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GeneE
50 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CD40
CD40 molecule
Chromosome 20 Β· 20q13.12
NCBI Gene: 958Ensembl: ENSG00000101017.15HGNC: HGNC:11919UniProt: A0A0S2Z349
626PubMed Papers
21Diseases
10Drugs
15Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneReceptor
RESEARCH IMPACT
Highly Studied
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
positive regulation of transcription by RNA polymerase IIprotein bindingubiquitin protein ligase bindingplasma membranehyper-IgM syndrome type 3rheumatoid arthritisGraves diseaseinflammatory bowel disease
✦AI Summary

CD40 is a type I transmembrane receptor of the tumor necrosis factor receptor superfamily constitutively expressed on hematopoietic cells including B cells, macrophages, and dendritic cells, as well as non-hematopoietic cells such as endothelial cells and platelets 1. CD40 functions as a receptor for CD40 ligand (CD40L/CD154), with this receptor-ligand interaction serving as an essential immune checkpoint molecule 2. Upon CD40 engagement by CD40L expressed on T cells, the receptor transduces TRAF6- and MAP3K8-mediated signals activating ERK, leading to production of proinflammatory cytokines, T helper cell function promotion, and macrophage activation 1. A critical function of CD40 signaling is enabling immunoglobulin isotype switching in B cells; defective CD40L causes hyper-IgM immunodeficiency characterized by absent circulating immunoglobulins except IgM 34. Beyond B cell immunity, CD40 signaling mediates broad immune and inflammatory responses including expression of adhesion molecules, cytokines, and apoptotic mediators 5. CD40 dysregulation associates with multiple pathologies: elevated CD40 expression in gastric carcinoma correlates with TNM stage, metastasis, and poor prognosis 6, while CD40/CD40L pathway activation in platelets contributes to atherosclerosis, inflammatory bowel disease, and diabetes 7. Consequently, CD40 represents a validated therapeutic target, with both agonistic and antagonistic monoclonal antibodies developed for oncological and autoimmune disease treatment 2.

Sources cited
1
CD40 is a TNFR superfamily member widely expressed on immune and non-immune cells; CD40/CD40L is an immune checkpoint molecule; structural basis for agonist (dacetuzumab) and antagonist (bleselumab) monoclonal antibody mechanisms
PMID: 38657446
2
CD40 is a 48 kDa type I transmembrane protein on hematopoietic cells; CD40L engagement by T cells induces proinflammatory cytokines, T helper function, and macrophage activation; CD40 is therapeutic target for autoimmune diseases and cancer
PMID: 31382872
3
CD40 expression in gastric carcinoma correlates with TNM stage, distant metastasis, lymphatic metastasis, and poor patient prognosis
PMID: 25665853
4
CD40 and CD154 are expressed on diverse hematopoietic and non-hematopoietic cells; CD40 ligation mediates broad immune/inflammatory responses and associates with autoimmune diseases, neurodegenerative disorders, cancer, and atherosclerosis
PMID: 11229815
5
Platelets express CD40 and CD40 ligand; CD40/CD40L pathway in platelets contributes to atherosclerosis, inflammatory bowel disease, and diabetes pathogenesis
PMID: 15952932
6
CD40L-CD40 interaction is essential for Ig isotype switching in B cells; defective CD40L causes hyper-IgM syndrome with absent circulating Ig except IgM
PMID: 7532459
7
CD40 signaling is essential for immunoglobulin heavy chain switching and production of all isotypes other than IgM; CD40 ligand is stimulatory for monocytes and T cells
PMID: 7510138
Disease Associationsβ“˜21
hyper-IgM syndrome type 3Open Targets
0.80Strong
rheumatoid arthritisOpen Targets
0.59Moderate
Graves diseaseOpen Targets
0.50Moderate
inflammatory bowel diseaseOpen Targets
0.48Moderate
Crohn's diseaseOpen Targets
0.47Moderate
non-Hodgkins lymphomaOpen Targets
0.46Moderate
multiple sclerosisOpen Targets
0.46Moderate
bipolar disorderOpen Targets
0.45Moderate
mucocutaneous lymph node syndromeOpen Targets
0.44Moderate
ThyrotoxicosisOpen Targets
0.44Moderate
mathematical abilityOpen Targets
0.44Moderate
ACPA-positive rheumatoid arthritisOpen Targets
0.44Moderate
systemic lupus erythematosusOpen Targets
0.38Weak
ulcerative colitisOpen Targets
0.37Weak
psoriasisOpen Targets
0.37Weak
chronic hepatitis B virus infectionOpen Targets
0.37Weak
post-traumatic stress disorderOpen Targets
0.36Weak
irritable bowel syndromeOpen Targets
0.36Weak
goiterOpen Targets
0.35Weak
ankylosing spondylitisOpen Targets
0.35Weak
Immunodeficiency with hyper-IgM 3UniProt
Pathogenic Variants15
NM_001250.6(CD40):c.430G>A (p.Glu144Lys)Likely pathogenic
Hyper-IgM syndrome type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 144
NM_001250.6(CD40):c.287_297del (p.Thr96fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 96
NM_001250.6(CD40):c.1del (p.Met1fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1
NM_001250.6(CD40):c.445G>A (p.Gly149Ser)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 149
NM_001250.6(CD40):c.87del (p.Lys29fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 29
NM_001250.6(CD40):c.497+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_001250.6(CD40):c.33G>A (p.Trp11Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 11
NM_001250.6(CD40):c.157G>T (p.Glu53Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 53
NM_001250.6(CD40):c.397C>T (p.Gln133Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 133
NM_001250.6(CD40):c.832_*1del (p.Ter278AlaextTer?)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2023β†’ Residue 278
NM_001250.6(CD40):c.646+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2023
NM_001250.6(CD40):c.95TAA[1] (p.Ile33del)Pathogenic
Hyper-IgM syndrome type 3
β˜†β˜†β˜†β˜†2010β†’ Residue 33
NM_001250.6(CD40):c.247T>C (p.Cys83Arg)Pathogenic
Hyper-IgM syndrome type 3
β˜†β˜†β˜†β˜†2010β†’ Residue 83
NM_001250.6(CD40):c.257-2A>TPathogenic
Hyper-IgM syndrome type 3
β˜†β˜†β˜†β˜†2003
NM_001250.6(CD40):c.408A>T (p.Thr136=)Pathogenic
Hyper-IgM syndrome type 3
β˜†β˜†β˜†β˜†2001β†’ Residue 136
View on ClinVar β†—
Drug Targets10
BLESELUMABPhase II
Tumor necrosis factor receptor superfamily member 5 inhibitor
CD40 LIGANDPhase II
Tumor necrosis factor receptor superfamily member 5 agonist
cutaneous melanoma
CDX-1140Phase II
Tumor necrosis factor receptor superfamily member 5 agonist
pancreatic carcinoma
DACETUZUMABPhase II
Tumor necrosis factor receptor superfamily member 5 inhibitor
non-Hodgkins lymphoma
GILORALIMABPhase I
Tumor necrosis factor receptor superfamily member 5 agonist
ISCALIMABPhase II
Tumor necrosis factor receptor superfamily member 5 inhibitor
Graves disease
LUCATUMUMABPhase II
Tumor necrosis factor receptor superfamily member 5 antagonist
lymphoma
PG-102Phase II
Tumor necrosis factor receptor superfamily member 5 inhibitor
SELICRELUMABPhase I/II
Tumor necrosis factor receptor superfamily member 5 agonist
SOTIGALIMABPhase II
Tumor necrosis factor receptor superfamily member 5 agonist
melanoma
Related Genes
CD8AProtein interaction100%TRAF5Protein interaction100%TRAF2Protein interaction100%IKBKGProtein interaction100%CD58Protein interaction100%RELProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Ovary
80%
Liver
43%
Heart
30%
Bone Marrow
9%
Brain
6%
Gene Interaction Network
Click a node to explore
CD40CD8ATRAF5TRAF2IKBKGCD58REL
PROTEIN STRUCTURE
Preparing viewer…
PDB1LB6 Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.68LoF Tolerant
pLIβ“˜
0.03Tolerant
Observed/Expected LoF0.46 [0.32–0.68]
RankingsWhere CD40 stands among ~20K protein-coding genes
  • #367of 20,598
    Most Researched626 Β· top 5%
  • #2,428of 5,498
    Most Pathogenic Variants15
  • #5,014of 17,882
    Most Constrained (LOEUF)0.68
Genes detectedCD40
Sources retrieved50 papers
Response timeβ€”
πŸ“„ Sources
50β–Ό
1
[CD40].
PMID: 28331104
Arerugi Β· 2017
1.00
2
CD40 and the effect of anti-CD40-binding on human multiple myeloma clonogenicity.
PMID: 8907262
Leuk Lymphoma Β· 1996
0.92
3
Crystal structures of human CD40 in complex with monoclonal antibodies dacetuzumab and bleselumab.
PMID: 38657446
Biochem Biophys Res Commun Β· 2024
0.90
4
Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies.
PMID: 29576376
Cancer Cell Β· 2018
0.84
5
CD40/anti-CD40 antibody complexes which illustrate agonist and antagonist structural switches.
PMID: 31382872
BMC Mol Cell Biol Β· 2019
0.80