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    BCKDHA branched chain keto acid dehydrogenase E1 subunit alpha [ Homo sapiens (human) ]

    Gene ID: 593, updated on 9-Dec-2024

    Summary

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    Official Symbol
    BCKDHAprovided by HGNC
    Official Full Name
    branched chain keto acid dehydrogenase E1 subunit alphaprovided by HGNC
    Primary source
    HGNC:HGNC:986
    See related
    Ensembl:ENSG00000248098 MIM:608348; AllianceGenome:HGNC:986
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    MSU; MSUD1; OVD1A; MSUD1A; BCKDE1A
    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.[provided by RefSeq, Sep 2009]
    Expression
    Ubiquitous expression in heart (RPKM 29.4), kidney (RPKM 27.9) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See BCKDHA in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (41397818..41425002)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (44219041..44246226)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (41903723..41930907)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14679 Neighboring gene B9 domain containing 2 Neighboring gene transmembrane protein 91 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10665 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:41885758-41885931 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:41889835-41890334 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:41892254-41892432 Neighboring gene exosome component 5 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:41903234-41903906 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:41903907-41904578 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:41912476-41913430 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:41913431-41914386 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14681 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10666 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10667 Neighboring gene VISTA enhancer hs1948 Neighboring gene UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 8 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14682 Neighboring gene distal membrane arm assembly component 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification. Mitsubuchi H, et al. J Inherit Metab Dis, 1992. PMID 1356170
    2. DNA carrier testing and newborn screening for maple syrup urine disease in Old Order Mennonite communities. Carleton SM, et al. Genet Test Mol Biomarkers, 2010 Apr. PMID 20136525, Free PMC Article
    3. Maple syrup urine disease in Cypriot families: identification of three novel mutations and biochemical characterization of the p.Thr211Met mutation in the E1alpha subunit. Georgiou T, et al. Genet Test Mol Biomarkers, 2009 Oct. PMID 19715473, Free PMC Article
    4. Revisiting MSUD in Portuguese Gypsies: evidence for a founder mutation and for a mutational hotspot within the BCKDHA gene. Quental S, et al. Ann Hum Genet, 2009 May. PMID 19456321
    5. Maple syrup urine disease due to a new large deletion at BCKDHA caused by non-homologous recombination. Quental S, et al. J Inherit Metab Dis, 2008 Dec. PMID 19085071

    See all (106) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.
      Title: Three novel mutations of the BCKDHA, BCKDHB and DBT genes in Chinese children with maple syrup urine disease.
    2. Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.
      Title: Association of BCAT2 and BCKDH polymorphisms with clinical, anthropometric and biochemical parameters in young adults.
    3. Six different novel genetic variants were validated in BCKDHB gene and BCKDHA gene, including c.523 T > C, c.659delA, c.550delT, c.863G > A and two gross deletions
      Title: Clinical characteristics and mutation analysis of five Chinese patients with maple syrup urine disease.
    4. pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease
      Title: In silico prediction of the pathogenic effect of a novel variant of BCKDHA leading to classical maple syrup urine disease identified using clinical exome sequencing.
    5. Data suggest that the following genetic modifications are involved in patients with maple syrup urine disease in Iran: (1) mutation in BCKDHA (branched chain keto acid dehydrogenase E1 alpha); (2) mutation in BCKDHB (branched chain keto acid dehydrogenase E1 subunit beta); (3) mutation in DBT (dihydrolipoamide branched chain transacylase E2; one patient).
      Title: Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease.
    6. we identified seven novel genetic variants: p.Leu549Pro, p.Glu564*, p.Leu641Pro in MUT, p.Tyr206Cys in PCCB, p.His194Arg, p.Val298Met in BCKDHA and p.Glu286_Met290del in BCKDHB gene. In silico and/or eukaryotic expression studies confirmed pathogenic effect of all novel genetic variants
      Title: Molecular and phenotypic characteristics of seven novel mutations causing branched-chain organic acidurias.
    7. Five novel mutations in BCKDHA were identified in MSUD patients.
      Title: Eleven novel mutations of the BCKDHA, BCKDHB and DBT genes associated with maple syrup urine disease in the Chinese population: Report on eight cases.
    8. The novel DBT mutation c.650-651insT was more prevalent than the deleted 4.7-kb heterozygote in the Amis population. The reported 4.7-kb deletion indicating a possible founder mutation may be preserved.
      Title: Different gene preferences of maple syrup urine disease in the aboriginal tribes of Taiwan.
    9. Targeted parallel sequencing revealed novel mutations in the gene BCKDHA for prenatal testing of maple syrup urine disease.
      Title: Integration of targeted sequencing and NIPT into clinical practice in a Chinese family with maple syrup urine disease.
    10. Data from infant/her heterozygous parents (first cousins) suggest homozygous mutation (S144I) in BCKDHA can result in maple syrup urine disease (IA); molecular modeling suggests this missense mutation in exon 4 affects protein stability. [CASE STUDY]
      Title: Identification of a novel homozygous mutation (S144I) in a Malay patient with maple syrup urine disease.
    Submit: New GeneRIF Correction See all GeneRIFs (24)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Potential readthrough

    Included gene: TMEM91

    Homology

    Clone Names

    • FLJ45695

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    contributes_to branched-chain alpha-keto acid dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables carboxy-lyase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in branched-chain amino acid catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in branched-chain amino acid catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in branched-chain amino acid catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    part_of branched-chain alpha-ketoacid dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of branched-chain alpha-ketoacid dehydrogenase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in mitochondrial matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HDA PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of oxoglutarate dehydrogenase complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
    Names
    2-oxoisovalerate dehydrogenase (lipoamide)
    BCKDH E1-alpha
    branched chain keto acid dehydrogenase E1 alpha protein
    branched chain keto acid dehydrogenase E1, alpha polypeptide
    branched-chain alpha-keto acid dehydrogenase E1 component alpha chain
    NP_000700.1
    NP_001158255.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_013004.1 RefSeqGene

      Range
      5030..32214
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000709.4 → NP_000700.1  2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000700.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK298188, BC023983, BQ018849
      Consensus CDS
      CCDS12581.1
      UniProtKB/Swiss-Prot
      B4DP47, E7EW46, P12694, Q16034, Q16472
      UniProtKB/TrEMBL
      B2R8A9
      Related
      ENSP00000269980.2, ENST00000269980.7
      Conserved Domains (2) summary
      PLN02374
      Location:17 → 413
      PLN02374; pyruvate dehydrogenase (acetyl-transferring)
      pfam00676
      Location:106 → 405
      E1_dh; Dehydrogenase E1 component

    2. NM_001164783.2 → NP_001158255.1  2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_001158255.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The resulting isoform (2) lacks one internal amino acid, compared to isoform 1.
      Source sequence(s)
      AB209828, AK298188, BI910860, BQ018849
      UniProtKB/TrEMBL
      B2R8A9, Q59EI3
      Conserved Domains (2) summary
      PLN02374
      Location:17 → 412
      PLN02374; pyruvate dehydrogenase (acetyl-transferring)
      pfam00676
      Location:106 → 404
      E1_dh; Dehydrogenase E1 component

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      41397818..41425002
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      44219041..44246226
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P12694.2 GenPept UniProtKB/Swiss-Prot:P12694

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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