FCGR3A (CD16a): Fc Gamma Receptor IIIa Gene
Genetic insights into FCGR3A, encoding the low-affinity Fc receptor CD16a, with implications in immunity, autoimmunity, and cancer immunotherapy.
Gene Information Card
| Symbol | FCGR3A |
|---|---|
| Full Name | Fc gamma receptor IIIa (CD16a) |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 2214 ncbi.nlm.nih.gov/gene/2214 |
| Ensembl ID | ENSG00000203747 |
| UniProt ID | P08637 |
| OMIM ID | 146740 |
| HGNC ID | 3619 |
| Aliases | CD16a, FCG3, FCGR3, IGFR3, CD16, FcRIIIa |
Description
The FCGR3A gene encodes the Fc gamma receptor IIIa (CD16a), a type I transmembrane glycoprotein expressed on natural killer (NK) cells, macrophages, and subsets of T cells. CD16a binds the Fc portion of immunoglobulin G (IgG) with low affinity, mediating antibody-dependent cellular cytotoxicity (ADCC), phagocytosis, and cytokine release. This receptor plays a critical role in immune defense, inflammation, and antibody-based therapies. Genetic variants, particularly the V158F polymorphism, influence receptor affinity and are associated with susceptibility to autoimmune diseases, infections, and differential responses to monoclonal antibody therapies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) | FCGR3A variants (e.g., F158) reduce receptor affinity for IgG, impairing immune complex clearance and promoting inflammation. | Multiple case-control studies; meta-analyses (e.g., OMIM, ClinVar) |
| Infectious diseases (e.g., HIV, malaria) | Low-affinity FCGR3A alleles may impair ADCC and opsonization, increasing susceptibility or severity. | Association studies; functional assays (PubMed indexed) |
| Cancer (e.g., lymphoma, solid tumors) | FCGR3A V158F polymorphism affects ADCC efficacy of therapeutic monoclonal antibodies (e.g., rituximab, trastuzumab), influencing treatment outcomes. | Clinical trials and pharmacogenetic studies (COSMIC, ClinVar) |
| Immune thrombocytopenia (ITP) | FCGR3A polymorphisms may alter Fc receptor function, affecting platelet clearance and response to IVIG. | Case-control studies; functional studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | High (e.g., ~200-300 nTPM) | High expression in NK cells and monocytes |
| Spleen | Moderate | Expression in macrophages and NK cells |
| Lung | Low to moderate | Alveolar macrophages |
| Liver | Low | Kupffer cells |
| Bone marrow | Moderate | NK cell precursors and monocytes |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NK-92 (NK cell line) | High | Constitutive expression |
| THP-1 (monocytic) | Moderate | Inducible by cytokines |
| U937 (histiocytic lymphoma) | Moderate | Expression after differentiation |
| Jurkat (T cell line) | Low | Minimal expression |
| Raji (B cell line) | Low | Not typically expressed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| V158F (rs396991) | SNP (missense) | ~40-50% allele frequency in Caucasians | V158 (valine) has higher affinity for IgG than F158 (phenylalanine); affects ADCC and disease susceptibility. |
| F158 (rs396991) | SNP (missense) | ~50-60% allele frequency | Lower affinity; associated with autoimmune diseases and reduced rituximab efficacy. |
| NA1/NA2 (CD16a isoforms) | Polymorphic variants | Variable | Affect glycosylation and receptor function; NA2 associated with lower affinity. |
| Somatic mutations in cancer | Rare | Low frequency | May alter receptor signaling or expression in tumor microenvironment (COSMIC). |
Mutation functional classification
Loss of Function (LOF)
Rare non-synonymous mutations that disrupt ligand binding or surface expression, leading to impaired ADCC and immune complex clearance.
Gain of Function (GOF)
V158 allele is considered a gain-of-function variant due to higher IgG affinity, enhancing ADCC and pro-inflammatory responses.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported; however, certain rare variants may interfere with receptor dimerization or signaling.
View complete mutation data：
Gene Ontology (GO)
| • plasma membrane (GO:0005886) | • integral component of plasma membrane (GO:0005887) |
| • IgG binding (GO:0019864) | • adaptive immune response (GO:0002250) |
| • phagocytosis (GO:0006911) | • antibody-dependent cellular cytotoxicity (GO:0001788) |
| • Fc-gamma receptor signaling pathway (GO:0038094) | • negative regulation of natural killer cell degranulation (GO:0043310) |
Pathways
• Fc gamma receptor-mediated phagocytosis (Reactome: R-HSA-2029480)
• Fcgamma receptor (FCGR) dependent ADCC (Reactome: R-HSA-2029481)
• Immune response - Fc epsilon receptor (FCERI) signaling (KEGG: hsa04664)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
Protein Summary
CD16a (Fc gamma receptor IIIa) is a 50-80 kDa glycosylated type I transmembrane protein encoded by FCGR3A. It consists of two extracellular Ig-like domains, a transmembrane region, and a short cytoplasmic tail. CD16a associates with the FcR gamma-chain (FcRγ) or CD3ζ for signal transduction. It binds IgG immune complexes with low affinity (Kd ~10^-6 M) and is crucial for ADCC by NK cells and for phagocytosis by macrophages. The V158F polymorphism affects receptor affinity and is a key pharmacogenetic marker for monoclonal antibody therapies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FCGR3A Knockout HEK293 Cell Line | EDJ-KQ17778 | Human | 2214 | Details Get a Quote |
| FCGR3A Knockout HeLa Cell Line | EDJ-KQ53211 | Human | 2214 | Details Get a Quote |
| FCGR3A Knockout A-549 Cell Line | EDJ-KQ61692 | Human | 2214 | Details Get a Quote |
| FCGR3A Knockout HCT 116 Cell Line | EDJ-KQ70178 | Human | 2214 | Details Get a Quote |
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