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Symbol CD40 contributors: mct/npt - updated : 04-11-2015
HGNC name CD40 molecule, TNF receptor superfamily member 5
HGNC id 11919
Corresponding disease
HIGM3 immunodeficiency with hyper IgM, syndrome 3
Location 20q13.12      Physical location : 44.746.905 - 44.758.384
Synonym name
  • tumor necrosis factor receptor superfamily, member 5
  • CD40 antigen
  • CD40L receptor
  • B-cell surface antigen CD40
  • nerve growth factor receptor-related B-lymphocyte activation molecule
  • Synonym symbol(s) p50, TNFRSF5, CDW40, Bp50, MGC9013
    TYPE functioning gene
    STRUCTURE 11.49 kb     9 Exon(s)
    MAPPING cloned Y linked N status confirmed
    Map cen - SRC - D20S106 - D20S187 - [D20S174 - PLCG1 - (D20S110 - D20S119 - D20S197 ) - ADA ADA - D20S17 - PPGB - D20S16 - D20S75 - D20S109 ] -D20S196 - qter
    Authors Asimakopoulos (95)
    Text [CD40 ]
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1616 - 277 - 2008 18713981
    8 - 1554 22.4 203 - 2008 18713981
    frameshift distinct C terminus
    9 - 1669 - 237 - 2008 18713981
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel     Homo sapiens
    Lymphoid/Immunelymph node   highly
     tonsils   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose    Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte Homo sapiens
    Blood/Hematopoieticmonocyte Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    not specificadipocyte Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal
  • extracytoplasmic cysteine-rich pseudorepeats typical for the TNFR superfamily
  • a preligand assembly domain (PLAD) in CRD1 mediating ligand-independent receptor assembly and signaling, and cysteine-rich domain 1 (CRD1) participated to dimerization and was also required for efficient receptor expression
  • a small cytoplasmic domain without catalytic activity and lacking the DEATH domain
  • conjugated GlycoP
    mono polymer homomer , trimer
    interspecies homolog to murine Tnfrsf5
    homolog to C.elegans Y57A10A.26
  • tumor necrosis factor receptor superfamily
  • CATEGORY immunity/defense , antigen , receptor membrane
        plasma membrane
    text type 1 membrane protein
    basic FUNCTION
  • pleiotropic modulator of immune response including germinal center formation
  • Ig isotype switching and T cell activation in part by activation of NKFBs through binding to TRAF proteins and JAK3
  • suppressor of apoptosis throught NFKB dependent upregulation of BCL2 family members
  • CD40 signaling is critical for innate and adaptive immunity against pathogens
  • regulator of retinal inflammation and neurovascular degeneration
  • adipocyte CD40 may contribute to obesity-related inflammation and insulin resistance
  • delivers signals regulating diverse cellular responses, including proliferation, differentiation, growth suppression, and cell death
  • CD40 signaling is an active termination signal for germinal center reaction
  • required for T cell-dependent humoral immunity, but it can also contribute to the pathogenesis of autoimmunity and B cell malignancy
  • its activation can reverse immune suppression and drive antitumor T cell responses
  • role for the CD40 pathway in regulating the immune reaction and fibrosis associated with pancreatic ductal adenocarcinoma by reeducation of tumor-associated macrophage
  • sCD40LG/CD40 axis triggers NFKB1 activation in platelets
  • activation of CD40 on B cells, macrophages, and dendritic cells by its ligand CD40LG is essential for the development of humoral and cellular immune responses
  • CD40 self-assembly modulates signaling, possibly by maintaining the receptor in a quiescent state
  • CD40-mediated maintenance of immune homeostasis in the adipose tissue microenvironment
  • CD40-induced signalling through ligation with its natural ligand (CD40LG) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor
  • has a pivotal role in B-cell-mediated immunity through various effector pathways including AKT1 kinase
  • CD4(+) T cells directly influence naive B cell development via CD40 signaling
  • CD40 expression on the surface of B lymphocytes is essential for their biological function and fate decision
  • co-stimulatory protein that is involved in T helper cell polarization and is found on the surface of antigen-presenting cells
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    signaling signal transduction
    host response against pathogens, NF-kappa B signaling pathway
    a component
    small molecule
  • interacting with TRAF2 and TRAF6 adaptor proteins that are positive regulators of CD40 signaling required to activate downstream kinase cascades and transcription factors
  • RIPK1 links the immunoregulatory CD40 receptor to apoptotic signaling in carcinomas
  • TRAF3 can serve as a negative regulator of CD40 signaling
  • CD40/CD40LG interaction induces SELE dependent adhesion of leukocytes to human endothelial cells and reduces endothelial cell migration by inhibiting the Akt/eNOS signaling pathway
  • in platelets, soluble CD40LG induces association of CD40 with its adaptor protein the TNFR associated factor 2 and triggers phosphorylation of CHUK
  • NFKB1 signaling pathway, which involves both NFKBIA and CHUK, plays an important role in platelet CD40 signaling, activation and aggregation in response to sCD40LG
  • novel role of a scaffolding protein SPAG9 in the regulation of surface CD40 expression and fine-tuning of dendritic cells function
  • TNFSF12 inhibits TRAF2-mediated CD40 signaling by destabilization of CD40 signaling complexes
  • CD40LG is released from T-cells by ADAM10 and ADAM17 upon CD40 ligation
  • FAF1 was able to interact with CD40, and CD40 ligation induced FAF1 expression in an NFKB1-dependent manner
  • NEDD4 constitutively interacts with CD40 and mediates K63-linked ubiquitination of TRAF3
  • ERK-1/2 inhibition or MAPK14 overexpression inhibited CD40-induced PTPN6 activation
  • novel role of SPAG9 scaffold protein in the bridging of CD40LG-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes
  • SQSTM1 is a critical regulator in CD40-mediated NFKB1 signaling via TRAF6
  • cell & other
    activated by CD40LG which plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis
    corresponding disease(s) HIGM3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    during adipocyte differentiation
    constitutional     --other  
    aberrant CD40-induced NFKB1 activation in human lupus B lymphocytes
  • to rheumatoid arthritis
  • to Crohn disease and multiple sclerosis
  • to variation of clinical disease manifestations in patients with systemic lupus erythematosus (SLE)
  • Variant & Polymorphism SNP , other
  • common variant increasing the risk of rheumatoid arthritis
  • CD40 rs1883832 increasing the risk of Crohn disease and multiple sclerosis
  • CD40 T variant might be negatively associated with some clinical disease manifestations in patients with SLE
  • Candidate gene
    Therapy target
    CD40-dependent mechanism for targeting tumor stroma in the treatment of pancreatic cancer
    CD40-knocked-out mice