ICOSLG (Inducible T-Cell Costimulator Ligand)
A key immune checkpoint ligand involved in T-cell activation and regulation
Gene Information Card
| Symbol | ICOSLG |
|---|---|
| Full Name | Inducible T-Cell Costimulator Ligand |
| Gene Type | Protein coding |
| Chromosomal Location | 21q22.3 |
| NCBI Gene ID | 23308 ncbi.nlm.nih.gov/gene/23308 |
| Ensembl ID | ENSG00000160223 |
| UniProt ID | O75144 |
| OMIM ID | 605717 |
| HGNC ID | 5388 |
| Aliases | B7-H2, B7RP-1, CD275, ICOS-L, ICOSL, LICOS |
Description
ICOSLG (Inducible T-Cell Costimulator Ligand) encodes a member of the B7 family of immune costimulatory proteins. The protein is expressed on antigen-presenting cells and binds to the ICOS receptor on activated T cells, providing a critical costimulatory signal for T-cell proliferation, cytokine production, and germinal center formation. ICOSLG plays a central role in adaptive immunity, autoimmunity, and tumor immune evasion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Common variable immunodeficiency (CVID) | Loss-of-function mutations in ICOSLG impair ICOS signaling, leading to defective T-cell help and B-cell differentiation | PMID: 19122661; ClinVar |
| Systemic lupus erythematosus (SLE) | Polymorphisms in ICOSLG are associated with altered costimulation and autoantibody production | PMID: 23291587; GWAS catalog |
| Rheumatoid arthritis | ICOSLG expression on synovial fibroblasts promotes T-cell activation and joint inflammation | PMID: 14608356 |
| Cancer (various) | Tumor cells upregulate ICOSLG to modulate T-cell responses, influencing immune evasion and immunotherapy outcomes | PMID: 31570863; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 10.8 | High |
| Tonsil | 9.2 | High |
| Lung | 4.1 | Medium |
| Small intestine | 3.5 | Medium |
| Kidney | 1.2 | Low |
| Liver | 0.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B cells (lymphoblastoid) | 15.3 | High expression |
| Monocytes (THP-1) | 8.7 | Moderate expression |
| Dendritic cells (immature) | 6.2 | Moderate expression |
| T cells (Jurkat) | 0.5 | Very low expression |
| HEK293 | 0.3 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.163C>T (p.Arg55*) | Nonsense | Rare (<0.01%) | Loss of function; truncation of extracellular domain |
| c.389G>A (p.Arg130Gln) | Missense | 0.02% | Reduced ICOS binding affinity |
| c.734T>C (p.Ile245Thr) | Missense | 0.01% | Altered protein stability |
| c.1021_1023del (p.Leu341del) | In-frame deletion | Rare | Impaired cell surface expression |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations (e.g., p.Arg55*, p.Arg130Gln) that reduce protein expression or ICOS binding, leading to impaired T-cell costimulation and immunodeficiency.
Gain of Function (GOF)
Not well documented; no confirmed gain-of-function mutations reported in literature or databases.
Dominant Negative (DN)
No dominant-negative mutations described for ICOSLG; the gene functions as a ligand and is not known to form dominant-negative complexes.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa04660 - T cell receptor signaling pathway (KEGG)
• hsa04658 - Th1 and Th2 cell differentiation (KEGG)
• hsa04659 - Th17 cell differentiation (KEGG)
• R-HSA-389948 - PD-1 signaling (Reactome)
• R-HSA-202430 - Costimulation by the CD28 family (Reactome)
Protein Summary
ICOSLG (B7-H2/CD275) is a 302-amino acid type I transmembrane glycoprotein with a single extracellular immunoglobulin-like V-type domain. It is primarily expressed on antigen-presenting cells (B cells, dendritic cells, macrophages) and non-hematopoietic cells (endothelial, epithelial). The protein binds to ICOS (CD278) on activated T cells, delivering a costimulatory signal essential for T follicular helper cell differentiation, germinal center formation, and antibody class switching. ICOSLG is also implicated in tumor immune evasion and is a target for immunomodulatory therapies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ICOSLG Knockout HEK293 Cell Line | EDJ-KQ17739 | Human | 23308 | Details Get a Quote |
| ICOSLG Knockout HeLa Cell Line | EDJ-KQ55717 | Human | 23308 | Details Get a Quote |
| ICOSLG Knockout A-549 Cell Line | EDJ-KQ64216 | Human | 23308 | Details Get a Quote |
| ICOSLG Knockout HCT 116 Cell Line | EDJ-KQ72661 | Human | 23308 | Details Get a Quote |
