ATP5F1C
Chr 10ATP synthase F1 subunit gamma
Also known as: ATP5C, ATP5C1, ATP5CL1
The protein is the gamma subunit of mitochondrial ATP synthase (Complex V), which produces ATP from ADP using the proton gradient generated by the respiratory chain and is essential for F1 catalytic domain assembly. Mutations cause autosomal recessive mitochondrial complex V deficiency, presenting as a severe mitochondrial disorder affecting multiple organ systems. The gene shows low constraint to loss-of-function variants, consistent with autosomal recessive inheritance where heterozygous carriers are typically unaffected.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
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
87 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 | 0 | 24 | 0 | 24 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 35 | 9 | 0 | 44 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 37 | 35 | 0 | 72 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ATP5F1C · 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 →External Resources
Links to major genomics databases and tools