Protein / target

Caspase-3

Encoded byCASP3P42574Homo sapiensSwiss-Prot

UniProt: P42574 Ensembl: ENSG00000164305 HGNC: HGNC:1504 NCBI Gene: 836

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Aspartic-type endopeptidase

Strongest disease association

Mucocutaneous Lymph Node Syndrome

Via encoding gene CASP3 · Genetic literature evidence · score 0.61

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

6 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis.

View complete UniProt function annotation

Thiol protease that acts as a major effector caspase involved in the execution phase of apoptosis (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:35338844, PubMed:35446120, PubMed:7596430). Following cleavage and activation by initiator caspases (CASP8, CASP9 and/or CASP10), mediates execution of apoptosis by catalyzing cleavage of many proteins (PubMed:18723680, PubMed:20566630, PubMed:23650375, PubMed:7596430). At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond (PubMed:10497198, PubMed:16374543, PubMed:7596430, PubMed:7774019). Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain (By similarity). Cleaves and activates caspase-6, -7 and -9 (CASP6, CASP7 and CASP9, respectively) (PubMed:7596430). Cleaves and inactivates interleukin-18 (IL18) (PubMed:37993714, PubMed:9334240). Involved in the cleavage of huntingtin (PubMed:8696339). Triggers cell adhesion in sympathetic neurons through RET cleavage (PubMed:21357690). Also involved in axon pruning during brain development (By similarity). Cleaves DSG2 in response to apoptosis resulting in a loss of full length DSG2 at desmosome cell junctions and subsequent loss of cell-cell adhesion (PubMed:17559062). Also cleaves JUP in response to apoptosis (PubMed:17559062). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress (PubMed:23152800). Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction (PubMed:30878284). Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (PubMed:35338844, PubMed:35446120). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (PubMed:23845944, PubMed:33725486). Cleaves BIRC6 following inhibition of BIRC6-caspase binding by DIABLO/SMAC (PubMed:36758104, PubMed:36758106)

Subcellular location

Cytoplasm

Domains and Gene Ontology detail (64)

Gene Ontology

Ccytoplasm
Ccytosol
Cdeath-inducing signaling complex
Cglutamatergic synapse
Cneuronal cell body
Cnucleoplasm
Cnucleus
Cpostsynaptic density
Faspartic-type endopeptidase activity
Fcyclin-dependent protein serine/threonine kinase inhibitor activity
Fcysteine-type endopeptidase activity
Fdeath receptor binding

277 aa · 32 kDa

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingGOGrowth-factor signallingGOLipid & lipoprotein metabolismUniProtImmune signallingUniProt · GOProteolysisUniProt · GOApoptosis & cell deathUniProt · GO

View supporting evidence

Synaptic signalling

·glutamatergic synapse
·postsynaptic density
·synapse pruning

Growth-factor signalling

·response to insulin-like growth factor stimulus

Lipid & lipoprotein metabolism

·Thiol protease that acts as a major effector caspase involved in the execution phase of…

Immune signalling

·Thiol protease that acts as a major effector caspase involved in the execution phase of…
·negative regulation of cytokine production
·positive regulation of pyroptotic inflammatory response
·pyroptotic inflammatory response

Proteolysis

·Thiol protease that acts as a major effector caspase involved in the execution phase of…
·aspartic-type endopeptidase activity
·cysteine-type endopeptidase activity
·peptidase activity

Apoptosis & cell death

·Thiol protease that acts as a major effector caspase involved in the execution phase of…
·apoptotic process
·glial cell apoptotic process
·leukocyte apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CASP3

Gene-level evidence surfaced through the gene CASP3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Mucocutaneous Lymph Node Syndrome

0.56Moderately supported

Genetic evidence dominant · Open Targets 0.46

Neurodegenerative Diseases

0.37Preliminary

Pathway evidence dominant · Open Targets 0.54 · no direct causal or clinical evidence

Carcinoma, Hepatocellular

0.30Limited support

Somatic mutation evidence dominant · Open Targets 0.21

Breast Neoplasms

0.30Limited support

Somatic mutation evidence dominant · Open Targets 0.21

Lung carcinoma

0.30Limited support

Somatic mutation evidence dominant · Open Targets 0.21

View evidence synthesis (5)

Mucocutaneous Lymph Node SyndromeModerately supported

0.56

agreement 0.42–0.70

Genetic94%Literature6%Genetic literaturedup

Open Targets aggregate 0.46 · 2 independent evidence families · 1 not counted as duplicate

Neurodegenerative DiseasesPreliminary

0.37

agreement 0.19–0.55

Pathway92%Literature8%

Open Targets aggregate 0.54 · 2 independent evidence families · no direct causal or clinical evidence

Carcinoma, HepatocellularLimited support

0.30

agreement 0.14–0.47

Somatic mutation60%Literature41%

Open Targets aggregate 0.21 · 2 independent evidence families

Breast NeoplasmsLimited support

0.30

agreement 0.14–0.47

Somatic mutation60%Literature40%

Open Targets aggregate 0.21 · 2 independent evidence families

Lung carcinomaLimited support

0.30

agreement 0.14–0.46

Somatic mutation61%Literature39%

Open Targets aggregate 0.21 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Neurodegenerative Diseases0.54

Mucocutaneous Lymph Node Syndrome0.46

Carcinoma, Hepatocellular0.21

Breast Neoplasms0.21

Lung carcinoma0.21

Leukemia, Myeloid, Acute0.21

Small Cell Lung Carcinoma0.20

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)

EMRICASANPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · High-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of catalytic activityToxCastregulation of transcription factor activityToxCast

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.