PDHA2
Chr 4ARpyruvate dehydrogenase E1 subunit alpha 2
Also known as: PDHAL, SPGF70
This protein forms part of the E1 subunit of the testis-specific pyruvate dehydrogenase complex, which catalyzes the conversion of pyruvate to acetyl-CoA and links glycolysis to the mitochondrial tricarboxylic acid cycle. Mutations cause spermatogenic failure 70, an autosomal recessive condition affecting male fertility. The gene shows low constraint to loss-of-function variants (pLI near zero, LOEUF 1.77), consistent with its tissue-specific expression and reproductive phenotype.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
79 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 1 | 12 | 0 | 13 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 58 | 3 | 0 | 61 |
Likely Benign | 0 | 0 | 0 | 0 | 0 |
Benign | 0 | 2 | 0 | 0 | 2 |
| Total | 0 | 61 | 18 | 0 | 79 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PDHA2 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools