PDHA1
Chr XXLDpyruvate dehydrogenase E1 subunit alpha 1
Also known as: E1alpha, PDHA, PDHAD, PDHCE1A, PHE1A
The protein encodes the E1 alpha subunit of the pyruvate dehydrogenase complex, which catalyzes the conversion of pyruvate to acetyl-CoA in mitochondria, providing the primary metabolic link between glycolysis and the citric acid cycle. Mutations cause pyruvate dehydrogenase E1-alpha deficiency through loss of function, resulting in lactic acidosis, developmental delay, and neurological dysfunction that can present as X-linked Leigh syndrome. The condition follows X-linked dominant inheritance with high penetrance.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PDHA1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools