TNFRSF18 (GITR): A Key Immune Checkpoint Receptor in T-Cell Regulation
Explore the genomic, functional, and clinical significance of TNFRSF18, a costimulatory receptor with emerging roles in cancer immunotherapy and autoimmune diseases.
Gene Information Card
| Symbol | TNFRSF18 |
|---|---|
| Full Name | TNF receptor superfamily member 18 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p36.33 |
| NCBI Gene ID | 8784 ncbi.nlm.nih.gov/gene/8784 |
| Ensembl ID | ENSG00000186891 |
| UniProt ID | Q9Y5U5 |
| OMIM ID | 603905 |
| HGNC ID | 11912 |
| Aliases | GITR, AITR, CD357 |
Description
TNFRSF18 encodes the glucocorticoid-induced TNFR-related protein (GITR), a type I transmembrane receptor belonging to the tumor necrosis factor receptor superfamily. GITR is expressed on regulatory T cells (Tregs) and activated conventional T cells, where it modulates immune responses. Its ligand, TNFSF18 (GITRL), is expressed on antigen-presenting cells. GITR signaling provides costimulatory signals to effector T cells and inhibits Treg suppressive activity, making it a key target in cancer immunotherapy and a modulator of autoimmune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various solid tumors) | GITR activation on effector T cells enhances anti-tumor immunity; GITR on Tregs may be targeted to reduce immunosuppression. | Preclinical models and early-phase clinical trials (e.g., anti-GITR antibodies) show enhanced tumor rejection (NCBI Gene, UniProt). |
| Autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis) | Polymorphisms in TNFRSF18 may alter GITR expression/function, affecting Treg activity and promoting autoimmunity. | Genetic association studies and functional assays (OMIM, ClinVar). |
| Inflammatory bowel disease (IBD) | GITR signaling may exacerbate intestinal inflammation by modulating T-cell responses. | Expression studies in IBD patients (UniProt, literature). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High | High expression in immune tissues |
| Spleen | High | High expression in immune tissues |
| Blood | Medium | Expressed in T cells |
| Bone marrow | Low | Low expression |
| Thymus | Medium | Expressed in developing T cells |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | High | T-cell line with high GITR expression |
| Ramos (B-cell lymphoma) | Low | B-cell line with low expression |
| K562 (CML) | Low | Myeloid line with low expression |
| A549 (Lung carcinoma) | Low | Epithelial line with low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.315C>T (p.Ser105Ser) | Synonymous | Rare | No known functional effect |
| c.487A>G (p.Ile163Val) | Missense | Rare | Potential impact on protein stability (in silico prediction) |
| c.625G>A (p.Val209Ile) | Missense | Rare | Unknown clinical significance |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in TNFRSF18.
Gain of Function (GOF)
No gain-of-function mutations reported; overexpression of wild-type GITR is associated with immune dysregulation.
Dominant Negative (DN)
No dominant-negative mutations described.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity | • tumor necrosis factor-activated receptor activity |
| • signal transduction | • immune response |
| • regulation of T cell activation | • negative regulation of regulatory T cell differentiation |
Pathways
• TNF receptor superfamily signaling
• T cell receptor signaling pathway
• Regulation of immune response
• NF-kappaB signaling
Protein Summary
The GITR protein is a 241-amino acid type I transmembrane receptor with an extracellular domain containing cysteine-rich repeats typical of TNFR superfamily members. It is expressed predominantly on T cells, especially regulatory T cells. Upon binding to GITRL, GITR recruits TRAF2 and activates NF-kappaB and MAPK pathways, leading to T-cell activation and cytokine production. GITR also modulates Treg suppressive function, making it a promising target for cancer immunotherapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNFRSF18 Knockout HEK293 Cell Line | EDJ-KQ17740 | Human | 8784 | Details Get a Quote |
| TNFRSF18 Knockout HCT 116 Cell Line | EDJ-KQ19813 | Human | 8784 | Details Get a Quote |
| TNFRSF18 Knockout HeLa Cell Line | EDJ-KQ55002 | Human | 8784 | Details Get a Quote |
| TNFRSF18 Knockout A-549 Cell Line | EDJ-KQ63487 | Human | 8784 | Details Get a Quote |
