Protein / target

Interleukin-33

Encoded byIL33O95760Homo sapiensSwiss-Prot

UniProt: O95760 Ensembl: ENSG00000137033 HGNC: HGNC:16028 NCBI Gene: 90865

Clinical-stage

Therapeutic maturity

Clinical candidates

Antibody-tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Interleukin-33 receptor binding

Strongest disease association

Asthma

Via encoding gene IL33 · Genetic evidence · score 0.92

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

2 papers · latest 2024

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

Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.

View complete UniProt function annotation

Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells (PubMed:16286016, PubMed:19841166). Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines (PubMed:17853410, PubMed:18836528). Also involved in activation of mast cells, basophils, eosinophils and natural killer cells (PubMed:17853410, PubMed:18836528). Acts as an enhancer of polarization of alternatively activated macrophages (PubMed:19841166). Acts as a chemoattractant for Th2 cells, and may function as an 'alarmin', that amplifies immune responses during tissue injury (PubMed:17853410, PubMed:18836528). Induces rapid UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (By similarity)

Subcellular location

NucleusChromosomeCytoplasmCytoplasmic vesicle, secretory vesicleSecreted

Domains and Gene Ontology detail (39)

Gene Ontology

Cchromosome
Ccytoplasm
Cextracellular region
Cextracellular space
Cnucleoplasm
Cnucleus
Ctransport vesicle
Fcytokine activity
Finterleukin-33 receptor binding
Pantibacterial innate immune response
PDNA-templated transcription
Pinflammatory response

270 aa · 31 kDa · 4 isoforms

Biological roles

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

Immune signallingGOTranscriptional regulationGO

View supporting evidence

Immune signalling

·cytokine activity
·interleukin-33 receptor binding
·antibacterial innate immune response
·inflammatory response

Transcriptional regulation

·DNA-templated transcription
·negative regulation of transcription by RNA polymerase II
·positive regulation of gene expression
·positive regulation of transcription by RNA polymerase II

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 IL33

Gene-level evidence surfaced through the gene IL33that 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.

Asthma

0.94Well supported

Genetic evidence dominant · Open Targets 0.72

Hypersensitivity

0.84Well supported

Genetic evidence dominant · Open Targets 0.64

Rhinitis, Allergic

0.80Well supported

Genetic evidence dominant · Open Targets 0.60

Chronic rhinosinusitis

0.73Moderately supported

Genetic evidence dominant · Open Targets 0.44

Nasal Polyps

0.71Moderately supported

Genetic evidence dominant · Open Targets 0.44

View evidence synthesis (5)

AsthmaWell supported

0.94

agreement 0.83–1.00

Genetic77%Literature12%Clinical11%

Open Targets aggregate 0.72 · 3 independent evidence families

HypersensitivityWell supported

0.84

agreement 0.70–0.98

Genetic93%Literature7%

Open Targets aggregate 0.64 · 2 independent evidence families

Rhinitis, AllergicWell supported

0.80

agreement 0.66–0.94

Genetic91%Literature10%

Open Targets aggregate 0.60 · 2 independent evidence families

Chronic rhinosinusitisModerately supported

0.73

agreement 0.59–0.87

Genetic97%Literature4%

Open Targets aggregate 0.44 · 2 independent evidence families

Nasal PolypsModerately supported

0.71

agreement 0.58–0.85

Genetic95%Literature6%

Open Targets aggregate 0.44 · 2 independent evidence families

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

Asthma0.72

Hypersensitivity0.64

Rhinitis, Allergic0.60

Respiratory Tract Diseases0.53

Childhood onset asthma0.50

Venous Thrombosis0.44

Chronic rhinosinusitis0.44

Nasal Polyps0.44

Drug development

3 compounds recorded · 3 in clinical development

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

View all recorded compounds (3)

ETOKIMABPhase 2

TORUDOKIMABPhase 2

ITEPEKIMABPhase 3

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

Antibodies — Strong

Advanced Clinical and UniProt loc high conf support this modality.

View underlying tractability evidence (3)

AB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high conf

Raw Open Targets tractability assessment buckets, by modality.