Back to discover

Protein / target

CD40 ligand

Encoded byCD40LGP29965Homo sapiensSwiss-Prot
Clinical-stage
Therapeutic maturity
6
Clinical candidates
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Protein serine/threonine kinase activator

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene CD40LG · Genetic evidence · score 0.67

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

1 papers · latest 2009

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 acts as a ligand to CD40/TNFRSF5.

View complete UniProt function annotation

Cytokine that acts as a ligand to CD40/TNFRSF5 (PubMed:1280226, PubMed:31331973). Costimulates T-cell proliferation and cytokine production (PubMed:8617933). Its cross-linking on T-cells generates a costimulatory signal which enhances the production of IL4 and IL10 in conjunction with the TCR/CD3 ligation and CD28 costimulation (PubMed:8617933). Induces the activation of NF-kappa-B (PubMed:15067037, PubMed:31331973). Induces the activation of kinases MAPK8 and PAK2 in T-cells (PubMed:15067037). Induces tyrosine phosphorylation of isoform 3 of CD28 (PubMed:15067037). Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4 (By similarity). Involved in immunoglobulin class switching (By similarity)

Subcellular location

Cell membraneCell surfaceSecreted
Domains and Gene Ontology detail (28)

Domains & features

THD

Gene Ontology

  • Ccell surface
  • Cexternal side of plasma membrane
  • Cextracellular space
  • Cmembrane
  • Cplasma membrane
  • FCD40 receptor binding
  • Fcytokine activity
  • Fintegrin binding
  • Fprotein serine/threonine kinase activator activity
  • Ftumor necrosis factor receptor binding
  • PB cell proliferation
  • PCD40 signaling pathway

261 aa · 29 kDa

Biological roles

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

Immune signallingUniProt · GOApoptosis & cell deathGO
View supporting evidence

Immune signalling

  • ·Cytokine that acts as a ligand to CD40/TNFRSF5 (PubMed:1280226, PubMed:31331973). Costim…
  • ·cytokine activity
  • ·B cell proliferation
  • ·inflammatory response

Apoptosis & cell death

  • ·negative regulation of apoptotic process
  • ·positive regulation of endothelial cell 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 CD40LG

Gene-level evidence surfaced through the gene CD40LGthat 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.

Genetic Diseases, Inborn
0.67Moderately supported

Genetic evidence dominant · Open Targets 0.41

Lupus Erythematosus, Systemic
0.58Moderately supported

Clinical evidence dominant · Open Targets 0.40

Common variable immunodeficiency
0.56Moderately supported

Genetic evidence dominant · Open Targets 0.40

Sjogren's Syndrome
0.46Limited support

Clinical evidence dominant · Open Targets 0.37

Colitis, Ulcerative
0.39Limited support

Genetic evidence dominant · Open Targets 0.21

View evidence synthesis (5)
Genetic Diseases, InbornModerately supported
0.67
agreement 0.540.81
Genetic99%Literature1%

Open Targets aggregate 0.41 · 2 independent evidence families

Lupus Erythematosus, SystemicModerately supported
0.58
agreement 0.480.69
Clinical63%Literature21%Genetic16%

Open Targets aggregate 0.40 · 3 independent evidence families

Common variable immunodeficiencyModerately supported
0.56
agreement 0.420.70
Genetic80%Literature20%

Open Targets aggregate 0.40 · 2 independent evidence families

Sjogren's SyndromeLimited support
0.46
agreement 0.310.62
Clinical95%Literature6%

Open Targets aggregate 0.37 · 2 independent evidence families

Colitis, UlcerativeLimited support
0.39
agreement 0.280.50
Genetic74%Clinical21%Literature4%

Open Targets aggregate 0.21 · 3 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
Genetic Diseases, Inborn0.41
Lupus Erythematosus, Systemic0.40
Common variable immunodeficiency0.40
Sjogren's Syndrome0.37
Neurodegenerative Diseases0.21
Colitis, Ulcerative0.21
Sarcoidosis0.19

Drug development

6 compounds recorded · 6 in clinical development

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

View all recorded compounds (6)
DAZODALIBEPPhase 3
DAPIROLIZUMAB PEGOLPhase 3
RAVAGALIMABPhase 2
TEGOPRUBARTPhase 2
TORALIZUMABPhase 1
RUPLIZUMABPhase 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 moleculesEmerging

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

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (8)
SM · Structure with LigandSM · High-Quality PocketAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2009

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

Most cited

Elgueta R · Immunological reviews · 2009

Recent

Europe PMC papers linked directly to this protein.