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    BCKDHB branched chain keto acid dehydrogenase E1 subunit beta [ Homo sapiens (human) ]

    Gene ID: 594, updated on 10-Dec-2024

    Summary

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    Official Symbol
    BCKDHBprovided by HGNC
    Official Full Name
    branched chain keto acid dehydrogenase E1 subunit betaprovided by HGNC
    Primary source
    HGNC:HGNC:987
    See related
    Ensembl:ENSG00000083123 MIM:248611; AllianceGenome:HGNC:987
    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
    E1B; OVD1B; MSUD1B; BCKDE1B; BCKDH E1-beta
    Summary
    This gene encodes the E1 beta subunit of branched-chain keto acid dehydrogenase, which is a multienzyme complex associated with the inner membrane of mitochondria. This enzyme complex functions in the catabolism of branched-chain amino acids. Mutations in this gene have been associated with maple syrup urine disease (MSUD), type 1B, a disease characterized by a maple syrup odor to the urine in addition to mental and physical retardation and feeding problems. Alternative splicing at this locus results in multiple transcript variants. [provided by RefSeq, Jan 2016]
    Expression
    Ubiquitous expression in liver (RPKM 2.7), fat (RPKM 2.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See BCKDHB in Genome Data Viewer
    Location:
    6q14.1
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (80106610..80466676)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (81315017..81677450)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (80816327..81172940)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene Rho GTPase activating protein 21 pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:80816184-80816684 Neighboring gene adenylate kinase 4 pseudogene 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:80921809-80922003 Neighboring gene ribosomal protein L17 pseudogene 25 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:81148056-81149255 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:81193272-81193889 Neighboring gene uncharacterized LOC112267962 Neighboring gene ribosomal protein SA pseudogene 72 Neighboring gene NANOG hESC enhancer GRCh37_chr6:81225104-81225623 Neighboring gene Sharpr-MPRA regulatory region 6183 Neighboring gene uncharacterized LOC105377869 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:81245601-81246800 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:81257567-81258766

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Structural organization and chromosomal localization of the gene for the E1 beta subunit of human branched chain alpha-keto acid dehydrogenase. Mitsubuchi H, et al. J Biol Chem, 1991 Aug 5. PMID 1860867
    2. The two active sites in human branched-chain alpha-keto acid dehydrogenase operate independently without an obligatory alternating-site mechanism. Li J, et al. J Biol Chem, 2007 Apr 20. PMID 17329260
    3. Branched chain alpha-keto acid dehydrogenase, E1-beta subunit gene is associated with premature ovarian failure. Kang H, et al. Fertil Steril, 2008 Mar. PMID 17524396
    4. A versatile conformational switch regulates reactivity in human branched-chain alpha-ketoacid dehydrogenase. Machius M, et al. Structure, 2006 Feb. PMID 16472748
    5. Structural and biochemical basis for novel mutations in homozygous Israeli maple syrup urine disease patients: a proposed mechanism for the thiamin-responsive phenotype. Chuang JL, et al. J Biol Chem, 2004 Apr 23. PMID 14742428

    See all (75) 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. Neonatal maple syrup urine disease in China: two novel mutations in the BCKDHB gene and literature review.
      Title: Neonatal maple syrup urine disease in China: two novel mutations in the BCKDHB gene and literature review.
    3. 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.
    4. Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease.
      Title: Identification of novel mutations in BCKDHB and DBT genes in Vietnamese patients with maple sirup urine disease.
    5. Two heterozygous mutations c.284G>C (p.Gly95Ala) and c.853C>T (p.Arg285*) of the BCKDHB gene were associated with a pedigree affected with maple syrup urine disease.
      Title: [Mutation analysis and prenatal diagnosis for a pedigree affected with maple syrup urine disease].
    6. 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.
    7. 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.
    8. 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.
    9. Five novel mutations in BCKDHB 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.
    10. we describe the presenting symptoms and clinical course of a Chinese boy with intermittent Intermittent maple syrup urine disease from BCKDHB gene mutation
      Title: Two novel compound heterozygous mutations in the BCKDHB gene that cause the intermittent form of 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

    EBI GWAS Catalog

    Description
    Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans.
    EBI GWAS Catalog
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
    EBI GWAS Catalog

    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

    Homology

    Clone Names

    • FLJ17880, FLJ44134, DKFZp686A09102

    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 
    contributes_to 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    contributes_to branched-chain alpha-keto acid dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-containing complex binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to cAMP IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to glucocorticoid IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to nutrient IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 IMP
    Inferred from Mutant Phenotype
    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 HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    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 beta, mitochondrial
    Names
    E1b-beta subunit of the branched-chain complex
    branched chain alpha-ketoacid dehydrogenase E1-beta subunit
    branched chain keto acid dehydrogenase E1 beta
    branched chain keto acid dehydrogenase E1, beta polypeptide
    branched-chain alpha-keto acid dehydrogenase E1 component beta chain
    testis secretory sperm-binding protein Li 240mP
    NP_000047.1
    NP_001305904.1
    NP_001410964.1
    NP_001410965.1
    NP_001410966.1
    NP_001410967.1
    NP_001410968.1
    NP_001410969.1
    NP_001410970.1
    NP_001410971.1
    NP_001410972.1
    NP_001410973.1
    NP_001410974.1
    NP_898871.1
    XP_005248813.1
    XP_047275163.1
    XP_047275166.1
    XP_047275167.1
    XP_047275168.1
    XP_047275169.1
    XP_047275170.1
    XP_054212115.1
    XP_054212118.1
    XP_054212120.1
    XP_054212122.1

    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_009775.3 RefSeqGene

      Range
      5063..244662
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000056.5 → NP_000047.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000047.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate segment in the 3' UTR compared to transcript variant 1. Both variants 1 and 2 encode the same protein (isoform 1).
      Source sequence(s)
      CA447889, U50708
      Consensus CDS
      CCDS4994.1
      UniProtKB/Swiss-Prot
      P21953, Q5T2J3, Q9BQL0
      UniProtKB/TrEMBL
      A0A0K2GN21, A0A140VKB3
      Related
      ENSP00000348880.5, ENST00000356489.9
      Conserved Domains (1) summary
      PTZ00182
      Location:66 → 390
      PTZ00182; 3-methyl-2-oxobutanate dehydrogenase; Provisional

    2. NM_001318975.1 → NP_001305904.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternate splice site in the 5' region and initiates translation at a downstream start codon compared to variant 1. The encoded isoform (2) is shorter than isoform 1. Variants 3 and 13 both encode the same isoform (2).
      Source sequence(s)
      AK304353, AL049696, CA447889, DC422376, M55575
      UniProtKB/TrEMBL
      B4E2N3, B7ZB80
      Conserved Domains (1) summary
      PTZ00182
      Location:1 → 320
      PTZ00182; 3-methyl-2-oxobutanate dehydrogenase; Provisional

    3. NM_001424035.1 → NP_001410964.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 3 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) encodes the longest isoform (3).
      Source sequence(s)
      AL049696, AL359715, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    4. NM_001424036.1 → NP_001410965.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 1 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL359715, AL391595
      UniProtKB/Swiss-Prot
      P21953, Q5T2J3, Q9BQL0
      UniProtKB/TrEMBL
      A0A0K2GN21, A0A140VKB3

    5. NM_001424037.1 → NP_001410966.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 4 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL359715, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    6. NM_001424038.1 → NP_001410967.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 5 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    7. NM_001424039.1 → NP_001410968.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 6 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    8. NM_001424040.1 → NP_001410969.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 7 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    9. NM_001424041.1 → NP_001410970.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 8 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    10. NM_001424042.1 → NP_001410971.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 9 precursor

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    11. NM_001424043.1 → NP_001410972.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 2

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595
      UniProtKB/TrEMBL
      B4E2N3, B7ZB80

    12. NM_001424044.1 → NP_001410973.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 10 precursor

      Status: REVIEWED

      Source sequence(s)
      AL391595
      UniProtKB/TrEMBL
      A0A0K2GN21

    13. NM_001424045.1 → NP_001410974.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 11 precursor

      Status: REVIEWED

      Source sequence(s)
      AL391595
      Related
      ENSP00000358775.4, ENST00000369760.8

    14. NM_183050.4 → NP_898871.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_898871.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes isoform 1. Both variants 1 and 2 encode the same protein (isoform 1).
      Source sequence(s)
      AL049696, CA447889, DC372349, M55575
      Consensus CDS
      CCDS4994.1
      UniProtKB/Swiss-Prot
      P21953, Q5T2J3, Q9BQL0
      UniProtKB/TrEMBL
      A0A0K2GN21, A0A140VKB3
      Related
      ENSP00000318351.5, ENST00000320393.9
      Conserved Domains (1) summary
      PTZ00182
      Location:66 → 390
      PTZ00182; 3-methyl-2-oxobutanate dehydrogenase; Provisional

    RNA

    1. NR_134945.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate internal exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AL049696, BC034481, CA447889

    2. NR_187561.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595

    3. NR_187562.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595

    4. NR_187563.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595

    5. NR_187564.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595

    6. NR_187565.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AL049696, AL391595

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      80106610..80466676
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047419211.1 → XP_047275167.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X9

      UniProtKB/TrEMBL
      A0A0K2GN21

    2. XM_047419212.1 → XP_047275168.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X9

      UniProtKB/TrEMBL
      A0A0K2GN21

    3. XM_047419210.1 → XP_047275166.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X8

      UniProtKB/TrEMBL
      A0A0K2GN21

    4. XM_047419207.1 → XP_047275163.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      P21953, Q5T2J3, Q9BQL0
      UniProtKB/TrEMBL
      A0A0K2GN21, A0A140VKB3

    5. XM_005248756.6 → XP_005248813.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X3

      UniProtKB/TrEMBL
      A0A0K2GN21
      Conserved Domains (2) summary
      cd07036
      Location:75 → 241
      TPP_PYR_E1-PDHc-beta_like; Pyrimidine (PYR) binding domain of the beta subunits of the E1 components of human pyruvate dehydrogenase complex (E1- PDHc) and related proteins
      pfam02780
      Location:262 → 346
      Transketolase_C; Transketolase, C-terminal domain

    6. XM_047419213.1 → XP_047275169.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X5

      UniProtKB/TrEMBL
      A0A0K2GN21

    7. XM_047419214.1 → XP_047275170.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X7

      UniProtKB/TrEMBL
      B4E2N3, B7ZB80

    RNA

    1. XR_001743546.3 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      81315017..81677450
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054356140.1 → XP_054212115.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      P21953, Q5T2J3, Q9BQL0
      UniProtKB/TrEMBL
      A0A0K2GN21, A0A140VKB3

    2. XM_054356143.1 → XP_054212118.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X3

      UniProtKB/TrEMBL
      A0A0K2GN21

    3. XM_054356145.1 → XP_054212120.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X5

      UniProtKB/TrEMBL
      A0A0K2GN21

    4. XM_054356147.1 → XP_054212122.1  2-oxoisovalerate dehydrogenase subunit beta, mitochondrial isoform X7

      UniProtKB/TrEMBL
      B4E2N3, B7ZB80

    RNA

    1. XR_008487369.1 RNA Sequence

    2. XR_008487371.1 RNA Sequence

    3. XR_008487372.1 RNA Sequence

    4. XR_008487373.1 RNA Sequence

    5. XR_008487370.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P21953.2 GenPept UniProtKB/Swiss-Prot:P21953

    Gene LinkOut

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