Target Information
| Target General Information | Top | |||||
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| Target ID |
T03573
(Former ID: TTDNC00464)
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| Target Name |
Immunoglobulin gamma Fc receptor IIB (FCGR2B)
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| Synonyms |
Low affinity immunoglobulin gamma Fc region receptor II-b; IgG Fc receptor II-b; FcRII-b; Fc-gamma-RIIb; Fc-gamma RII-b; FCG2B; CDw32 B; CD32 B
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| Gene Name |
FCGR2B
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 8 Target-related Diseases | + | ||||
| 1 | Diabetes mellitus [ICD-11: 5A10] | |||||
| 2 | Lupus erythematosus [ICD-11: 4A40] | |||||
| 3 | Sjogren syndrome [ICD-11: 4A43] | |||||
| 4 | B-cell lymphoma [ICD-11: 2A86] | |||||
| 5 | Leukaemia [ICD-11: 2A60-2B33] | |||||
| 6 | Mature B-cell leukaemia [ICD-11: 2A82] | |||||
| 7 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| 8 | Autoimmune disease [ICD-11: 4A40-4A45] | |||||
| 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.
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| BioChemical Class |
Immunoglobulin
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| UniProt ID | ||||||
| Sequence |
MGILSFLPVLATESDWADCKSPQPWGHMLLWTAVLFLAPVAGTPAAPPKAVLKLEPQWIN
VLQEDSVTLTCRGTHSPESDSIQWFHNGNLIPTHTQPSYRFKANNNDSGEYTCQTGQTSL SDPVHLTVLSEWLVLQTPHLEFQEGETIVLRCHSWKDKPLVKVTFFQNGKSKKFSRSDPN FSIPQANHSHSGDYHCTGNIGYTLYSSKPVTITVQAPSSSPMGIIVAVVTGIAVAAIVAA VVALIYCRKKRISALPGYPECREMGETLPEKPANPTNPDEADKVGAENTITYSLLMHPDA LEEPDDQNRI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | Xmab 5871 | Drug Info | Phase 2 | Autoimmune diabetes | [2] | |
| 2 | BI 1206 | Drug Info | Phase 1/2 | Chronic lymphocytic leukaemia | [3] | |
| 3 | MGD010 | Drug Info | Phase 1 | Autoimmune disease | [4] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Xmab 5871 | Drug Info | [1], [5] | |||
| 2 | MGD010 | Drug Info | [4] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Phagosome | hsa04145 | Affiliated Target |
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| Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
| Osteoclast differentiation | hsa04380 | Affiliated Target |
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| Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
| B cell receptor signaling pathway | hsa04662 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Fc gamma R-mediated phagocytosis | hsa04666 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 9 | Degree centrality | 9.67E-04 | Betweenness centrality | 2.16E-04 |
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| Closeness centrality | 2.17E-01 | Radiality | 1.38E+01 | Clustering coefficient | 1.94E-01 |
| Neighborhood connectivity | 2.86E+01 | Topological coefficient | 1.73E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 7 KEGG Pathways | + | ||||
| 1 | Phagosome | |||||
| 2 | Osteoclast differentiation | |||||
| 3 | B cell receptor signaling pathway | |||||
| 4 | Fc gamma R-mediated phagocytosis | |||||
| 5 | Staphylococcus aureus infection | |||||
| 6 | Tuberculosis | |||||
| 7 | Measles | |||||
| NetPath Pathway | [+] 1 NetPath Pathways | + | ||||
| 1 | Leptin Signaling Pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Fc-epsilon receptor I signaling in mast cells | |||||
| 2 | BCR signaling pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell | |||||
| References | Top | |||||
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| REF 1 | CD19 as an attractive target for antibody-based therapy. MAbs. 2012 Sep-Oct;4(5):571-7. | |||||
| REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035125) | |||||
| REF 3 | ClinicalTrials.gov (NCT02933320) BI-1206 and an Anti-CD20 Antibody in Patients With CD32b Positive B-cell Lymphoma or Leukaemia. U.S. National Institutes of Health. | |||||
| REF 4 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 5 | Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801. | |||||
| REF 6 | Clinical pipeline report, company report or official report of BioInvent. | |||||
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