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

Gene ID: 5160, updated on 11-Apr-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_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (19343927..19361718)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (18926645..18944454)
105.20220307 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: 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. T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes. Wang CH, et al. J Clin Endocrinol Metab, 2022 Aug 18. PMID 35731579
  2. MAPK signalling-induced phosphorylation and subcellular translocation of PDHE1α promotes tumour immune evasion. Zhang Y, et al. Nat Metab, 2022 Mar. PMID 35315437
  3. Pyruvate Dehydrogenase Complex Deficiency Due to PDHA1 Mutation-A Rare Treatable Cause for Episodic Ataxia in Children. Pavuluri H, et al. Indian J Pediatr, 2022 May. PMID 35132535
  4. Differential expression of pyruvate dehydrogenase E1A and its inactive phosphorylated form among breast cancer subtypes. Zaher DM, et al. Life Sci, 2021 Nov 1. PMID 34384830
  5. Novel presentations associated with a PDHA1 variant - Alternating hemiplegia in Hemizygote proband and Guillain Barre Syndrome in Heterozygote mother. Sen K, et al. Eur J Paediatr Neurol, 2021 Mar. PMID 33592356, Free PMC Article

See all (197) 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

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)

Genotypes

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 protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables pyruvate dehydrogenase (NAD+) activity IEA
Inferred from Electronic Annotation
more info
  
enables pyruvate dehydrogenase (acetyl-transferring) activity IBA
Inferred from Biological aspect of Ancestor
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 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_2023_10

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

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

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