LAG3 Gene: Function, Expression, and Clinical Significance | Biomedical Resource

The LAG3 gene encodes the lymphocyte activation gene 3 protein, a type I transmembrane protein belonging to the immunoglobulin superfamily. LAG3 is expressed on activated T cells, natural killer (NK) cells, and plasmacytoid dendritic cells, where it negatively regulates T cell activation and proliferation. It binds to MHC class II molecules with high affinity, and its engagement leads to inhibition of T cell receptor signaling. LAG3 is a key immune checkpoint receptor, and its blockade is being explored in cancer immunotherapy. Additionally, LAG3 has been implicated in autoimmune diseases and chronic infections, where its expression on exhausted T cells contributes to immune dysfunction.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T cell receptor signaling pathway (KEGG hsa04660)

• PD-1/PD-L1 checkpoint pathway (KEGG hsa05235)

• Immune checkpoint regulation (Reactome: R-HSA-389948)

• Costimulation by the CD28 family (Reactome: R-HSA-388841)

The LAG3 protein (CD223) is a 498-amino acid type I transmembrane glycoprotein with four extracellular immunoglobulin-like domains (D1-D4). The D1 domain contains a unique 'extra loop' that is critical for MHC class II binding. LAG3 is expressed on activated T cells, NK cells, and plasmacytoid dendritic cells. It negatively regulates T cell activation by competing with CD4 for MHC class II binding and by transmitting inhibitory signals via its cytoplasmic domain. LAG3 is cleaved by ADAM10/17 metalloproteases, releasing a soluble form (sLAG3) that can be detected in serum. LAG3 plays a role in regulatory T cell function and is a target for cancer immunotherapy.