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Protein / target

Interleukin-21

Encoded byIL21Q9HBE4Homo sapiensSwiss-Prot
UniProt: Q9HBE4Ensembl: ENSG00000138684HGNC: HGNC:6005NCBI Gene: 59067
Clinical-stage
Therapeutic maturity
1
Clinical candidates
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Interleukin-2 receptor binding

Strongest disease association

Hypothyroidism

Via encoding gene IL21 · Genetic evidence · score 0.70

Therapeutic position

Clinically advancing target

Research activity

Emerging research

1 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 with immunoregulatory activity.

View complete UniProt function annotation

Cytokine with immunoregulatory activity. May promote the transition between innate and adaptive immunity. Induces the production of IgG(1) and IgG(3) in B-cells (By similarity). Implicated in the generation and maintenance of T follicular helper (Tfh) cells and the formation of germinal-centers. Together with IL6, control the early generation of Tfh cells and are critical for an effective antibody response to acute viral infection (By similarity). May play a role in proliferation and maturation of natural killer (NK) cells in synergy with IL15. May regulate proliferation of mature B- and T-cells in response to activating stimuli. In synergy with IL15 and IL18 stimulates interferon gamma production in T-cells and NK cells (PubMed:11081504, PubMed:15178704). During T-cell mediated immune response may inhibit dendritic cells (DC) activation and maturation (By similarity)

Subcellular location

Secreted
Domains and Gene Ontology detail (27)

Gene Ontology

  • Cextracellular region
  • Cextracellular space
  • Cplasma membrane
  • Fcytokine activity
  • Fcytokine receptor binding
  • Finterleukin-2 receptor binding
  • Pcell maturation
  • Pcell surface receptor signaling pathway via JAK-STAT
  • Pcellular response to virus
  • Pdefense response to virus
  • Pgerminal center B cell differentiation
  • Pimmunoglobulin mediated immune response

162 aa · 19 kDa · 2 isoforms

Biological roles

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

Cell proliferation & survivalGOImmune signallingUniProt · GO
View supporting evidence

Cell proliferation & survival

  • ·positive regulation of cell population proliferation

Immune signalling

  • ·Cytokine with immunoregulatory activity. May promote the transition between innate and a…
  • ·cytokine activity
  • ·cytokine receptor binding
  • ·interleukin-2 receptor binding

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 IL21

Gene-level evidence surfaced through the gene IL21that 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.

Hypothyroidism
0.70Moderately supported

Genetic evidence dominant · Open Targets 0.42

Crohn's Disease
0.68Moderately supported

Genetic evidence dominant · Open Targets 0.41

Psoriasis
0.67Moderately supported

Genetic evidence dominant · Open Targets 0.39

Asthma
0.65Moderately supported

Genetic evidence dominant · Open Targets 0.39

Celiac Disease
0.63Moderately supported

Genetic evidence dominant · Open Targets 0.38

View evidence synthesis (5)
HypothyroidismModerately supported
0.70
agreement 0.56–0.84
Genetic99%Literature1%

Open Targets aggregate 0.42 · 2 independent evidence families

Crohn's DiseaseModerately supported
0.68
agreement 0.57–0.79
Genetic85%Clinical12%Literature3%

Open Targets aggregate 0.41 · 3 independent evidence families

PsoriasisModerately supported
0.67
agreement 0.54–0.79
Genetic79%Literature15%RNA expression6%

Open Targets aggregate 0.39 · 3 independent evidence families

AsthmaModerately supported
0.65
agreement 0.51–0.79
Genetic89%Literature11%

Open Targets aggregate 0.39 · 2 independent evidence families

Celiac DiseaseModerately supported
0.63
agreement 0.49–0.77
Genetic94%Literature6%

Open Targets aggregate 0.38 · 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
Hypothyroidism0.42
Crohn's Disease0.41
Psoriasis0.39
Asthma0.39
Celiac Disease0.38
Psoriasis vulgaris0.34
Neurodegenerative Diseases0.33
Inflammatory Bowel Diseases0.29
Myxedema0.29

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)
NNC0114-0006Phase 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 — Emerging

Feasibility evidence (structure with ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (5)
SM · Structure with LigandAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 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

Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity.50 cites

Hamouda AEI · Nature communications · 2024

Recent

Intratumoral delivery of lipid nanoparticle-formulated mRNA encoding IL-21, IL-7, and 4-1BBL induces systemic anti-tumor immunity.

Hamouda AEI · Nature communications · 2024

Europe PMC papers linked directly to this protein.