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Gene Review

FCGR3A  -  Fc fragment of IgG, low affinity IIIa,...

Homo sapiens

Synonyms: CD16, CD16A, CD16a, CD16a antigen, FCG3, ...
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Disease relevance of FCGR3A


Psychiatry related information on FCGR3A

  • Means (SD) for CD14/CD16 in HIV-negative controls and in AIDS non-dementia and AIDS dementia patients were 6.5% (4), 16% (13), and 37% (21), respectively (p = 0.008 between the two groups of patients) [5].
  • Eight clinical scales (hypochondriasis, depression, hysteria, psychopathic deviate, paranoia, psychasthenia, schizophrenia, and hypomania) as well as cortisol level, CD3, CD4, CD8, and CD16 markers by group were compared [6].

High impact information on FCGR3A


Chemical compound and disease context of FCGR3A


Biological context of FCGR3A


Anatomical context of FCGR3A


Associations of FCGR3A with chemical compounds


Physical interactions of FCGR3A

  • Three types of FcR react with IgG: Fc gamma RI is a high-affinity receptor binding IgG monomers whereas Fc gamma RII and Fc gamma RIII are low-affinity receptors binding IgG immune complexes; the three types of Fc gamma R are members of the Ig superfamily [27].
  • A consistent proportion of CD16 marker-positive LGL bound VIP-coated spheres (24%, and approximately 15% of B cells also showed this ability [28].

Enzymatic interactions of FCGR3A


Regulatory relationships of FCGR3A

  • CD16 (Fc gamma R type III), a low affinity IgG Fc receptor, is found in two forms, a transmembrane Fc gamma RIIIa expressed by NK cells and monocytes and a phosphatidylinositol-linked Fc gamma RIIIb present on neutrophils [30].
  • Recent studies in gene knockout mice have demonstrated that the negative signaling by CD32B plays a critical role in preventing immune complex (IC)-mediated autoimmune diseases by regulating the activation signal delivered by CD16A [31].
  • Under these conditions, accumulation and transcription of both IFN-gamma and TNF mRNA induced by CD16 ligands, but not that induced by rIL-2, is completely abolished and neither cytokine can be detected at significant levels in the supernatant fluids of cells so treated [32].
  • In this study TGF-beta is shown to induce expression of the gp50-65 receptor for Fc gamma RIII on otherwise negative peripheral blood monocytes [33].
  • The ability of CD45 mAbs to stimulate NK cells appears not to be dependent on CD16, as CD45 mAbs of both IgG1 and IgG2a isotypes were equally stimulatory, as were F(ab')2 compared with whole anti-CD45 mAbs [34].

Other interactions of FCGR3A

  • Response to alemtuzumab was similar regardless of FCGR3A polymorphism (V/V, 25%; V/F, 40%; F/F, 32%) or FCGR2A polymorphism (A/A, 40%; H/A, 32%; H/H, 33%) [1].
  • CD38 ligation by agonistic monoclonal antibodies induced signals leading to activation of the lytic machinery of natural killer (NK) cells from adults; similar signals could not be reproduced in YT and NKL, 2 CD16(-) human NK-like lines [35].
  • Production of TNF-alpha by human V gamma 9V delta 2 T cells via engagement of Fc gamma RIIIA, the low affinity type 3 receptor for the Fc portion of IgG, expressed upon TCR activation by nonpeptidic antigen [36].
  • Fc gamma receptor type IIIA (CD16a) is a receptor expressed on macrophages that selectively binds IgG molecules, an important rheumatoid factor in RA [25].
  • Binding of mIgG or 3G8 to Fc gamma RIIIA induced divergent effects of functions of cultured NK cells: 3G8 mAb + IL-2 induced dose-dependent inhibition of proliferation attributable to apoptosis; in contrast, mIgG + IL-2 significantly increased NK cell proliferation [37].

Analytical, diagnostic and therapeutic context of FCGR3A


  1. FCGR3A and FCGR2A polymorphisms may not correlate with response to alemtuzumab in chronic lymphocytic leukemia. Lin, T.S., Flinn, I.W., Modali, R., Lehman, T.A., Webb, J., Waymer, S., Moran, M.E., Lucas, M.S., Farag, S.S., Byrd, J.C. Blood (2005) [Pubmed]
  2. No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease. Willot, S., Vermeire, S., Ohresser, M., Rutgeerts, P., Paintaud, G., Belaiche, J., De Vos, M., Van Gossum, A., Franchimont, D., Colombel, J.F., Watier, H., Louis, E. Pharmacogenet. Genomics (2006) [Pubmed]
  3. Association of FCGR2A and FCGR2A-FCGR3A haplotypes with susceptibility to giant cell arteritis. Morgan, A.W., Robinson, J.I., Barrett, J.H., Martin, J., Walker, A., Babbage, S.J., Ollier, W.E., Gonzalez-Gay, M.A., Isaacs, J.D. Arthritis Res. Ther. (2006) [Pubmed]
  4. The beta subunit of the Fc epsilon RI is associated with the Fc gamma RIII on mast cells. Kurosaki, T., Gander, I., Wirthmueller, U., Ravetch, J.V. J. Exp. Med. (1992) [Pubmed]
  5. Unique monocyte subset in patients with AIDS dementia. Pulliam, L., Gascon, R., Stubblebine, M., McGuire, D., McGrath, M.S. Lancet (1997) [Pubmed]
  6. Psychological profile in oral lichen planus. Ivanovski, K., Nakova, M., Warburton, G., Pesevska, S., Filipovska, A., Nares, S., Nunn, M.E., Angelova, D., Angelov, N. Journal of clinical periodontology. (2005) [Pubmed]
  7. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Homsy, J., Meyer, M., Tateno, M., Clarkson, S., Levy, J.A. Science (1989) [Pubmed]
  8. Functional separation of pseudopod extension and particle internalization during Fc gamma receptor-mediated phagocytosis. Lowry, M.B., Duchemin, A.M., Robinson, J.M., Anderson, C.L. J. Exp. Med. (1998) [Pubmed]
  9. Reconstitution of human Fc gamma RIII cell type specificity in transgenic mice. Li, M., Wirthmueller, U., Ravetch, J.V. J. Exp. Med. (1996) [Pubmed]
  10. Activation of monocyte effector genes and STAT family transcription factors by inflammatory synovial fluid is independent of interferon gamma. Sengupta, T.K., Chen, A., Zhong, Z., Darnell, J.E., Ivashkiv, L.B. J. Exp. Med. (1995) [Pubmed]
  11. Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand interaction. Kanakaraj, P., Duckworth, B., Azzoni, L., Kamoun, M., Cantley, L.C., Perussia, B. J. Exp. Med. (1994) [Pubmed]
  12. Fc gamma RIIIa and Fc gamma RIIa polymorphisms do not predict response to rituximab in B-cell chronic lymphocytic leukemia. Farag, S.S., Flinn, I.W., Modali, R., Lehman, T.A., Young, D., Byrd, J.C. Blood (2004) [Pubmed]
  13. Signal transduction events and Fc gamma R engagement in human neutrophils stimulated with immune complexes. Walker, B.A., Hagenlocker, B.E., Stubbs, E.B., Sandborg, R.R., Agranoff, B.W., Ward, P.A. J. Immunol. (1991) [Pubmed]
  14. In vitro packaging of an infectious recombinant adeno-associated virus 2. Ding, L., Lu, S., Munshi, N.C. Gene Ther. (1997) [Pubmed]
  15. Association of Fcgamma receptor IIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian populations. Chu, Z.T., Tsuchiya, N., Kyogoku, C., Ohashi, J., Qian, Y.P., Xu, S.B., Mao, C.Z., Chu, J.Y., Tokunaga, K. Tissue Antigens (2004) [Pubmed]
  16. Patterns of low-affinity immunoglobulin receptor polymorphisms in stroke and homozygous sickle cell disease. Taylor, J.G., Tang, D., Foster, C.B., Serjeant, G.R., Rodgers, G.P., Chanock, S.J. Am. J. Hematol. (2002) [Pubmed]
  17. Analysis of Fcgamma receptor haplotypes in rheumatoid arthritis: FCGR3A remains a major susceptibility gene at this locus, with an additional contribution from FCGR3B. Morgan, A.W., Barrett, J.H., Griffiths, B., Subramanian, D., Robinson, J.I., Keyte, V.H., Ali, M., Jones, E.A., Old, R.W., Ponchel, F., Boylston, A.W., Situnayake, R.D., Markham, A.F., Emery, P., Isaacs, J.D. Arthritis Res. Ther. (2006) [Pubmed]
  18. Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation. Azzoni, L., Kamoun, M., Salcedo, T.W., Kanakaraj, P., Perussia, B. J. Exp. Med. (1992) [Pubmed]
  19. Genetic risk factors for infection in patients with early rheumatoid arthritis. Hughes, L.B., Criswell, L.A., Beasley, T.M., Edberg, J.C., Kimberly, R.P., Moreland, L.W., Seldin, M.F., Bridges, S.L. Genes Immun. (2004) [Pubmed]
  20. Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized description of FCGR3B alleles. Bertrand, G., Duprat, E., Lefranc, M.P., Marti, J., Coste, J. Tissue Antigens (2004) [Pubmed]
  21. Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells. Salcedo, T.W., Kurosaki, T., Kanakaraj, P., Ravetch, J.V., Perussia, B. J. Exp. Med. (1993) [Pubmed]
  22. Identification of an unusual Fc gamma receptor IIIa (CD16) on natural killer cells in a patient with recurrent infections. de Vries, E., Koene, H.R., Vossen, J.M., Gratama, J.W., von dem Borne, A.E., Waaijer, J.L., Haraldsson, A., de Haas, M., van Tol, M.J. Blood (1996) [Pubmed]
  23. Soluble Fc gamma RIIIa is present in plasma and is derived from natural killer cells. de Haas, M., Kleijer, M., Minchinton, R.M., Roos, D., von dem Borne, A.E. J. Immunol. (1994) [Pubmed]
  24. Tyrosine phosphorylation of a gamma-chain homodimer associated with Fc gamma RIII (CD16) in cultured human monocytes. Masuda, M., Verhoeven, A.J., Roos, D. J. Immunol. (1993) [Pubmed]
  25. 17 beta-estradiol regulates cytokine release through modulation of CD16 expression in monocytes and monocyte-derived macrophages. Kramer, P.R., Kramer, S.F., Guan, G. Arthritis Rheum. (2004) [Pubmed]
  26. Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc{gamma}RIIIa-158 V/V and V/F polymorphism. Hatjiharissi, E., Xu, L., Santos, D.D., Hunter, Z.R., Ciccarelli, B.T., Verselis, S., Modica, M., Cao, Y., Manning, R.J., Leleu, X., Dimmock, E.A., Kortsaris, A., Mitsiades, C., Anderson, K.C., Fox, E.A., Treon, S.P. Blood (2007) [Pubmed]
  27. Fc receptors and immunoglobulin binding factors. Fridman, W.H. FASEB J. (1991) [Pubmed]
  28. High affinity specific binding of vasoactive intestinal peptide to human circulating T cells, B cells and large granular lymphocytes. Ottaway, C.A., Lay, T.E., Greenberg, G.R. J. Neuroimmunol. (1990) [Pubmed]
  29. Ubiquitination and degradation of Syk and ZAP-70 protein tyrosine kinases in human NK cells upon CD16 engagement. Paolini, R., Molfetta, R., Piccoli, M., Frati, L., Santoni, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  30. Regulation of production of soluble Fc gamma receptors type III in normal and pathological conditions. Moldovan, I., Galon, J., Maridonneau-Parini, I., Roman Roman, S., Mathiot, C., Fridman, W.H., Sautès-Fridman, C. Immunol. Lett. (1999) [Pubmed]
  31. Functional regulation of human neutrophil Fc gamma receptors. Selvaraj, P., Fifadara, N., Nagarajan, S., Cimino, A., Wang, G. Immunol. Res. (2004) [Pubmed]
  32. Fc gamma R(CD16) interaction with ligand induces Ca2+ mobilization and phosphoinositide turnover in human natural killer cells. Role of Ca2+ in Fc gamma R(CD16)-induced transcription and expression of lymphokine genes. Cassatella, M.A., Anegón, I., Cuturi, M.C., Griskey, P., Trinchieri, G., Perussia, B. J. Exp. Med. (1989) [Pubmed]
  33. Selective induction of Fc gamma RIII on human monocytes by transforming growth factor-beta. Welch, G.R., Wong, H.L., Wahl, S.M. J. Immunol. (1990) [Pubmed]
  34. CD45-cross-linking stimulates IFN-gamma production in NK cells. Shen, F., Xu, X.L., Graf, L.H., Chong, A.S. J. Immunol. (1995) [Pubmed]
  35. Human CD38 and CD16 are functionally dependent and physically associated in natural killer cells. Deaglio, S., Zubiaur, M., Gregorini, A., Bottarel, F., Ausiello, C.M., Dianzani, U., Sancho, J., Malavasi, F. Blood (2002) [Pubmed]
  36. Production of TNF-alpha by human V gamma 9V delta 2 T cells via engagement of Fc gamma RIIIA, the low affinity type 3 receptor for the Fc portion of IgG, expressed upon TCR activation by nonpeptidic antigen. Lafont, V., Liautard, J., Liautard, J.P., Favero, J. J. Immunol. (2001) [Pubmed]
  37. Divergent effects of Fc gamma RIIIA ligands on the functional activities of human natural killer cells in vitro. Sulica, A., Metes, D., Gherman, M., Whiteside, T.L., Herberman, R.B. Eur. J. Immunol. (1996) [Pubmed]
  38. FCGR2A polymorphism is correlated with clinical outcome after immunotherapy of neuroblastoma with anti-GD2 antibody and granulocyte macrophage colony-stimulating factor. Cheung, N.K., Sowers, R., Vickers, A.J., Cheung, I.Y., Kushner, B.H., Gorlick, R. J. Clin. Oncol. (2006) [Pubmed]
  39. A new set of monoclonal antibodies against human Fc gamma RII (CD32) and Fc gamma RIII (CD16): characterization and use in various assays. Vely, F., Gruel, N., Moncuit, J., Cochet, O., Rouard, H., Dare, S., Galon, J., Sautes, C., Fridman, W.H., Teillaud, J.L. Hybridoma (1997) [Pubmed]
  40. FCGR3A gene polymorphisms may correlate with response to frontline R-CHOP therapy for diffuse large B-cell lymphoma. Kim, D.H., Jung, H.D., Kim, J.G., Lee, J.J., Yang, D.H., Park, Y.H., Do, Y.R., Shin, H.J., Kim, M.K., Hyun, M.S., Sohn, S.K. Blood (2006) [Pubmed]
  41. Human glomerular mesangial cells express CD16 and may be stimulated via this receptor. Morcos, M., Hänsch, G.M., Schönermark, M., Ellwanger, S., Härle, M., Heckl-Ostreicher, B. Kidney Int. (1994) [Pubmed]
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