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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CASP3
caspase 3
Chromosome 4 · 4q35.1
NCBI Gene: 836Ensembl: ENSG00000164305.20HGNC: HGNC:1504UniProt: A8MVM1
1,254PubMed Papers
20Diseases
1Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisHub GeneProtease
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of pyroptotic inflammatory responsepositive regulation of amyloid-beta formationpeptidase activitynucleusneurodegenerative diseasemucocutaneous lymph node syndromeresponse to vaccineresponse to water
✦AI Summary

CASP3 encodes caspase-3, a thiol protease functioning as a major effector caspase in the execution phase of apoptosis 123. Following activation by initiator caspases (CASP8, CASP9, CASP10), caspase-3 catalyzes proteolytic cleavage of numerous substrates including poly(ADP-ribose) polymerase (PARP1), caspases-6, -7, and -9, and interleukin-18 45. Beyond canonical apoptosis, CASP3 cleaves huntingtin, desmogleins, and AKT1 in response to oxidative stress, regulates cell adhesion through RET cleavage, and mediates phosphatidylserine exposure on apoptotic cells 678. Additionally, CASP3 participates in pyroptosis via gasdermin-E activation and negatively regulates type I interferon production during viral infection by cleaving antiviral proteins CGAS, IRF3, and MAVS 910. CASP3 dysfunction is implicated in cancer development; somatic mutations occur in multiple tumor types with altered expression correlating to disease progression 11. CASP3 polymorphisms associate with Kawasaki disease susceptibility 12, and elevated CASP3 correlates with increased apoptosis in diabetic kidney disease 13. The dual role of CASP3—promoting apoptosis while suppressing inflammatory responses—makes it a critical therapeutic target across multiple pathologies.

Sources cited
1
CASP3 dysfunction is implicated in cancer development; somatic mutations occur in multiple tumor types with altered expression correlating to disease progression .
PMID: 15127291
2
CASP3 polymorphisms associate with Kawasaki disease susceptibility , and elevated CASP3 correlates with increased apoptosis in diabetic kidney disease .
PMID: 31884867
3
CASP3 polymorphisms associate with Kawasaki disease susceptibility , and elevated CASP3 correlates with increased apoptosis in diabetic kidney disease .
PMID: 39988817
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.54Moderate
mucocutaneous lymph node syndromeOpen Targets
0.46Moderate
response to vaccineOpen Targets
0.39Weak
response to waterOpen Targets
0.32Weak
response to stimulusOpen Targets
0.25Weak
acute myeloid leukemiaOpen Targets
0.21Weak
hepatocellular carcinomaOpen Targets
0.21Weak
papillary thyroid carcinomaOpen Targets
0.20Weak
breast carcinomaOpen Targets
0.19Weak
small cell lung carcinomaOpen Targets
0.19Weak
gastric carcinomaOpen Targets
0.19Weak
lung adenocarcinomaOpen Targets
0.19Weak
esophageal adenocarcinomaOpen Targets
0.19Weak
urinary bladder carcinomaOpen Targets
0.19Weak
head and neck squamous cell carcinomaOpen Targets
0.19Weak
colon adenocarcinomaOpen Targets
0.19Weak
skin basal cell carcinomaOpen Targets
0.19Weak
cervical squamous cell carcinomaOpen Targets
0.19Weak
gastric adenocarcinomaOpen Targets
0.19Weak
multiple myelomaOpen Targets
0.19Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets1
EMRICASANPhase II
Caspase inhibitor
Hepatic fibrosis
Related Genes
TP53Protein interaction100%MAPK3Protein interaction99%KCNJ11Protein interaction99%DIABLOProtein interaction99%BIRC6Protein interaction99%BIRC7Protein interaction99%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
65%
Heart
48%
Lung
45%
Brain
43%
Ovary
26%
Gene Interaction Network
Click a node to explore
CASP3TP53MAPK3KCNJ11DIABLOBIRC6BIRC7
PROTEIN STRUCTURE
Preparing viewer…
PDB2DKO · 1.06 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.86LoF Tolerant
pLIⓘ
0.07Tolerant
Observed/Expected LoF0.49 [0.30–0.86]
RankingsWhere CASP3 stands among ~20K protein-coding genes
  • #114of 20,598
    Most Researched1,254 · top 1%
  • #7,513of 17,882
    Most Constrained (LOEUF)0.86
Genes detectedCASP3
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Combining mendelian randomization analysis and network toxicology strategy to identify causality and underlying mechanisms of environmental pollutants with glioblastoma: A study of Methyl-4-hydroxybenzoate.
PMID: 39536568
Ecotoxicol Environ Saf · 2024
1.00
2
CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders.
PMID: 37674109
BMC Psychiatry · 2023
0.90
3
Genetic Polymorphisms in the Apoptosis-Associated Gene CASP3 and the Risk of Lung Cancer in Chinese Population.
PMID: 27723786
PLoS One · 2016
0.88
4
Collaborative role of calcitriol with buparlisib in the tongue squamous cell carcinoma cell line by modulating the Casp3 and Akt1 gene expression.
PMID: 41243960
Dent Med Probl · 2025
0.80
5
Somatic mutations of CASP3 gene in human cancers.
PMID: 15127291
Hum Genet · 2004
0.80