FCGR2B

Summary

FCGR2B (Fc gamma receptor IIb, HGNC:3618) is a protein-coding gene on chromosome 1q23.3, encoding Low affinity immunoglobulin gamma Fc region receptor II-b (P31994). Receptor for the Fc region of complexed or aggregated immunoglobulins gamma.

The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2213 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 41
• Clinical variants (ClinVar): 53 total
• Phenotypes (HPO): 53
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_001394477

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3618
Approved symbol	FCGR2B
Name	Fc gamma receptor IIb
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CD32, CD32B, FcgammaRIIb, FcGRIIB
Ensembl gene	ENSG00000072694
Ensembl biotype	protein_coding
OMIM	604590
Entrez	2213

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000236937, ENST00000358671, ENST00000367961, ENST00000480308, ENST00000485778, ENST00000674150, ENST00000880972, ENST00000880973, ENST00000880974, ENST00000880975

RefSeq mRNA: 13 — MANE Select: NM_001394477 NM_001002273, NM_001002274, NM_001002275, NM_001190828, NM_001386000, NM_001386001, NM_001386002, NM_001386003, NM_001386004, NM_001386005, NM_001386006, NM_001394477, NM_004001

CCDS: CCDS30924, CCDS30925, CCDS53414

Canonical transcript exons

ENST00000358671 — 8 exons

Exon	Start	End
ENSE00000789244	161675257	161675313
ENSE00000796505	161677328	161677365
ENSE00001863715	161677476	161678654
ENSE00002055777	161663143	161663353
ENSE00003522298	161671392	161671649
ENSE00003633964	161672975	161673229
ENSE00003670063	161670252	161670272
ENSE00003740242	161673960	161674073

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 92.97.

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	92.97	gold quality
right coronary artery	UBERON:0001625	90.75	gold quality
blood	UBERON:0000178	89.25	gold quality
spleen	UBERON:0002106	89.03	gold quality
monocyte	CL:0000576	88.18	gold quality
leukocyte	CL:0000738	88.03	gold quality
lymph node	UBERON:0000029	88.03	gold quality
mononuclear cell	CL:0000842	87.92	gold quality
layer of synovial tissue	UBERON:0007616	87.67	gold quality
synovial joint	UBERON:0002217	86.59	gold quality
granulocyte	CL:0000094	86.32	gold quality
vermiform appendix	UBERON:0001154	86.03	gold quality
pericardium	UBERON:0002407	85.75	gold quality
gall bladder	UBERON:0002110	85.55	gold quality
omental fat pad	UBERON:0010414	85.31	gold quality
peritoneum	UBERON:0002358	85.25	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.23	gold quality
superficial temporal artery	UBERON:0001614	85.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.77	gold quality
adipose tissue	UBERON:0001013	84.04	gold quality
calcaneal tendon	UBERON:0003701	83.36	gold quality
connective tissue	UBERON:0002384	83.17	gold quality
smooth muscle tissue	UBERON:0001135	82.99	gold quality
rectum	UBERON:0001052	82.91	gold quality
decidua	UBERON:0002450	82.82	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.24	gold quality
liver	UBERON:0002107	82.05	gold quality
adrenal tissue	UBERON:0018303	81.78	gold quality
caecum	UBERON:0001153	81.54	gold quality
right lobe of liver	UBERON:0001114	81.47	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	45.92
E-ANND-3	yes	22.72
E-HCAD-9	yes	21.60
E-MTAB-6701	yes	13.01
E-MTAB-9801	yes	4.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APP, GATA4, NFKB, YY1, ZNF91

miRNA regulators (miRDB)

55 targeting FCGR2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548AI	99.69	69.24	1494
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-570-5P	99.69	69.24	1494
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-4261	99.59	70.30	3415

Literature-anchored findings (GeneRIF, showing 40)

• The inhibitory receptor, Fc gamma RIIb2, is expressed on circulating human monocytes. In human primary monocytes Fc gamma RIIb2 expression is increased by IL-4, a Th2 cytokine and decreased by IFN-gamma, a Th1 cytokine. (PMID:11123333)
• Although there is no phenotypic difference in Fc gamma RII expression (Fc gamma RIIb predominating on both adult and cord B cells), the inhibitory Fc gamma RIIb is expressed at lower levels on cord cells. (PMID:11423173)
• Here we demonstrate for the first time FcgammaRIIb protein expression and function in human monocytes (PMID:11741917)
• association of a new polymorphism of FCGR2B (I232T) with susceptibility to SLE in the Japanese. (PMID:12115230)
• human malignant melanoma cells express the inhibitory low-affinity Fc(gamma) receptor Fc(gamma)RIIB1 in 40% of tested metastases (PMID:12438452)
• hypothesized that inhibitory signaling through FcgammaRIIb would be counter-productive in germinal center cells undergoing selection by affinity maturation (PMID:12516568)
• Fcgamma receptor IIb polymorphisms are associated with susceptibility to systemic lupus erythematosus in Thais (PMID:12753656)
• The differential activity of FCGR2B alleles suggests a novel mechanism of FcgammaRIIb regulation that may influence the risk of autoimmune disease. (PMID:14613290)
• FCGR2B is a common susceptibility factor to SLE in the Asians (PMID:14651519)
• no association between fcgammar2b and systemic lupus erythematosus in Swedish population (PMID:15077320)
• results indicated that the presence of CD72-*2 allele decreases risk for human systemic lupus erythematosus conferred by FCGR2B-232Thr, possibly by increasing the AS isoform of CD72 (PMID:15459183)
• Signals underlying FcgammaRIIB-driven apoptosis are dependent on disruption of mitochondrial potential. (PMID:15506939)
• results imply a novel functional role of CD13 and Fc gamma receptors (CD32 and CD64)as members of a multimeric receptor complex (PMID:15883031)
• FcgammaRIIbl and b2 are both functional inhibitory receptors in the phagocytic process. (PMID:16051361)
• Ile232Thr substitution affects the localization and function of FcgammaRIIB; this molecular mechanism may link the polymorphism and susceptibility to systemic lupus erythematosus. (PMID:16115811)
• a recently described SLE-associated polymorphism of FcgammaRIIb (FcgammaRIIbT(232)), encoding a single transmembrane amino acid substitution, is functionally impaired (PMID:16170323)
• Review of polymorphic screening studies of Japanese, Thai, and Chinese populations indicates that FCGR2B is a susceptibility gene associated with systemic lupus erythematosus. (PMID:16227149)
• SHIP1 is necessary for FcgammaRIIB to negatively regulate B cell activation (PMID:16406061)
• the FcgammaRIIB-50T-225C haplotype might be a susceptible factor of SLE in the Chinese population (PMID:16531013)
• The response to either dimeric IgG or aggregated IgG (aIgG) was assessed and related to differences in the ratio of FcgammaRIIa to FcgammaRIIb2 mRNA in granulocytes (PMID:16551965)
• FcgammaRIIb expression and synthesis occur throughout the placental vascular tree but do not extend into the umbilical cord. (PMID:16600368)
• in human aortic endothelial cells, CRP upregulates monocyte-endothelial adhesion by activation of NF-kappaB through engaging the Fcgamma receptors CD32 and CD64. (PMID:16603696)
• analysis of CD32B, which is expressed in B-cell lymphoma, and a panel of its monoclonal antibodies (PMID:16757681)
• Unlike the Fc gamma RIIa receptor isoform, expression of Fc gamma RIIb is not detected in extracts of cultured human skin mast cell preparations. (PMID:16785568)
• immature MPC-1- myeloma cells expressed CD32 more weakly than mature, MPC-1+ cells; Myeloma cells lacking CD19 expression are less sensitive to CD32-mediated growth suppression than are CD19+ normal plasma cells. (PMID:16818279)
• Results suggest that FcgammaRIIB may be impaired at a critical checkpoint in systemic lupus erythematosus in the regulation of memory B cells. (PMID:16923849)
• CD32-IgG interaction could directly drive capture and activation of flowing neutrophils, or potentiate activation of cells captured by other routes. (PMID:16934243)
• Susceptibility to type 1 Autoimmune hepatitis in Japanese patients is not influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms. (PMID:17020818)
• The inhibitory signaling abnormality of CD32 possibly contributes to the mechanism of hyperactivity of human SLE B cells. (PMID:17077019)
• activating protein 1 has a role in the transcriptional regulation of the human FCGR2B promoter mediated by the -343 G -> C polymorphism associated with systemic lupus erythematosus (PMID:17130130)
• FCGR2B 695T>C polymorphism is a critical determinant of severity in rheumatoid arthritis and is a potential therapeutic target. (PMID:17133580)
• The FcgammaRIIb transmembrane polymorphism is a strong disease susceptibility candidate in epistasis with other genetic effects in Taiwanese and other Asian populations. (PMID:17133600)
• FCGR2B expression is patently reduced in mature DCs, and is modulated by treatment with cytokines. The regulated expression of activating and inhibitory FcgRs in DCs emerges as a critical checkpoint in the process of Ag uptake and cross-presentation. (PMID:17142741)
• These results demonstrate that FcgammaRIIb is important in controlling the immune response to malarial parasites. (PMID:17435165)
• Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human dendritic cells and monocytes induces a type I interferon response program. (PMID:17502666)
• RA patients do not fail to up-regulate FcgammaRIIb upon synovial inflammation, but suggests that the balance between expression of the inhibitory FcgammaRIIb and activating FcgammaRs may be in favour of the latter throughout the disease course (PMID:17521421)
• The researchers evidence of altered gene expression in the FCGR2B gene after both aerobic and exhaustive exercise. (PMID:17873550)
• We demonstrate that the expression of the inhibitory receptors Fc gamma RII and CR1 is up-regulated on peripheral memory B cells of healthy controls, whereas this up-regulation is considerably impaired on the memory B cells of SLE patients. (PMID:18182380)
• role of FcgammaRIIB and FcgammaRIIIA gene in susceptibility to systemic lupus erythematosus and to examine possible susceptible haplotypes between two genes (PMID:18625651)
• FcgammaRIIb SNP 187-Ile/Thr may influence the Rheumatoid Arthritis phenotypes in Taiwanese RA. (PMID:18633424)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcgr2b	ENSMUSG00000026656
mus_musculus	Fcgr3	ENSMUSG00000059498
rattus_norvegicus	Fcgr2b	ENSRNOG00000046452
rattus_norvegicus	Fcgr2a	ENSRNOG00000046663
rattus_norvegicus	Fcgr2a	ENSRNOG00000049422
rattus_norvegicus	Fcgr2al1	ENSRNOG00000058500

Paralogs (17): FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCRLB (ENSG00000162746), FCGR3B (ENSG00000162747), FCRL4 (ENSG00000163518), FCRL1 (ENSG00000163534), FCER1A (ENSG00000179639), FCRL6 (ENSG00000181036), C17orf99 (ENSG00000187997), FCGR3A (ENSG00000203747), FCGR2C (ENSG00000244682), PECAM1 (ENSG00000261371), MILR1 (ENSG00000271605)

Protein

Protein identifiers

Low affinity immunoglobulin gamma Fc region receptor II-b — P31994 (reviewed: P31994)

Alternative names: CDw32, Fc-gamma RII-b

All UniProt accessions (1): P31994

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B-cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.

Subunit / interactions. Interacts with INPP5D/SHIP1. Interacts with FGR. Interacts with LYN. Interacts with the Fc region of IgG1, IgG3 and IgG4 isotypes assembled in immune complexes. (Microbial infection) Isoform IIB1 interacts with measles virus protein N. Protein N is released in the blood following lysis of measles infected cells. This interaction presumably block inflammatory immune response.

Subcellular location. Cell membrane.

Tissue specificity. Is the most broadly distributed Fc-gamma-receptor. Expressed in monocyte, neutrophils, macrophages, basophils, eosinophils, Langerhans cells, B-cells, platelets cells and placenta (endothelial cells). Not detected in natural killer cells.

Post-translational modifications. Phosphorylated by the SRC-type Tyr-kinases LYN and BLK.

Disease relevance. Systemic lupus erythematosus (SLE) [MIM:152700] A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Polymorphism. FCGR2B polymorphisms can influence susceptibility or resistance to malaria [MIM:611162].

Isoforms (5)

UniProt ID	Names	Canonical?
P31994-1	IIB1	yes
P31994-2	IIB2
P31994-3	IIB3
P31994-4	4
P31994-5	5

RefSeq proteins (13): NP_001002273, NP_001002274, NP_001002275, NP_001177757, NP_001372929, NP_001372930, NP_001372931, NP_001372932, NP_001372933, NP_001372934, NP_001372935, NP_001381406, NP_003992 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050488	Ig_Fc_receptor	Family

Pfam: PF13895

UniProt features (45 total): strand 17, sequence variant 4, sequence conflict 4, glycosylation site 3, splice variant 3, helix 3, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9M5B	X-RAY DIFFRACTION	1.66
2FCB	X-RAY DIFFRACTION	1.74
5OCC	X-RAY DIFFRACTION	2.5
3WJJ	X-RAY DIFFRACTION	2.6
9OUV	X-RAY DIFFRACTION	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31994-F1	78.81	0.57

Antibody-complex structures (SAbDab): 2 — 5OCC, 9M5B

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 292

Disulfide bonds (2): 71–113, 152–196

Glycosylation sites (3): 180, 187, 106

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

MSigDB gene sets: 651 (showing top): PID_BCR_5PATHWAY, GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ANTIGEN_PROCESSING_AND_PRESENTATION_OF_PEPTIDE_OR_POLYSACCHARIDE_ANTIGEN_VIA_MHC_CLASS_II, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_DENDRITIC_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS

GO Biological Process (48): antibody-dependent cellular cytotoxicity (GO:0001788), negative regulation of type I hypersensitivity (GO:0001811), negative regulation of antibody-dependent cellular cytotoxicity (GO:0001814), negative regulation of cytokine production (GO:0001818), immune effector process (GO:0002252), follicular dendritic cell activation (GO:0002266), mature B cell differentiation involved in immune response (GO:0002313), follicular B cell differentiation (GO:0002316), immune complex clearance by monocytes and macrophages (GO:0002436), negative regulation of dendritic cell antigen processing and presentation (GO:0002605), regulation of B cell antigen processing and presentation (GO:0002622), negative regulation of immunoglobulin production (GO:0002638), regulation of adaptive immune response (GO:0002819), negative regulation of acute inflammatory response to antigenic stimulus (GO:0002865), positive regulation of humoral immune response (GO:0002922), negative regulation of humoral immune response mediated by circulating immunoglobulin (GO:0002924), receptor-mediated endocytosis (GO:0006898), phagocytosis (GO:0006909), phagocytosis, engulfment (GO:0006911), defense response (GO:0006952), inflammatory response (GO:0006954), cell surface receptor signaling pathway (GO:0007166), response to bacterium (GO:0009617), immunoglobulin mediated immune response (GO:0016064), antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886), cerebellum development (GO:0021549), negative regulation of B cell proliferation (GO:0030889), negative regulation of interleukin-10 production (GO:0032693), positive regulation of tumor necrosis factor production (GO:0032760), Fc-gamma receptor signaling pathway (GO:0038094), negative regulation of macrophage activation (GO:0043031), negative regulation of cytotoxic T cell degranulation (GO:0043318), regulation of innate immune response (GO:0045088), positive regulation of JNK cascade (GO:0046330), negative regulation of phagocytosis (GO:0050765), positive regulation of phagocytosis (GO:0050766), negative regulation of immune response (GO:0050777), negative regulation of B cell receptor signaling pathway (GO:0050859), negative regulation of B cell activation (GO:0050869), cellular response to molecule of bacterial origin (GO:0071219)

GO Molecular Function (6): amyloid-beta binding (GO:0001540), IgG receptor activity (GO:0019770), low-affinity IgG receptor activity (GO:0019772), IgG binding (GO:0019864), protein-containing complex binding (GO:0044877), protein binding (GO:0005515)

GO Cellular Component (5): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), dendritic spine (GO:0043197), cell body (GO:0044297), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of immunoglobulin mediated immune response	2
endocytosis	2
binding	2
cellular anatomical structure	2
type IIa hypersensitivity	1
leukocyte mediated cytotoxicity	1
regulation of type I hypersensitivity	1
negative regulation of hypersensitivity	1
type I hypersensitivity	1
antibody-dependent cellular cytotoxicity	1
negative regulation of type IIa hypersensitivity	1
regulation of antibody-dependent cellular cytotoxicity	1
negative regulation of leukocyte mediated cytotoxicity	1
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
immune system process	1
cell activation	1
B cell activation involved in immune response	1
mature B cell differentiation	1
immune response	1
mature B cell differentiation involved in immune response	1
immune complex clearance	1
dendritic cell antigen processing and presentation	1
negative regulation of antigen processing and presentation	1
regulation of dendritic cell antigen processing and presentation	1
B cell antigen processing and presentation	1
regulation of antigen processing and presentation	1
regulation of B cell mediated immunity	1
immunoglobulin production	1
regulation of immunoglobulin production	1
negative regulation of production of molecular mediator of immune response	1
adaptive immune response	1
regulation of immune response	1
acute inflammatory response to antigenic stimulus	1
negative regulation of acute inflammatory response	1
negative regulation of inflammatory response to antigenic stimulus	1
regulation of acute inflammatory response to antigenic stimulus	1
regulation of humoral immune response	1

Protein interactions and networks

STRING

2370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCGR2B	CLEC7A	Q9BXN2	990
FCGR2B	LGALS3	P17931	988
FCGR2B	CD19	P15391	926
FCGR2B	PTPRC	P08575	894
FCGR2B	ITGAM	P11215	891
FCGR2B	INPP5D	Q92835	890
FCGR2B	LYN	P07948	867
FCGR2B	FGL2	Q14314	865
FCGR2B	FCGRT	P55899	855
FCGR2B	IGF2	P01344	848
FCGR2B	CD4	P01730	817
FCGR2B	FCGR1A	P12314	809
FCGR2B	FCER1G	P30273	805
FCGR2B	ITGAX	P20702	804
FCGR2B	CD72	P21854	803

IntAct

57 interactions, top by confidence:

A	B	Type	Score
INPP5D	FCGR2B	psi-mi:“MI:0407”(direct interaction)	0.700
INPP5D	FCGR2B	psi-mi:“MI:0914”(association)	0.700
INPP5D	FCGR2B	psi-mi:“MI:0915”(physical association)	0.700
PTPN6	FCGR2B	psi-mi:“MI:0915”(physical association)	0.670
PTPN6	FCGR2B	psi-mi:“MI:0914”(association)	0.670
KLK6	FCGR2B	psi-mi:“MI:0915”(physical association)	0.560
FCGR2B	IGHG1	psi-mi:“MI:0407”(direct interaction)	0.560
IGHG1	FCGR2B	psi-mi:“MI:0407”(direct interaction)	0.560

BioGRID (25): FCGR2A (Affinity Capture-MS), MARS2 (Affinity Capture-MS), GSK3A (Affinity Capture-MS), GSK3A (Affinity Capture-MS), FCGR2A (Affinity Capture-MS), MARS2 (Affinity Capture-MS), PTPN6 (Reconstituted Complex), FCGR2B (Protein-peptide), FCGR2B (Protein-peptide), GAB1 (Protein-peptide), GRB2 (Protein-peptide), FCGR2B (Protein-peptide), FCGR2B (Protein-peptide), LYN (Reconstituted Complex), MAPK1 (Reconstituted Complex)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A5D7V5, A7TZE6, A7TZF0, A7TZF3, A7XUX6, A7XV04, A7XV07, A8K4G0, A8MVZ5, O70355, P08508, P18892, P24071, P31994, P55803, P78410, P79391, Q13410, Q16653, Q29ZQ1, Q3KPI0, Q58DF9, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6Q8B3, Q6UXZ3, Q6XJV4, Q6XJV6, Q7KYR7, Q7TST0, Q7YR73, Q8BTP3, Q8K249, Q8TD46

Diamond homologs: A0A0B4J1G0, A3RFZ7, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12314, P12318, P12319, P12371, P20489, P26151, P27645, P31994, P31995, P79107, Q09TM2, Q09TM4, Q28110, Q28942, Q3B8P2, Q5DRQ8, Q60513, Q63203, Q6BAA4, Q6XPU4, Q8SPV8, Q8SPW2, Q920A9, Q92637, Q96PJ5, Q96RD9, Q9N2I5, Q68SN8

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
“Immune complexes”	“up-regulates activity”	FCGR2B
FCGR2B	“down-regulates activity”	TLR4
MARCHF9	“down-regulates quantity by destabilization”	FCGR2B	ubiquitination
LYN	“up-regulates activity”	FCGR2B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of KIT signaling	5	200.3×	1e-09
Signaling by CSF1 (M-CSF) in myeloid cells	7	161.5×	9e-13
Downstream signal transduction	6	152.3×	1e-10
Interleukin-3, Interleukin-5 and GM-CSF signaling	6	126.9×	2e-10
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	5	119.0×	2e-08
FCGR3A-mediated IL10 synthesis	5	97.6×	4e-08
RET signaling	5	86.5×	6e-08
Signaling by SCF-KIT	5	82.8×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	6	129.0×	1e-09
T cell costimulation	5	117.0×	7e-08
negative regulation of T cell receptor signaling pathway	5	114.5×	7e-08
epidermal growth factor receptor signaling pathway	5	77.4×	4e-07
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	24.5×	5e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MLYM.

Clinical variants and AI predictions

ClinVar

53 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1086 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161664982:GCAA:G	donor_gain	1.0000
1:161664985:A:AG	donor_gain	1.0000
1:161671585:G:GT	donor_gain	1.0000
1:161671585:G:T	donor_gain	1.0000
1:161671660:G:GT	donor_gain	1.0000
1:161673958:A:AG	acceptor_gain	1.0000
1:161673959:G:GG	acceptor_gain	1.0000
1:161674069:TTCAG:T	donor_loss	1.0000
1:161674070:TCAG:T	donor_loss	1.0000
1:161674071:CAG:C	donor_loss	1.0000
1:161674072:AG:A	donor_loss	1.0000
1:161674073:GG:G	donor_loss	1.0000
1:161674074:GTTT:G	donor_loss	1.0000
1:161674075:T:G	donor_loss	1.0000
1:161677326:A:AG	acceptor_gain	1.0000
1:161677327:G:GG	acceptor_gain	1.0000
1:161664985:A:G	donor_gain	0.9900
1:161670272:GGTA:G	donor_loss	0.9900
1:161670273:G:A	donor_loss	0.9900
1:161670274:T:A	donor_loss	0.9900
1:161671391:GCA:G	acceptor_gain	0.9900
1:161671559:TTC:T	donor_gain	0.9900
1:161672973:A:AG	acceptor_gain	0.9900
1:161672973:AGAGT:A	acceptor_gain	0.9900
1:161672974:G:GA	acceptor_gain	0.9900
1:161672974:GA:G	acceptor_gain	0.9900
1:161672974:GAGTG:G	acceptor_gain	0.9900
1:161673226:CAAGG:C	donor_loss	0.9900
1:161673227:AAGGT:A	donor_loss	0.9900
1:161673231:T:G	donor_loss	0.9900

AlphaMissense

2030 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161673037:T:A	C152S	0.995
1:161673038:G:C	C152S	0.995
1:161673169:T:A	C196S	0.994
1:161673170:G:C	C196S	0.994
1:161671590:A:G	Y111C	0.993
1:161673037:T:C	C152R	0.991
1:161671510:G:C	W84C	0.989
1:161671510:G:T	W84C	0.989
1:161671590:A:C	Y111S	0.989
1:161673164:A:G	Y194C	0.989
1:161673171:C:G	C196W	0.989
1:161671595:T:A	C113S	0.988
1:161671596:G:C	C113S	0.988
1:161673039:C:G	C152W	0.988
1:161671589:T:G	Y111D	0.987
1:161673038:G:A	C152Y	0.987
1:161671469:T:A	C71S	0.986
1:161671470:G:C	C71S	0.986
1:161673032:T:C	L150P	0.986
1:161673048:G:C	W155C	0.986
1:161673048:G:T	W155C	0.986
1:161673169:T:C	C196R	0.985
1:161673170:G:A	C196Y	0.985
1:161671619:A:C	S121R	0.984
1:161671621:C:A	S121R	0.984
1:161671621:C:G	S121R	0.984
1:161673163:T:G	Y194D	0.983
1:161671432:G:C	W58C	0.981
1:161671432:G:T	W58C	0.981
1:161671508:T:A	W84R	0.981

dbSNP variants (sampled 300 via entrez): RS1000035949 (1:161660013 C>A), RS1000428236 (1:161656154 G>C), RS1001028923 (1:161651316 C>T), RS1001099411 (1:161677783 A>T), RS1001168691 (1:161675625 G>A), RS1001481223 (1:161652287 T>C), RS1001592930 (1:161647051 G>A,C), RS1001701154 (1:161667284 G>A), RS1002114093 (1:161678407 T>C), RS1002114156 (1:161668212 C>T), RS1002159686 (1:161674435 A>G), RS1002171173 (1:161674702 A>G,T), RS1003191531 (1:161648856 A>G), RS1003779054 (1:161670830 G>A,C), RS1003944919 (1:161653838 C>T)

Disease associations

OMIM: gene MIM:604590 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
systemic lupus erythematosus	Supportive	Unknown

Mondo (1): systemic lupus erythematosus (MONDO:0007915)

Orphanet (0):

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000093	Proteinuria
HP:0000123	Nephritis
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000709	Psychosis
HP:0000716	Depression
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001596	Alopecia
HP:0001701	Pericarditis
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001945	Fever
HP:0002039	Anorexia
HP:0002072	Chorea
HP:0002102	Pleuritis
HP:0002716	Lymphadenopathy
HP:0002725	Systemic lupus erythematosus
HP:0003453	Antineutrophil antibody positivity
HP:0003493	Antinuclear antibody positivity
HP:0003613	Antiphospholipid antibody positivity
HP:0005421	Decreased circulating complement C3 concentration
HP:0005764	Polyarticular arthritis
HP:0007417	Discoid lupus rash

GWAS associations

41 associations (top):

Study	Trait	p-value
GCST000964_2	Ulcerative colitis	2.000000e-20
GCST001392_16	Lipid metabolism phenotypes	1.000000e-10
GCST001725_37	Inflammatory bowel disease	2.000000e-38
GCST003155_37	Systemic lupus erythematosus	1.000000e-12
GCST003445_14	Response to cyclophosphamide in systemic lupus erythematosus with lupus nephritis	3.000000e-08
GCST004131_77	Inflammatory bowel disease	9.000000e-14
GCST004133_13	Ulcerative colitis	2.000000e-18
GCST004609_126	Monocyte percentage of white cells	7.000000e-11
GCST004610_104	White blood cell count	1.000000e-11
GCST004613_2	Sum neutrophil eosinophil counts	1.000000e-11
GCST004614_119	Granulocyte count	2.000000e-11
GCST004615_81	Hemoglobin concentration	4.000000e-11
GCST004620_8	Sum basophil neutrophil counts	3.000000e-12
GCST004626_7	Myeloid white cell count	7.000000e-12
GCST004629_15	Neutrophil count	3.000000e-12
GCST005146_29	Birth weight	2.000000e-09
GCST005989_4	Serum total protein levels	4.000000e-17
GCST006585_526	Blood protein levels	0.000000e+00
GCST006959_93	Rheumatoid arthritis	3.000000e-06
GCST008362_143	Birth weight	4.000000e-10
GCST008362_93	Birth weight	4.000000e-11
GCST008363_18	Offspring birth weight	8.000000e-09
GCST008576_2	IgG levels	2.000000e-42
GCST008576_3	IgG levels	9.000000e-32
GCST008576_8	IgG levels	4.000000e-08
GCST010241_85	Apolipoprotein A1 levels	3.000000e-13
GCST010242_457	HDL cholesterol levels	7.000000e-11
GCST90002379_11	Basophil count	7.000000e-12
GCST90002379_13	Basophil count	3.000000e-12
GCST90002380_89	Basophil percentage of white cells	2.000000e-21

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004529	lipid measurement
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0004344	birth weight
EFO:0005939	parental genotype effect measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007992	basophil percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4662940 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1050501	FCGR2B		0.00	0

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects expression, increases expression	3
Lipopolysaccharides	affects cotreatment, decreases expression, increases expression, affects response to substance	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
cinnamaldehyde	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
tamibarotene	affects expression	1
Acetaminophen	decreases expression, affects cotreatment	1
Cadmium	decreases expression	1
Eugenol	increases expression	1
Methotrexate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Oxazolone	increases expression	1
Quercetin	increases expression	1
Silicon Dioxide	decreases expression	1
Trinitrobenzenesulfonic Acid	increases expression	1
Valproic Acid	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Cellosaurus cell lines

9 cell lines: 5 spontaneously immortalized cell line, 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1E20	TZM-bl/FcgammaRIIb	Cancer cell line	Female
CVCL_B8FX	Abcam HCT 116 FCGR2B KO	Cancer cell line	Male
CVCL_B8VR	Abcam MCF-7 FCGR2B KO	Cancer cell line	Female
CVCL_B9I4	Abcam A-549 FCGR2B KO	Cancer cell line	Male
CVCL_DE95	CHO-K1.Cl-0206	Spontaneously immortalized cell line	Female
CVCL_E2SY	Genomeditech CHO-K1 H_FCGR2B(CD32B)	Spontaneously immortalized cell line	Female
CVCL_E6QE	Genomeditech CHO-K1 H_FCGR2B(CD32B) aAPC	Spontaneously immortalized cell line	Female
CVCL_KA29	CHO-K1/CD32B 232Ile	Spontaneously immortalized cell line	Female
CVCL_KA30	CHO-K1/CD32B 232Thr	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients