FCGR3B

Summary

FCGR3B (Fc gamma receptor IIIb, HGNC:3620) is a protein-coding gene on chromosome 1q23.3, encoding Low affinity immunoglobulin gamma Fc region receptor III-B (O75015). Receptor for the Fc region of immunoglobulins gamma.

The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1.

Source: NCBI Gene 2215 — RefSeq curated summary.

At a glance

• Gene–disease (curated): systemic lupus erythematosus (Supportive, GenCC)
• GWAS associations: 16
• Clinical variants (ClinVar): 56 total
• Phenotypes (HPO): 54
• Druggable target: yes
• MANE Select transcript: NM_001244753

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3620
Approved symbol	FCGR3B
Name	Fc gamma receptor IIIb
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HNA-1, CD16, CD16b, FcgammaRIIIb, FcRIIIb
Ensembl gene	ENSG00000162747
Ensembl biotype	protein_coding
OMIM	610665
Entrez	2215

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000367964, ENST00000421702, ENST00000533780, ENST00000534776, ENST00000650385, ENST00000699523, ENST00000908291, ENST00000908292, ENST00000908293

RefSeq mRNA: 7 — MANE Select: NM_001244753 NM_000570, NM_001244753, NM_001271035, NM_001271036, NM_001271037, NM_001421934, NM_001421936

CCDS: CCDS41433, CCDS91090

Canonical transcript exons

ENST00000650385 — 5 exons

Exon	Start	End
ENSE00001446007	161623196	161624639
ENSE00001446008	161631055	161631176
ENSE00002379007	161626145	161626402
ENSE00002412392	161629778	161630035
ENSE00003687594	161630368	161630388

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 99.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.5207 / max 2081.7511, expressed in 104 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15651	3.9853	76
15652	0.4148	29
15650	0.1206	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.58	gold quality
periodontal ligament	UBERON:0008266	98.81	gold quality
trabecular bone tissue	UBERON:0002483	98.66	gold quality
granulocyte	CL:0000094	98.10	gold quality
spleen	UBERON:0002106	93.35	gold quality
bone marrow	UBERON:0002371	92.95	gold quality
palpebral conjunctiva	UBERON:0001812	92.55	gold quality
bone marrow cell	CL:0002092	89.39	gold quality
germinal epithelium of ovary	UBERON:0001304	89.34	gold quality
right lung	UBERON:0002167	87.81	gold quality
decidua	UBERON:0002450	87.33	gold quality
vermiform appendix	UBERON:0001154	86.92	gold quality
leukocyte	CL:0000738	86.85	gold quality
mononuclear cell	CL:0000842	85.69	gold quality
monocyte	CL:0000576	85.43	gold quality
superficial temporal artery	UBERON:0001614	84.80	gold quality
gall bladder	UBERON:0002110	83.69	gold quality
caecum	UBERON:0001153	81.59	gold quality
upper lobe of left lung	UBERON:0008952	81.12	gold quality
upper lobe of lung	UBERON:0008948	80.49	gold quality
lung	UBERON:0002048	80.43	gold quality
epithelial cell of pancreas	CL:0000083	79.87	silver quality
nasal cavity epithelium	UBERON:0005384	79.58	silver quality
layer of synovial tissue	UBERON:0007616	78.63	silver quality
parietal pleura	UBERON:0002400	78.56	gold quality
pleura	UBERON:0000977	78.07	gold quality
placenta	UBERON:0001987	77.28	gold quality
mucosa of urinary bladder	UBERON:0001259	77.22	gold quality
biceps brachii	UBERON:0001507	77.01	silver quality
choroid plexus epithelium	UBERON:0003911	76.75	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-150728	yes	5249.56
E-MTAB-9801	yes	4335.98
E-MTAB-9221	yes	3243.11
E-ANND-3	yes	11.85
E-MTAB-6678	yes	9.68

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA4, YY1, ZNF140, ZNF91

miRNA regulators (miRDB)

58 targeting FCGR3B, 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-6758-5P	100.00	66.21	1470
HSA-MIR-4682	100.00	68.89	1258
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-6856-5P	100.00	65.47	1298
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-199A-3P	99.75	70.48	929
HSA-MIR-199B-3P	99.75	70.48	929
HSA-MIR-3129-5P	99.75	70.46	914
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-520A-5P	99.35	66.72	1632

Literature-anchored findings (GeneRIF, showing 40)

• expression of FcgammaRIIIB on human peripheral blood eosinophils increases in allergic conditions (PMID:11897993)
• Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes. (PMID:12115243)
• expression of mRNA specific for the FcgammaRIIIA and FcgammaRIIIB subclasses are upregulated by interferon-gamma on human keratinocytes (PMID:12445195)
• Fcgamma receptor IIIb polymorphisms are associated with susceptibility to systemic lupus erythematosus in Thais (PMID:12753656)
• Polymorphism of the Fc gamma IIIb receptor influences neither susceptibility nor clinical disease course of multiple sclerosis. (PMID:12864991)
• it is concluded that the FCGR3B*1(Fc fragment of IgG, low affinity IIIb receptor for CD16) gene is the more frequent variant in a Chinese population from Zhejiang Province (PMID:12898191)
• Homotypic cross-linking of neutrophil Fc gamma RIIIb results in significant release of alpha-defensins capable of recruiting mononuclear, dendritic, and T cells to antineutrophil cytoplasmic antibody (ANCA)-induced granuloma. (PMID:14634123)
• The FCGR3B receptor is constituted by a unique FCGR3B polypeptide chain. (PMID:15245367)
• FcgammaRIIIB gene polymorphisms is associated with rheumatic fever (PMID:15369725)
• Variation in the FcgammaR3B gene is associated with distinct Brazilian populations (PMID:15713217)
• Results suggest that Fc gammaRIII genotypes may represent mild disease-modifying factors in GBS. (PMID:15833371)
• We found a total deficiency of FcgammaRIIIb on neutrophils, which could partially explain the unusually severe clinical presentation of meningococcal septic shock (PMID:15889368)
• Although FcgammaRIIIB polymorphism was not associated with the development of SLE in Korean, thrombocytopenia was associated with FcgammaRIIIB NA2/NA2 genotype, and NA2 allele. (PMID:15934433)
• results may suggest an association between smoking and periodontal disease progression in elderly people with NA2 polymorphism (PMID:15974849)
• High-density detergent-resistant membranes play a role in CD16b signalling in human neutrophils. (PMID:16171455)
• Increased association with an FCGR3A-FCGR3B haplotype suggests that other polymorphic variants or in linkage disequilibrium may also contribute to rheumatoid arthritis pathogenesis. (PMID:16356189)
• The expression of CD16 predicts the functional capacity of NK cells infiltrating renal cell carcinoma and can be used to characterize subgroups of renal cell carcinoma. (PMID:16467081)
• In humans, low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated with glomerulonephritis in the autoimmune disease systemic lupus erythematosus. (PMID:16482158)
• FcgammaRIIIb acts as a membrane adaptor for PR3 (PMID:16598772)
• FCGR3B deficiency is associated with systemic lupus erythematosus, microscopic polyangiitis and Wegener’s granulomatosis (PMID:17529978)
• FcgammaRIIIb NA1/NA2 heterozygote genotype frequency was increased in end stage renal disease (ESRD) patients in Chinese; present findings showed that FcgammaRIIIb genotype is related to ESRD susceptibility (PMID:17584599)
• The FCGR2A 131RR and FCGR3A 158VV genotypes were over-represented [OR: 1.67 (1.05-2.63) and 2.04 (1.06-4.00), respectively] whereas the FCGR3B NA2NA2 was under-represented in patients with cryptococcosis (28% vs. 40% in controls). (PMID:17710620)
• Fcgr3b genotype influences the disease susceptibility and severity of IgA nephropathy in Chinese. (PMID:17847104)
• Promoter polymorphisms of FCGR2A, FCGR3A and FCGR3B were not convincingly associated with infections after chemotherapy and stem cell transplantation in multiple myeloma. (PMID:18452102)
• Copy number of FCGR3B, which is associated with systemic lupus erythematosus, correlates with protein expression and immune complex uptake (PMID:18559452)
• the genotype frequencies and allelic distributions of the Fcgamma R (receptor)IIa, FcgammaRIIIa and FcgammaRIIIb gene polymorphisms were significantly different between BD patients and healthy controls and associated with disease severity, age of onset (PMID:19026120)
• Our results challenge the two dogmas 1) that basophils do not express FcgammaRIII and 2) that FcgammaRIIIB is exclusively expressed by neutrophils. (PMID:19201911)
• the nonfucosylated anti-CD20 effectively enhanced neutrophil phagocytosis solely by enhancing binding for the phagocytosis coreceptor FcgammaRIIIb (PMID:19218011)
• Only FCGR3A, FCGR2C and FCGR3B show copy number variation, in contrast to FCGR2A and FCGR2B. (PMID:19309690)
• FCGR3B gene variants are differentially transcribed between cell types and tissues, increasing the likelihood of the presence of variant FcgammaRIII receptors on the cell surface. (PMID:19317341)
• Evidence for gene recombination in FCGR3 gene variants. (PMID:19320901)
• FcgammaRIIIB, but not FcgammaRIIA, activates a unique signaling pathway leading to the nuclear-restricted phosphorylation of ERK and Elk-1, independently of Syk, PI3K, or MEK (PMID:19342628)
• carriage of allele H131 of the FcgammaRIIa gene and a combination of this allele with allele NA2 of the FcgammaRIIIb gene might influence the patient’s response to endodontic treatment of teeth with apical periodontitis (PMID:19720214)
• Association of gene dosage variation in the FCGR3B gene with risk of autoimmune diseases is reported. (PMID:19741716)
• The data suggest that FCGR3B CNV was not associated with lupus nephritis development or progression in this Chinese population (PMID:19946035)
• Results of the present study suggest that subjects carrying at least one copy of the FcgammaRIIIb-NA2 allele might be associated with susceptibility to aggressive periodontitis. (PMID:20041976)
• The Fcggamma RIIIB NA1/NA2 polymorphism was associated with both aggressive and chronic periodontitis (review). (PMID:20149216)
• Our results suggest that FcgammaRIIIb might not be a susceptibility gene for SLE and lupus nephritis. (PMID:20300756)
• FcgammaRIIIB could mediate phagocytosis in human neutrophils but much less efficiently than FcgammaRIIA (PMID:20356573)
• differences in monocyte CD14CD16 expansion represent an important tool for exploring the role of selective inflammatory pathways in heart failure progression (PMID:20364047)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fcgr4	ENSMUSG00000059089
rattus_norvegicus	Fcgr3a	ENSRNOG00000024382

Paralogs (17): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), FCRL3 (ENSG00000160856), FCRLB (ENSG00000162746), 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 III-B — O75015 (reviewed: O75015)

Alternative names: Fc-gamma RIII-beta, FcR-10, IgG Fc receptor III-1

All UniProt accessions (4): A0A3B3ISU3, E9PNY5, O75015, H0Y4U3

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the Fc region of immunoglobulins gamma. Low affinity receptor. Binds complexed or aggregated IgG and also monomeric IgG. Contrary to III-A, is not capable to mediate antibody-dependent cytotoxicity and phagocytosis. May serve as a trap for immune complexes in the peripheral circulation which does not activate neutrophils.

Subunit / interactions. Monomer. Interacts with INPP5D/SHIP1. Interacts with the Fc region of IgGs with a preference for IgG1 and IgG3 isotypes.

Subcellular location. Cell membrane. Secreted.

Tissue specificity. Expressed specifically by polymorphonuclear leukocytes (neutrophils). Also expressed by stimulated eosinophils.

Post-translational modifications. Glycosylated. Glycosylation plays an inhibitory role in the interaction with IgG3. The soluble form is produced by a proteolytic cleavage.

Polymorphism. There are three allelic forms of FCGR3B: FCGR3B01 (HNA-1a, NA-1), FCGR3B02 (HNA-1b, NA-2) and FCGR3B03 (HNA-1c, SH). FCGR3B01 and FCGR3B02 are detectable with antibodies against the biallelic neutrophil-specific antigen system NA. The more active FCGR3B01 allele has been associated with severe renal disease in certain forms of systemic vasculitides.

Miscellaneous. Encoded by one of two nearly identical genes: FCGR3A and FCGR3B (Shown here) which are expressed in a tissue-specific manner. The ‘Phe-203’ in FCGR3A determines the transmembrane domains whereas the Ser-203 in FCGR3B determines the GPI-anchoring.

RefSeq proteins (7): NP_000561, NP_001231682, NP_001257964, NP_001257965, NP_001257966, NP_001408863, NP_001408865 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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 (43 total): strand 19, glycosylation site 6, sequence variant 5, helix 3, disulfide bond 2, mutagenesis site 2, domain 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
1FNL	X-RAY DIFFRACTION	1.8
6EAQ	X-RAY DIFFRACTION	2.22
1E4J	X-RAY DIFFRACTION	2.5
1T83	X-RAY DIFFRACTION	3
1E4K	X-RAY DIFFRACTION	3.2
1T89	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75015-F1	89.04	0.73

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): 200

Disulfide bonds (2): 47–89, 128–172

Glycosylation sites (6): 180, 187, 56, 63, 82, 92

Mutagenesis-validated functional residues (2):

Position	Phenotype
203	abolishes membrane anchoring via glycosylphosphatidylinositol.
203	has no effect on membrane anchoring via glycosylphosphatidylinositol.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 249 (showing top): FERRANDO_TAL1_NEIGHBORS, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, MODULE_45, GOCC_CELL_SURFACE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_B_CELL_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_LYMPHOCYTE_MEDIATED_IMMUNITY, GOBP_FC_RECEPTOR_SIGNALING_PATHWAY, ZIC1_01

GO Biological Process (4): antibody-dependent cellular cytotoxicity (GO:0001788), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), Fc-gamma receptor signaling pathway (GO:0038094)

GO Molecular Function (3): IgG receptor activity (GO:0019770), IgG binding (GO:0019864), GPI anchor binding (GO:0034235)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), secretory granule membrane (GO:0030667), extracellular exosome (GO:0070062), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
type IIa hypersensitivity	1
leukocyte mediated cytotoxicity	1
immune system process	1
response to stimulus	1
signal transduction	1
Fc receptor signaling pathway	1
immunoglobulin receptor activity	1
IgG binding	1
Fc-gamma receptor signaling pathway	1
immunoglobulin binding	1
phospholipid binding	1
glycolipid binding	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
extracellular vesicle	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

3296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCGR3B	CD19	P15391	998
FCGR3B	FCER1G	P30273	996
FCGR3B	CD247	P20963	994
FCGR3B	NCAM1	P13591	990
FCGR3B	TNFRSF8	P28908	986
FCGR3B	CD33	P20138	959
FCGR3B	NCR1	O76036	955
FCGR3B	ITGAM	P11215	947
FCGR3B	CD8A	P01732	941
FCGR3B	CD4	P01730	940
FCGR3B	ANPEP	P15144	930
FCGR3B	IFNG	P01579	924
FCGR3B	TYROBP	O43914	922
FCGR3B	CD7	P09564	920
FCGR3B	KLRK1	P26718	919

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FCGR3B	IL6	psi-mi:“MI:0915”(physical association)	0.400
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
FCGR3B	NRP2	psi-mi:“MI:0914”(association)	0.350
FCGR3B	CLGN	psi-mi:“MI:0914”(association)	0.350
FCGR3B	FCGR3A	psi-mi:“MI:0914”(association)	0.350
spoVR	FCGR3B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (64): GK (Affinity Capture-MS), NRP2 (Affinity Capture-MS), NR2F2 (Affinity Capture-MS), COX16 (Affinity Capture-MS), ATP12A (Affinity Capture-MS), CD109 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), OAF (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), WDR34 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS), LRRC8C (Affinity Capture-MS), LRRC8E (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

2 interactions.

A	Effect	B	Mechanism
ZNF91	“down-regulates quantity by repression”	FCGR3B	“transcriptional regulation”
ZNF140	“down-regulates quantity by repression”	FCGR3B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

901 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161631888:T:A	donor_gain	1.0000
1:161629776:A:AC	donor_gain	0.9900
1:161629777:C:CC	donor_gain	0.9900
1:161629842:T:A	donor_gain	0.9900
1:161630033:CTT:C	acceptor_gain	0.9900
1:161630036:C:CC	acceptor_gain	0.9900
1:161630308:ATGG:A	donor_gain	0.9900
1:161630389:C:CC	acceptor_gain	0.9900
1:161629770:CAACT:C	donor_loss	0.9800
1:161629771:AACT:A	donor_loss	0.9800
1:161629772:ACTCA:A	donor_loss	0.9800
1:161629773:C:G	donor_loss	0.9800
1:161629774:TCACC:T	donor_loss	0.9800
1:161629775:C:CA	donor_loss	0.9800
1:161629776:A:C	donor_loss	0.9800
1:161629777:C:A	donor_loss	0.9800
1:161630034:TT:T	acceptor_gain	0.9800
1:161630045:C:CT	acceptor_gain	0.9800
1:161630387:AACTG:A	acceptor_loss	0.9800
1:161630388:ACTG:A	acceptor_loss	0.9800
1:161630389:CTGC:C	acceptor_loss	0.9800
1:161631882:TTA:T	donor_loss	0.9800
1:161631883:TA:T	donor_loss	0.9800
1:161631884:A:T	donor_loss	0.9800
1:161631884:ACCTT:A	donor_gain	0.9800
1:161631885:C:CG	donor_loss	0.9800
1:161631885:CCTTC:C	donor_gain	0.9800
1:161631902:AGGT:A	donor_gain	0.9800
1:161624638:ACCTA:A	acceptor_loss	0.9700
1:161624640:C:CA	acceptor_loss	0.9700

AlphaMissense

1525 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161626207:C:G	C172S	0.992
1:161626208:A:T	C172S	0.992
1:161626339:C:G	C128S	0.992
1:161626340:A:T	C128S	0.992
1:161629831:C:G	C89S	0.991
1:161629832:A:T	C89S	0.991
1:161629957:C:G	C47S	0.989
1:161629958:A:T	C47S	0.989
1:161629917:C:A	W60C	0.988
1:161629917:C:G	W60C	0.988
1:161629837:T:C	Y87C	0.987
1:161626329:C:A	W131C	0.985
1:161626329:C:G	W131C	0.985
1:161626207:C:T	C172Y	0.984
1:161629837:T:G	Y87S	0.983
1:161629806:A:C	S97R	0.982
1:161629806:A:T	S97R	0.982
1:161629808:T:G	S97R	0.982
1:161629838:A:C	Y87D	0.982
1:161626340:A:G	C128R	0.981
1:161629919:A:G	W60R	0.980
1:161629919:A:T	W60R	0.980
1:161626206:G:C	C172W	0.978
1:161626214:A:C	Y170D	0.978
1:161626301:A:C	Y141D	0.978
1:161626338:A:C	C128W	0.977
1:161626339:C:T	C128Y	0.977
1:161626208:A:G	C172R	0.976
1:161626398:C:A	W108C	0.975
1:161626398:C:G	W108C	0.975

dbSNP variants (sampled 300 via entrez): RS1000183088 (1:161628951 T>C), RS1000234421 (1:161624830 G>T), RS1000244279 (1:161625725 A>G), RS1001907883 (1:161626977 G>A,C), RS1001919244 (1:161627229 T>C), RS1003518859 (1:161622766 C>G), RS1003583608 (1:161628478 A>G,T), RS1003593454 (1:161628784 C>A,T), RS1004431325 (1:161632031 G>A,T), RS1004701025 (1:161633305 TG>T,TGG), RS1004786602 (1:161624432 T>A,C), RS1006474833 (1:161626671 T>A,C), RS1006583053 (1:161630635 A>C), RS1008262760 (1:161632354 T>A,C), RS1008628103 (1:161624104 G>A)

Disease associations

OMIM: gene MIM:610665 | 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

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000093	Proteinuria
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000716	Depression
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000952	Jaundice
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001596	Alopecia
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001904	Autoimmune neutropenia
HP:0001945	Fever
HP:0002039	Anorexia
HP:0002072	Chorea
HP:0002090	Pneumonia
HP:0002716	Lymphadenopathy
HP:0003453	Antineutrophil antibody positivity
HP:0003493	Antinuclear antibody positivity
HP:0005268	Miscarriage
HP:0005421	Decreased circulating complement C3 concentration
HP:0005764	Polyarticular arthritis
HP:0005968	Temperature instability
HP:0007417	Discoid lupus rash
HP:0009800	Maternal diabetes

GWAS associations

16 associations (top):

Study	Trait	p-value
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
GCST004631_44	Basophil percentage of white cells	5.000000e-11
GCST004634_3	Basophil percentage of granulocytes	1.000000e-11
GCST005552_1	Systemic sclerosis (anti-centromere-positive)	6.000000e-14
GCST005555_4	Limited cutaneous systemic scleroderma	3.000000e-13
GCST006585_2088	Blood protein levels	6.000000e-53
GCST010083_114	Hemoglobin levels	8.000000e-24
GCST90002379_12	Basophil count	3.000000e-18
GCST90002380_88	Basophil percentage of white cells	1.000000e-35
GCST90002380_89	Basophil percentage of white cells	2.000000e-21
GCST90002383_339	Hematocrit	6.000000e-11
GCST90002393_160	Monocyte count	2.000000e-21

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0008536	anti-centromere-antibody-positive systemic scleroderma
EFO:1001017	limited scleroderma
EFO:0004509	hemoglobin measurement
EFO:0005090	basophil count
EFO:0004348	hematocrit
EFO:0005091	monocyte count

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): CHEMBL5842 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
tetrathiomolybdate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Clozapine	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Nickel	increases expression	1
Ozone	increases expression	1
Tretinoin	increases expression	1
Ziram	increases expression	1
Zymosan	decreases response to substance	1
Antirheumatic Agents	decreases expression	1
Zinc Sulfate	increases expression	1
Particulate Matter	increases abundance, 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
CHEMBL1039869	Binding	Inhibition of heat aggregated human IgG binding to human Fc-gamma-R3b	2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases. — J Med Chem

Cellosaurus cell lines

6 cell lines: 5 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_I210	HGDP00210	Transformed cell line	Female
CVCL_I913	HGDP00913	Transformed cell line	Male
CVCL_I996	HGDP00996	Transformed cell line	Female
CVCL_K362	C0092	Transformed cell line	Male
CVCL_K974	UKTS8802	Transformed cell line	Sex unspecified
CVCL_KA23	CHO-K1/CD16B	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