FCRL4

protein-coding

Fc receptor like 4, the group of CD molecules|Immunoglobulin like domain containing|Fc receptors

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 has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. [provided by RefSeq, Apr 2009]

MANE transcript

NM_031282.3

Inheritance

—

ClinVar variants

U:72B:11

Top phenotype

Non-immune hydrops fetalis

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr1:157,573,747-157,598,085

External References & Databases

Ensembl (ENSG00000163518)

Transcript & Mutation Effects

hg38 • Region Span ~24.3 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 FCRL4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 79

not providedTotal: 3

Non-immune hydrops fetalisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031282.3. 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					1 clinvar	1
missense			71 clinvar	8 clinvar	2 clinvar	81
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	72	8	3	83

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031282.3	RefSeq	NP_112572.1	12	MANE Select
ENST00000271532.2	Ensembl	ENSP00000271532.1	12	MANE Select
XM_011510034.2	RefSeq	XP_011508336.1	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

adaptive immune response

Molecular Function

protein binding

Cellular Component

plasma membrane
cell surface
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000271532
Coding exons: 12
Length: 24332
Individuals with no LoFs: 125673
Homozygous LoFs: 0
Heterozygous LoFs: 73
Defined: 125746
p: 0.000290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.577	302	275	1.10	0.0000144	3281
Missense (PolyPhen)		67	77.581	0.86361		1011
Synonymous	0.399	106	111	0.952	0.00000605	1046
Loss of Function	1.81	19	29.6	0.642	0.00000161	314

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00032	0.00032	rare
South Asian	0.00013	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as an inhibitor of the B-cell receptor signaling. May function in the B-cell-mediated immune response. {ECO:0000269|PubMed:14597715}.;
Disease: DISEASE: Note=A chromosomal aberration involving FCRL4 is found in non-Hodgkin lymphoma (NHG). Translocation t(1;1)(p36.3; q21.1-2). {ECO:0000269|PubMed:12619161}.; DISEASE: Note=A chromosomal aberration involving FCRL4 is found in multiple myeloma (MM). Translocation t(1;14)(q21;q32) that forms a FCRL4-IGHA1 fusion protein. {ECO:0000269|PubMed:11290337}.;

Recessive Scores

pRec: 0.0856

Intolerance Scores

LoFtool: 0.835
RVIS EVS: 0.51
RVIS percentile EVS: 80.3

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0365

Gene Damage Prediction

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