FCRL3

Fc receptor like 3, the group of Fc receptors|Immunoglobulin like domain containing|CD molecules

Basic information

Region (hg38): 1:157674321-157700769

Links

ENSG00000160856 ∙ NCBI:115352 ∙ OMIM:606510 ∙ HGNC:18506 ∙ Uniprot:Q96P31 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FCRL3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FCRL3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			42	9	4	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	42	9	5

Variants in FCRL3

This is a list of pathogenic ClinVar variants found in the FCRL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-157678753-T-C			Benign (Feb 24, 2021)
1-157678811-C-T		not specified	Uncertain significance (Feb 15, 2023)
1-157678840-T-C		not specified	Uncertain significance (Apr 20, 2023)
1-157680707-T-C		not specified	Uncertain significance (Dec 27, 2023)
1-157680762-C-T		not specified	Uncertain significance (Jun 22, 2021)
1-157680982-A-T		not specified	Uncertain significance (Jul 13, 2022)
1-157681008-T-C		not specified	Likely benign (Feb 07, 2023)
1-157681067-G-A		not specified	Likely benign (May 17, 2023)
1-157681084-C-T			Benign (Apr 10, 2018)
1-157683244-C-T		not specified	Uncertain significance (Mar 18, 2024)
1-157689809-C-T		not specified	Likely benign (Sep 16, 2021)
1-157689852-C-T		not specified	Uncertain significance (Dec 26, 2023)
1-157689888-C-A		not specified	Uncertain significance (Dec 14, 2023)
1-157689888-C-T		not specified	Likely benign (Feb 27, 2024)
1-157690266-A-G		not specified	Uncertain significance (Mar 23, 2023)
1-157690269-G-A		not specified	Uncertain significance (Aug 21, 2023)
1-157690365-C-T		not specified	Uncertain significance (Jun 24, 2022)
1-157690408-C-T		not specified	Uncertain significance (Aug 30, 2021)
1-157690431-G-A		not specified	Uncertain significance (Jun 22, 2023)
1-157690438-A-C		not specified	Uncertain significance (Sep 14, 2022)
1-157690461-A-G		not specified	Uncertain significance (Jan 23, 2024)
1-157690495-C-T		not specified	Uncertain significance (Sep 22, 2021)
1-157690528-C-T		not specified	Uncertain significance (Jun 02, 2023)
1-157695358-T-C		not specified	Likely benign (Nov 03, 2023)
1-157695377-T-C		not specified	Uncertain significance (Mar 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FCRL3	protein_coding	protein_coding	ENST00000368184	14	26537

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.97e-21	0.00309	125612	0	136	125748	0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.17	453	388	1.17	0.0000197	4729
Missense in Polyphen		131	110.38	1.1868		1476
Synonymous	-1.14	180	161	1.11	0.00000908	1503
Loss of Function	0.255	32	33.6	0.953	0.00000172	392

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00177	0.00176
Ashkenazi Jewish	0.000993	0.000993
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.000218	0.000217
South Asian	0.00241	0.00232
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:23857366). 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 (PubMed:19843936). 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 (PubMed:20190142, PubMed:19494275). {ECO:0000269|PubMed:19494275, ECO:0000269|PubMed:19843936, ECO:0000269|PubMed:20190142, ECO:0000269|PubMed:23857366}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:15838509, ECO:0000269|PubMed:16176992, ECO:0000269|PubMed:16476711, ECO:0000269|PubMed:16859508, ECO:0000269|PubMed:17133579, ECO:0000269|PubMed:17179172, ECO:0000269|PubMed:17763442, ECO:0000269|PubMed:22392608, ECO:0000269|PubMed:26746625}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Note=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. {ECO:0000269|PubMed:15838509, ECO:0000269|PubMed:16384851, ECO:0000269|PubMed:17952073, ECO:0000269|PubMed:25862376, ECO:0000269|PubMed:26629249}.
• Pathway: TCR (Consensus)

Intolerance Scores

• loftool: 0.949
• rvis_EVS: 1.25
• rvis_percentile_EVS: 93.48

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.112
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.199

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Gene ontology

• Biological process: negative regulation of immunoglobulin production;positive regulation of B cell proliferation;regulation of toll-like receptor 9 signaling pathway;positive regulation of MAPK cascade;regulation of B cell differentiation;negative regulation of B cell receptor signaling pathway;regulation of B cell activation;regulation of calcium ion import;positive regulation of protein serine/threonine phosphatase activity
• Cellular component: plasma membrane;cell surface;integral component of membrane
• Molecular function: kinase binding;phosphatase binding;protein phosphatase binding;protein tyrosine kinase binding