TLR2 Gene: Function, Expression, Mutations & Associated Diseases

TLR2 (Toll Like Receptor 2) is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLR2 recognizes a wide variety of microbial components, including lipoproteins, peptidoglycan, and lipoteichoic acid from Gram-positive bacteria, as well as zymosan from fungi. It forms heterodimers with TLR1 or TLR6 to discriminate between different ligands. Upon ligand binding, TLR2 activates NF-κB and MAPK signaling pathways, leading to cytokine production and inflammatory responses. TLR2 is expressed on the surface of immune cells such as macrophages, dendritic cells, and neutrophils, and also on non-immune cells like epithelial and endothelial cells. Genetic variations in TLR2 have been associated with increased susceptibility to infections, sepsis, and inflammatory diseases.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Toll-like receptor signaling pathway (KEGG: hsa04620)

• NF-kappa B signaling pathway (KEGG: hsa04064)

• MyD88-dependent cascade (Reactome: R-HSA-166058)

• Innate Immune System (Reactome: R-HSA-168249)

TLR2 is a 784-amino acid type I transmembrane protein with an extracellular leucine-rich repeat (LRR) domain and a cytoplasmic Toll/IL-1 receptor (TIR) domain. The LRR domain mediates recognition of pathogen-associated molecular patterns (PAMPs), while the TIR domain recruits adaptor proteins such as MyD88 to initiate downstream signaling. TLR2 forms functional heterodimers with TLR1 or TLR6, enabling recognition of triacylated and diacylated lipoproteins, respectively. The protein is heavily glycosylated and localized primarily to the plasma membrane, though it can also be found in endosomes. TLR2 signaling is critical for host defense against bacteria, fungi, and viruses, and its dysregulation contributes to chronic inflammatory and autoimmune diseases.