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25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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APAF1
apoptotic peptidase activating factor 1
Chromosome 12 · 12q23.1
NCBI Gene: 317Ensembl: ENSG00000120868.16HGNC: HGNC:576UniProt: O14727
222PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingextracellular exosomecytosolprotein-containing complexneurodegenerative diseasebreast benign neoplasmAbnormality of the gastrointestinal tractcervical carcinoma
✦AI Summary

APAF1 (apoptotic peptidase activating factor 1) is the molecular core of the apoptosome, a multiprotein complex that mediates the mitochondrial pathway of apoptosis 1. Upon cytochrome c release from mitochondria, oligomeric APAF1 binds cytochrome c and ATP to activate pro-caspase-9, which subsequently activates caspase-3 and executes programmed cell death 2. APAF1 represents the human homolog of C. elegans CED-4, highlighting evolutionary conservation of apoptotic machinery 2. Beyond canonical apoptosis, APAF1 participates in pyroptosis through formation of the Apaf-1 pyroptosome in response to mitochondrial permeability transition, activating caspase-4 and GSDME-mediated cell death under sterile conditions 3. APAF1 dysregulation contributes to multiple pathologies. During development, APAF1 deficiency causes embryonic lethality with impaired neuronal apoptosis and developmental abnormalities 4. In cancer, APAF1 mutations promote malignant transformation; conversely, lncRNA-mediated APAF1 inhibition blocks apoptosome assembly and induces multidrug resistance in gastric cancer 5. APAF1 upregulation associates with sepsis progression and correlates with altered immune infiltration 6. These findings establish APAF1 as a critical regulator of cell death with therapeutic implications in cancer and inflammatory diseases.

Sources cited
1
APAF1 is the human homolog of C. elegans CED-4 and serves as an apoptotic protease activating factor that activates caspase-9
PMID: 10578178
2
APAF1 is the molecular core of the apoptosome mediating the mitochondrial pathway of cell death
PMID: 12767258
3
APAF1 assembles into a pyroptosome complex with caspase-4 in response to mitochondrial permeability transition to trigger pyroptosis
PMID: 33308446
4
APAF1 deficiency causes embryonic lethality and impaired developmental apoptosis; APAF1 mutations contribute to malignant transformation in melanomas
PMID: 11706994
5
APAF1 binding by lncRNA blocks apoptosome assembly and prevents caspase-9/3 activation, promoting multidrug resistance in gastric cancer
PMID: 35975461
6
APAF1 is upregulated in sepsis and serves as a diagnostic marker related to PANoptosis progression
PMID: 40815447
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
breast benign neoplasmOpen Targets
0.34Weak
Abnormality of the gastrointestinal tractOpen Targets
0.30Weak
cervical carcinomaOpen Targets
0.28Weak
genetic disorderOpen Targets
0.15Weak
neural tube defectOpen Targets
0.12Weak
bipolar disorderOpen Targets
0.12Weak
schizophreniaOpen Targets
0.11Weak
neoplasmOpen Targets
0.09Suggestive
musculoskeletal system diseaseOpen Targets
0.09Suggestive
melanomaOpen Targets
0.09Suggestive
anorexia nervosaOpen Targets
0.08Suggestive
attention deficit hyperactivity disorderOpen Targets
0.08Suggestive
Tourette syndromeOpen Targets
0.08Suggestive
amyotrophic lateral sclerosisOpen Targets
0.08Suggestive
Parkinson diseaseOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
lymphomaOpen Targets
0.08Suggestive
major depressive disorderOpen Targets
0.08Suggestive
pachyonychia congenitaOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
BCL2L11Protein interaction100%XIAPProtein interaction100%PMAIP1Protein interaction100%CYCSProtein interaction99%HSPA4Protein interaction99%AVENProtein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
43%
Lung
29%
Ovary
28%
Heart
13%
Liver
12%
Gene Interaction Network
Click a node to explore
APAF1BCL2L11XIAPPMAIP1CYCSHSPA4AVEN
PROTEIN STRUCTURE
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PDB1CY5 · 1.30 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.66LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.46–0.66]
RankingsWhere APAF1 stands among ~20K protein-coding genes
  • #1,837of 20,598
    Most Researched222 · top 10%
  • #4,864of 17,882
    Most Constrained (LOEUF)0.66
Genes detectedAPAF1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Apaf-1 Pyroptosome Senses Mitochondrial Permeability Transition.
PMID: 33308446
Cell Metab · 2021
1.00
2
Apoptosis-based therapies.
PMID: 12120092
Nat Rev Drug Discov · 2002
0.90
3
Apaf1 and the apoptotic machinery.
PMID: 10578178
Cell Death Differ · 1999
0.80
4
Large transient assemblies of Apaf1 constitute the apoptosome in cells.
PMID: 41136486
Nat Commun · 2025
0.76
5
A metabolic cell death program downstream of SARM1 couples NAD
PMID: 41364765
Proc Natl Acad Sci U S A · 2025
0.72