Low affinity immunoglobulin gamma Fc region receptor III-A (FCGR3A) (FCGR3A)

Low affinity immunoglobulin gamma Fc region receptor III-A, commonly known as FCGR3A or CD16a, is a surface glycoprotein found on natural killer (NK) cells, monocytes, and macrophages (UniProt P08637). It serves as a critical link between the humoral and cellular immune systems by binding the Fc portion of IgG antibodies, thereby triggering effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis. In the specific context of Fc-fusion recombinant Factor VIII (rFVIII) variants like Efmoroctocog alfa, the Fc domain is engineered to extend the protein's half-life by engaging the neonatal Fc receptor (FcRn) for cellular recycling (PubMed: 25331712). However, the interaction with FcγRIIIA is a significant factor in the drug's profile, as it can mediate the internalization of the FVIII-Fc complex by antigen-presenting cells, potentially influencing the risk of developing inhibitory antibodies—a major complication in hemophilia treatment (PubMed: 22923446). Furthermore, genetic polymorphisms in FCGR3A, such as the V158F variant, affect the binding affinity to the Fc region and can lead to inter-patient variability in the clearance and efficacy of these therapeutic fusion proteins (PubMed: 10713390).

Other names

CD16aFc-gamma RIII-alphaFCRIIIFCRIIIAFc fragment of IgG receptor IIIa

The receptor binds the Fc portion of IgG1-based fusion proteins or antibodies, mediating effector functions like ADCC or facilitating cellular uptake and clearance by immune cells.