ATP5F1E
Chr 20ARATP synthase F1 subunit epsilon
Also known as: ATP5E, ATPE, MC5DN3
ATP5F1E encodes the epsilon subunit of mitochondrial ATP synthase, which catalyzes ATP synthesis utilizing the electrochemical proton gradient across the inner mitochondrial membrane during oxidative phosphorylation. Biallelic mutations cause mitochondrial complex V (ATP synthase) deficiency, nuclear type 3, inherited in an autosomal recessive pattern. The pathogenic mechanism appears to involve gain-of-function effects.
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
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
60 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 | 15 | 0 | 16 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 10 | 8 | 0 | 18 |
Likely Benign | 0 | 1 | 6 | 7 | 14 |
Benign | 0 | 0 | 9 | 0 | 9 |
| Total | 0 | 12 | 41 | 7 | 60 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP5F1E · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →No open access results found
External Resources
Links to major genomics databases and tools