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7 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ATP5F1C
ATP synthase F1 subunit gamma
Chromosome 10 · 10p14
NCBI Gene: 509Ensembl: ENSG00000165629.21HGNC: HGNC:833UniProt: B4DL14
232PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
mitochondrionprotein bindingmembraneproton-transporting ATP synthase complexlate-onset Alzheimers diseasescleritisdiaphragm diseaseexternal ear disease
✦AI Summary

ATP5F1C encodes the gamma subunit of mitochondrial ATP synthase (Complex V), a critical component of the F1 catalytic head domain. This subunit functions as part of the rotational mechanism that couples proton translocation across the inner mitochondrial membrane to ATP synthesis from ADP 1. The gamma subunit works with the central stalk to enable the rotary catalysis essential for oxidative phosphorylation, and is necessary for F1 assembly intermediate formation 12. ATP5F1C expression correlates with cellular ATP production capacity and mitochondrial function. Dysregulation of ATP5F1C is implicated in multiple pathological conditions: in diabetic kidney disease, Rheb1 deficiency increases ATP5F1C acetylation, impairing mitochondrial ATP production and accelerating podocyte senescence 3. In cancer, ATP5F1C overexpression marks metastatic cells with enhanced ATP production, proliferation, and stemness; ATP5F1C knockdown or targeting with bedaquiline reduces metastatic capacity 4. Additionally, ATP5F1C is involved in magnesium-ATP formation and serum magnesium homeostasis in type 2 diabetes 5. ATP5F1C expression is also upregulated during COVID-19 infection as a compensatory response to viral-induced mitochondrial dysfunction 6. These findings establish ATP5F1C as a therapeutic target in metabolic disease, cancer, and viral infection.

Sources cited
1
ATP5F1C is the gamma subunit of mitochondrial ATP synthase that participates in the rotary mechanism coupling proton translocation to ATP synthesis
PMID: 37244256
2
ATP5F1C with delta subunit is essential for F1 assembly intermediate formation during ATP synthase biogenesis
PMID: 29499186
3
Rheb1 deficiency promotes ATP5F1C acetylation, causing mitochondrial dysfunction and podocyte senescence in diabetic kidney disease
PMID: 39389178
4
ATP5F1C is overexpressed in metastatic cancer cells; ATP5F1C knockdown or bedaquiline treatment reduces ATP production and metastatic capacity
PMID: 33986463
5
ATP5F1C is involved in Mg2+-ATP formation and associated with serum magnesium levels in type 2 diabetes
PMID: 38279093
6
ATP5F1C expression is upregulated in COVID-19 patients as a compensatory response to viral-induced mitochondrial dysfunction
PMID: 41141600
Disease Associationsⓘ20
late-onset Alzheimers diseaseOpen Targets
0.35Weak
scleritisOpen Targets
0.28Weak
diaphragm diseaseOpen Targets
0.06Suggestive
external ear diseaseOpen Targets
0.06Suggestive
glioblastoma multiformeOpen Targets
0.04Suggestive
neoplasmOpen Targets
0.03Suggestive
adverse effectOpen Targets
0.02Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.02Suggestive
type 2 diabetes mellitusOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
bacteriemiaOpen Targets
0.01Suggestive
Parkinson diseaseOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
ovarian carcinomaOpen Targets
0.01Suggestive
breast cancerOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.01Suggestive
neuroblastomaOpen Targets
0.01Suggestive
schizophreniaOpen Targets
0.01Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.01Suggestive
neurodegenerative diseaseOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NDUFS2Protein interaction100%UQCRFS1Protein interaction100%NDUFV1Protein interaction100%COX5BProtein interaction100%UQCRC2Protein interaction100%CYC1Protein interaction100%
Tissue Expression6 tissues
Heart
100%
Brain
37%
Liver
31%
Lung
16%
Bone Marrow
16%
Ovary
13%
Gene Interaction Network
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ATP5F1CNDUFS2UQCRFS1NDUFV1COX5BUQCRC2CYC1
PROTEIN STRUCTURE
Preparing viewer…
PDB8H9E · 2.53 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.78LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.52 [0.36–0.78]
RankingsWhere ATP5F1C stands among ~20K protein-coding genes
  • #1,720of 20,598
    Most Researched232 · top 10%
  • #6,416of 17,882
    Most Constrained (LOEUF)0.78
Genes detectedATP5F1C
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
Rheb1 deficiency elicits mitochondrial dysfunction and accelerates podocyte senescence through promoting Atp5f1c acetylation.
PMID: 39389178
Cell Signal · 2024
1.00
2
Comprehensive Genomic Analysis of Cemento-Ossifying Fibroma.
PMID: 37995913
Mod Pathol · 2024
0.83
3
Genome-wide association study of serum magnesium in type 2 diabetes.
PMID: 38279093
Genes Nutr · 2024
0.67
4
Bedaquiline, an FDA-approved drug, inhibits mitochondrial ATP production and metastasis in vivo, by targeting the gamma subunit (ATP5F1C) of the ATP synthase.
PMID: 33986463
Cell Death Differ · 2021
0.50
5
Peripheral blood, lung and brain gene signatures in recovered and deceased patients with COVID-19.
PMID: 41141600
In Silico Pharmacol · 2025
0.33