PDHA1: Pyruvate Dehydrogenase E1 Subunit Alpha 1
A critical enzyme in glucose metabolism and mitochondrial energy production
Gene Information Card
| Symbol | PDHA1 |
|---|---|
| Full Name | Pyruvate Dehydrogenase E1 Subunit Alpha 1 |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.12 |
| NCBI Gene ID | 5160 ncbi.nlm.nih.gov/gene/5160 |
| Ensembl ID | ENSG00000131828 |
| UniProt ID | P08559 |
| OMIM ID | 300502 |
| HGNC ID | 8806 |
| Aliases | PDHA, PHE1A, PDHCE1A |
Description
PDHA1 encodes the E1 alpha subunit of the pyruvate dehydrogenase complex (PDC), a mitochondrial multienzyme complex that catalyzes the irreversible conversion of pyruvate to acetyl-CoA, linking glycolysis to the citric acid cycle. This gene is X-linked and essential for aerobic glucose metabolism. Mutations in PDHA1 cause pyruvate dehydrogenase E1-alpha deficiency, leading to metabolic acidosis and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pyruvate dehydrogenase E1-alpha deficiency | Loss-of-function mutations reduce PDC activity, impairing acetyl-CoA production and causing lactic acidosis | ClinVar, OMIM |
| Leigh syndrome | PDHA1 mutations disrupt mitochondrial energy metabolism, leading to neurodegeneration | OMIM, NCBI |
| X-linked lactic acidosis | Deficient pyruvate oxidation results in elevated lactate and neurological symptoms | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | High |
| Heart | 10.2 | High |
| Liver | 8.1 | Medium |
| Skeletal muscle | 15.3 | High |
| Kidney | 7.4 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.8 | High expression |
| HepG2 | 9.5 | Medium expression |
| SH-SY5Y | 13.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.787C>T (p.Arg263Cys) | Missense | Common | Reduced PDC activity, associated with Leigh syndrome |
| c.1015C>T (p.Arg339Trp) | Missense | Rare | Loss of function, lactic acidosis |
| c.1A>G (p.Met1?) | Start loss | Rare | Complete loss of protein, severe deficiency |
Mutation functional classification
Loss of Function (LOF)
Most PDHA1 mutations are loss-of-function, reducing or abolishing PDC activity, leading to metabolic acidosis and neurological impairment.
Gain of Function (GOF)
No gain-of-function mutations reported for PDHA1.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with complex assembly, though X-linked inheritance typically manifests in males.
View complete mutation data：
Gene Ontology (GO)
| • pyruvate dehydrogenase (acetyl-transferring) activity (GO:0004739) | • pyruvate metabolic process (GO:0006090) |
| • mitochondrion (GO:0005739) | • pyruvate dehydrogenase complex (GO:0045254) |
Pathways
• Pyruvate metabolism (KEGG: hsa00620)
• Citric acid cycle (KEGG: hsa00020)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
The PDHA1 protein (E1 alpha subunit) is a 390-amino-acid component of the pyruvate dehydrogenase complex. It contains a thiamine pyrophosphate (TPP) binding domain and a catalytic domain essential for decarboxylation of pyruvate. The protein is localized in the mitochondrial matrix and is regulated by phosphorylation. Defects in PDHA1 impair energy production, particularly in tissues with high oxidative demand such as brain and muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PDHA1 Knockout HEK293 Cell Line | EDJ-KQ3983 | Human | 5160 | Details Get a Quote |
| PDHA1 Knockout HeLa Cell Line | EDJ-KQ17955 | Human | 5160 | Details Get a Quote |
| PDHA1 Knockout A-549 Cell Line | EDJ-KQ21160 | Human | 5160 | Details Get a Quote |
| PDHA1 Knockout HCT 116 Cell Line | EDJ-KQ21161 | Human | 5160 | Details Get a Quote |
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