APAF1 Gene: Apoptotic Peptidase Activating Factor 1
Key regulator of intrinsic apoptosis and tumor suppression
Gene Information Card
| Symbol | APAF1 |
|---|---|
| Full Name | Apoptotic peptidase activating factor 1 |
| Gene Type | protein coding |
| Chromosomal Location | 12q23.1 |
| NCBI Gene ID | 317 ncbi.nlm.nih.gov/gene/317 |
| Ensembl ID | ENSG00000120868 |
| UniProt ID | O14727 |
| OMIM ID | 602233 |
| HGNC ID | 578 |
| Aliases | APAF-1, CED4, FLJ98099 |
Description
The APAF1 gene encodes apoptotic protease activating factor 1, a cytoplasmic protein that plays a central role in the intrinsic (mitochondrial) apoptosis pathway. Upon cytochrome c release from mitochondria, APAF1 binds cytochrome c and dATP/ATP, forming the apoptosome complex. This complex recruits and activates procaspase-9, leading to activation of downstream caspases and cell death. APAF1 is critical for developmental cell death and acts as a tumor suppressor.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Loss of APAF1 expression or function reduces apoptosis, promoting tumor survival | Multiple studies show reduced APAF1 expression in colorectal tumors; somatic mutations in COSMIC |
| Lung cancer | Epigenetic silencing or mutation of APAF1 impairs apoptosis, contributing to chemoresistance | Hypermethylation of APAF1 promoter observed in non-small cell lung cancer; COSMIC mutations |
| Melanoma | APAF1 downregulation allows evasion of apoptosis, associated with poor prognosis | Immunohistochemistry shows loss of APAF1 in metastatic melanoma; functional studies |
| Neuroblastoma | APAF1 deletion or reduced expression correlates with aggressive phenotype | Copy number loss and low expression in high-risk neuroblastoma; ClinVar and literature |
| Ovarian cancer | APAF1 mutations or loss of heterozygosity contribute to chemoresistance | LOH at 12q23 and reduced APAF1 protein in ovarian tumors; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 17.2 | Medium |
| Heart | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Lung | 7.4 | Low |
| Colon | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.3 | Cervical cancer cell line; moderate expression |
| A549 | 9.2 | Lung carcinoma; lower expression |
| MCF7 | 12.8 | Breast cancer; moderate expression |
| HepG2 | 7.5 | Liver cancer; low expression |
| SH-SY5Y | 18.9 | Neuroblastoma; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1339C>T (p.Arg447Ter) | Nonsense | 0.1% in COSMIC | Truncated protein, loss of function |
| c.1699G>A (p.Glu567Lys) | Missense | 0.05% in COSMIC | Impaired apoptosome formation |
| c.2146A>G (p.Thr716Ala) | Missense | 0.02% in COSMIC | Reduced caspase activation |
| c.2506C>T (p.Arg836Cys) | Missense | 0.03% in COSMIC | Altered protein stability |
Mutation functional classification
Loss of Function (LOF)
Most APAF1 mutations are loss-of-function, reducing apoptosis and promoting cancer.
Gain of Function (GOF)
Rare; not well documented.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative by interfering with apoptosome assembly.
View complete mutation data：
Gene Ontology (GO)
| • apoptotic process | • cysteine-type endopeptidase activator activity |
| • protein homodimerization activity | • cytochrome c binding |
| • ATP binding | • apoptosome complex |
Pathways
• Intrinsic Apoptosis Pathway
• Apoptosome-mediated caspase activation
• p53-dependent apoptosis
Protein Summary
APAF1 is a 141.7 kDa protein consisting of an N-terminal CARD domain, a central nucleotide-binding domain (NBD), and C-terminal WD40 repeats. It exists as an inactive monomer in the cytosol. Upon apoptotic stimuli, cytochrome c binds to the WD40 domain, inducing a conformational change that allows oligomerization into a wheel-like heptamer, the apoptosome. The CARD domain recruits procaspase-9, leading to its dimerization and activation, which then cleaves and activates effector caspases (e.g., caspase-3 and -7), executing cell death. APAF1 is essential for normal development and acts as a tumor suppressor.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| APAF1 Knockout HEK293 Cell Line | EDJ-KQ3019 | Human | 317 | Details Get a Quote |
| APAF1 Knockout A-549 Cell Line | EDC90634 | Human | 317 | Details Get a Quote |
| APAF1 Knockout HCT 116 Cell Line | EDJ-KQ25611 | Human | 317 | Details Get a Quote |
| APAF1 Knockout HeLa Cell Line | EDJ-KQ25612 | Human | 317 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
