Target Information

Target General Information

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Target ID

T59001

Target Name

Immunoglobulin gamma Fc receptor IIIA (FCGR3A)

Synonyms

FCGR3A

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Gene Name

FCGR3A

Target Type

Clinical trial target

[1]

Disease

[+] 6 Target-related Diseases

Hodgkin lymphoma [ICD-11: 2B30]

Mature T-cell lymphoma [ICD-11: 2A90]

Mycosis fungoides [ICD-11: 2B01]

Lymphoma [ICD-11: 2A80-2A86]

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Multiple myeloma [ICD-11: 2A83]

Function

Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis.

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BioChemical Class

Immunoglobulin

UniProt ID

FCG3A_HUMAN

Sequence

MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQGAYSPEDNSTQW
FHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSDPVQLEVHIGWLLLQAPRWVFKE
EDPIHLRCHSWKNTALHKVTYLQNGKGRKYFHHNSDFYIPKATLKDSGSYFCRGLFGSKN
VSSETVNITITQGLAVSTISSFFPPGYQVSFCLVMVLLFAVDTGLYFSVKTNIRSSTRDW
KDHKFKWRKDPQDK

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 3 Clinical Trial Drugs

AFM13

Drug Info

Phase 2

Hodgkin lymphoma

[2]

AFM24

Drug Info

Phase 1/2

Solid tumour/cancer

[3]

RG6296

Drug Info

Phase 1

Multiple myeloma

[4]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

RG6296

Drug Info

[6]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
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

Different Human System Profiles of Target

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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

Protein Name	Pfam ID	Percentage of Identity (%)	E value
Neuroplastin (NPTN)	PF13927	27.517 (41/149)	6.51E-04
Titin (TTN)		25.907 (50/193)	8.59E-04
Neural cell adhesion molecule 2 (NCAM2)	PF00041 ; PF07679 ; PF13927 More >>	23.889 (43/180)	2.00E-03
Neural cell adhesion molecule L1 (L1CAM)	PF13882 ; PF00041 ; PF07679 ; PF13927 More >>	22.283 (41/184)	4.00E-03
MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1)	PF13927 ; PF00629	24.390 (50/205)	5.00E-03


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.

KEGG Pathway	Pathway ID	Affiliated Target
Phagosome	hsa04145	Affiliated Target
Class: Cellular Processes => Transport and catabolism	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Neutrophil extracellular trap formation	hsa04613	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Natural killer cell mediated cytotoxicity	hsa04650	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Fc gamma R-mediated phagocytosis	hsa04666	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	9	Degree centrality	9.67E-04	Betweenness centrality	1.58E-04
Closeness centrality	2.03E-01	Radiality	1.35E+01	Clustering coefficient	3.61E-01
Neighborhood connectivity	2.08E+01	Topological coefficient	1.85E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

Bispecific antibodies rise again. Nat Rev Drug Discov. 2014 Nov;13(11):799-801.

REF 2

ClinicalTrials.gov (NCT02321592) GHSG-AFM13 An Open-label, Multicenter Phase II Trial With AFM13 in Patients With Relapsed or Refractory Hodgkin Lymphoma. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04259450) Study to Assess AFM24 in Advanced Solid Cancers. U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT04434469) A Study Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma. U.S. National Institutes of Health.

REF 5

Clinical pipeline report, company report or official report of Affimed Therapeutics.

REF 6

Clinical pipeline report, company report or official report of Genentech.

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