FCRL3

Summary

FCRL3 (Fc receptor like 3, HGNC:18506) is a protein-coding gene on chromosome 1q23.1, encoding Fc receptor-like protein 3 (Q96P31). Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation.

This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 115352 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 142 total
• MANE Select transcript: NM_052939

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18506
Approved symbol	FCRL3
Name	Fc receptor like 3
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FCRH3, IRTA3, IFGP3, SPAP2a, SPAP2, SPAP2b, SPAP2c, SPAP2d, SPAP2e, CD307c, MAIA
Ensembl gene	ENSG00000160856
Ensembl biotype	protein_coding
OMIM	606510
Entrez	115352

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 6 protein_coding_CDS_not_defined, 5 protein_coding, 3 nonsense_mediated_decay

ENST00000368184, ENST00000368186, ENST00000457799, ENST00000468507, ENST00000473231, ENST00000477837, ENST00000478179, ENST00000480682, ENST00000485028, ENST00000492769, ENST00000494724, ENST00000496769, ENST00000870123, ENST00000955375

RefSeq mRNA: 2 — MANE Select: NM_052939 NM_001320333, NM_052939

CCDS: CCDS1167, CCDS81385

Canonical transcript exons

ENST00000368184 — 15 exons

Exon	Start	End
ENSE00001075698	157697140	157697424
ENSE00001446514	157700662	157700769
ENSE00001865061	157676481	157678856
ENSE00003481968	157678942	157678973
ENSE00003483486	157680981	157681099
ENSE00003505625	157689798	157689917
ENSE00003522475	157700459	157700585
ENSE00003550862	157699692	157699712
ENSE00003587320	157690255	157690533
ENSE00003616387	157680702	157680770
ENSE00003664161	157683217	157683244
ENSE00003665244	157698384	157698629
ENSE00003676141	157695329	157695607
ENSE00003680439	157696040	157696327
ENSE00003688594	157697659	157697919

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 96.56.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.5527 / max 399.4406, expressed in 118 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15275	1.7665	84
15278	0.8417	82
15279	0.3409	66
15276	0.1694	51
15277	0.1233	42
15274	0.1182	37
15272	0.0984	36
15273	0.0943	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	96.56	gold quality
granulocyte	CL:0000094	93.70	gold quality
lymph node	UBERON:0000029	92.39	gold quality
spleen	UBERON:0002106	91.58	gold quality
vermiform appendix	UBERON:0001154	90.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.32	gold quality
blood	UBERON:0000178	84.80	gold quality
epithelium of nasopharynx	UBERON:0001951	82.36	gold quality
caecum	UBERON:0001153	81.86	gold quality
tonsil	UBERON:0002372	80.36	gold quality
bone marrow cell	CL:0002092	77.44	gold quality
epithelial cell of pancreas	CL:0000083	74.79	silver quality
superficial temporal artery	UBERON:0001614	74.59	gold quality
pancreatic ductal cell	CL:0002079	74.04	gold quality
bone marrow	UBERON:0002371	71.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.53	gold quality
mucosa of transverse colon	UBERON:0004991	69.49	gold quality
tibialis anterior	UBERON:0001385	69.29	silver quality
rectum	UBERON:0001052	68.83	gold quality
gall bladder	UBERON:0002110	67.17	gold quality
colonic epithelium	UBERON:0000397	66.20	gold quality
leukocyte	CL:0000738	65.81	gold quality
small intestine	UBERON:0002108	65.73	gold quality
monocyte	CL:0000576	63.33	gold quality
palpebral conjunctiva	UBERON:0001812	62.19	gold quality
right lung	UBERON:0002167	59.75	gold quality
right lobe of liver	UBERON:0001114	59.56	gold quality
upper lobe of left lung	UBERON:0008952	59.30	gold quality
upper lobe of lung	UBERON:0008948	58.45	gold quality
thymus	UBERON:0002370	58.39	silver quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	24.92
E-ANND-3	yes	7.99
E-MTAB-6386	no	1998.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting FCRL3, 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-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4687-3P	99.48	66.41	968
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-12131	99.48	68.72	1673
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-185-5P	99.35	68.60	2497
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-216B-3P	98.55	67.19	1223
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-4691-3P	98.11	66.83	1204

Literature-anchored findings (GeneRIF, showing 40)

• molecular cloning and characterization of SPAP2 (PMID:12051764)
• Single nucleotide polymorphism in Graves’ disease in a large UK Caucasian Graves’ disease data set. (PMID:16384851)
• This gene will not have a substantial effect in determining susceptibility to RArheumatoid arthritis in populations of Northern European descent. (PMID:16859508)
• Susceptibility to type 1 autoimmune hepatitis in Japanese patients is not influenced by FcgammaRIIA, FcgammaRIIB, or FCRL3 polymorphisms. (PMID:17020818)
• Findings from a large case-control sample of patients with alopecia areata (AA) do not support an association between FCRL3 and susceptibility to AA. (PMID:17117947)
• Both the FCRL3 and PTPN22 genes play roles in rheumatoid arthritis susceptibility, but in different individuals. (PMID:17133579)
• The association of the -169C/T SNP in FCRL3 with rheumatoid arthritis and systemic lupus erythematosus that was observed in Japanese patients was not replicated in a Korean population. (PMID:17133581)
• Susceptibility to autoimmunity at the FCRL3 locus. (PMID:17200162)
• The FCRL3 gene is involved in inflammatory bowel disease (IBD) genetic susceptibility by an epistatic interaction with HLA-DRB1*0103. (PMID:17389014)
• there is an epistatic interaction between genes in chromosomes 6p21 and 1q21-22, marked, respectively, by HLA-DRB1*0103 and FCRL3-169 AG (PMID:17389014)
• An increased susceptibility associated to the -169 T allele was found when MS patients. (PMID:17617473)
• results of these meta-analyses provide no evidence that the FCRL3 -169TC polymorphism plays a significant role in determining rheumatoid arthritis risk in whites of European descent (PMID:17763442)
• we found suggestive evidence for association of the FCRL3 -169CC genotype, corresponding to the susceptibility genotype for rheumatoid arthritis (PMID:17961971)
• RA was associated with the C allele (odds ratio (OR) = 1.16, 95% CI 1.01 to 1.33) and the CC genotype (OR = 1.30, 95% CI 1.01 to 1.67) of the FCRL3 -169T>C SNP. Clinical subgroup analysis indicated that this was connected to the polyarticular subgroup. (PMID:18065500)
• FCRL3 gene single nucleotide polymorphism was associated with rheumatoid arthritis (PMID:18087673)
• Two SNPs (rs7528684/FCRL3_3 and rs7522061/N28D), which were in high linkage disequilibrium (r(2) = 0.87), differed between MS cases and controls. (PMID:18313765)
• Genetic variations in FCRL3 were not associated with systemic lupus erythematosus in Chinese population. (PMID:18556175)
• Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia. (PMID:18704934)
• The -110 G allele and haplotype CGCG of FCRL3 are positively associated with Behcet’s disease(BD) in Chinese population. Haplotype ATCG might be protective haplotype for BD. (PMID:19050767)
• FcRL3 gene promoter variant is associated with peripheral arthritis in Crohn’s disease. (PMID:19235910)
• PTPN22 rs3789604 and FCRL3 rs7528684 polymorphisms are protective against Graves’ disease. (PMID:19438904)
• Our study confirms the previous association of HLA-DR4 and HLA-DRw53 with Vogt-Koyanagi-Harada(VKH) syndrome but fails to demonstrate an association between FCRL3 polymorphisms and VKH syndrome. (PMID:19452015)
• FCRL3 may be involved in human-specific mechanisms to control the generation of nTreg cells (PMID:19494275)
• This meta-analysis demonstrates that the FCRL3 169CC genotype (recessive effect) may confer susceptibility to systemic lupus erythematosus, especially in Asian-derived population. (PMID:19565352)
• functional variants in FCRL3, SLC22A4 and MHC2TA do not show a convincing effect on RA susceptibility in the United Kingdom. (PMID:19605748)
• The FCRL3 gene does not appear associated with susceptibility to HLA-B27-positive ankylosing spondylitis in Han Chinese population. (PMID:19657722)
• Meta-analysis suggests that the FCRL3 -169 C/T polymorphism is a significant risk factor for rheumatoid arthritis in Asians, but not in Europeans. (PMID:19690864)
• Augmented inhibition of BCR-mediated signaling by FCRL3 with the disease-risk genotype alter the activation threshold and promote tolerance breakdown in B cells. (PMID:19843936)
• The FCRL3 -169CT promoter single-nucleotide polymorphism, which is associated with systemic lupus erythematosus in a Japanese population, predicts expression of receptor protein on CD19+B cells. (PMID:19877046)
• The polymorphisms of the promoter A/G,exon 2 C/G,exon 4 C/T in the FcRL3 gene were risk factors to Graves disease in Chongqing Han population. (PMID:19953494)
• FcRL3 expression is associated with T(reg) dysfunction (PMID:20190142)
• These results suggest that FCRL3 polymorphisms and haplotypes may contribute to genetic susceptibility to rheumatoid arthritis in a Chinese population. (PMID:20732364)
• The functional FCRL3 SNP -169T/C appears to play important roles in the development of certain phenotypes such as systemic lupus erythematosus leukopenia and rheumatoid arthritis disease severity in Taiwanese patients with these diseases. (PMID:21078711)
• A significant association of fcrl3_3 with primary biliary cirrhosis only in Japanese. (PMID:21299530)
• the FCRL3 C-169T polymorphism may play an important role in the pathogenesis of endometriosis and/or infertility. (PMID:21529967)
• genetic polymorphism is associated with endometriosis in Brazilian population (PMID:21663782)
• FCRL3 -169C/C genotype is associated with anti-citrullinated protein antibody-positive rheumatoid arthritis and with radiographic progression. (PMID:21885492)
• Findings support a possible gene-gene interaction for FOXP3/FCRL3 polymorphisms, leading to a cumulative effect on endometriosis development. (PMID:22341374)
• Polymorphisms of the FCRL3 gene may contribute to the progression of joint destruction rather than susceptibility to rheumatoid arthritis. (PMID:22386693)
• A functional variant in FCRL3 is associated with higher Fc receptor-like 3 expression on T cell subsets and rheumatoid arthritis disease activity. (PMID:22392608)

Cross-species orthologs

0 orthologs

Paralogs (17): FCGR2B (ENSG00000072694), FCRLA (ENSG00000132185), FCRL2 (ENSG00000132704), FCGR2A (ENSG00000143226), FCRL5 (ENSG00000143297), FCGR1A (ENSG00000150337), 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

Fc receptor-like protein 3 — Q96P31 (reviewed: Q96P31)

Alternative names: Fc receptor homolog 3, IFGP family protein 3, Immune receptor translocation-associated protein 3, MAIA, SH2 domain-containing phosphatase anchor protein 2

All UniProt accessions (2): Q96P31, R4GNJ6

UniProt curated annotations — full annotation on UniProt →

Function. Promotes TLR9-induced B-cell proliferation, activation and survival but inhibits antibody production and suppresses plasma cell differentiation. Enhances activation of NF-kappa-B and MAPK signaling pathways in TLR9 stimulated B-cells. Has inhibitory potentional on B-cell receptor (BCR)-mediated signaling, possibly through association with SH2 domain-containing phosphatases. Inhibits cell tyrosine phosphorylation, calcium mobilization and activation-induced cell death induced through BCR signaling. Regulatory T-cells expressing FCRL3 exhibit a memory phenotype, are relatively nonresponsive to antigenic stimulation in presence of IL2 and have reduced capacity to suppress the proliferation of effector T-cells. Acts as a human-specific epitope on the cell surface of oocytes (oolemma) and plays a role during sperm-egg adhesion and fusion. Interacts with the IZUMO1-IZUMO1R/JUNO sperm-egg complex and replaces IZUMO1R/JUNO as IZUMO1 receptor during fertilization, thereby permitting species-specific gamete fusion.

Subunit / interactions. Interacts (via phosphorylated ITIM motifs) with phosphatases INPP5D, PTPN6 and PTPN11. Interacts (via ITIM motifs) SYK and ZAP70. Interacts with IZUMO1R/JUNO. Interacts (via extracellular domain) with IZUMO1; the interaction replaces IZUMO1R/JUNO as IZUMO1 receptor after adhesion between sperm and egg.

Subcellular location. Cell membrane. Cell projection. Microvillus membrane.

Tissue specificity. Primarily expressed in secondary lymphoid tissues by mature subsets of B-cells. Low expression on transitional B cells which increases to higher surface expression on mature and memory B-cells with innate-like features (at protein level). Expressed a low levels in naive and germinal center B-cells but also expressed in NK cells (at protein level). Expressed in unfertilized oocytes (at protein level). Expressed in a population of thymically derived naturally occurring regulatory T-cells that exhibits a memory phenotype, specialized in suppressing immune response to self-antigens. Detected in spleen, lymph node, peripheral blood lymphocytes, thymus, bone marrow, kidney, salivary gland, adrenal gland and uterus.

Post-translational modifications. Phosphorylated on cytoplasmic tyrosines; required for interaction with protein tyrosine phosphatases and protein tyrosine kinases.

Disease relevance. Rheumatoid arthritis (RA) [MIM:180300] An inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Disease susceptibility is associated with variants affecting the gene represented in this entry. Genetic variation in FCRL3 may influence susceptibility to autoimmune disorders, including Graves disease or multiple sclerosis. Graves disease is an autoimmune disorder associated with overactivity of the thyroid gland and hyperthyroidism. Multiple sclerosis is an autoimmune/inflammatory neurodegenerative disease which mainly affects young adults and is characterized by destruction of myelin in the central nervous system.

Isoforms (7)

UniProt ID	Names	Canonical?
Q96P31-1	1, Spap2a	yes
Q96P31-2	2, Spap2b
Q96P31-3	3, Spap2c
Q96P31-4	4, Spap2d
Q96P31-5	5
Q96P31-6	6
Q96P31-7	7

RefSeq proteins (2): NP_001307262, NP_443171* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050488	Ig_Fc_receptor	Family

Pfam: PF00047, PF13895, PF13927

UniProt features (50 total): splice variant 9, domain 6, disulfide bond 6, sequence variant 5, short sequence motif 4, modified residue 4, mutagenesis site 4, region of interest 2, compositionally biased region 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96P31-F1	77.46	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 (4): 650, 662, 692, 722

Disulfide bonds (6): 44–82, 120–163, 211–260, 309–358, 404–451, 497–544

Glycosylation sites (1): 561

Mutagenesis-validated functional residues (4):

Position	Phenotype
650	no effect on inhibition of cell death. no effect on interaction with inpp5d, ptpn6 and ptpn11. loss of phosphorylation,
662	reduces inhibition of cell death. decreases interaction with inpp5d and ptpn6. no effect on interaction with ptpn11. los
692	partially reduces inhibition of cell death. decreases interaction with inpp5d and ptpn11. no effect on interaction with
722	no effect on inhibition of cell death. no effect on interaction with inpp5d, ptpn6 and ptpn11. loss of phosphorylation,

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 137 (showing top): GOBP_REGULATION_OF_B_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_SINGLE_FERTILIZATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_B_CELL_ACTIVATION, GOBP_TOLL_LIKE_RECEPTOR_9_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, GOBP_B_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_B_CELL_PROLIFERATION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (11): negative regulation of immunoglobulin production (GO:0002638), immune response (GO:0006955), cell surface receptor signaling pathway (GO:0007166), single fertilization (GO:0007338), positive regulation of B cell proliferation (GO:0030890), regulation of toll-like receptor 9 signaling pathway (GO:0034163), positive regulation of MAPK cascade (GO:0043410), regulation of B cell differentiation (GO:0045577), negative regulation of B cell receptor signaling pathway (GO:0050859), regulation of B cell activation (GO:0050864), regulation of calcium ion import (GO:0090279)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), kinase binding (GO:0019900), phosphatase binding (GO:0019902), protein binding (GO:0005515)

GO Cellular Component (6): external side of plasma membrane (GO:0009897), cell surface (GO:0009986), microvillus membrane (GO:0031528), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
enzyme binding	2
immunoglobulin production	1
regulation of immunoglobulin production	1
negative regulation of production of molecular mediator of immune response	1
immune system process	1
response to stimulus	1
signal transduction	1
fertilization	1
regulation of B cell proliferation	1
B cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of B cell activation	1
toll-like receptor 9 signaling pathway	1
regulation of cytoplasmic pattern recognition receptor signaling pathway	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of intracellular signal transduction	1
B cell differentiation	1
regulation of lymphocyte differentiation	1
regulation of B cell activation	1
B cell receptor signaling pathway	1
regulation of B cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
B cell activation	1
regulation of lymphocyte activation	1
regulation of calcium ion transport	1
calcium ion import	1
signaling receptor activity	1
binding	1
plasma membrane	1
cell surface	1
side of membrane	1
microvillus	1
cell projection membrane	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1106 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FCRL3	PTPN22	Q9Y2R2	780
FCRL3	PIGR	P01833	750
FCRL3	ZAP70	P43403	726
FCRL3	SYK	P43405	701
FCRL3	PTPN11	Q06124	640
FCRL3	CTLA4	P16410	526
FCRL3	TSHR	P16473	515
FCRL3	MUC1	P13931	497
FCRL3	PADI4	Q9UM07	479
FCRL3	SAMSN1	Q9NSI8	475
FCRL3	HLA-DRB1	P01911	455
FCRL3	RNASET2	O00584	444
FCRL3	KIAA1143	Q96AT1	431
FCRL3	ANKRD35	Q8N283	425
FCRL3	BCL9	O00512	424

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FCRL3	MAP4K3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (25): HSPA8 (Affinity Capture-MS), FCRL3 (Two-hybrid), FCRL3 (Two-hybrid), FCRL3 (Two-hybrid), FCRL3 (Two-hybrid), FCRL3 (Two-hybrid), FCRL3 (Two-hybrid), CMTM5 (Two-hybrid), PTPN6 (Affinity Capture-Western), PTPN6 (Reconstituted Complex), PTPN11 (Reconstituted Complex), ZAP70 (Reconstituted Complex), SYK (Reconstituted Complex), MAP4K3 (Affinity Capture-MS), UBASH3A (Affinity Capture-MS)

ESM2 similar proteins: A0A0K2S4Q6, A2A7V7, A6NI73, A8K4G0, O43699, O75019, O75022, O75023, O75871, O76036, P0C191, P20138, P24071, P40198, P59901, P80943, Q08708, Q13410, Q28110, Q3U497, Q496F6, Q64JA4, Q6GTX8, Q6ISS4, Q6PI73, Q6UXZ3, Q7TSN2, Q863H2, Q8C567, Q8K249, Q8MJZ2, Q8MJZ7, Q8N149, Q8N423, Q8N6C8, Q8NHJ6, Q8NHL6, Q8VBT3, Q8VCH2, Q95JB9

Diamond homologs: A1YIY0, P12314, P23505, Q6DN72, Q7L513, Q96LA5, Q96LA6, Q96P31, Q96RD9, A0A0B4J1G0, A3RFZ7, E2RP87, G1T7E7, G1TR84, H0VDZ8, M3XWH1, O75015, P08101, P08508, P08637, P0DTI4, P12318, P12319, P12371, P20489, P26151, P27645, P31994, P31995, P79107, Q09TM2, Q09TM4, Q28110, Q28942, Q5DRQ8, Q60513, Q63203, Q68SN8, Q6BAA4, Q6XPU4

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	FCRL3	phosphorylation
FCRL3	“up-regulates activity”	SYK	binding
FCRL3	“up-regulates activity”	ZAP70	binding
FCRL3	“up-regulates activity”	PTPN6	binding
FCRL3	“up-regulates activity”	PTPN11	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	109
Likely benign	15
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2112 predictions. Top by Δscore:

Variant	Effect	Δscore
1:157678856:CC:C	acceptor_loss	1.0000
1:157678856:CCTGG:C	acceptor_gain	1.0000
1:157678857:C:CC	acceptor_gain	1.0000
1:157680767:TTTA:T	acceptor_gain	1.0000
1:157680768:TTA:T	acceptor_gain	1.0000
1:157680771:C:CC	acceptor_gain	1.0000
1:157700457:A:AC	donor_gain	1.0000
1:157700458:C:CC	donor_gain	1.0000
1:157678852:AGTTC:A	acceptor_gain	0.9900
1:157678853:GTTC:G	acceptor_gain	0.9900
1:157678854:TTC:T	acceptor_gain	0.9900
1:157678855:TC:T	acceptor_gain	0.9900
1:157678860:G:C	acceptor_gain	0.9900
1:157678860:G:GC	acceptor_gain	0.9900
1:157680697:CTTA:C	donor_loss	0.9900
1:157680699:TAC:T	donor_gain	0.9900
1:157680699:TACCT:T	donor_loss	0.9900
1:157680700:AC:A	donor_loss	0.9900
1:157680769:TA:T	acceptor_gain	0.9900
1:157680769:TAC:T	acceptor_loss	0.9900
1:157680771:C:CG	acceptor_loss	0.9900
1:157680772:T:A	acceptor_loss	0.9900
1:157681100:C:CC	acceptor_gain	0.9900
1:157697811:T:TA	donor_gain	0.9900
1:157700458:CT:C	donor_gain	0.9900
1:157700545:T:C	donor_gain	0.9900
1:157700664:T:A	donor_gain	0.9900
1:157690534:C:CC	acceptor_gain	0.9800
1:157695346:A:AC	donor_gain	0.9800
1:157695347:C:CC	donor_gain	0.9800

AlphaMissense

4757 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:157696206:C:A	W322C	0.969
1:157696206:C:G	W322C	0.969
1:157696212:G:C	F320L	0.968
1:157696212:G:T	F320L	0.968
1:157696214:A:G	F320L	0.968
1:157697859:C:G	C120S	0.964
1:157697860:A:T	C120S	0.964
1:157696065:G:C	S369R	0.962
1:157696065:G:T	S369R	0.962
1:157696067:T:G	S369R	0.962
1:157696208:A:G	W322R	0.962
1:157696208:A:T	W322R	0.962
1:157695388:C:G	C451S	0.959
1:157695389:A:T	C451S	0.959
1:157696246:C:G	C309S	0.956
1:157696247:A:T	C309S	0.956
1:157690455:C:G	C497S	0.951
1:157690456:A:T	C497S	0.951
1:157696099:C:G	C358S	0.950
1:157696100:A:T	C358S	0.950
1:157695375:A:C	N455K	0.949
1:157695375:A:T	N455K	0.949
1:157697165:G:C	S273R	0.947
1:157697165:G:T	S273R	0.947
1:157697167:T:G	S273R	0.947
1:157695529:C:G	C404S	0.946
1:157695530:A:T	C404S	0.946
1:157696246:C:T	C309Y	0.946
1:157697306:G:C	F226L	0.946
1:157697306:G:T	F226L	0.946

dbSNP variants (sampled 300 via entrez): RS1000151000 (1:157697061 A>G,T), RS1000297160 (1:157677634 C>G,T), RS1000376176 (1:157702396 T>C), RS1000504315 (1:157683381 C>G,T), RS1000518006 (1:157685264 T>C), RS1000562785 (1:157690552 T>A,C), RS1000669885 (1:157696873 T>C), RS1000717272 (1:157696517 C>A,T), RS1000757377 (1:157676873 T>C,G), RS1000785338 (1:157679321 G>A,T), RS1000927425 (1:157702164 A>G), RS1000989291 (1:157692477 A>G,T), RS1001236298 (1:157687352 T>C), RS1001276255 (1:157702368 C>A), RS1001342103 (1:157693826 C>A)

Disease associations

OMIM: gene MIM:606510 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001198_45	Multiple sclerosis	3.000000e-06
GCST001200_1	Graves’ disease	2.000000e-13
GCST002318_109	Rheumatoid arthritis	2.000000e-07
GCST002943_21	IgA nephropathy	2.000000e-07
GCST003814_10	Selective IgA deficiency	9.000000e-07
GCST004381_1	Insulinoma-associated antigen 2 autoantibody levels in type 1 diabetes	8.000000e-09
GCST006048_40	Rheumatoid arthritis (ACPA-positive)	1.000000e-08
GCST006585_1150	Blood protein levels	7.000000e-182
GCST006959_172	Rheumatoid arthritis	1.000000e-08
GCST007123_1	Multiple sclerosis and LDL levels (pleiotropy)	1.000000e-06
GCST009597_115	Multiple sclerosis	3.000000e-16
GCST011781_2	IgA nephropathy	5.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004866	autoantibody measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Zoledronic Acid	increases expression	1
Amiodarone	increases expression	1
Vehicle Emissions	decreases methylation	1
Caffeine	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.