TLR8 Gene: Function, Mutations, and Associated Diseases | Innate Immunity

TLR8 (Toll Like Receptor 8) is a member of the Toll-like receptor (TLR) family, which plays a fundamental role in pathogen recognition and activation of innate immunity. TLR8 is predominantly expressed in myeloid cells and recognizes single-stranded RNA (ssRNA) from viruses and endogenous RNA degradation products. Upon ligand binding, TLR8 recruits MYD88 and triggers NF-κB and IRF signaling pathways, leading to pro-inflammatory cytokine production. TLR8 is encoded on the X chromosome and is closely related to TLR7. Mutations in TLR8 are associated with X-linked immunodeficiency and autoinflammatory conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

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

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

• NF-κB activation (Reactome: R-HSA-975110)

• IRF7-mediated type I interferon signaling (Reactome: R-HSA-933541)

TLR8 is a 1,041-amino acid transmembrane protein with an extracellular leucine-rich repeat (LRR) domain responsible for ligand recognition, a transmembrane domain, and a cytoplasmic Toll/IL-1 receptor (TIR) domain that initiates downstream signaling. The protein is localized to endosomal membranes and is activated by uridine-rich ssRNA and certain synthetic agonists (e.g., imidazoquinolines). TLR8 exists as a preformed dimer; ligand binding induces conformational changes that recruit MYD88. Post-translational modifications include N-glycosylation essential for proper folding and trafficking. UniProt ID: Q9NR97.