BCKDK Gene

Name	branched chain ketoacid dehydrogenase kinase
Description	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 BCKD. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BCKDK (branched‐chain α‐keto acid dehydrogenase kinase) is a key regulator of branched‐chain amino acid (BCAA) catabolism. By phosphorylating and thereby inactivating the branched‐chain α‐keto acid dehydrogenase (BCKDH) complex, BCKDK governs the flux of BCAA oxidation, which is essential for maintaining proper BCAA levels and normal metabolic homeostasis. Disruption or inactivation of BCKDK—through genetic mutations that eliminate its kinase activity—leads to unchecked BCKDH activity, causing abnormally low levels of BCAAs. Such dysregulation has been associated with neurodevelopmental deficits including autism spectrum disorders, developmental delay, microcephaly, and seizures, highlighting its critical role in brain function and neural development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its metabolic regulation in the nervous system, BCKDK has emerged as an important player in cancer biology. Elevated expression of BCKDK has been reported in several malignancies—including colorectal, ovarian, and non‐small cell lung cancers—where it promotes tumorigenesis by activating the MEK/ERK signaling cascade, thereby enhancing cell proliferation, migration, and epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": " Structure‐based design studies have even led to the development of specific BCKDK inhibitors that bind novel allosteric sites to relieve its negative regulation of BCKDH, thereby offering promising therapeutic avenues for conditions associated with aberrant BCAA metabolism.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, under conditions where the conventional pyruvate dehydrogenase kinases are absent, BCKDK can act in a compensatory manner to phosphorylate the pyruvate dehydrogenase complex, indicating a broader regulatory role that connects BCAA catabolism with glucose oxidation and overall energy metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of BCKDK as not only a gatekeeper of BCAA homeostasis essential for neurological function, but also as a modulator of oncogenic signaling pathways. Its dysregulation contributes to both metabolic and proliferative disorders, suggesting that therapeutic strategies aimed at modulating BCKDK activity may have broad clinical applications.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mandar A Joshi, Nam Ho Jeoung, Mariko Obayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired growth and neurological abnormalities in branched-chain alpha-keto acid dehydrogenase kinase-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20060869"}], "href": "https://doi.org/10.1042/BJ20060869"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16875466"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16875466"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Angels García-Cazorla, Alfonso Oyarzabal, Joana Fort, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22513"}], "href": "https://doi.org/10.1002/humu.22513"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24449431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24449431"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "François Boemer, Claire Josse, Géraldine Luis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel Loss of Function Variant in BCKDK Causes a Treatable Developmental and Epileptic Encephalopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23042253"}], "href": "https://doi.org/10.3390/ijms23042253"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35216372"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35216372"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qin Tian, Ping Yuan, Chuntao Quan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation of BCKDK of BCAA catabolism at Y246 by Src promotes metastasis of colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-020-1262-z"}], "href": "https://doi.org/10.1038/s41388-020-1262-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32238881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32238881"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Huashun Li, Dongyang Yu, Lianbing Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCKDK Promotes Ovarian Cancer Proliferation and Migration by Activating the MEK/ERK Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2022/3691635"}], "href": "https://doi.org/10.1155/2022/3691635"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35498541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35498541"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yanhui Wang, Jiawei Xiao, Wenna Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCKDK alters the metabolism of non-small cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Lung Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.21037/tlcr-21-885"}], "href": "https://doi.org/10.21037/tlcr-21-885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35070754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35070754"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Lia Heinemann-Yerushalmi, Lital Bentovim, Neta Felsenthal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BCKDK regulates the TCA cycle through PDC in the absence of PDK family during embryonic development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2021.03.007"}], "href": "https://doi.org/10.1016/j.devcel.2021.03.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33773101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33773101"}]}]}]}
Synonyms	BCKDKD
Proteins	BCKD_HUMAN
NCBI Gene ID	10295
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

BCKDK has 5,853 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 135 datasets.

Click the + buttons to view associations for BCKDK from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

BCKDK Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCKDK gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCKDK gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of BCKDK gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of BCKDK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of BCKDK gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of BCKDK gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of BCKDK gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BCKDK gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of BCKDK gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of BCKDK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of BCKDK gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of BCKDK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with BCKDK gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with BCKDK protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of BCKDK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of BCKDK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of BCKDK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with BCKDK gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with BCKDK gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of BCKDK gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing BCKDK protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of BCKDK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing BCKDK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing BCKDK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing BCKDK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing BCKDK protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with BCKDK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with BCKDK protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of BCKDK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with BCKDK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with BCKDK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with BCKDK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of BCKDK protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by BCKDK gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving BCKDK gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with BCKDK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with BCKDK gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with BCKDK gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with BCKDK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with BCKDK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.