CLEC4E Gene (Mincle): Function, Expression, and Disease Associations | Biomedical Database

CLEC4E (C-type lectin domain family 4 member E), commonly known as Mincle (macrophage-inducible C-type lectin), is a type II transmembrane protein primarily expressed on myeloid cells. It functions as a pattern recognition receptor (PRR) that recognizes specific carbohydrate ligands, including mycobacterial trehalose dimycolate (TDM, cord factor) and certain fungal components. Upon ligand binding, CLEC4E signals through the Fc receptor gamma-chain (FcRγ) to activate NF-κB and MAPK pathways, promoting pro-inflammatory cytokine production and innate immune responses. It is involved in the host defense against pathogens, particularly Mycobacterium tuberculosis, and has been implicated in sterile inflammation and autoimmune conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Fc gamma receptor (FcγR)-mediated signaling

• Syk (Spleen Tyrosine Kinase) signaling

• CARD9 (Caspase recruitment domain-containing protein 9) signaling

• NF-kappa B signaling

• MAPK signaling

The CLEC4E protein, Mincle, is a 219-amino acid type II transmembrane receptor with a single extracellular C-type lectin-like domain (CTLD). It forms a homodimer and associates with the immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein FcRγ. Ligand binding induces phosphorylation of the ITAM, recruiting Syk kinase, which activates downstream signaling cascades including CARD9, NF-κB, and MAPKs. This leads to the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-12) and chemokines, orchestrating innate immune responses. Mincle is crucial for recognizing mycobacterial cord factor and certain fungal species, and also senses damage-associated molecular patterns (DAMPs) from necrotic cells, linking it to sterile inflammation.