CD40LG Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the CD40LG gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | CD40LG |
|---|---|
| Full Name | CD40 ligand |
| Gene Type | protein coding |
| Chromosomal Location | Xq26.3 |
| NCBI Gene ID | 959 ncbi.nlm.nih.gov/gene/959 |
| Ensembl ID | ENSG00000102245 |
| UniProt ID | P29965 |
| OMIM ID | 300386 |
| HGNC ID | 11935 |
| Aliases | CD40L, TNFSF5, HIGM1, IMD3, gp39, TRAP |
Description
The CD40LG gene encodes CD40 ligand, a type II transmembrane protein primarily expressed on activated T cells. It binds to CD40 on antigen-presenting cells, playing a critical role in T-cell-dependent B-cell activation, immunoglobulin class switching, and germinal center formation. Mutations in CD40LG cause X-linked hyper-IgM syndrome, characterized by recurrent infections and defective humoral immunity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked hyper-IgM syndrome (HIGM1) | Loss-of-function mutations in CD40LG impair CD40 signaling, preventing B-cell class switch recombination and somatic hypermutation, leading to deficient IgG, IgA, and IgE production. | ClinVar, OMIM |
| Immunodeficiency with hyper-IgM, type 3 | Same as HIGM1; allelic variants. | OMIM |
| Common variable immunodeficiency (CVID) (rare association) | Some CD40LG variants may contribute to CVID phenotype, though not primary cause. | ClinVar |
| Infections (e.g., Pneumocystis jirovecii, Cryptosporidium) | Defective T-cell-B-cell interaction leads to impaired antibody responses and increased susceptibility to opportunistic infections. | OMIM, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tonsil | 0.0 | Not detected |
| Lymph node | 0.0 | Not detected |
| Spleen | 0.0 | Not detected |
| Thymus | 0.0 | Not detected |
| Bone marrow | 0.0 | Not detected |
| Appendix | 0.0 | Not detected |
| Lung | 0.0 | Not detected |
| Blood | 0.0 | Not detected |
| Skeletal muscle | 0.0 | Not detected |
| Heart | 0.0 | Not detected |
| Liver | 0.0 | Not detected |
| Kidney | 0.0 | Not detected |
| Brain | 0.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| T cells (activated) | Not available | CD40LG is transiently expressed on activated CD4+ T cells; not detected in resting cells. |
| Th1/Th2 subsets | Not available | Expression is upregulated upon TCR engagement. |
| Platelets | Not available | Express CD40LG after activation, contributing to inflammation. |
| NK cells | Not available | Low expression upon activation. |
| Mast cells | Not available | Expression induced by inflammatory stimuli. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.475G>A (p.Gly159Arg) | Missense | Rare | Impairs CD40 binding; causes HIGM1. |
| c.520T>C (p.Cys174Arg) | Missense | Rare | Disrupts disulfide bond, affecting protein stability. |
| c.785C>T (p.Pro262Leu) | Missense | Rare | Reduces CD40LG expression and function. |
| c.289C>T (p.Arg97*) | Nonsense | Rare | Truncated protein, loss of function. |
| c.346+1G>A | Splice site | Rare | Aberrant splicing, loss of function. |
| c.1A>G (p.Met1?) | Start codon loss | Rare | No protein synthesis. |
Mutation functional classification
Loss of Function (LOF)
Most CD40LG mutations are loss-of-function, leading to absent or non-functional CD40 ligand, causing X-linked hyper-IgM syndrome.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CD40LG.
Dominant Negative (DN)
Since CD40LG is X-linked and expressed as a trimer, some missense mutations may exert a dominant-negative effect by forming mixed trimers with wild-type protein, reducing overall function.
View complete mutation data：
Gene Ontology (GO)
| • cytokine activity | • CD40 receptor binding |
| • tumor necrosis factor receptor superfamily binding | • protein homodimerization activity |
| • signal transduction | • immune response |
| • B cell proliferation | • immunoglobulin production |
| • T cell costimulation | • positive regulation of NF-kappaB transcription factor activity |
Pathways
• CD40/CD40L signaling pathway
• T cell receptor signaling pathway
• B cell receptor signaling pathway
• Cytokine-cytokine receptor interaction
• NF-kappaB signaling pathway
Protein Summary
CD40 ligand (CD40LG) is a 261-amino acid type II transmembrane protein that forms homotrimers on the cell surface. It binds to CD40 on B cells, dendritic cells, and macrophages, triggering intracellular signaling cascades that lead to B-cell activation, class switching, and antibody production. The protein is cleaved by metalloproteinases to produce a soluble form that retains biological activity. Defects in CD40LG cause X-linked hyper-IgM syndrome, a primary immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD40LG Knockout HEK293 Cell Line | EDJ-KQ554 | Human | 959 | Details Get a Quote |
| CD40LG Knockout HeLa Cell Line | EDJ-KQ52842 | Human | 959 | Details Get a Quote |
| CD40LG Knockout A-549 Cell Line | EDJ-KQ61309 | Human | 959 | Details Get a Quote |
| CD40LG Knockout HCT 116 Cell Line | EDJ-KQ69803 | Human | 959 | Details Get a Quote |
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