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

Summary

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: mouse all
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Genomic context

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_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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	Compare labs

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

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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

PDHA1 (e-PCR)
- UniSTS:498178

RH65815 (e-PCR)
- UniSTS:1029

MAOA (e-PCR), detects polymorphism
- UniSTS:480279

Pdha1 (e-PCR), detects polymorphism
- UniSTS:144154

RH81017 (e-PCR)
- UniSTS:84251

GDB:186145 (e-PCR)
- UniSTS:155474

DXS9734 (e-PCR)
- UniSTS:43864

GDB:192510 (e-PCR)
- UniSTS:99711

GDB:677354 (e-PCR)
- UniSTS:98999

RH93821 (e-PCR)
- UniSTS:92110

GDB:180536 (e-PCR)
- UniSTS:155108

GDB:438035 (e-PCR)
- UniSTS:99044

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 more info	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 more info	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

EC 1.2.4.1

NP_001166925.1

EC 1.2.4.1

NP_001166926.1

EC 1.2.4.1

NP_001166927.1

EC 1.2.4.1

XP_016885063.1

EC 1.2.4.1

XP_054183156.1

EC 1.2.4.1

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

NG_016781.1 RefSeqGene

Range

5035..22826

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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
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
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 ...