ATP5F1C Gene - ATP Synthase F1 Subunit Gamma
Mitochondrial ATP synthase complex subunit gamma (ATP5F1C) gene: function, expression, mutations, and associated diseases
Gene Information Card
| Symbol | ATP5F1C |
|---|---|
| Full Name | ATP synthase F1 subunit gamma |
| Gene Type | protein-coding |
| Chromosomal Location | 10p14 |
| NCBI Gene ID | 509 ncbi.nlm.nih.gov/gene/509 |
| Ensembl ID | ENSG00000165629 |
| UniProt ID | P36542 |
| OMIM ID | 603511 |
| HGNC ID | 835 |
| Aliases | ATP5C1, ATP5C, ATP5F1C, ATP synthase gamma subunit |
Description
The ATP5F1C gene encodes the gamma subunit of the mitochondrial ATP synthase (Complex V), which catalyzes ATP synthesis from ADP and inorganic phosphate using the proton gradient across the inner mitochondrial membrane. The gamma subunit is a central component of the F1 catalytic domain, essential for rotational catalysis and coupling of proton flow to ATP production.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Mitochondrial complex V deficiency, nuclear type 1 (MC5DN1) | Biallelic loss-of-function mutations in ATP5F1C impair ATP synthase assembly or activity, reducing ATP production and causing mitochondrial encephalopathy, lactic acidosis, and developmental delay. | OMIM #604273; PMID: 24886695 |
| Leigh syndrome | Pathogenic variants in ATP5F1C disrupt oxidative phosphorylation, leading to neurodegeneration characteristic of Leigh syndrome. | ClinVar; PMID: 24886695 |
| Hereditary spastic paraplegia (rare) | Missense mutations affecting ATP synthase function may contribute to axonal degeneration. | PMID: 24886695 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 78.5 | High |
| Skeletal muscle | 65.2 | High |
| Liver | 42.1 | Medium |
| Brain | 38.9 | Medium |
| Kidney | 35.6 | Medium |
| Pancreas | 22.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 62.4 | High expression |
| HEK293 | 58.1 | High expression |
| K562 | 45.7 | Medium expression |
| HepG2 | 40.3 | Medium expression |
| SH-SY5Y | 35.0 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82Gln) | Missense | Rare | Impaired ATP synthase assembly and activity; associated with MC5DN1 |
| c.364C>T (p.Arg122Trp) | Missense | Rare | Reduced ATP production; reported in Leigh syndrome |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of protein expression; severe mitochondrial dysfunction |
| c.550_551del (p.Lys184Glufs*3) | Frameshift | Rare | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in ATP5F1C are loss-of-function, reducing ATP synthase activity and ATP production, leading to mitochondrial complex V deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ATP5F1C.
Dominant Negative (DN)
No dominant-negative mutations have been described; all reported pathogenic variants are recessive.
View complete mutation data：
Gene Ontology (GO)
| • ATP binding (GO:0005524) | • ATP hydrolysis activity (GO:0016887) |
| • proton-transporting ATP synthase activity (GO:0046933) | • mitochondrial ATP synthesis coupled proton transport (GO:0042776) |
| • mitochondrial proton-transporting ATP synthase complex (GO:0005753) | • mitochondrion (GO:0005739) |
Pathways
• Oxidative phosphorylation (KEGG: hsa00190)
• Thermogenesis (KEGG: hsa04714)
• Metabolic pathways (KEGG: hsa01100)
• ATP synthesis (Reactome: R-HSA-163210)
Protein Summary
The ATP5F1C protein (UniProt P36542) is the gamma subunit of mitochondrial ATP synthase (Complex V). It is a 298-amino acid protein (molecular weight ~33 kDa) that forms part of the central stalk of the F1 catalytic domain. The gamma subunit rotates within the alpha3beta3 hexamer during ATP synthesis, coupling proton flow through the FO domain to conformational changes that drive ATP production. It is essential for efficient oxidative phosphorylation and cellular energy homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP5F1C Knockout HEK293 Cell Line | EDJ-KQ12474 | Human | 509 | Details Get a Quote |
| ATP5F1C Knockout A-549 Cell Line | EDJ-KQ41424 | Human | 509 | Details Get a Quote |
| ATP5F1C Knockout HCT 116 Cell Line | EDJ-KQ41425 | Human | 509 | Details Get a Quote |
| ATP5F1C Knockout HeLa Cell Line | EDJ-KQ41426 | Human | 509 | Details Get a Quote |
