BCKDK

branched chain keto acid dehydrogenase kinase

Basic information

Region (hg38): 16:31106107-31112791

Links

ENSG00000103507

∙ NCBI:10295 ∙ OMIM:614901 ∙ HGNC:16902 ∙ Uniprot:O14874 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

branched-chain keto acid dehydrogenase kinase deficiency (Strong), mode of inheritance: AR
branched-chain keto acid dehydrogenase kinase deficiency (Strong), mode of inheritance: AR
branched-chain keto acid dehydrogenase kinase deficiency (Supportive), mode of inheritance: AR
branched-chain keto acid dehydrogenase kinase deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Branched-chain ketoacid dehydrogenase kinase deficiency	AR	Biochemical	Individuals may present with features such as autism, microcephaly, and epilepsy, and dietary management (eg, with high protein diet and branch-chain amino acid supplementation) has been shown to result in laboratory-based and clinical improvement	Biochemical; Dermatologic; Neurologic	22956686; 36729635

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BCKDK gene.

Branched-chain_keto_acid_dehydrogenase_kinase_deficiency (96 variants)
Inborn_genetic_diseases (47 variants)
not_provided (44 variants)
not_specified (9 variants)
BCKDK-related_disorder (8 variants)
Maple_syrup_urine_disease,_mild_variant (1 variants)
Maple_syrup_urine_disease_type_1A (1 variants)
Intellectual_disability (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BCKDK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005881.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2 clinvar	37 clinvar	1 clinvar	40
missense	1 clinvar	1 clinvar	81 clinvar	4 clinvar		87
nonsense	1 clinvar	4 clinvar				5
start loss						0
frameshift	2 clinvar	1 clinvar				3
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	1 clinvar			3
Total	5	7	84	41	1

Highest pathogenic variant AF is 0.0000167285

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BCKDK	protein_coding	protein_coding	ENST00000394951	11	6683

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000566	0.974	125718	0	29	125747	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.64	209	287	0.728	0.0000204	2664
Missense in Polyphen		56	100.07	0.5596		957
Synonymous	-0.181	124	121	1.02	0.00000865	868
Loss of Function	2.00	10	19.6	0.511	9.17e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000178
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000165	0.000163
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:24449431}.;
Disease: DISEASE: 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.;
Pathway: Branched-chain amino acid catabolism;Metabolism of amino acids and derivatives;Metabolism (Consensus)

Recessive Scores

pRec: 0.123

Intolerance Scores

loftool: 0.664
rvis_EVS: -0.54
rvis_percentile_EVS: 20.54

Haploinsufficiency Scores

pHI: 0.193
hipred: N
hipred_score: 0.464
ghis: 0.511

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.929

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Bckdk
Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; muscle phenotype;

Gene ontology

Biological process: protein phosphorylation;cellular amino acid catabolic process;branched-chain amino acid catabolic process;phosphorylation
Cellular component: mitochondrion;mitochondrial matrix;mitochondrial alpha-ketoglutarate dehydrogenase complex
Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;[3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] kinase activity