TISIDB

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Single-pass type I membrane protein Secreted. Note=Exists also as a soluble receptor.
Domain	PF13895 Immunoglobulin domain
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002431 Fc receptor mediated stimulatory signaling pathway GO:0002433 immune response-regulating cell surface receptor signaling pathway involved in phagocytosis GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006909 phagocytosis GO:0038093 Fc receptor signaling pathway GO:0038094 Fc-gamma receptor signaling pathway GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
Molecular Function	GO:0019864 IgG binding GO:0019865 immunoglobulin binding
Cellular Component	GO:0009897 external side of plasma membrane GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04145 Phagosome hsa04380 Osteoclast differentiation hsa04650 Natural killer cell mediated cytotoxicity hsa04666 Fc gamma R-mediated phagocytosis
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-2029481: FCGR activation R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell R-HSA-168249: Innate Immune System R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation R-HSA-2029485: Role of phospholipids in phagocytosis

> KEGG and Reactome Pathway

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KEGG

hsa04145 Phagosome
hsa04380 Osteoclast differentiation
hsa04650 Natural killer cell mediated cytotoxicity
hsa04666 Fc gamma R-mediated phagocytosis

Reactome

R-HSA-1280218: Adaptive Immune System
R-HSA-2029481: FCGR activation
R-HSA-2029480: Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-168256: Immune System
R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-168249: Innate Immune System
R-HSA-2029482: Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485: Role of phospholipids in phagocytosis

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between FCGR3A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between FCGR3A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27777574	Colorectal carcinoma	Promote immunity	CRC-NK cells displayed underexpression of CD16, NKG2D, DNAM-1, CD161, NKp46, and NKp30 activating receptors, while inhibitory receptors CD85j and NKG2A were overexpressed. This inhibited phenotype affected cytotoxic functionality against CRC cells and interferon-γ production.
18307255	B cell non-Hodgkin lymphoma; Chronic Lymphocytic Leukemia; Breast Carcinoma	Promote immunity (T and NK cell function); increase the efficacy of immunotherapy	Our results show that CD16(+)V gamma 9 V delta 2 T cells recognize monoclonal antibody coated tumor cells via CD16 and exert ADCC similar to that observed with NK cells, even when target cells are relatively resistant to monoclonal antibodies or V gamma 9 V delta 2 T cells alone.
27496866	Head and Neck Carcinoma	Promote immunity (NK cell function); essential for immunotherapy	Cetuximab, an EGFR-specific antibody (mAb), modestly improves clinical outcome in patients with head and neck cancer (HNC). Cetuximab mediates natural killer (NK) cell:dendritic cell (DC) cross-talk by cross-linking FcγRIIIa, which is important for inducing antitumor cellular immunity. Cetuximab-activated NK cells upregulate the costimulatory receptor CD137 (4-1BB), which, when triggered by agonistic mAb urelumab, might enhance NK-cell functions, to promote T-cell-based immunity.
23690482	Acute Myeloid Leukemia	Promote immunity (NK cell function); essential for immunotherapy	We determined whether a novel bispecific killer cell engager (BiKE) signaling through CD16 and targeting CD33 could activate NK cells at high potency against acute myelogenous leukemia (AML) targets. Combination treatment with CD16 × 33 BiKE and ADAM17 inhibitor resulted in inhibition of CD16 shedding in NK cells, and enhanced NK cell activation.
27742794	Renal Cell Carcinoma	Promote immunity	FCGR Polymorphisms Influence Response to IL2 in Metastatic Renal Cell Carcinoma. Fc-gamma receptors (FCGRs) are expressed on immune cells, bind to antibodies, and trigger antibody-induced cell-mediated antitumor responses when tumor-reactive antibodies are present. The affinity of the FCGR/antibody interaction is variable and dependent upon FCGR polymorphisms. When higher-affinity genotypes for FCGR2A, FCGR3A, and FCGR2C were considered together, they were associated with significantly increased tumor shrinkage and prolonged survival in response to HD-IL2.

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of FCGR3A in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of FCGR3A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.468	0.4
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.637	0.809
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.344	0.86
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.71	0.274
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.166	0.897
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.835	0.335
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.002	0.997
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.214	0.916
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.23	0.918
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.24	0.602
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.271	0.742
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.414	0.0733

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of FCGR3A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	0	2.7	-2.7	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	15.4	0	15.4	0.482
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	22.2	18.8	3.4	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	40	11.1	28.9	0.505
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	28.6	-28.6	0.491
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	10.5	0	10.5	0.135
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FCGR3A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FCGR3A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FCGR3A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FCGR3A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of FCGR3A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between FCGR3A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	FCGR3A
Name	Fc fragment of IgG, low affinity IIIa, receptor (CD16a)
Aliases	CD16a; Fc fragment of IgG, low affinity IIIa, receptor for (CD16); FCGRIII; FCRIIIA; IGFR3; IMD20; CD16a ant ......
Chromosomal Location	1q23
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting FCGR3A collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting FCGR3A.

ID	Name	Drug Type	Targets	#Targets
DB00002	Cetuximab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, EGFR, FCGR1A, FCGR2A, FCGR2B, FCGR2C, ......	12
DB00005	Etanercept	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	14
DB00028	Immune Globulin Human	Biotech	C3, C4A, C4B, C5, FCGR1A, FCGR1B, FCGR2A, FCGR2B, FCGR2C, FCGR3A, ......	11
DB00051	Adalimumab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	12
DB00054	Abciximab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	14
DB00056	Gemtuzumab ozogamicin	Biotech	C1QA, C1QB, C1QC, C1R, C1S, CD33, FCGR1A, FCGR2A, FCGR2B, FCGR2C, ......	12
DB00072	Trastuzumab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, EGFR, ERBB2, FCGR1A, FCGR2A, FCGR2B, F ......	13
DB00073	Rituximab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	12
DB00074	Basiliximab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	13
DB00075	Muromonab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, CD247, CD3D, CD3E, CD3G, FCGR1A, FCGR2 ......	15
DB00078	Ibritumomab tiuxetan	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	12
DB00081	Tositumomab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	11
DB00087	Alemtuzumab	Biotech	C1QA, C1QB, C1QC, C1R, CD52, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3 ......	11
DB00092	Alefacept	Biotech	C1QA, C1QB, C1QC, C1R, CD2, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	11
DB00095	Efalizumab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	11
DB00108	Natalizumab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	12
DB00110	Palivizumab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	10
DB00111	Daclizumab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	12
DB00112	Bevacizumab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	11
DB06607	Catumaxomab	Biotech	CD3E, EPCAM, FCGR1A, FCGR2A, FCGR3A, FCGR3B	6
DB11767	Sarilumab	Biotech	FCGR1A, FCGR2A, FCGR2B, FCGR3A, FCGR3B, IL6R	6
DB12023	Benralizumab	Biotech	FCGR3A, IL5RA	2

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