HAVCR2 Gene (TIM-3): Function, Expression, Mutations, and Disease Associations | Biomedical Reference

HAVCR2 (Hepatitis A Virus Cellular Receptor 2) encodes T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), a type I transmembrane receptor expressed on immune cells, particularly T cells. TIM-3 functions as an immune checkpoint, negatively regulating T cell responses and promoting T cell exhaustion in chronic infections and cancer. It binds ligands such as galectin-9, CEACAM1, and HMGB1. Genetic variants in HAVCR2 are associated with susceptibility to certain cancers and immune-mediated diseases, including subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T cell receptor signaling pathway

• Immune checkpoint pathway

• PD-1/PD-L1 and TIM-3 signaling in T cell exhaustion

• Galectin-9/TIM-3 interaction pathway

The TIM-3 protein is a 301-amino acid type I membrane protein with an N-terminal immunoglobulin V-like domain, a mucin-like domain, a transmembrane domain, and a cytoplasmic tail containing tyrosine phosphorylation motifs. It is expressed on IFN-γ-producing CD4+ and CD8+ T cells, Tregs, NK cells, dendritic cells, and macrophages. TIM-3 binds to various ligands, including galectin-9, CEACAM1, HMGB1, and phosphatidylserine, to modulate immune responses. Its cytoplasmic tail recruits phosphatases (e.g., SHP2) to inhibit T cell receptor signaling, leading to T cell exhaustion. Post-translational modifications, such as glycosylation, affect its stability and function.