LILRB4 Gene: Function, Expression, and Clinical Significance

LILRB4 (Leukocyte Immunoglobulin Like Receptor B4), also known as ILT3, LIR5, and CD85K, is a member of the leukocyte immunoglobulin-like receptor (LIR) family. It is an inhibitory receptor expressed primarily on myeloid cells, including monocytes, macrophages, and dendritic cells. LILRB4 binds to class I MHC molecules and transmits an inhibitory signal through its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs), thereby modulating immune responses. It plays a critical role in immune tolerance and has been implicated in cancer immune evasion, particularly in acute myeloid leukemia (AML).

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Immune System (Reactome: R-HSA-168256)

• Signaling by Interleukins (Reactome: R-HSA-449147)

• Class I MHC mediated antigen processing & presentation (Reactome: R-HSA-983169)

LILRB4 is a transmembrane glycoprotein with four extracellular immunoglobulin-like domains and a cytoplasmic tail containing three ITIMs. It functions as an inhibitory receptor by recruiting phosphatases such as SHP-1 and SHP-2 upon ligand binding, thereby dampening immune cell activation. The protein is heavily glycosylated and exists as a monomer on the cell surface. Its expression is restricted to myeloid lineage cells, and it is upregulated in various hematologic malignancies, making it a potential target for immunotherapy.