Protein / target

Tumor necrosis factor receptor superfamily member 5

Encoded byCD40P25942Homo sapiensSwiss-Prot

UniProt: P25942 Ensembl: ENSG00000101017 HGNC: HGNC:11919 NCBI Gene: 958

Clinical-stage

Therapeutic maturity

Clinical candidates

Antibody-tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Ubiquitin protein ligase binding

Strongest disease association

Arthritis, Rheumatoid

Via encoding gene CD40 · Genetic evidence · score 0.93

Therapeutic position

Clinically advancing target

Antibodies

Research activity

Emerging research

4 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

Receptor for TNFSF5/CD40LG.

View complete UniProt function annotation

Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated signals that activate ERK in macrophages and B cells, leading to induction of immunoglobulin secretion (By similarity)

Subcellular location

Cell membraneSecreted

Domains and Gene Ontology detail (37)

Gene Ontology

CCD40 receptor complex
Ccell surface
Cexternal side of plasma membrane
Cextracellular exosome
Cneuronal cell body
Cplasma membrane
Cvaricosity
Fantigen binding
Fenzyme binding
Fprotein domain specific binding
Fsignaling receptor activity
Fubiquitin protein ligase binding

277 aa · 31 kDa · 2 isoforms

Biological roles

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

Cell migrationGOImmune signallingUniProt · GO

View supporting evidence

Cell migration

·positive regulation of blood vessel endothelial cell migration

Immune signalling

·Receptor for TNFSF5/CD40LG (PubMed:31331973). Transduces TRAF6- and MAP3K8-mediated sign…
·antigen binding
·B cell activation
·B cell mediated immunity

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 CD40

Gene-level evidence surfaced through the gene CD40that 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.

Arthritis, Rheumatoid

0.95Well supported

Genetic evidence dominant · Open Targets 0.60

Graves' Disease

0.90Well supported

Genetic evidence dominant · Open Targets 0.57

Inflammatory Bowel Diseases

0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Crohn's Disease

0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Multiple Sclerosis

0.78Well supported

Genetic evidence dominant · Open Targets 0.48

View evidence synthesis (5)

Arthritis, RheumatoidWell supported

0.95

agreement 0.84–1.00

Genetic80%Literature12%Clinical9%

Open Targets aggregate 0.60 · 3 independent evidence families

Graves' DiseaseWell supported

0.90

agreement 0.80–1.00

Genetic86%Clinical11%Literature3%

Open Targets aggregate 0.57 · 3 independent evidence families

Inflammatory Bowel DiseasesWell supported

0.82

agreement 0.68–0.96

Genetic95%Literature5%

Open Targets aggregate 0.50 · 2 independent evidence families

Crohn's DiseaseWell supported

0.82

agreement 0.69–0.94

Genetic94%Literature4%RNA expression2%

Open Targets aggregate 0.50 · 3 independent evidence families

Multiple SclerosisWell supported

0.78

agreement 0.64–0.92

Genetic91%Literature9%

Open Targets aggregate 0.48 · 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

Arthritis, Rheumatoid0.60

Graves' Disease0.57

Inflammatory Bowel Diseases0.50

Crohn's Disease0.50

Multiple Sclerosis0.48

Bipolar Disorder0.48

Mucocutaneous Lymph Node Syndrome0.45

Thyrotoxicosis0.45

Drug development

10 compounds recorded · 10 in clinical development

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

View all recorded compounds (10)

LUCATUMUMABPhase 2

SELICRELUMABPhase 1 2

SOTIGALIMABPhase 2

PG-102Phase 2

DACETUZUMABPhase 2

CD40 LIGANDPhase 2

BLESELUMABPhase 2

GILORALIMABPhase 1

ISCALIMABPhase 2

CDX-1140Phase 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

Antibodies — Strong

Advanced Clinical and GO CC high conf support this modality.

Protein degraders — Emerging

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

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (7)

AB · Advanced ClinicalAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Half-life DataPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

regulation of gene expressionToxCast

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.