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Symbol CD40LG contributors: npt/mct - updated : 04-11-2015
HGNC name CD40 ligand (TNF superfamily, member 5, hyper-IgM syndrome)
HGNC id 11935
Corresponding disease
HIGM1 immunodeficiency with hyper IgM, syndrome 1
Location Xq26.3      Physical location : 135.730.335 - 135.742.548
Synonym name
  • CD40 ligand on B cell
  • tumor necrosis factor (ligand) superfamily, member 5 (hyper-IgM syndrome)
  • T-B cell-activating molecule
  • CD40 ligand, membrane form
  • CD40 ligand, soluble form
  • TNF-related activation protein
  • Synonym symbol(s) CD40L, gp39, TNFSF5, RP3-527F8.3, CD154, HIGM1, IGM, IMD3, T-BAM, TRAP,
    TYPE functioning gene
    STRUCTURE 12.21 kb     5 Exon(s)
    regulatory sequence Promoter
    Binding site   enhancer
    text structure
  • T-cell-specific transcriptional enhancer located just upstream of the promoter (
  • MAPPING cloned Y linked   status confirmed
    Map cen - HPRT1 - DXS10 - DXS177 - DXS144E - CD40LG - DXS1256 - DXS300 - DXS1041 - DXS1062 - DXS99 - DXS274 - qter
    Authors Pilia (94,97), Consensus (95)
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    - - - - - - 2008 18849075
  • sCD40L production is blocked by Zn(2+)-dependent metalloproteinase inhibitors
  • role of sCD40L in numerous disease pathologies and having ability to activate proximal and distal immune responses
  • significantly higher expression in pre-eclampsia than in normal pregnant women
  • induces proliferation and migration of vascular smooth muscle cells (VSMCs) through activation of matrix metalloproteinases (MMPs)
  • 5 - 1840 - 261 - 2008 18849075
  • mCD40L
  • important immunoregulatory protein expressed by T cells, induced by the calcium
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessels     Homo sapiens
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet Homo sapiens
    Cardiovascularendothelial cell Homo sapiens
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    at STAGE
    PHYSICAL PROPERTIES fibrous ,globular
  • four cysteine rich domains (CRDs)
  • a transmembrane domain
  • a signaling intracellular C-terminus
  • conjugated GlycoP
  • tumor necrosis factor family
  • CATEGORY signaling cytokine
        plasma membrane
  • type II transmembrane protein
  • expressed on the surface of activated CD4+ T cells
  • basic FUNCTION
  • involved in Ig class switching
  • potentially involved in pathogenic cytokine production in inflammatory bone disease
  • IgE production in presence of IL-4
  • playing a regulatory role in bone mineralization, in (regulating bone mass and in osteoclastogenesis
  • its expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells
  • costimulatory molecule expressed on T cells, and is also expressed and functional on platelets
  • platelet CD40LG plays a pivotal role in atherosclerosis, not only by affecting platelet-platelet interactions but especially by activating leukocytes, thereby increasing platelet-leukocyte and leukocyte-endothelium interactions
  • activation of CD40 by CD40LG plays a crucial role for the development and progression of a variety of inflammatory processes including atherosclerosis
  • is a thrombo-inflammatory molecule that predicts cardiovascular events
  • sCD40LG/CD40 axis triggers NFKB1 activation in platelets
  • soluble CD40LG is an important inducer of the NFKB1 signaling pathway activation in platelets independently of the MAPK14 pathway
  • IL21 and CD40LG collaborate through at least two distinct mechanisms to synergistically promote PRDM1 activation and plasma cells (PCs) differentiation
  • 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
  • may contribute directly to atherogenesis by activating endothelial cells and recruiting monocytes to them
  • soluble form of CD40LG(sCD40LG), which results from the shedding of membrane-bound CD40LG, plays a key role in the production of proinflammatory cytokines and has been linked to various autoimmune and vascular disorders
  • CD40-induced signalling through ligation with its natural ligand (CD40LG) is dependent on recruitment of TRAF molecules to the cytoplasmic domain of the receptor
  • role of sCD40LG in foam cell formation during atherosclerosis, which further confirms the importance of sCD40LG in atherosclerosis
    PHYSIOLOGICAL PROCESS immunity/defense
    a component
    small molecule
  • inducing tissue factor F3 in endothelial cells, under the mediation of AP1, NF-kappa B, EGR1
  • can influence RANKL signaling through T cell priming
  • CD40/CD40LG interaction induces E-selectin 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
  • is released from T-cells by ADAM10 and ADAM17 upon CD40 ligation
  • RAC1 controls surface mobilization of CD40LG on activated platelets and MMP9 secretion from neutrophils
  • may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors
  • novel role of SPAG9 scaffold protein in the bridging of CD40LG-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes
  • cell & other
    Other cleaved by ADAM-10 protease to generate sCD40L
    corresponding disease(s) HIGM1
    related resource CD40Ldefectdatabase
    Susceptibility to Kawasaki disease with coronary artey lesions
    Variant & Polymorphism SNP in intron 4 associated with Kawasaki dsease with coronary artey lesions
    Candidate gene
  • biomarker for the diagnosis of prostatic inflammation in benign prostatic hyperplasia
  • Therapy target