Back to discover

Protein / target

Interleukin-18

Encoded byIL18Q14116Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
3
Clinical candidates
Antibody-tractable
Druggability
Advanced Clinical
8
Research papers

Protein at a glance

Biological role

Interleukin-18 receptor binding

Strongest disease association

Smoking initiation

Via encoding gene IL18 · Genetic evidence · score 0.21

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

8 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

Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses.

View complete UniProt function annotation

Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses (PubMed:10653850). Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators (PubMed:14528293, PubMed:25500532, PubMed:37993714). Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells (PubMed:10653850). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33883744)

Subcellular location

Cytoplasm, cytosolSecreted
Domains and Gene Ontology detail (42)

Gene Ontology

  • Ccytosol
  • Cextracellular region
  • Cextracellular space
  • Fcytokine activity
  • Finterleukin-18 receptor binding
  • Pangiogenesis
  • Pcell-cell signaling
  • Pcellular response to lipopolysaccharide
  • Pcholesterol homeostasis
  • Pcytokine-mediated signaling pathway
  • Pdefense response to Gram-positive bacterium
  • Pestablishment of skin barrier

193 aa · 22 kDa · 2 isoforms

Biological roles

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

Lipid & lipoprotein metabolismGOImmune signallingUniProt · GO
View supporting evidence

Lipid & lipoprotein metabolism

  • ·cholesterol homeostasis
  • ·triglyceride homeostasis

Immune signalling

  • ·Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-h…
  • ·cytokine activity
  • ·interleukin-18 receptor binding
  • ·cytokine-mediated signaling pathway

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 IL18

Gene-level evidence surfaced through the gene IL18that 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.

Lymphohistiocytosis, Hemophagocytic
0.41Limited support

Clinical evidence dominant · Open Targets 0.28

Diabetes Mellitus, Type 2
0.23Preliminary

Literature evidence dominant · Open Targets 0.13

Smoking initiation
0.21Preliminary

Genetic evidence dominant · Open Targets 0.13

Lupus Erythematosus, Systemic
0.19Preliminary

Literature evidence dominant · Open Targets 0.13

Pulmonary Disease, Chronic Obstructive
0.19Preliminary

Literature evidence dominant · Open Targets 0.12

View evidence synthesis (5)
Lymphohistiocytosis, HemophagocyticLimited support
0.41
agreement 0.250.56
Clinical72%Literature28%

Open Targets aggregate 0.28 · 2 independent evidence families

Diabetes Mellitus, Type 2Preliminary
0.23
agreement 0.080.39
Literature54%Clinical46%

Open Targets aggregate 0.13 · 2 independent evidence families

Smoking initiationPreliminary
0.21
agreement 0.090.33
Genetic100%

Open Targets aggregate 0.13 · 1 independent evidence family

Lupus Erythematosus, SystemicPreliminary
0.19
agreement 0.060.33
Literature71%Genetic29%

Open Targets aggregate 0.13 · 2 independent evidence families

Pulmonary Disease, Chronic ObstructivePreliminary
0.19
agreement 0.030.34
Literature71%Clinical29%

Open Targets aggregate 0.12 · 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
Lymphohistiocytosis, Hemophagocytic0.28
Diabetes Mellitus, Type 20.13
Smoking initiation0.13
Lupus Erythematosus, Systemic0.13
Arthritis, Rheumatoid0.12
Pulmonary Disease, Chronic Obstructive0.12
Neoplasms0.12
Acute Kidney Injury0.12
Infections0.12

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)
TADEKINIG ALFAPhase 3
CAMOTESKIMABPhase 2
GSK-1070806Phase 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

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

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

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (7)
AB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Research activity

8 papers · to 2024

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Europe PMC papers linked directly to this protein.