FCGR2B (Fc fragment of IgG, low affinity IIb, receptor (CD32))
2002-02-01 Mary Callanan , Dominique Leroux AffiliationLymphoma Research Group - Groupe de Recherche sur les Lymphomes - EMI0353, Institut Albert Bonniot, Université Joseph Fourier Grenoble 1, La Tronche 38706, France
Identity
HGNC
LOCATION
1q23.3
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CD32,CD32B,FCG2,FCGR2,FCGR2C,FcRII-c,IGFR2
FUSION GENES
DNA/RNA
Description
The FCGR2B gene spans a 15kb genomic region; Gene orientation : centromere - 3 FCGR2B 5 - telomere; 8 exons (denoted S1, S2, EC1, EC2, TM, IC1, IC2, IC3). S1 and S2 encode the signal peptide domain, EC1 and EC2 encode the extracellular domain, TM encodes the transmembrane domain and IC1, IC2, IC3 encode the intracytoplasmic region.
Transcription
1.7kb mRNA. Two alternately spliced mRNA exist in humans; FcgRIIb1 and FcgRIIb2 (a 19 aa insertion encoded by IC1 is present in b1 but not in b2).
Proteins
Note
called Fc gamma RIIB
Description
40kD transmembrane glycoprotein that possesses an intracytoplasmic Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) (encoded by IC3).
Expression
B, myeloid and mast cells.
Localisation
Transmembrane.
Function
Low affinity IgG Fc receptor. Founding member ITIM family of immune inhibitory receptors. Fc gamma RIIB functions to down-regulate activatory responses mediated by Immunoreceptor Tyrosine-based Inhibition Motif (ITAM) bearing receptors such as the B-cell receptor on B cells. For example, on B-cells, negative regulation of B-cell receptor activatory signalling is initiated through co-recruitment of BCR and Fc gamma RIIB to IgG/ immune complexes. This leads to tyrosyl phosphorylation of the Fc gamma RIIB ITIM motif / recruitment of the inositol phosphatase SHIP and activation of the adaptor protein Dok - these events ultimately lead to the inhibition of ITAM-dependant Ca++ mobilisation and cellular proliferation (reduced MAPK signalling), respectively.
A proapoptotic signal through the Fc gamma RIIB transmembrane sequence has been described in conditions of homo-aggregation of Fc gamma RII on murine B cells.
A proapoptotic signal through the Fc gamma RIIB transmembrane sequence has been described in conditions of homo-aggregation of Fc gamma RII on murine B cells.
Homology
Contains two immunoglobulin-like C2 domains.
Implicated in
Entity name
1q21-23 rearrangements in NHL (Nnon-Hodgkins Lymphoma)
Disease
NHL (< 5% of cases with 1q21-23 breaks)
Prognosis
It is now known that cytogenetically determined 1q21-23 breaks can target a diversity of 1q21-23 genes. Early data has suggested a poor prognosis for 1q21 rearrangements in diffuse large cell lymphoma.
Cytogenetics
Deregulation of the FCGR2B gene by chromosomal translocation was first demonstrated in 3 NHL patients that showed a t(1;22)(q22;q22) in association with a t(14;18)(q32;q21). Two further cases of NHL with rearrangements affecting the FCGR2B region have since been identified. Both cases also showed t(14;18)(see below for description). This suggests a role for this deregulation in lymphoma progression.
Hybrid gene
Dysregulation of the FCGR2B gene has been identified as a consequence of a t(1;22)(q22;q11) (3 patients) and t(1;14)(q21;q32) (1 patient). The FCGR2B coding sequence and promoter region appear to remain intact in these translocations. The principal consequence is overexpression of the Fc gamma RIIb2 isoform of Fc gamma RIIB. Deregulation of FCGR2B most likely occurs as a consequence of Ig gene transcriptional enhancer activity. Other mechanisms may exist ; an NHL patient with dup(1)(q21q25) and rearrangement in the FCGR2B region has also been identified.
Fusion protein
None
Oncogenesis
Contribution of FCGR2B deregulation to lymphoma development or progression is currently not known.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 10618414 | 2000 | The IgG Fc receptor, FcgammaRIIB, is a target for deregulation by chromosomal translocation in malignant lymphoma. | Callanan MB et al |
| 11753646 | 2001 | Deregulation of FCGR2B expression by 1q21 rearrangements in follicular lymphomas. | Chen W et al |
| 9143687 | 1997 | Fc receptor biology. | Daëron M et al |
| 11021804 | 2000 | Immune inhibitory receptors. | Ravetch JV et al |
Other Information
Locus ID:
NCBI: 2213
MIM: 604590
HGNC: 3618
Ensembl: ENSG00000072694
Variants:
dbSNP: 2213
ClinVar: 2213
TCGA: ENSG00000072694
COSMIC: FCGR2B
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000072694 | ENST00000236937 | P31994 |
| ENSG00000072694 | ENST00000358671 | P31994 |
| ENSG00000072694 | ENST00000367961 | P31994 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA451743 | trastuzumab | Chemical | Literature, MultilinkAnnotation | not associated | 18347005 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34859644 | 2024 | Evaluation of the FCGR2B polymorphism in children with immune thrombocytopenia. | 0 |
| 38147316 | 2024 | FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment. | 3 |
| 34859644 | 2024 | Evaluation of the FCGR2B polymorphism in children with immune thrombocytopenia. | 0 |
| 38147316 | 2024 | FcγRIIB Is an Immune Checkpoint Limiting the Activity of Treg-Targeting Antibodies in the Tumor Microenvironment. | 3 |
| 36930102 | 2023 | FCGR2A as one novel potential target for poor survival prognosis of clear cell renal cell carcinoma. | 1 |
| 36997299 | 2023 | Mutation of the TGN1412 anti-CD28 monoclonal antibody lower hinge confers specific FcγRIIb binding and retention of super-agonist activity. | 1 |
| 37611081 | 2023 | FcγRIIB expressed on CD8(+) T cells limits responsiveness to PD-1 checkpoint inhibition in cancer. | 2 |
| 37634276 | 2023 | FcγRIIB expression increases during primary biliary cholangitis. | 1 |
| 37713871 | 2023 | FCGR2B as a prognostic and immune microenvironmental marker for gliomas based on transcriptomic analysis. | 1 |
| 37844994 | 2023 | C-reactive protein impairs immune response of CD8(+) T cells via FcγRIIb-p38MAPK-ROS axis in multiple myeloma. | 2 |
| 36930102 | 2023 | FCGR2A as one novel potential target for poor survival prognosis of clear cell renal cell carcinoma. | 1 |
| 36997299 | 2023 | Mutation of the TGN1412 anti-CD28 monoclonal antibody lower hinge confers specific FcγRIIb binding and retention of super-agonist activity. | 1 |
| 37611081 | 2023 | FcγRIIB expressed on CD8(+) T cells limits responsiveness to PD-1 checkpoint inhibition in cancer. | 2 |
| 37634276 | 2023 | FcγRIIB expression increases during primary biliary cholangitis. | 1 |
| 37713871 | 2023 | FCGR2B as a prognostic and immune microenvironmental marker for gliomas based on transcriptomic analysis. | 1 |
Citation
Mary Callanan ; Dominique Leroux
FCGR2B (Fc fragment of IgG, low affinity IIb, receptor (CD32))
Atlas Genet Cytogenet Oncol Haematol. 2002-02-01
Online version: http://atlasgeneticsoncology.org/gene/397/fcgr2b-(fc-fragment-of-igg-low-affinity-iib-receptor-(cd32))
