ATP5IF1
protein-codingATP synthase inhibitory factor subunit 1, the group of Mitochondrial complex V: ATP synthase subunits
Gene summary
Enables several functions, including ATPase binding activity; angiostatin binding activity; and mitochondrial proton-transporting ATP synthase complex binding activity. Involved in several processes, including mitochondrial depolarization; negative regulation of cardiac muscle cell apoptotic process; and obsolete positive regulation of proteolysis involved in protein catabolic process. Located in cell surface and mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]
- ATPIF1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~10.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ATP5IF1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016311.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 14 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 15 | 0 | 0 | 15 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057395.1 | 3 | MANE Select | |
| Ensembl | ENSP00000335203.5 | 3 | MANE Select | |
| RefSeq | NP_835497.1 | 3 | Standard | |
| RefSeq | NP_835498.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| atp5if1a | Danio rerio | Structure: nucleate erythrocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Electron Transport Chain
Biological Process
- angiogenesis
- negative regulation of endothelial cell proliferation
- generation of precursor metabolites and energy
- heme biosynthetic process
- erythrocyte differentiation
Molecular Function
- enzyme inhibitor activity
- calmodulin binding
- enzyme binding
- ATPase inhibitor activity
- protein homodimerization activity
Cellular Component
- mitochondrion
- cell surface
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000335514
- Coding exons
- 3
- Length
- 10798
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 57
- Defined
- 125747
- p
- 0.000227
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.119 | 67 | 64.3 | 1.04 | 0.00000336 | 691 |
| Missense (PolyPhen) | 14 | 18.238 | 0.76764 | 216 | ||
| Synonymous | 0.439 | 22 | 24.8 | 0.888 | 0.00000121 | 198 |
| Loss of Function | 0.0407 | 6 | 6.11 | 0.982 | 2.79e-7 | 57 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.0010 | 0.0010 | notable |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.00033 | 0.00033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase. Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing FECH to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme. {ECO:0000269|PubMed:12110673, ECO:0000269|PubMed:15528193, ECO:0000269|PubMed:19559621, ECO:0000269|PubMed:23135403}.;
Recessive Scores
- pRec
- 0.0967
Intolerance Scores
- RVIS EVS
- 0.08
- RVIS percentile EVS
- 59.76
Essentials
- Essential (gene trap)
- N