FCRL3

protein-coding

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

Gene summary

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. [provided by RefSeq, Feb 2016]

MANE transcript

NM_052939.4

Inheritance

—

ClinVar variants

U:116B:19

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr1:157,674,321-157,700,769

External References & Databases

Ensembl (ENSG00000160856)

Transcript & Mutation Effects

hg38 • Region Span ~26.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FCRL3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 123

not providedTotal: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_052939.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar		1 clinvar	3
missense			112 clinvar	16 clinvar	2 clinvar	130
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	116	16	3	135

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_052939.4	RefSeq	NP_443171.2	14	MANE Select
ENST00000368184.8	Ensembl	ENSP00000357167.3	14	MANE Select
NM_001320333.2	RefSeq	NP_001307262.1	15	Standard
ENST00000368186.10	Ensembl	ENSP00000357169.5	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Molecular Function

kinase binding
phosphatase binding
protein phosphatase binding
protein tyrosine kinase binding

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368184
Coding exons: 14
Length: 26537
Individuals with no LoFs: 125612
Homozygous LoFs: 0
Heterozygous LoFs: 136
Defined: 125748
p: 0.000541

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.17	453	388	1.17	0.0000197	4729
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0013	notable
Latino/Admixed American	0.00046	0.00046	rare
Ashkenazi Jewish	0.00099	0.00099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.0024	0.0023	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Intolerance Scores

LoFtool: 0.949
RVIS EVS: 1.25
RVIS percentile EVS: 93.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.199

Gene Damage Prediction

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