic Ovary Syndrome	Polycystic ovary syndrome	Pubtator	33678329	Associate	★☆☆☆☆ Found in Text Mining only