TIGIT Gene: Function, Expression, Mutations & Clinical Significance | Biomedical SEO

TIGIT (T cell immunoreceptor with Ig and ITIM domains) is an immune checkpoint receptor encoded by the TIGIT gene located on chromosome 3q13.31. It is a type I transmembrane protein belonging to the poliovirus receptor (PVR) family, containing an extracellular immunoglobulin variable (IgV) domain, a transmembrane domain, and an intracellular tail with an immunoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoglobulin tail tyrosine (ITT) motif. TIGIT is expressed on various immune cells, including T cells, natural killer (NK) cells, and regulatory T cells (Tregs). It binds to ligands such as CD155 (PVR) and CD112 (PVRL2) on antigen-presenting cells and tumor cells, delivering inhibitory signals that suppress T cell and NK cell activation. TIGIT plays a critical role in immune homeostasis, tolerance, and evasion of antitumor immunity, making it a promising target for cancer immunotherapy.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• TIGIT signaling pathway (inhibitory immune checkpoint)

• PD-1/PD-L1 and TIGIT crosstalk in T cell exhaustion

• PVR/CD155 signaling pathway

• NK cell mediated cytotoxicity pathway

• T cell receptor signaling pathway

TIGIT is a 244-amino acid type I transmembrane protein with a signal peptide, an extracellular IgV domain, a transmembrane region, and a cytoplasmic tail containing ITIM and ITT motifs. It functions as an inhibitory receptor on T cells and NK cells. Upon binding to its ligands (CD155, CD112), TIGIT recruits phosphatases (e.g., SHP1/SHP2) via its ITIM motif, attenuating activating signals. It also competes with the costimulatory receptor CD226 (DNAM-1) for ligand binding, further suppressing immune responses. TIGIT is a key regulator of immune tolerance and is exploited by tumors to evade immune surveillance. Therapeutic antibodies targeting TIGIT are in clinical trials for cancer treatment.