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] See more...

Aliases for BCKDK Gene

Aliases for BCKDK Gene

  • Branched Chain Keto Acid Dehydrogenase Kinase 2 3 5
  • [3-Methyl-2-Oxobutanoate Dehydrogenase [Lipoamide]] Kinase, Mitochondrial 3 4
  • BCKD-Kinase 3 4
  • EC 2.7.11.4 4 51
  • BCKDHKIN 3 4
  • 3-Methyl-2-Oxobutanoate Dehydrogenase [Lipoamide] Kinase, Mitochondrial 3
  • Branched Chain Alpha-Ketoacid Dehydrogenase Kinase 3
  • Branched-Chain Alpha-Ketoacid Dehydrogenase Kinase 4
  • Branched Chain Ketoacid Dehydrogenase Kinase 3
  • EC 2.7.11 51
  • BCKDKD 3
  • BCKDK 5
  • BDK 3

External Ids for BCKDK Gene

Previous GeneCards Identifiers for BCKDK Gene

  • GC16P030201
  • GC16P031616
  • GC16P031116
  • GC16P031155
  • GC16P031027
  • GC16P031024
  • GC16P031117
  • GC16P028680
  • GC16P031107
  • GC16P031114
  • GC16P031302
  • GC16P031325
  • GC16P031329
  • GC16P031414
  • GC16P031141
  • GC16P031152
  • GC16P031169
  • GC16P031195
  • GC16P031233
  • GC16P031246
  • GC16P031260
  • GC16P031286

Summaries for BCKDK Gene

Entrez Gene Summary for BCKDK Gene

  • 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]

GeneCards Summary for BCKDK Gene

BCKDK (Branched Chain Keto Acid Dehydrogenase Kinase) is a Protein Coding gene. Diseases associated with BCKDK include Branched-Chain Keto Acid Dehydrogenase Kinase Deficiency and Maple Syrup Urine Disease. Among its related pathways are Viral mRNA Translation and Metabolism. Gene Ontology (GO) annotations related to this gene include protein kinase activity and kinase activity. An important paralog of this gene is PDK1.

UniProtKB/Swiss-Prot Summary for BCKDK Gene

  • Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex.

Gene Wiki entry for BCKDK Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for BCKDK Gene

Genomics for BCKDK Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for BCKDK Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around BCKDK on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for BCKDK

Top Transcription factor binding sites by QIAGEN in the BCKDK gene promoter:
  • AML1a
  • C/EBPbeta
  • COMP1
  • E47
  • Ik-1
  • Pax-5
  • SRF
  • SRF (504 AA)
  • Tal-1

Genomic Locations for BCKDK Gene

Genomic Locations for BCKDK Gene
chr16:31,106,107-31,117,651
(GRCh38/hg38)
Size:
11,545 bases
Orientation:
Plus strand
chr16:31,117,428-31,124,112
(GRCh37/hg19)
Size:
6,685 bases
Orientation:
Plus strand

Genomic View for BCKDK Gene

Genes around BCKDK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
BCKDK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for BCKDK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for BCKDK Gene

Proteins for BCKDK Gene

  • Protein details for BCKDK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14874-BCKD_HUMAN
    Recommended name:
    [3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial
    Protein Accession:
    O14874
    Secondary Accessions:
    • A8MY43
    • Q6FGL4
    • Q96G95
    • Q96IN5

    Protein attributes for BCKDK Gene

    Size:
    412 amino acids
    Molecular mass:
    46360 Da
    Quaternary structure:
    • Monomer.

    Alternative splice isoforms for BCKDK Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for BCKDK Gene

Selected DME Specific Peptides for BCKDK Gene

O14874:
  • YCQLVRQLLDDHKDVVTLLAEGLRESRK
  • KNAMRAT

Post-translational modifications for BCKDK Gene

Domains & Families for BCKDK Gene

Gene Families for BCKDK Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for BCKDK Gene

InterPro:
Blocks:
  • ATP-binding region, ATPase-like
  • Bacterial sensor protein C-terminal signature
ProtoNet:

Suggested Antigen Peptide Sequences for BCKDK Gene

GenScript: Design optimal peptide antigens:
  • Branched-chain alpha-ketoacid dehydrogenase kinase (BCKD_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O14874

UniProtKB/Swiss-Prot:

BCKD_HUMAN :
  • Belongs to the PDK/BCKDK protein kinase family.
Family:
  • Belongs to the PDK/BCKDK protein kinase family.
genes like me logo Genes that share domains with BCKDK: view

Function for BCKDK Gene

Molecular function for BCKDK Gene

UniProtKB/Swiss-Prot Function:
Catalyzes the phosphorylation and inactivation of the branched-chain alpha-ketoacid dehydrogenase complex, the key regulatory enzyme of the valine, leucine and isoleucine catabolic pathways. Key enzyme that regulate the activity state of the BCKD complex.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[3-methyl-2-oxobutanoate dehydrogenase]-L-serine + ATP = [3-methyl-2-oxobutanoate dehydrogenase]-O-phospho-L-serine + ADP + H(+); Xref=Rhea:RHEA:17301, Rhea:RHEA-COMP:13695, Rhea:RHEA-COMP:13696, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.4;.

Enzyme Numbers (IUBMB) for BCKDK Gene

Phenotypes From GWAS Catalog for BCKDK Gene

Gene Ontology (GO) - Molecular Function for BCKDK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity ISS --
GO:0005515 protein binding IPI 18985028
GO:0005524 ATP binding IEA,ISS --
genes like me logo Genes that share ontologies with BCKDK: view
genes like me logo Genes that share phenotypes with BCKDK: view

Human Phenotype Ontology for BCKDK Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

  • Taconic Biosciences Mouse Models for BCKDK

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BCKDK

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for BCKDK Gene

Localization for BCKDK Gene

Subcellular locations from UniProtKB/Swiss-Prot for BCKDK Gene

Mitochondrion matrix. Mitochondrion.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for BCKDK gene
Compartment Confidence
mitochondrion 5
plasma membrane 1
extracellular 1
cytoskeleton 1
peroxisome 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for BCKDK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA,TAS 11839747
GO:0005759 mitochondrial matrix IEA,TAS --
GO:0005947 mitochondrial alpha-ketoglutarate dehydrogenase complex TAS 11839747
genes like me logo Genes that share ontologies with BCKDK: view

Pathways & Interactions for BCKDK Gene

genes like me logo Genes that share pathways with BCKDK: view

Pathways by source for BCKDK Gene

SIGNOR curated interactions for BCKDK Gene

Inactivates:

Gene Ontology (GO) - Biological Process for BCKDK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IEA --
GO:0009063 cellular amino acid catabolic process NAS 2403034
GO:0009083 branched-chain amino acid catabolic process TAS 11839747
GO:0016310 phosphorylation IEA,TAS 11839747
GO:0042593 glucose homeostasis IBA 21873635
genes like me logo Genes that share ontologies with BCKDK: view

Drugs & Compounds for BCKDK Gene

(4) Drugs for BCKDK Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine 5'-[gamma-thio]triphosphate Experimental Pharma Target 0
2-Ketobutyric acid Experimental Pharma 0
ATP Investigational Nutra Agonist, Activator, Partial agonist, Antagonist, Full agonist, Gating inhibitor, Pore Blocker, Potentiation 0

(1) Additional Compounds for BCKDK Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist 58-64-0
genes like me logo Genes that share compounds with BCKDK: view

Transcripts for BCKDK Gene

mRNA/cDNA for BCKDK Gene

3 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for BCKDK

Alternative Splicing Database (ASD) splice patterns (SP) for BCKDK Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b · 3c ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14a · 14b · 14c
SP1: - - - -
SP2: - - -
SP3: - - - -
SP4: - - - - - - - - - - - -
SP5: -
SP6:
SP7:
SP8: - -

Relevant External Links for BCKDK Gene

GeneLoc Exon Structure for
BCKDK

Expression for BCKDK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for BCKDK Gene

Protein differential expression in normal tissues from HIPED for BCKDK Gene

This gene is overexpressed in Salivary gland (6.9) and Gallbladder (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for BCKDK Gene



Protein tissue co-expression partners for BCKDK Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for BCKDK

SOURCE GeneReport for Unigene cluster for BCKDK Gene:

Hs.513520

mRNA Expression by UniProt/SwissProt for BCKDK Gene:

O14874-BCKD_HUMAN
Tissue specificity: Ubiquitous.

Evidence on tissue expression from TISSUES for BCKDK Gene

  • Liver(4.6)
  • Lung(4.3)
  • Nervous system(4.3)
  • Muscle(3.1)
  • Kidney(2.6)
  • Heart(2.5)
  • Skin(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for BCKDK Gene

Germ Layers:
  • ectoderm
Systems:
  • nervous
Regions:
Head and neck:
  • brain
  • head
genes like me logo Genes that share expression patterns with BCKDK: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for BCKDK Gene

Orthologs for BCKDK Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for BCKDK Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia BCKDK 30 31
  • 99.6 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia BCKDK 30 31
  • 90.7 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia BCKDK 30 31
  • 90.05 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia BCKDK 31
  • 90 (a)
OneToOne
Mouse
(Mus musculus)
Mammalia Bckdk 30 17 31
  • 87.94 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Bckdk 30
  • 87.62 (n)
Platypus
(Ornithorhynchus anatinus)
Mammalia BCKDK 31
  • 76 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia BCKDK 31
  • 83 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia bckdk 30
  • 75.92 (n)
Str.19966 30
African clawed frog
(Xenopus laevis)
Amphibia Xl.32994 30
Zebrafish
(Danio rerio)
Actinopterygii bckdk 30 31
  • 72.85 (n)
OneToOne
Dr.25159 30
A. gosspyii yeast
(Eremothecium gossypii)
Saccharomycetes AGOS_ADL116C 30
  • 45.34 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PKP1 30 31 33
  • 45.04 (n)
OneToMany
K. Lactis Yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0E04533g 30
  • 43.07 (n)
Bread mold
(Neurospora crassa)
Ascomycetes NCU04349 30
  • 50.05 (n)
Species where no ortholog for BCKDK was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for BCKDK Gene

ENSEMBL:
Gene Tree for BCKDK (if available)
TreeFam:
Gene Tree for BCKDK (if available)
Aminode:
Evolutionary constrained regions (ECRs) for BCKDK: view image

Paralogs for BCKDK Gene

Paralogs for BCKDK Gene

(2) SIMAP similar genes for BCKDK Gene using alignment to 8 proteins:

  • BCKD_HUMAN
  • A8MY43_HUMAN
  • H3BNP3_HUMAN
  • H3BQP2_HUMAN
  • H3BS02_HUMAN
  • H3BTL2_HUMAN
  • H3BUV3_HUMAN
  • Q96G95_HUMAN
genes like me logo Genes that share paralogs with BCKDK: view

Variants for BCKDK Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for BCKDK Gene

SNP ID Clinical significance and condition Chr 16 pos Variation AA Info Type
640951 Uncertain Significance: Branched-chain keto acid dehydrogenase kinase deficiency 31,109,500(+) TC/T INTRON_VARIANT
650837 Uncertain Significance: Branched-chain keto acid dehydrogenase kinase deficiency 31,109,416(+) A/G MISSENSE_VARIANT
709678 Likely Benign: not provided 31,111,196(+) G/A SYNONYMOUS_VARIANT
720197 Likely Benign: Branched-chain keto acid dehydrogenase kinase deficiency 31,111,859(+) A/G INTRON_VARIANT
756783 Likely Benign: Branched-chain keto acid dehydrogenase kinase deficiency 31,109,780(+) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for BCKDK Gene

Structural Variations from Database of Genomic Variants (DGV) for BCKDK Gene

Variant ID Type Subtype PubMed ID
nsv457483 CNV loss 19166990
nsv571820 CNV loss 21841781
nsv833193 CNV gain+loss 17160897

Variation tolerance for BCKDK Gene

Residual Variation Intolerance Score: 13.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.06; 21.61% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for BCKDK Gene

Human Gene Mutation Database (HGMD)
BCKDK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
BCKDK

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for BCKDK Gene

Disorders for BCKDK Gene

MalaCards: The human disease database

(6) MalaCards diseases for BCKDK Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
branched-chain keto acid dehydrogenase kinase deficiency
  • bckdkd
maple syrup urine disease
  • dihydrolipoamide dehydrogenase deficiency
autism
  • autistic disorder
organic acidemia
  • organic acid metabolism disorder
epilepsy
  • epilepsy syndrome
- elite association - COSMIC cancer census association via MalaCards
Search BCKDK in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

BCKD_HUMAN
  • Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD) [MIM:614923]: A metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids. {ECO:0000269 PubMed:22956686, ECO:0000269 PubMed:24449431}. Note=The disease is caused by mutations affecting the gene represented in this entry. A diet enriched in branched amino acids (BCAAs) allows to normalize plasma BCAA levels. This suggests that it may be possible to treat patients with mutations in BCKDK with BCAA supplementation.

Additional Disease Information for BCKDK

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with BCKDK: view

No data available for Genatlas for BCKDK Gene

Publications for BCKDK Gene

  1. Two novel mutations in the BCKDK (branched-chain keto-acid dehydrogenase kinase) gene are responsible for a neurobehavioral deficit in two pediatric unrelated patients. (PMID: 24449431) García-Cazorla A … Agulló SB (Human mutation 2014) 3 4
  2. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  3. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41
  4. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4
  5. Tissue-specific translation of murine branched-chain alpha-ketoacid dehydrogenase kinase mRNA is dependent upon an upstream open reading frame in the 5'-untranslated region. (PMID: 15302860) Muller EA … Danner DJ (The Journal of biological chemistry 2004) 3 23

Products for BCKDK Gene

Sources for BCKDK Gene