FcRIIc

Fc gamma receptor IIc (FcγRIIc) is an activating member of the Fc gamma receptor family that binds the Fc portion of immunoglobulin G (IgG). It is encoded by the FCGR2C gene, located within the human FCGR gene cluster on chromosome 1. The protein is a membrane glycoprotein with extracellular immunoglobulin-like domains and relies on association with the common gamma chain to initiate signaling through immunoreceptor tyrosine-based activation motifs (ITAMs).

Genetics and expression of FCGR2C are variable among individuals. The locus is subject to copy number variation, and the FCGR2C gene can exist as an open reading frame (ORF) allele or as alleles containing premature stop codons that prevent expression. In those with a functional ORF, FcγRIIc can be expressed on the surface of natural killer cells, neutrophils, and some monocytes, whereas in others the receptor is absent or nonfunctional due to the ORF-disrupting variants. Deletions at the FCGR2C locus can also occur, further influencing receptor expression.

Functionally, FcγRIIc participates in Fc receptor–mediated effector responses by binding IgG-coated targets and triggering cellular activation via the FcR gamma chain. This leads to processes such as phagocytosis and antibody-dependent cellular cytotoxicity (ADCC), contributing to clearance of immune complexes and infected or malignant cells.

Clinical relevance of FCGR2C variation has been explored in diverse contexts, including susceptibility to autoimmune diseases and variability in responses to monoclonal antibody therapies. The specific impact of FCGR2C genotype can be population-dependent, reflecting the complex organization and polymorphism of the FCGR gene cluster.