Alt. symbols: TNFRSF5 | p50 | Bp50

Approved name: CD40 molecule
Alt. names: tumor necrosis factor receptor superfamily, member 5, CD40 molecule, TNF receptor superfamily member 5

Location: 20q13.12: 46118271 - 46129863 (+)
Gene type: protein_coding, 14 transcripts.

Scores: LoFtool: 0.148000 | pLI: 0.65823750 | LOEUF: 0.422

HGNC: 11919

NCBI: 958, RefSeq: NG_007279.1

Ensembl: ENSG00000101017.15

LRG_40 | Status: public

OMIM: 109535

Expression | ProteinAtlas

CD40 encodes a cell surface receptor that is expressed on the surface of antigen-presenting cells, including all mature B cells, most mature B-cell malignancies, and some early B-cell acute lymphocytic leukemias, but is not expressed on plasma cells (Clark, 1990). It is also expressed on monocytes, dendritic cells, endothelial cells, and epithelial cells. When CD40 ligand (CD154), which is found on the surface of T cells, attaches to CD40 (its natural receptor protein), this triggers a series of chemical signals that instruct B cells to mature and switch from being immunoglobulin M (IgM) class secreting cells to immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin E (IgE) producing B cells. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction.

Biallelic missense, splice site and non-frameshift deletion mutations in CD40 cause autosomal recessive Immunodeficiency with hyper-IgM, type 3 (HIGM3) [MIM:606843]. Mutations in the CD40 gene impair the receptor’s ability to interact with CD40 ligand, preventing subsequent signaling. Thus, this condition phenocopies X-linked HIGM1 due to CD40LG mutations - both feature impaired B cell isotype switching and maturation, as well as the inability to mount an antibody-specific immune response and fo rm germinal centers (PMID: 11675497). Patients with CD40 mutations suffer from recurrent and severe respiratory, gastrointestinal (i.e. chronic diarrhea, mucositis, esophagitis, hepatobiliary disease) and skin/soft tissue infections by opportunistic bacteria and fungi (i.e. Pseudomonas, Pneumocystis, Candida, Cryptosporidium) (PMID: 11675497, 12584544, 15661021, 22342113, 25511220, 30131802). Revy et al. (1998) noted that the susceptibility to intracellular parasites seen in both CD40 and CD40L patients was unlikely due to defective humoral immunity alone. They suggested that this may be the result of defective T-cell-macrophage-dendritic cell crosstalk, as macrophages also rely on the CD40-CD40L pathway for activation (PMID: 9842907), while Fontana et al. (2003) also noted improper maturation of dendritic cells from CD40 patients, leading to a defect in T-cell priming and interferon-γ secretion (PMID: 12893749). Though these patients do have IgA deficiency, this is typically seen in conjunction with low levels of IgG and IgE as well as elevated levels of IgM. [Load More]