Gene: BCKDHA

Alternate names for this Gene: BCKDE1A|MSU|MSUD1|OVD1A

Gene Summary: The branched-chain alpha-keto acid (BCAA) dehydrogenase (BCKD) complex is an innter mitochondrial enzyme complex that catalyzes the second major step in the catabolism of the branched-chain amino acids leucine, isoleucine, and valine. The BCKD complex consists of three catalytic components: a heterotetrameric (alpha2-beta2) branched-chain alpha-keto acid decarboxylase (E1), a dihydrolipoyl transacylase (E2), and a dihydrolipoamide dehydrogenase (E3). This gene encodes the alpha subunit of the decarboxylase (E1) component. Mutations in this gene result in maple syrup urine disease, type IA. Multiple transcript variants encoding different isoforms have been found for this gene.

Gene is located in Chromosome: 19

Location in Chromosome : 19q13.2

Description of this Gene: branched chain keto acid dehydrogenase E1 subunit alpha

Type of Gene: protein-coding

rs4674 in BCKDHA gene and Body Height PMID 31562340 2019 Characterizing rare and low-frequency height-associated variants in the Japanese population.

PMID 25282103 2014 Defining the role of common variation in the genomic and biological architecture of adult human height.

rs137852870 in BCKDHA gene and Maple Syrup Urine Disease PMID 21844576 2011 Three Korean patients with maple syrup urine disease: four novel mutations in the BCKDHA gene.

PMID 9582350 1998 Impaired assembly of E1 decarboxylase of the branched-chain alpha-ketoacid dehydrogenase complex in type IA maple syrup urine disease.

PMID 8037208 1994 Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.

PMID 14567968 2004 Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression.

PMID 21098507 2011 Phenylbutyrate therapy for maple syrup urine disease.

PMID 7883996 1995 Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients.

PMID 24881969 2014 Nutrition management guideline for maple syrup urine disease: an evidence- and consensus-based approach.

PMID 2703538 1989 Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.

PMID 14517957 2003 Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease.

PMID 2241958 1990 A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients.

PMID 1867199 1991 Occurrence of a Tyr393----Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population.

PMID 16468966 2006 Elective liver transplantation for the treatment of classical maple syrup urine disease.

PMID 1885764 1991 Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex.

PMID 11507102 2001 Natural osmolyte trimethylamine N-oxide corrects assembly defects of mutant branched-chain alpha-ketoacid decarboxylase in maple syrup urine disease.

PMID 8161368 1993 Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex.

PMID 2060625 1991 Based on this gene structure, exon 9 contains the Tyr393----Asn mutation previously identified in the E1 alpha subunit of Mennonite and other maple syrup urine disease (MSUD) patients.

PMID 26257134 2015 Identification of mutations, genotype-phenotype correlation and prenatal diagnosis of maple syrup urine disease in Indian patients.

PMID 19480318 2009 Molecular genetics of maple syrup urine disease in the Turkish population.

PMID 2060625 1991 Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex.

PMID 22727569 2012 Analysis of gene mutations in Chinese patients with maple syrup urine disease.

PMID 16786533 2006 Mutational spectrum of maple syrup urine disease in Spain.

PMID 19715473 2009 Maple syrup urine disease in Cypriot families: identification of three novel mutations and biochemical characterization of the p.Thr211Met mutation in the E1alpha subunit.

PMID 22593002 2012 Molecular genetic analysis of MSUD from India reveals mutations causing altered protein truncation affecting the C-termini of E1α and E1β.

PMID 17922217 2007 Description of the mutations in 15 subjects with variant forms of maple syrup urine disease.

PMID 26232051 2015 Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis.

PMID 25255367 2015 Development of DNA confirmatory and high-risk diagnostic testing for newborns using targeted next-generation DNA sequencing.

PMID 25087612 2014 Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.

PMID 18378174 2008 Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community.

PMID 19456321 2009 Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene.

PMID 26901124 2016 Identification of six novel mutations in Iranian patients with maple syrup urine disease and their in silico analysis.

PMID 11069910 2001 Roles of active site and novel K+ ion-binding site residues in human mitochondrial branched-chain alpha-ketoacid decarboxylase/dehydrogenase.

PMID 10745006 2000 Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease.

PMID 11825067 2002 Evidence of common ancestry for the maple syrup urine disease (MSUD) Y438N allele in non-Mennonite MSUD patients.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 10694918 1998 A nonsense mutation (R242X) in the branched-chain alpha-keto acid dehydrogenase E1alpha subunit gene (BCKDHA) as a cause of maple syrup urine disease. Mutations in brief no. 160. Online.

PMID 26830710 2016 Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

rs137852870 in BCKDHA gene and Maple syrup urine disease, type 1A PMID 14567968 2004 Relationship of causative genetic mutations in maple syrup urine disease with their clinical expression.

PMID 2703538 1989 Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.

PMID 12888983 2003 Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania.

PMID 14517957 2003 Identification of twelve novel mutations in patients with classic and variant forms of maple syrup urine disease.

PMID 19480318 2009 Molecular genetics of maple syrup urine disease in the Turkish population.

PMID 26830710 2016 Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.

PMID 8037208 1994 Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex.

PMID 27403441 2016 Mass Spectrometry-Based Metabolomic and Proteomic Strategies in Organic Acidemias.

PMID 21098507 2011 Phenylbutyrate therapy for maple syrup urine disease.

PMID 10694918 1998 A nonsense mutation (R242X) in the branched-chain alpha-keto acid dehydrogenase E1alpha subunit gene (BCKDHA) as a cause of maple syrup urine disease. Mutations in brief no. 160. Online.

PMID 23765052 2014 Next-generation carrier screening.

PMID 21228398 2011 Carrier testing for severe childhood recessive diseases by next-generation sequencing.

PMID 24374108 2014 Validation for clinical use of, and initial clinical experience with, a novel approach to population-based carrier screening using high-throughput, next-generation DNA sequencing.

rs4802117 in BCKDHA gene and RDW - Red blood cell distribution width result PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs4802117 in BCKDHA gene and Red cell distribution width determination PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.