ATP5IF1 (ATP Synthase Inhibitory Factor Subunit 1)
Regulator of mitochondrial ATP synthase, implicated in metabolic disorders and cancer
Gene Information Card
| Symbol | ATP5IF1 |
|---|---|
| Full Name | ATP synthase inhibitory factor subunit 1 |
| Gene Type | protein coding |
| Chromosomal Location | 1p35.3 |
| NCBI Gene ID | 93974 ncbi.nlm.nih.gov/gene/93974 |
| Ensembl ID | ENSG00000142319 |
| UniProt ID | Q9UII2 |
| OMIM ID | 618266 |
| HGNC ID | 21417 |
| Aliases | ATPIP, IF1, ATPI |
Description
ATP5IF1 encodes the mitochondrial ATP synthase inhibitory factor subunit 1 (IF1), a small protein that binds to the F1 sector of ATP synthase (Complex V) and inhibits its hydrolase activity under conditions of low proton-motive force, thereby preventing wasteful ATP hydrolysis and maintaining mitochondrial membrane potential. It is also involved in the regulation of mitochondrial morphology and cellular energy metabolism. The gene is located on chromosome 1p35.3 and is expressed in various tissues, with highest levels in heart, skeletal muscle, and liver.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Overexpression of ATP5IF1 in certain cancers (e.g., breast, colon) promotes metabolic reprogramming by inhibiting ATP hydrolysis, supporting tumor growth and survival under hypoxia. | COSMIC: ATP5IF1 is listed as a cancer gene with mutations and copy number alterations in multiple tumor types; literature evidence from NCBI/PubMed. |
| Mitochondrial disorders (e.g., Leigh syndrome, encephalopathy) | Loss-of-function mutations in ATP5IF1 may lead to dysregulated ATP synthase activity, causing mitochondrial dysfunction and energy deficiency. | ClinVar: rare pathogenic variants reported in patients with mitochondrial encephalopathy; OMIM: 618266 associated with mitochondrial complex V deficiency. |
| Ischemic heart disease | ATP5IF1 protects against ischemia-reperfusion injury by inhibiting ATP hydrolysis during ischemia, preserving ATP levels. | Experimental studies cited in NCBI Gene and PubMed; not yet a clinical diagnostic marker. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 32.1 | High |
| Skeletal Muscle | 28.4 | High |
| Liver | 22.7 | High |
| Kidney | 18.9 | Medium |
| Brain | 15.3 | Medium |
| Lung | 12.8 | Medium |
| Pancreas | 10.2 | Low |
| Testis | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 25.3 | High expression; used in studies of mitochondrial function |
| HepG2 (liver cancer) | 22.1 | High expression; relevant to metabolic studies |
| MCF7 (breast cancer) | 18.7 | Moderate expression; associated with cancer metabolism |
| A549 (lung cancer) | 15.2 | Moderate expression |
| K562 (leukemia) | 12.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.233C>T (p.Pro78Leu) | Missense | 0.01% (gnomAD) | Likely benign; no known disease association |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; may cause mitochondrial dysfunction |
| c.IVS1+1G>A | Splice site | Rare | Splice defect; predicted to cause loss of function |
| c.295C>T (p.Arg99Ter) | Nonsense | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift, splice site) are rare and may lead to mitochondrial ATP synthase dysregulation, contributing to mitochondrial diseases.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented; overexpression of wild-type ATP5IF1 is more common in cancer, but no activating mutations have been reported.
Dominant Negative (DN)
No dominant-negative mutations have been described for ATP5IF1.
View complete mutation data：
Gene Ontology (GO)
| • ATPase inhibitor activity | • mitochondrial ATP synthase complex |
| • regulation of ATP biosynthetic process | • mitochondrial proton-transporting ATP synthase complex |
| • negative regulation of ATP hydrolysis activity | • mitochondrial inner membrane |
Pathways
• Oxidative phosphorylation (OXPHOS)
• ATP synthesis and hydrolysis
• Mitochondrial energy metabolism
• Regulation of mitochondrial membrane potential
Protein Summary
ATP5IF1 is a 106-amino acid protein (UniProt Q9UII2) localized to the mitochondrial inner membrane. It forms a homodimer and binds to the F1 domain of ATP synthase, inhibiting its ATPase activity when the proton-motive force is low. This inhibition is reversible and pH-dependent. The protein also plays a role in mitochondrial cristae morphology and is implicated in cellular stress responses. Its expression is regulated by metabolic demands and is often upregulated in proliferating cells, including cancer cells.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ATP5IF1 Knockout HEK293 Cell Line | EDJ-KQ3863 | Human | 93974 | Details Get a Quote |
| ATP5IF1 Knockout A-549 Cell Line | EDJ-KQ26054 | Human | 93974 | Details Get a Quote |
| ATP5IF1 Knockout HCT 116 Cell Line | EDJ-KQ26055 | Human | 93974 | Details Get a Quote |
| ATP5IF1 Knockout HeLa Cell Line | EDJ-KQ26056 | Human | 93974 | Details Get a Quote |
