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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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API5
apoptosis inhibitor 5
Chromosome 11 · 11p12
NCBI Gene: 8539Ensembl: ENSG00000166181.14HGNC: HGNC:594UniProt: B4DDR3
121PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly Constrained
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nuclear speckprotein bindingfibroblast growth factor bindingnegative regulation of apoptotic processmathematical abilityresponse to stimulusAbnormality of refractionjaw disease
✦AI Summary

API5 (apoptosis inhibitor 5) is a multifunctional nuclear protein that primarily functions as an antiapoptotic factor through multiple regulatory mechanisms 1. API5 inhibits apoptosis by binding to and negatively regulating ACIN1, suppressing ACIN1 cleavage by CASP3 and preventing ACIN1-mediated DNA fragmentation 1. The protein undergoes critical post-translational modifications including acetylation at K251 by p300 histone acetyltransferase, which maintains protein stability, while HDAC1-mediated deacetylation promotes instability and regulates subcellular localization 2. API5 also undergoes SUMOylation at K404, which enhances MDA5-dependent IFN-β production for antiviral immunity 3. Additionally, SRPK1-dependent phosphorylation at S464 prevents autophagic degradation of cytosolic RNA sensors RIG-I and MDA5, promoting antiviral responses 4. Beyond apoptosis regulation, API5 functions in mRNA nuclear export through interaction with nuclear FGF2, regulating bulk mRNA export and specific transcripts like c-MYC and cyclin D1 5. API5 can also be secreted by γδ intraepithelial lymphocytes to protect Paneth cells from death in Crohn's disease models 6. Elevated API5 expression is associated with various cancers and poor prognosis, making it a potential therapeutic target 1.

Sources cited
1
API5 is a multifunctional nuclear protein that functions as an antiapoptotic factor and is associated with cancer
PMID: 38275765
2
API5 undergoes acetylation at K251 by p300 and deacetylation by HDAC1, regulating protein stability and localization
PMID: 34385547
3
API5 undergoes SUMOylation at K404 which enhances MDA5-dependent IFN-β production
PMID: 34372697
4
SRPK1-dependent phosphorylation at S464 prevents autophagic degradation of RNA sensors RIG-I and MDA5
PMID: 40641422
5
API5 interacts with nuclear FGF2 to regulate mRNA nuclear export including c-MYC and cyclin D1
PMID: 32383752
6
API5 is secreted by γδ IELs to protect Paneth cells from death in Crohn's disease models
PMID: 36198790
Disease Associationsⓘ20
mathematical abilityOpen Targets
0.33Weak
response to stimulusOpen Targets
0.28Weak
Abnormality of refractionOpen Targets
0.27Weak
jaw diseaseOpen Targets
0.27Weak
refractive errorOpen Targets
0.26Weak
chronic kidney diseaseOpen Targets
0.21Weak
adolescent idiopathic scoliosisOpen Targets
0.20Weak
smoking initiationOpen Targets
0.19Weak
AnxietyOpen Targets
0.19Weak
Abruptio PlacentaeOpen Targets
0.19Weak
liver diseaseOpen Targets
0.18Weak
preeclampsiaOpen Targets
0.17Weak
deficiency anemiaOpen Targets
0.17Weak
nerve plexus diseaseOpen Targets
0.17Weak
osteoporosisOpen Targets
0.17Weak
placental retentionOpen Targets
0.17Weak
neoplasmOpen Targets
0.10Weak
breast cancerOpen Targets
0.09Suggestive
cervical cancerOpen Targets
0.09Suggestive
cancerOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NAA38Shared pathway100%NAA35Shared pathway100%GMEB1Shared pathway100%POLR2BProtein interaction100%FGF2Protein interaction96%ACIN1Protein interaction79%
Tissue Expression6 tissues
Brain
100%
Liver
51%
Heart
42%
Bone Marrow
40%
Lung
37%
Ovary
36%
Gene Interaction Network
Click a node to explore
API5NAA38NAA35GMEB1POLR2BFGF2ACIN1
PROTEIN STRUCTURE
Preparing viewer…
PDB3U0R · 2.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.21Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.10 [0.05–0.21]
RankingsWhere API5 stands among ~20K protein-coding genes
  • #3,873of 20,598
    Most Researched121 · top quartile
  • #511of 17,882
    Most Constrained (LOEUF)0.21 · top 5%
Genes detectedAPI5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The γδ IEL effector API5 masks genetic susceptibility to Paneth cell death.
PMID: 36198790
Nature · 2022
1.00
2
Evolution and Structure of API5 and Its Roles in Anti-Apoptosis.
PMID: 33319655
Protein Pept Lett · 2021
0.90
3
API5 Phosphorylation Promotes Antiviral Immunity by Inhibiting Degradation of Cytosolic RNA Sensor RLRs.
PMID: 40641422
Adv Sci (Weinh) · 2025
0.80
4
Interplay between p300 and HDAC1 regulate acetylation and stability of Api5 to regulate cell proliferation.
PMID: 34385547
Sci Rep · 2021
0.70
5
Regulation of mRNA export through API5 and nuclear FGF2 interaction.
PMID: 32383752
Nucleic Acids Res · 2020
0.60