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    PDHA1 pyruvate dehydrogenase E1 subunit alpha 1 [ Homo sapiens (human) ]

    Gene ID: 5160, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PDHA1provided by HGNC
    Official Full Name
    pyruvate dehydrogenase E1 subunit alpha 1provided by HGNC
    Primary source
    HGNC:HGNC:8806
    See related
    Ensembl:ENSG00000131828 MIM:300502; AllianceGenome:HGNC:8806
    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
    PDHA; PDHAD; PHE1A; E1alpha; PDHCE1A
    Summary
    The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle. The PDH complex is composed of multiple copies of three enzymatic components: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide dehydrogenase (E3). The E1 enzyme is a heterotetramer of two alpha and two beta subunits. This gene encodes the E1 alpha 1 subunit containing the E1 active site, and plays a key role in the function of the PDH complex. Mutations in this gene are associated with pyruvate dehydrogenase E1-alpha deficiency and X-linked Leigh syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]
    Expression
    Ubiquitous expression in heart (RPKM 64.2), fat (RPKM 35.1) and 25 other tissues See more
    Orthologs
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    Genomic context

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    See PDHA1 in Genome Data Viewer
    Location:
    Xp22.12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (19343927..19361718)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (18926645..18944454)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (19362045..19379836)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene RNA, 7SL, cytoplasmic 48, pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:19002034-19002534 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29461 Neighboring gene uncharacterized LOC101928415 Neighboring gene phosphorylase kinase regulatory subunit alpha 2 Neighboring gene adhesion G protein-coupled receptor G2 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chrX:19125111-19125740 Neighboring gene ReSE screen-validated silencer GRCh37_chrX:19182810-19182961 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29462 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:19278446-19278946 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:19309116-19309616 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chrX:19309617-19310117 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:19391289-19392229 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29463 Neighboring gene mitogen-activated protein kinase kinase kinase 15 Neighboring gene eukaryotic translation initiation factor 5 pseudogene 2 Neighboring gene SH3 domain containing kinase binding protein 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:19643274-19644473 Neighboring gene uncharacterized LOC124905255

    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. The acute effects of differential dietary fatty acids on human skeletal muscle pyruvate dehydrogenase activity. Bradley NS, et al. J Appl Physiol (1985), 2008 Jan. PMID 17947500
    2. Mutation analysis of the pyruvate dehydrogenase E1 alpha gene in eight patients with a pyruvate dehydrogenase complex deficiency. Lissens W, et al. Hum Mutat, 1996. PMID 8664900
    3. Three new mutations of the pyruvate dehydrogenase alpha subunit: a point mutation (M181V), 3 bp deletion (-R282), and 16 bp insertion/frameshift (K358SVS-->TVDQS). Tripatara A, et al. Hum Mutat, 1996. PMID 8844217
    4. Refined localization of the pyruvate dehydrogenase E1 alpha gene (PDHA1) by linkage analysis. Børglum AD, et al. Hum Genet, 1997 Jan. PMID 9003499
    5. Mitochondrial and nuclear genes present conflicting portraits of human origins. Hey J. Mol Biol Evol, 1997 Feb. PMID 9029794

    See all (216) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation.
      Title: PDHA1 hyperacetylation-mediated lactate overproduction promotes sepsis-induced acute kidney injury via Fis1 lactylation.
    2. T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes.
      Title: T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes.
    3. MAPK signalling-induced phosphorylation and subcellular translocation of PDHE1alpha promotes tumour immune evasion.
      Title: MAPK signalling-induced phosphorylation and subcellular translocation of PDHE1α promotes tumour immune evasion.
    4. Pyruvate Dehydrogenase Complex Deficiency Due to PDHA1 Mutation-A Rare Treatable Cause for Episodic Ataxia in Children.
      Title: Pyruvate Dehydrogenase Complex Deficiency Due to PDHA1 Mutation-A Rare Treatable Cause for Episodic Ataxia in Children.
    5. Differential expression of pyruvate dehydrogenase E1A and its inactive phosphorylated form among breast cancer subtypes.
      Title: Differential expression of pyruvate dehydrogenase E1A and its inactive phosphorylated form among breast cancer subtypes.
    6. Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother.
      Title: Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother.
    7. Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis.
      Title: Phosphorylation of PDHA by AMPK Drives TCA Cycle to Promote Cancer Metastasis.
    8. LDHA/PDHA1 changes in Head and Neck Squamous Cell Carcinoma (HNSCC) resulted in a broad metabolic reprogramming while intracellular molecules including polyunsaturated fatty acids and nitrogen metabolism related metabolites underlie the malignant changes.
      Title: Determination of Pyruvate Metabolic Fates Modulates Head and Neck Tumorigenesis.
    9. PGC1alpha reversed the Warburg effect by upregulating the expression of pyruvate dehydrogenase E1 alpha 1 subunit and mitochondrial pyruvate carrier 1 to increase pyruvate flux into the mitochondria for oxidation, whereas simultaneously promoting mitochondrial biogenesis and fusion to mediate the metabolic switch to oxidative phosphorylation.
      Title: PGC1α promotes cholangiocarcinoma metastasis by upregulating PDHA1 and MPC1 expression to reverse the Warburg effect.
    10. We demonstrate here that silencing of PDHA1 expression prevents proliferation of HUVECs and inhibits angiogenesis in vitro as well as in vivo
      Title: The role of glycolysis and mitochondrial respiration in the formation and functioning of endothelial tip cells during angiogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (48)

    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

    Associated conditions

    Description Tests
    Pyruvate dehydrogenase E1-alpha deficiency
    MedGen: C1839413 OMIM: 312170 GeneReviews: Primary Pyruvate Dehydrogenase Complex Deficiency Overview
    		not available

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-09-27)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2022-09-27)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr enhances PPARbeta/delta agonist GW501516-induced pyruvate dehydrogenase kinase 4 (PDK4) protein expression and phosphorylation of pyruvate dehydrogenase alpha 1 (PDHE1alpha) at serine 293 in cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables pyruvate dehydrogenase (NAD+) activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    contributes_to pyruvate dehydrogenase (acetyl-transferring) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in acetyl-CoA biosynthetic process from pyruvate IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in acetyl-CoA biosynthetic process from pyruvate IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in glucose metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in tricarboxylic acid cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HDA PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleus HDA PubMed 
    part_of pyruvate dehydrogenase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of pyruvate dehydrogenase complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial
    Names
    PDHE1-A type I
    pyruvate dehydrogenase (lipoamide) alpha 1
    pyruvate dehydrogenase E1 alpha 1 subunit
    pyruvate dehydrogenase alpha 1
    pyruvate dehydrogenase complex, E1-alpha polypeptide 1
    NP_000275.1
    NP_001166925.1
    NP_001166926.1
    NP_001166927.1
    XP_016885063.1
    XP_054183156.1

    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_016781.1 RefSeqGene

      Range
      5035..22826
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000284.4 → NP_000275.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_000275.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform 1.
      Source sequence(s)
      AL732326, BU170389, DC361191, L13318, R49470
      Consensus CDS
      CCDS14192.1
      UniProtKB/Swiss-Prot
      A5YVE9, B2R5P7, B7Z3T7, B7Z3X5, P08559, Q53H41, Q5JPT8, Q9NP12, Q9UBJ8, Q9UBU0, Q9UNG4, Q9UNG5
      UniProtKB/TrEMBL
      Q53GE3
      Related
      ENSP00000394382.2, ENST00000422285.7
      Conserved Domains (1) summary
      TIGR03182
      Location:58 → 370
      PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit

    2. NM_001173454.2 → NP_001166925.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_001166925.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an additional in-frame coding exon compared to variant 1, resulting in a longer isoform (2) compared to isoform 1.
      Source sequence(s)
      AK293250, AL732326, BU170389, DC361191, R49470
      Consensus CDS
      CCDS55380.1
      UniProtKB/TrEMBL
      Q5JPU2
      Related
      ENSP00000406473.2, ENST00000423505.6
      Conserved Domains (1) summary
      TIGR03182
      Location:96 → 408
      PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit

    3. NM_001173455.2 → NP_001166926.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 3 precursor

      See identical proteins and their annotated locations for NP_001166926.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) uses an alternative acceptor splice site at one of the coding exons compared to variant 1, resulting in a longer isoform (3) compared to isoform 1.
      Source sequence(s)
      AK296341, AL732326, DC361191, R49470
      Consensus CDS
      CCDS55381.1
      UniProtKB/TrEMBL
      Q53GE3
      Related
      ENSP00000348062.6, ENST00000355808.10
      Conserved Domains (1) summary
      TIGR03182
      Location:58 → 377
      PDH_E1_alph_y; pyruvate dehydrogenase E1 component, alpha subunit

    4. NM_001173456.2 → NP_001166927.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform 4 precursor

      See identical proteins and their annotated locations for NP_001166927.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) is missing an in-frame coding exon compared to variant 1, resulting in a shorter isoform (4) compared to isoform 1.
      Source sequence(s)
      AK296341, AK296457, AL732326, DC361191, R49470
      Consensus CDS
      CCDS55382.1
      UniProtKB/TrEMBL
      Q53GE3
      Related
      ENSP00000440761.1, ENST00000540249.5
      Conserved Domains (1) summary
      cl01629
      Location:58 → 339
      TPP_enzymes; Thiamine pyrophosphate (TPP) enzyme family, TPP-binding module; found in many key metabolic enzymes which use TPP (also known as thiamine diphosphate) as a cofactor. These enzymes include, among others, the E1 components of the pyruvate, the acetoin and ...

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      19343927..19361718
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017029574.3 → XP_016885063.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q5JPU2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      18926645..18944454
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327181.1 → XP_054183156.1  pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q5JPU2
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08559.3 GenPept UniProtKB/Swiss-Prot:P08559

    Gene LinkOut

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