TNFSF18 (TNF Superfamily Member 18)
A cytokine ligand in the tumor necrosis factor family, involved in T-cell activation and immune regulation.
Gene Information Card
| Symbol | TNFSF18 |
|---|---|
| Full Name | TNF Superfamily Member 18 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q25.1 |
| NCBI Gene ID | 8995 ncbi.nlm.nih.gov/gene/8995 |
| Ensembl ID | ENSG00000169248 |
| UniProt ID | Q9UNG2 |
| OMIM ID | 604587 |
| HGNC ID | 11931 |
| Aliases | GITRL, TL6, hGITRL, AITRL |
Description
TNFSF18 (TNF Superfamily Member 18) encodes a cytokine ligand of the tumor necrosis factor (TNF) family. It is also known as GITRL (glucocorticoid-induced TNF receptor ligand). The protein is a type II transmembrane protein that binds to its receptor TNFRSF18 (GITR) on T cells, playing a key role in T-cell activation, proliferation, and immune regulation. TNFSF18 is expressed on antigen-presenting cells and endothelial cells, and its signaling modulates both adaptive and innate immune responses. Dysregulation of TNFSF18 is implicated in autoimmune diseases, inflammatory conditions, and cancer, making it a target for immunotherapeutic strategies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus) | Overexpression of TNFSF18 enhances T-cell activation and pro-inflammatory cytokine production, contributing to autoimmunity. | PMID: 16920917; NCBI Gene |
| Cancer (various solid tumors) | Tumor-expressed TNFSF18 may promote immune evasion by modulating Treg cell activity and suppressing anti-tumor immunity. | PMID: 23983241; COSMIC |
| Inflammatory bowel disease | Increased TNFSF18 expression in intestinal mucosa correlates with disease severity and T-cell infiltration. | PMID: 20138983; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 9.8 | Medium |
| Small intestine | 6.5 | Low |
| Colon | 5.2 | Low |
| Lung | 3.1 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (monocytic leukemia) | 8.7 | High expression after LPS stimulation |
| Jurkat (T-cell leukemia) | 2.3 | Low baseline expression |
| HeLa (cervical carcinoma) | 1.5 | Very low expression |
| HUVEC (endothelial) | 6.1 | Moderate expression, upregulated by TNF-alpha |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.314C>T (p.Pro105Leu) | Missense | <0.01% (gnomAD) | Unknown functional effect; rare variant |
| c.487G>A (p.Val163Ile) | Missense | <0.01% (gnomAD) | Predicted benign; no known disease association |
| c.1A>G (p.Met1?) | Start loss | <0.001% | Likely loss of function; not reported in disease |
Mutation functional classification
Loss of Function (LOF)
No confirmed loss-of-function mutations reported in TNFSF18; start-loss variant (c.1A>G) is predicted to cause loss of function.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
Pathways
• TNF signaling pathway (KEGG: hsa04668)
• NF-kappa B signaling pathway (KEGG: hsa04064)
• GITR signaling (Reactome: R-HSA-5607764)
Protein Summary
The TNFSF18 protein (GITRL) is a 177-amino-acid type II transmembrane protein with a short cytoplasmic domain, a transmembrane region, and an extracellular TNF homology domain. It forms homotrimers and binds to the GITR receptor (TNFRSF18) on T cells. The interaction promotes T-cell activation, proliferation, and survival, and modulates regulatory T-cell (Treg) function. The protein is expressed on antigen-presenting cells, endothelial cells, and some tumor cells. Its structure and function are conserved across mammals, and it is a target for immunomodulatory therapies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFSF18 Knockout HEK293 Cell Line | EDJ-KQ6425 | Human | 8995 | Details Get a Quote |
| TNFSF18 Knockout HCT 116 Cell Line | EDJ-KQ18268 | Human | 8995 | Details Get a Quote |
| TNFSF18 Knockout HeLa Cell Line | EDJ-KQ55051 | Human | 8995 | Details Get a Quote |
| TNFSF18 Knockout A-549 Cell Line | EDJ-KQ63534 | Human | 8995 | Details Get a Quote |
