FCGR2B
Fc Gamma Receptor IIb (CD32B): An Inhibitory Immune Checkpoint Receptor
Gene Information Card
| Symbol | FCGR2B |
|---|---|
| Full Name | Fc Fragment Of IgG Receptor IIb |
| Gene Type | Protein coding |
| Chromosomal Location | 1q23.3 |
| NCBI Gene ID | 2213 ncbi.nlm.nih.gov/gene/2213 |
| Ensembl ID | ENSG00000072694 |
| UniProt ID | P31994 |
| OMIM ID | 604590 |
| HGNC ID | 3618 |
| Aliases | CD32, CD32B, FCG2, IGFR2, FcgammaRIIB |
Description
The FCGR2B gene encodes the Fc gamma receptor IIb (FcγRIIB, CD32B), a low-affinity receptor for the Fc region of immunoglobulin G (IgG). It is the only inhibitory Fcγ receptor in humans, containing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. Upon binding IgG immune complexes, FcγRIIB recruits phosphatases such as SHIP-1 to dampen activating signals from B-cell receptors (BCR) and other Fcγ receptors, thereby regulating antibody production, immune complex clearance, and inflammatory responses. The gene is located within the FCGR gene cluster on chromosome 1q23.3 and is expressed primarily on B cells, dendritic cells, macrophages, and basophils.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Systemic Lupus Erythematosus (SLE) | Reduced expression or function of FcγRIIB impairs inhibitory signaling in B cells and dendritic cells, leading to increased autoantibody production and immune complex deposition. Polymorphisms (e.g., rs1050501, I232T) are associated with SLE susceptibility. | OMIM #604590; ClinVar; NCBI Gene |
| Rheumatoid Arthritis | Loss-of-function variants in FCGR2B may contribute to dysregulated immune complex clearance and enhanced inflammatory responses in synovial tissue. | NCBI Gene; OMIM |
| Malaria | FcγRIIB polymorphisms influence antibody-mediated clearance of Plasmodium falciparum-infected erythrocytes, affecting susceptibility to severe malaria. | NCBI Gene; PubMed |
| Cancer (e.g., B-cell lymphoma, melanoma) | FcγRIIB expression on tumor cells or tumor-infiltrating immune cells can inhibit antitumor antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis, promoting immune evasion. | COSMIC; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 11.2 | Medium |
| Lymph node | 9.8 | Medium |
| Blood (whole) | 7.5 | Low |
| Bone marrow | 6.3 | Low |
| Lung | 4.1 | Low |
| Small intestine | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-cell (Raji) | 15.2 | High expression |
| Monocyte (THP-1) | 8.9 | Medium expression |
| Macrophage (differentiated THP-1) | 12.4 | High expression |
| Dendritic cell (immature) | 10.1 | Medium expression |
| T-cell (Jurkat) | 0.5 | Very low/absent |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1050501 (I232T) | Missense (SNP) | ~10-15% in European populations; higher in Asian populations | Reduces FcγRIIB inhibitory function; associated with SLE and autoimmune susceptibility |
| rs1801274 (H131R) | Missense (SNP) | ~40-50% in various populations | Alters IgG2 binding affinity; affects immune complex clearance |
| c.695T>C (p.Ile232Thr) | Missense | Rare in general population | Loss of ITIM signaling; linked to SLE |
| FCGR2B deletion | Copy number loss | Rare | Complete loss of FcγRIIB expression; severe autoimmune phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense variants (e.g., I232T) and deletions that impair ITIM signaling or reduce surface expression lead to loss of inhibitory function, resulting in B-cell hyperactivation and autoantibody production.
Gain of Function (GOF)
No well-characterized gain-of-function mutations are reported in the literature. Overexpression of wild-type FcγRIIB can occur in certain cancers and may suppress antitumor immunity.
Dominant Negative (DN)
Heterozygous missense mutations that disrupt receptor dimerization or signaling may exert dominant-negative effects by interfering with wild-type receptor function, though specific examples are not well documented.
View complete mutation data：
Gene Ontology (GO)
| • Fc-gamma receptor I complex binding | • IgG binding |
| • immune response | • negative regulation of B cell receptor signaling |
| • negative regulation of mast cell activation | • phagocytosis |
| • recognition | • signal transduction |
| • immunoglobulin mediated immune response |
Pathways
• Fc gamma R-mediated phagocytosis (KEGG: hsa04666)
• B cell receptor signaling pathway (KEGG: hsa04662)
• Immune System (Reactome: R-HSA-168256)
• Fcgamma receptor (FCGR) dependent phagocytosis (Reactome: R-HSA-2029481)
Protein Summary
Fc gamma receptor IIb (FcγRIIB, CD32B) is a 310-amino-acid transmembrane glycoprotein with two extracellular Ig-like domains and a cytoplasmic tail containing a single ITIM motif. It binds IgG immune complexes with low affinity and is the sole inhibitory Fcγ receptor in humans. FcγRIIB is expressed on B cells, dendritic cells, macrophages, and basophils, where it negatively regulates activating signals from BCR and activating Fcγ receptors. Its function is critical for maintaining immune tolerance, preventing autoimmunity, and modulating antibody responses. Dysregulation of FcγRIIB expression or function is implicated in systemic lupus erythematosus, rheumatoid arthritis, and cancer immune evasion. Therapeutic targeting of FcγRIIB is being explored to enhance antitumor immunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FCGR2B Knockout HEK293 Cell Line | EDJ-KQ17777 | Human | 2213 | Details Get a Quote |
| FCGR2B Knockout HeLa Cell Line | EDJ-KQ53210 | Human | 2213 | Details Get a Quote |
| FCGR2B Knockout A-549 Cell Line | EDJ-KQ61691 | Human | 2213 | Details Get a Quote |
| FCGR2B Knockout HCT 116 Cell Line | EDJ-KQ70177 | Human | 2213 | Details Get a Quote |
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