FCGR2A
Fc Gamma Receptor IIa (CD32a): A Key Immune Receptor in Antibody-Mediated Responses
Gene Information Card
| Symbol | FCGR2A |
|---|---|
| Full Name | Fc Fragment of IgG Receptor IIa |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 2212 ncbi.nlm.nih.gov/gene/2212 |
| Ensembl ID | ENSG00000143226 |
| UniProt ID | P12318 |
| OMIM ID | 146790 |
| HGNC ID | 3616 |
| Aliases | CD32, CD32A, FCG2, FCGR2, FCGR2A1, FcRII-a, IGFR2 |
Description
The FCGR2A gene encodes Fc gamma receptor IIa (FcγRIIa, CD32a), a low-affinity receptor for the Fc region of immunoglobulin G (IgG). It is expressed on the surface of various immune cells, including macrophages, neutrophils, dendritic cells, and platelets. FcγRIIa mediates phagocytosis, endocytosis, antibody-dependent cellular cytotoxicity (ADCC), and the release of inflammatory mediators. A common single nucleotide polymorphism (rs1801274) resulting in an H131R substitution alters the receptor's affinity for IgG2 and is associated with susceptibility to infections and autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic lupus erythematosus (SLE) | FCGR2A polymorphisms (e.g., R131 variant) reduce clearance of IgG2-containing immune complexes, promoting tissue deposition and inflammation. | OMIM: 146790; ClinVar; multiple case-control studies |
| Kawasaki disease | FCGR2A variants (rs1801274) are associated with increased risk and coronary artery aneurysm development. | GWAS (PMID: 18305461); ClinVar |
| Periodontitis | The R131 allele impairs FcγRIIa-mediated phagocytosis of Aggregatibacter actinomycetemcomitans, increasing susceptibility. | NCBI Gene; multiple association studies |
| Meningococcal disease | Reduced FcγRIIa function (R131) impairs opsonophagocytosis of Neisseria meningitidis, increasing infection risk. | PMID: 10577907; ClinVar |
| Idiopathic thrombocytopenic purpura (ITP) | FcγRIIa polymorphisms influence platelet clearance and response to IVIG therapy. | OMIM: 146790; clinical studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Whole blood | 56.2 | High |
| Spleen | 34.1 | High |
| Lung | 18.5 | Medium |
| Bone marrow | 15.3 | Medium |
| Liver | 5.2 | Low |
| Small intestine | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Monocytes | 89.7 | High expression |
| Neutrophils | 72.4 | High expression |
| Macrophages | 65.1 | High expression |
| Dendritic cells | 48.3 | Medium expression |
| Platelets | 12.6 | Low expression |
| B lymphocytes | 8.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1801274 (H131R) | Missense | ~50% in Europeans; ~30% in East Asians | H131 (high responder) binds IgG2 efficiently; R131 (low responder) shows reduced IgG2 binding, associated with infection and autoimmune risk. |
| rs1050501 (Q27X) | Nonsense | Rare (<1%) | Premature stop codon; loss of function; associated with reduced FcγRIIa expression and altered immune response. |
| rs1801274 (H131R) in cis with rs1050501 | Haplotype | Variable | Compound effect on receptor function and disease susceptibility. |
Mutation functional classification
Loss of Function (LOF)
rs1050501 (Q27X) introduces a premature stop codon, leading to truncated, non-functional FcγRIIa protein.
Gain of Function (GOF)
Not clearly documented for FCGR2A; the H131 variant shows higher affinity for IgG2 but is considered a functional variant rather than a gain-of-function mutation.
Dominant Negative (DN)
Not reported for FCGR2A.
View complete mutation data：
Gene Ontology (GO)
| • Fc-gamma receptor I complex | • Fc-gamma receptor activity |
| • IgG binding | • immune response |
| • phagocytosis | • antibody-dependent cellular cytotoxicity |
| • signal transduction | • cell surface receptor signaling pathway |
| • innate immune response | • inflammatory response |
Pathways
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
• Natural killer cell mediated cytotoxicity (KEGG: hsa04650)
• Osteoclast differentiation (KEGG: hsa04380)
• Leishmaniasis (KEGG: hsa05140)
• Staphylococcus aureus infection (KEGG: hsa05150)
• Tuberculosis (KEGG: hsa05152)
• Fc epsilon RI signaling pathway (KEGG: hsa04664)
Protein Summary
Fc gamma receptor IIa (FcγRIIa, CD32a) is a 40-50 kDa transmembrane glycoprotein encoded by the FCGR2A gene. It consists of two extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail containing an immunoreceptor tyrosine-based activation motif (ITAM). FcγRIIa binds the Fc region of IgG, particularly IgG1 and IgG3, with low affinity. The receptor is expressed on myeloid cells and platelets, and its engagement triggers phagocytosis, endocytosis, ADCC, and cytokine release. The H131R polymorphism (rs1801274) is a key functional variant affecting IgG2 binding and disease susceptibility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FCGR2A Knockout HEK293 Cell Line | EDJ-KQ17776 | Human | 2212 | Details Get a Quote |
| FCGR2A Knockout HeLa Cell Line | EDJ-KQ53209 | Human | 2212 | Details Get a Quote |
| FCGR2A Knockout A-549 Cell Line | EDJ-KQ61690 | Human | 2212 | Details Get a Quote |
| FCGR2A Knockout HCT 116 Cell Line | EDJ-KQ70176 | Human | 2212 | Details Get a Quote |
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