TIGIT
Chr 3T cell immunoreceptor with Ig and ITIM domains
Also known as: VSIG9, VSTM3, WUCAM
TIGIT encodes an inhibitory immune receptor that suppresses T-cell and NK cell activation by binding to ligands PVR/CD155 and NECTIN2/CD112 on antigen-presenting cells, thereby modulating immune responses through inhibition of PI3K, MAPK, and NF-kappa-B signaling pathways. The gene shows low constraint to loss-of-function variation (pLI 0.02, LOEUF 1.05), and no Mendelian diseases have been established from mutations in this gene. TIGIT is primarily studied in the context of cancer immunotherapy and autoimmune diseases rather than pediatric neurogenetic disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
TIGIT · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Rare Tumor Focused Platform Study of Innovative Therapies and Technologies (PLATFORM2)
NOT YET RECRUITINGTiragolumab and Atezolizumab in Advanced Pan-cancer Patients
RECRUITINGGPC3-CAR-T Cells for Immunotherapy of Cancer With GPC3 Expression
RECRUITINGNK521 in the Treatment of Malignant Ascites Associated With Advanced Solid Tumors
RECRUITINGCombination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas
RECRUITINGPreoperative Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck
RECRUITINGExternal Resources
Links to major genomics databases and tools