CLEC6A Gene - C-Type Lectin Domain Family 6 Member A

CLEC6A encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. The encoded protein is a type II transmembrane receptor expressed primarily on dendritic cells and macrophages. It functions as a pattern recognition receptor (PRR) that recognizes carbohydrate structures on pathogens, particularly fungal cell wall components such as mannan. Ligand binding triggers intracellular signaling via the ITAM-containing adaptor Fc receptor gamma-chain (FCER1G), leading to activation of NF-κB and production of pro-inflammatory cytokines. CLEC6A plays a critical role in antifungal immunity and has been implicated in inflammatory and autoimmune conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Fc epsilon receptor (FCERI) signaling

• NF-kappa B signaling

• Toll-like receptor signaling (crosstalk)

• Dectin-2 mediated antifungal immunity

CLEC6A (Dectin-2) is a 209-amino acid type II transmembrane C-type lectin receptor. It contains a single extracellular C-type lectin-like domain (CTLD) that recognizes high-mannose structures on fungal cell walls. The short cytoplasmic tail lacks a signaling motif; instead, CLEC6A associates with the ITAM-containing adaptor Fc receptor gamma-chain (FCER1G) via a charged residue in its transmembrane domain. Upon ligand binding, Src family kinases phosphorylate the ITAM, recruiting Syk kinase and activating downstream pathways including NF-κB and MAPK. This leads to production of TNF-α, IL-6, IL-10, and IL-23, promoting Th17 responses essential for antifungal defense. CLEC6A is also involved in the recognition of self-glycoproteins and has been linked to autoimmune and inflammatory diseases.