FCGR2A

Summary

FCGR2A (Fc gamma receptor IIa, HGNC:3616) is a protein-coding gene on chromosome 1q23.3, encoding Low affinity immunoglobulin gamma Fc region receptor II-a (P12318). Binds to the Fc region of immunoglobulins gamma. In precision oncology, FCGR2A H167R confers sensitivity to Trastuzumab in Her2-receptor Positive Breast Cancer (CIViC Level B).

This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2212 — RefSeq curated summary.

At a glance

• GWAS associations: 35
• Clinical variants (ClinVar): 86 total
• Phenotypes (HPO): 56
• Druggable target: yes
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• MANE Select transcript: NM_001136219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3616
Approved symbol	FCGR2A
Name	Fc gamma receptor IIa
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CD32, CD32A, IGFR2, CDw32, Fc-gamma-RIIa, FcgammaRIIa
Ensembl gene	ENSG00000143226
Ensembl biotype	protein_coding
OMIM	146790
Entrez	2212

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 7 protein_coding, 4 protein_coding_CDS_not_defined, 4 retained_intron, 3 nonsense_mediated_decay

ENST00000271450, ENST00000367972, ENST00000459885, ENST00000461298, ENST00000467525, ENST00000467654, ENST00000471026, ENST00000473080, ENST00000482233, ENST00000483665, ENST00000486608, ENST00000491841, ENST00000497474, ENST00000536731, ENST00000699277, ENST00000699278, ENST00000699279, ENST00000967690

RefSeq mRNA: 4 — MANE Select: NM_001136219 NM_001136219, NM_001375296, NM_001375297, NM_021642

CCDS: CCDS30922, CCDS44264, CCDS91088

Canonical transcript exons

ENST00000271450 — 7 exons

Exon	Start	End
ENSE00002379979	161506334	161506591
ENSE00003463328	161510834	161510956
ENSE00003625660	161513895	161513932
ENSE00003626261	161505987	161506007
ENSE00003707183	161509820	161510074
ENSE00003976146	161505457	161505552
ENSE00003976147	161517975	161519829

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 99.34.

FANTOM5 (CAGE): breadth broad, TPM avg 56.9624 / max 8303.7926, expressed in 587 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6255	39.7751	538
6253	11.3157	491
6257	3.0427	258
6254	2.5291	385
6258	0.1955	99
6256	0.0525	23
6259	0.0518	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.34	gold quality
monocyte	CL:0000576	99.10	gold quality
leukocyte	CL:0000738	99.08	gold quality
granulocyte	CL:0000094	98.47	gold quality
placenta	UBERON:0001987	98.33	gold quality
vermiform appendix	UBERON:0001154	97.31	gold quality
right lung	UBERON:0002167	96.72	gold quality
metanephric glomerulus	UBERON:0004736	96.19	silver quality
spleen	UBERON:0002106	96.14	gold quality
upper lobe of left lung	UBERON:0008952	95.92	gold quality
gall bladder	UBERON:0002110	95.40	gold quality
layer of synovial tissue	UBERON:0007616	94.96	gold quality
right coronary artery	UBERON:0001625	94.53	gold quality
descending thoracic aorta	UBERON:0002345	94.18	gold quality
vastus lateralis	UBERON:0001379	94.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.01	gold quality
lung	UBERON:0002048	93.76	gold quality
bone marrow	UBERON:0002371	93.51	gold quality
omental fat pad	UBERON:0010414	93.50	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.42	silver quality
bone marrow cell	CL:0002092	93.36	gold quality
thoracic aorta	UBERON:0001515	92.83	gold quality
smooth muscle tissue	UBERON:0001135	92.74	gold quality
tibial nerve	UBERON:0001323	92.73	gold quality
ascending aorta	UBERON:0001496	92.63	gold quality
trachea	UBERON:0003126	92.45	gold quality
left coronary artery	UBERON:0001626	92.01	gold quality
adipose tissue	UBERON:0001013	91.98	gold quality
rectum	UBERON:0001052	91.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.06	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	2061.99
E-GEOD-135922	yes	1632.66
E-ENAD-20	yes	594.71
E-MTAB-8498	yes	520.48
E-HCAD-1	yes	78.62
E-MTAB-6701	yes	72.04
E-CURD-122	yes	66.64
E-MTAB-8142	yes	53.05
E-MTAB-8410	yes	50.12
E-HCAD-10	yes	47.02
E-GEOD-84465	yes	43.42
E-MTAB-10553	yes	33.42
E-GEOD-134144	yes	30.80
E-CURD-88	yes	22.93
E-CURD-112	yes	15.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, NFATC1

miRNA regulators (miRDB)

69 targeting FCGR2A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 40)

• REVIEW: In FcgRIIA humanized transgenic mice there is an important interplay of platelet activation and splenic clearance. Reduction of splenic clearance or antibody activation of platelets in an FcgRIIA-dependent manner leads to thrombosis, shock, death. (PMID:11913983)
• Early events that follow Fc gamma RIIA cross-linking include translocation to a detergent-insoluble fraction rapidly followed by degradation of the receptor–events which occur in parallel to those leading to signal transduction though Fc gamma RIIA. (PMID:11937562)
• implicated as a possible disease modifying gene in rheumatoid arthritis (PMID:12064825)
• Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis (PMID:12115187)
• Polymorphism of this receptor correlates with renal allograft survival. (PMID:12493400)
• The results suggest that Fc gamma RIIa polymorphism is not a risk factor for rheumatoid arthritis. (PMID:12508778)
• regulation of FcgammaR-mediated activation of human myeloid cells by the expression and function of the inositol phosphatase SHIP-2 (PMID:12690104)
• SHP-1 associates with this protein to modulate signaling events in myeloid cells. (PMID:12832410)
• putative susceptibility and severity factor [for periodontitis] (PMID:12834496)
• The FcgammaRIIA-R/H131 polymorphism is an important determinant of predisposition to antiphospholipid syndrome, with different influences on SLE and APS susceptibility per se. (PMID:12847687)
• FcgammaRIIa cross-linking causes irreversible aggregation of human platelets (PMID:12857726)
• Polymorphism of the Fc gamma IIa receptor influences neither susceptibility nor clinical disease course of multiple sclerosis. (PMID:12864991)
• PECAM-1 and Fc gamma RIIa are colocalized on the platelet membrane and PECAM-1 down-regulates Fc gamma RIIa-mediated platelet responses. (PMID:12893767)
• Fc gamma RIIa on natural IFN-alpha-producing cells/plasmacytoid dendritic cells is involved in the activation of IFN-alpha production by interferogenic immune complexes, but it may also mediate inhibitory signals. (PMID:12960360)
• A skewed distribution of Fc gamma RIIA genotypes is reported in Dutch myasthenia gravis patients. (PMID:14597109)
• Fc gamma RIIA-mediated binding of murine IgG1 immune complexes to apoptotic human neutrophils profoundly augments phagocytosis by human macrophages but leads to proinflammatory cytokine production. (PMID:14734773)
• An abnormal distribution of the FcgRIIa allotypes may contribute to the pathogenesis of renal disease in Brazilian systemic lupus erythematosus patients. (PMID:15004265)
• conclude that the G507A polymorphism does not contribute to risk of myocardial infarction, either alone of in combination with established cardiovascular risk factors (PMID:15140146)
• H/H131 genotype may be associated with chronic periodontitis risk (and disease severity) in Caucasian smokers (PMID:15152814)
• evaluated the association between Fc gamma RIIa polymorphism and acute kidney graft rejection (PMID:15171001)
• fusion of cross-linked FcgammaRII and rafts requires generation of cell surface ceramide (PMID:15194692)
• study suggests that the IgG2-binding Fc gamma RIIa-His/His131 genotype is associated with enhanced susceptibility to placental malaria in HIV-positive women but not in HIV-negative women (PMID:15319871)
• a sustained rise in [Ca 2+ ]i due to an increase in the frequency and amplitude of transient calcium spiking in single platelets was dependent upon engagement of both P-selectin and FcgammaRIIA (PMID:15351857)
• Variations in Fcgamma receptor IIA is associated with susceptibility to Pseudomonas aeruginosa infection in patients with cystic fibrosis (PMID:15367919)
• FcgammaRIIA gene polymorphisms is associated with rheumatic fever (PMID:15369725)
• Polymorphism could be useful markers for potential risk of rejection in kidney transplantation. (PMID:15371685)
• the H131 allele of FcgammaRIIa protects against advanced peripheral atherosclerosis (PMID:15583733)
• There was no correlation between the presence of anti-Fc gammaRIIa or anti-GPIb alpha autoantibodies and the Fc gammaRIIa-R/H131 polymorphism, nor the incidence of thromboembolism, nor HLA class II alleles. (PMID:15735807)
• analysis of C-reactive protein binding to FcgammaRI, FcgammaRIIa, and C1q (PMID:15878871)
• decreased FcR expression could potentially represent a form of compensatory biological response to an adverse lipid profile in which sensitivity of platelets to collagen may be relatively down regulated in type 2 diabetes. (PMID:16005880)
• These results indicate that FcgammaRIIA can be activated in human platelets downstream [of]G-protein-coupled receptors by low concentrations of agonists. (PMID:16169188)
• Phosphorylation of FcgammaRIIA is required for efficient binding of IgG-opsonized particles to receptors; inhibition of FcgammaRIIA phosphorylation correlates with impairment of FcgammaRIIA clustering. (PMID:16177087)
• FcgammaRIIa is a very important factor in the pathogenesis of autoimmune inflammation (PMID:16200626)
• Polymorphisms of FcgammaRIIa influence the severity of IgAN in Japanese patients but not the incidence, suggesting that IgG-IC may play important roles in the progression and prognosis of this disease via FcgammaRs. (PMID:16221721)
• The Patelet FcgammaRIIA is stably overexpressed in type 2 diabetes and may also play a role in collagen-mediated platelet activation. (PMID:16421008)
• FcgammaRIIa gene polymorphism is associated with recurrent infectious diseases in children (PMID:16550341)
• 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)
• FCGR2A from rheumatoid arthritis sera and synovial fluid influence tnf-alphaproduction by peripheral blood mononuclear cells. (PMID:16569263)
• CREB activation is involved in up-regulation of Fc gammaRIIA expression in myeloid lineages. (PMID:16709925)
• Organized association of FcgammaRIIa monomers is essential for optimal receptor signaling. (PMID:16751395)

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): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), 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-a — P12318 (reviewed: P12318)

Alternative names: CDw32, Fc-gamma RII-a

All UniProt accessions (8): P12318, A0A8V8TN00, A0A8V8TN30, A0A8V8TPS4, F5GX41, F5GXY9, V9GY55, V9GY83

UniProt curated annotations — full annotation on UniProt →

Function. Binds to the Fc region of immunoglobulins gamma. Low affinity receptor. By binding to IgG it initiates cellular responses against pathogens and soluble antigens. Promotes phagocytosis of opsonized antigens.

Subunit / interactions. Binds the Fc region of antigen-complexed IgG1, IgG2, IgG3 and IgG4 isotypes. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2, regulating its function. Interacts with APCS and FGR. Interacts with HCK.

Subcellular location. Cell membrane.

Tissue specificity. Found on monocytes, neutrophils and eosinophil platelets.

Post-translational modifications. Phosphorylated by SRC-type Tyr-kinases such as LYN, BLK, FYN, HCK and SYK.

Isoforms (2)

UniProt ID	Names	Canonical?
P12318-1	1	yes
P12318-2	2

RefSeq proteins (4): NP_001129691, NP_001362225, NP_001362226, NP_067674 (=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 (42 total): strand 19, sequence variant 4, helix 3, glycosylation site 2, disulfide bond 2, topological domain 2, domain 2, modified residue 2, signal peptide 1, chain 1, splice variant 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
3RY4	X-RAY DIFFRACTION	1.5
8CHA	X-RAY DIFFRACTION	1.81
1FCG	X-RAY DIFFRACTION	2
9N5P	X-RAY DIFFRACTION	2.01
3RY5	X-RAY DIFFRACTION	2.3
9MCX	X-RAY DIFFRACTION	2.38
3D5O	X-RAY DIFFRACTION	2.8
1H9V	X-RAY DIFFRACTION	3
3RY6	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12318-F1	77.04	0.54

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 (2): 288, 304

Disulfide bonds (2): 62–104, 143–187

Glycosylation sites (2): 97, 178

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2029481	FCGR activation
R-HSA-2029482	Regulation of actin dynamics for phagocytic cup formation
R-HSA-2029485	Role of phospholipids in phagocytosis
R-HSA-6798695	Neutrophil degranulation
R-HSA-9664323	FCGR3A-mediated IL10 synthesis

MSigDB gene sets: 473 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, MCLACHLAN_DENTAL_CARIES_UP, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, SWEET_KRAS_ONCOGENIC_SIGNATURE, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, MODULE_45, MODULE_64, GOCC_CELL_SURFACE, MODULE_128, MODULE_478, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (6): antibody-dependent cellular cytotoxicity (GO:0001788), cell surface receptor signaling pathway (GO:0007166), positive regulation of tumor necrosis factor production (GO:0032760), positive regulation of phagocytosis (GO:0050766), immune system process (GO:0002376), Fc-gamma receptor signaling pathway (GO:0038094)

GO Molecular Function (3): IgG receptor activity (GO:0019770), IgG binding (GO:0019864), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	3
Innate Immune System	1
Anti-inflammatory response favouring Leishmania parasite infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
type IIa hypersensitivity	1
leukocyte mediated cytotoxicity	1
signal transduction	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
phagocytosis	1
positive regulation of endocytosis	1
regulation of phagocytosis	1
biological_process	1
Fc receptor signaling pathway	1
immunoglobulin receptor activity	1
IgG binding	1
Fc-gamma receptor signaling pathway	1
immunoglobulin binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
secretory granule	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2524 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCGR2A	CRP	P02741	990
FCGR2A	PF4	P02776	891
FCGR2A	IGF2	P01344	886
FCGR2A	SYK	P43405	883
FCGR2A	FCGRT	P55899	857
FCGR2A	ITGAM	P11215	848
FCGR2A	FCGR1A	P12314	846
FCGR2A	FCER1G	P30273	840
FCGR2A	FCAR	P24071	833
FCGR2A	PTPRC	P08575	831
FCGR2A	FCGR3A	P08637	814
FCGR2A	CD4	P01730	813
FCGR2A	ITGAX	P20702	801
FCGR2A	CD8A	P01732	770
FCGR2A	GP6	Q9HCN6	765

IntAct

23 interactions, top by confidence:

A	B	Type	Score
FCGR2A	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	FCGR2A	psi-mi:“MI:0915”(physical association)	0.560
FCGR2A	CRP	psi-mi:“MI:0915”(physical association)	0.400
	FCGR2A	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	BTNL8	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	CD72	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	ILDR1	psi-mi:“MI:0915”(physical association)	0.400
MOG	FCGR2A	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	MPZ	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	LCN2	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	PDGFRB	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	SEMA3G	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	TARM1	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	TIGIT	psi-mi:“MI:0915”(physical association)	0.400
FCGR2A	STAMBP	psi-mi:“MI:0914”(association)	0.350
FCGR2B	FCGR2A	psi-mi:“MI:0914”(association)	0.350
SYK	FCGR2A	psi-mi:“MI:0914”(association)	0.350

BioGRID (71): UBQLN1 (Two-hybrid), FCGR2A (Affinity Capture-MS), FCGR2C (Affinity Capture-MS), EEA1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PROSC (Affinity Capture-MS), FAHD2A (Affinity Capture-MS), PPP3R1 (Affinity Capture-MS), APEX1 (Affinity Capture-MS), UBE2D2 (Affinity Capture-MS), PRTFDC1 (Affinity Capture-MS), ARPIN (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), ADPRHL2 (Affinity Capture-MS), PTPN11 (Affinity Capture-MS)

ESM2 similar proteins: A0A0B4J1G0, A0A0G2KBC9, A3RFZ7, B6A8R8, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12314, P12318, P12319, P12371, P13597, P13598, P20489, P26151, P27645, P31995, P35330, P50283, P51866, P79107, P82957, Q00238, Q08481, Q09TM2, Q09TM4, Q14952, Q28942, Q3B8P2, Q3SWT0, Q5NKV1, Q5NKV2, Q60513

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

7 interactions.

A	Effect	B	Mechanism
SYK	“up-regulates activity”	FCGR2A	phosphorylation
BLK	“up-regulates activity”	FCGR2A	phosphorylation
FYN	“up-regulates activity”	FCGR2A	phosphorylation
LYN	“up-regulates activity”	FCGR2A	phosphorylation

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

1342 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161509818:A:AG	acceptor_gain	1.0000
1:161509818:AGAAT:A	acceptor_gain	1.0000
1:161509819:G:GG	acceptor_gain	1.0000
1:161509819:GA:G	acceptor_gain	1.0000
1:161509819:GAA:G	acceptor_gain	1.0000
1:161509819:GAAT:G	acceptor_gain	1.0000
1:161509819:GAATG:G	acceptor_gain	1.0000
1:161510071:CAAGG:C	donor_loss	1.0000
1:161510072:AAGG:A	donor_loss	1.0000
1:161510074:GGTAT:G	donor_loss	1.0000
1:161510076:T:G	donor_loss	1.0000
1:161510832:A:AG	acceptor_gain	1.0000
1:161510833:G:GA	acceptor_gain	1.0000
1:161510833:GT:G	acceptor_gain	1.0000
1:161510952:TTCAG:T	donor_loss	1.0000
1:161510953:TCAGG:T	donor_loss	1.0000
1:161510954:CAGG:C	donor_loss	1.0000
1:161510955:AGGTT:A	donor_loss	1.0000
1:161510956:GGT:G	donor_loss	1.0000
1:161510957:GTTT:G	donor_loss	1.0000
1:161510958:T:A	donor_loss	1.0000
1:161513891:ACAG:A	acceptor_loss	1.0000
1:161513892:CA:C	acceptor_loss	1.0000
1:161513893:A:AG	acceptor_gain	1.0000
1:161513893:AG:A	acceptor_loss	1.0000
1:161513894:G:GA	acceptor_gain	1.0000
1:161513894:GCC:G	acceptor_gain	1.0000
1:161513894:GCCA:G	acceptor_gain	1.0000
1:161513930:GAG:G	donor_gain	1.0000
1:161513931:AGG:A	donor_loss	1.0000

AlphaMissense

2102 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161509882:T:A	C143S	0.994
1:161509883:G:C	C143S	0.994
1:161510014:T:A	C187S	0.992
1:161510015:G:C	C187S	0.992
1:161506532:A:G	Y102C	0.991
1:161509893:G:C	W146C	0.990
1:161509893:G:T	W146C	0.990
1:161509882:T:C	C143R	0.988
1:161506532:A:C	Y102S	0.987
1:161506452:G:C	W75C	0.986
1:161506452:G:T	W75C	0.986
1:161506537:T:A	C104S	0.984
1:161506538:G:C	C104S	0.984
1:161506531:T:G	Y102D	0.983
1:161506450:T:A	W75R	0.982
1:161506450:T:C	W75R	0.982
1:161509824:G:C	W123C	0.981
1:161509824:G:T	W123C	0.981
1:161510016:C:G	C187W	0.981
1:161506411:T:A	C62S	0.980
1:161506412:G:C	C62S	0.980
1:161509883:G:A	C143Y	0.980
1:161509884:C:G	C143W	0.980
1:161506561:A:C	S112R	0.978
1:161506563:C:A	S112R	0.978
1:161506563:C:G	S112R	0.978
1:161510015:G:A	C187Y	0.977
1:161510008:T:G	Y185D	0.976
1:161510009:A:G	Y185C	0.976
1:161506539:C:G	C104W	0.975

dbSNP variants (sampled 300 via entrez): RS1000016627 (1:161508554 T>C), RS1000398158 (1:161516398 A>G), RS1000443142 (1:161504369 T>A), RS1000666994 (1:161503751 G>T), RS1000837579 (1:161523429 T>G), RS1001343776 (1:161506554 C>A,T), RS1001959048 (1:161518675 A>C), RS1002059418 (1:161509603 C>G), RS1002108704 (1:161523889 C>A,T), RS1002299155 (1:161511052 A>G), RS1002430010 (1:161509348 T>C), RS1002524660 (1:161513235 G>A), RS1002746645 (1:161521312 A>G), RS1003094547 (1:161507649 G>A,T), RS1003696192 (1:161507544 T>G)

Disease associations

OMIM: gene MIM:146790 | disease phenotypes: MIM:152700, MIM:601744, MIM:219700, MIM:611162

GenCC curated gene-disease

Mondo (3): systemic lupus erythematosus (MONDO:0007915), cystic fibrosis (MONDO:0009061), malaria, susceptibility to (MONDO:0021024)

Orphanet (3): Systemic lupus erythematosus (Orphanet:536), Cystic fibrosis (Orphanet:586), Malaria (Orphanet:673)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000123	Nephritis
HP:0000155	Oral ulcer
HP:0000709	Psychosis
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001394	Cirrhosis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001596	Alopecia
HP:0001648	Cor pulmonale
HP:0001701	Pericarditis
HP:0001733	Pancreatitis
HP:0001738	Exocrine pancreatic insufficiency
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001944	Dehydration
HP:0002014	Diarrhea
HP:0002035	Rectal prolapse
HP:0002099	Asthma
HP:0002102	Pleuritis
HP:0002105	Hemoptysis
HP:0002110	Bronchiectasis
HP:0002150	Hypercalciuria
HP:0002240	Hepatomegaly
HP:0002570	Steatorrhea
HP:0002595	Ileus

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST000529_1	Ulcerative colitis	2.000000e-12
GCST000624_7	Ulcerative colitis	3.000000e-09
GCST000964_2	Ulcerative colitis	2.000000e-20
GCST001322_1	Kawasaki disease	7.000000e-11
GCST001392_16	Lipid metabolism phenotypes	1.000000e-10
GCST001725_37	Inflammatory bowel disease	2.000000e-38
GCST002014_2	Helicobacter pylori serologic status	2.000000e-08
GCST002188_2	Functional impairment in major depressive disorder, bipolar disorder and schizophrenia	3.000000e-06
GCST002318_108	Rheumatoid arthritis	5.000000e-07
GCST002318_176	Rheumatoid arthritis	1.000000e-07
GCST002463_7	Systemic lupus erythematosus	9.000000e-06
GCST003155_37	Systemic lupus erythematosus	1.000000e-12
GCST003156_25	Systemic lupus erythematosus	1.000000e-12
GCST003599_12	Systemic lupus erythematosus	7.000000e-06
GCST003622_25	Systemic lupus erythematosus	6.000000e-11
GCST004131_77	Inflammatory bowel disease	9.000000e-14
GCST004133_13	Ulcerative colitis	2.000000e-18
GCST004604_16	Hematocrit	3.000000e-09
GCST004859_1	Kawasaki disease	1.000000e-07
GCST005529_45	Ankylosing spondylitis	1.000000e-09
GCST005529_52	Ankylosing spondylitis	1.000000e-09
GCST005537_142	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-32
GCST005537_143	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-09
GCST005752_115	Systemic lupus erythematosus	2.000000e-14
GCST006048_41	Rheumatoid arthritis (ACPA-positive)	3.000000e-07
GCST006585_495	Blood protein levels	0.000000e+00
GCST006863_3	Takayasu arteritis	6.000000e-12
GCST006959_177	Rheumatoid arthritis	2.000000e-06
GCST006959_81	Rheumatoid arthritis	1.000000e-06
GCST007400_52	Systemic lupus erythematosus	1.000000e-09

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004529	lipid measurement
EFO:0005412	functional impairment measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003550	Cystic Fibrosis	C06.689.202; C08.381.187; C16.320.190; C16.614.213
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5841 (SINGLE PROTEIN)

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
FCGR2A H167R	Trastuzumab	Her2-receptor Positive Breast Cancer	Sensitivity/Response	CIViC B	EID1088

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

PharmGKB clinical annotations

5 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1801274	Efficacy	3	adalimumab;infliximab	Rheumatoid arthritis
rs1801274	Efficacy	3	cetuximab	Colorectal Neoplasms;Head and Neck Neoplasms
rs1801274	Efficacy	3	rituximab	Rheumatoid arthritis
rs1801274	Efficacy	3	trastuzumab	Breast Neoplasms
rs1801274	Efficacy	4	adalimumab;etanercept;infliximab	Psoriasis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1801274	FCGR2A	3	6.75	5	cetuximab;rituximab;adalimumab;infliximab;adalimumab;etanercept;infliximab;trastuzumab

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Immunoglobulin like domain containing proteins

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression, increases expression	3
Silicon Dioxide	decreases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
thallium sulfate	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	affects cotreatment, increases expression, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Allergens	affects cotreatment, decreases expression	1
Vehicle Emissions	affects cotreatment, decreases expression	1
Biological Factors	increases expression	1
Cadmium	decreases expression, increases abundance	1
Calcitriol	decreases expression	1
Cannabinoids	affects methylation, increases abundance	1
Cisplatin	increases expression	1
Coal	increases abundance, increases expression	1
Cytarabine	increases expression	1
Heparin	affects binding	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Methotrexate	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Antirheumatic Agents	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1039868	Binding	Inhibition of heat aggregated human IgG binding to human Fc-gamma-R2a	2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases. — J Med Chem

Cellosaurus cell lines

10 cell lines: 5 cancer cell line, 5 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1E19	TZM-bl/FcgammaRIIa	Cancer cell line	Female
CVCL_A7ZU	Jurkat-Lucia NFAT-CD32	Cancer cell line	Male
CVCL_B8FW	Abcam HCT 116 FCGR2A KO	Cancer cell line	Male
CVCL_B8VQ	Abcam MCF-7 FCGR2A KO	Cancer cell line	Female
CVCL_B9I3	Abcam A-549 FCGR2A KO	Cancer cell line	Male
CVCL_DE93	CHO-K1.Cl-0204	Spontaneously immortalized cell line	Female
CVCL_DE94	CHO-K1.Cl-0205	Spontaneously immortalized cell line	Female
CVCL_E6QD	Genomeditech CHO-K1 H_FCGR2A(CD32A)	Spontaneously immortalized cell line	Female
CVCL_KA27	CHO-K1/CD32A 131His	Spontaneously immortalized cell line	Female
CVCL_KA28	CHO-K1/CD32A 131Arg	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