KIR2DL1 Gene: Function, Expression, and Clinical Significance

KIR2DL1 is a member of the killer cell immunoglobulin-like receptor (KIR) gene family located on chromosome 19q13.42. It encodes a transmembrane glycoprotein expressed on natural killer (NK) cells and a subset of T cells. KIR2DL1 functions as an inhibitory receptor that recognizes HLA-C allotypes carrying the C2 epitope (Lys80). Upon ligand binding, the long cytoplasmic tail containing immunoreceptor tyrosine-based inhibitory motifs (ITIMs) recruits phosphatases, suppressing NK cell cytotoxicity and cytokine release. This gene plays a critical role in immune surveillance, pregnancy, and response to viral infections and cancer.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)

• Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (Reactome: R-HSA-198933)

• Signaling by KIR2DL1 (Reactome: R-HSA-2172127)

KIR2DL1 is a type I transmembrane glycoprotein of 348 amino acids, with two extracellular immunoglobulin-like domains (D1 and D2), a transmembrane region, and a long cytoplasmic tail containing two ITIMs. The D1 and D2 domains form a binding site for HLA-C molecules carrying the C2 epitope (asparagine at position 77 and lysine at position 80). Upon ligand engagement, ITIMs are phosphorylated by Src family kinases, recruiting SHP-1 and SHP-2 phosphatases, which dephosphorylate key signaling molecules, thereby inhibiting NK cell cytotoxicity and cytokine production. KIR2DL1 is expressed clonally on NK cells and contributes to the 'missing-self' recognition of target cells lacking appropriate HLA-C ligands.