FCGR2B

protein-coding

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

Gene summary

The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

Previous symbols:

FCG2
FCGR2

MANE transcript

NM_001394477.1

Inheritance

ClinVar variants

U:31B:11

Top phenotype

systemic lupus erythematosus

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr1:161,663,143-161,678,654

External References & Databases

Ensembl (ENSG00000072694)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

systemic lupus erythematosusLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0007915

Submitter: PanelApp Australia

systemic lupus erythematosusNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007915

Submitter: Labcorp Genetics (formerly Invitae)

systemic lupus erythematosusSUPPORTIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0007915

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FCGR2B variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 10

Systemic lupus erythematosusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001394477.1. 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	3 clinvar		4
missense			27 clinvar	5 clinvar	3 clinvar	35
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	31	8	3	42

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001394477.1	RefSeq	NP_001381406.1	8	MANE Select
ENST00000358671.10	Ensembl	ENSP00000351497.5	8	MANE Select
NM_001002273.3	RefSeq	NP_001002273.1	7	Standard
NM_001002274.3	RefSeq	NP_001002274.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

B cell receptor signaling pathway - Homo sapiens (human)
Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Staphylococcus aureus infection - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)

Biological Process

negative regulation of type I hypersensitivity
negative regulation of antibody-dependent cellular cytotoxicity
follicular dendritic cell activation
mature B cell differentiation involved in immune response
follicular B cell differentiation

Molecular Function

amyloid-beta binding
protein binding
low-affinity IgG receptor activity
IgG binding
protein-containing complex binding

Cellular Component

plasma membrane
integral component of plasma membrane
external side of plasma membrane
dendritic spine
cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358671
Coding exons: 8
Length: 97344
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125725
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.108	131	135	0.974	0.00000718	2000
Missense (PolyPhen)		27	38.974	0.69277		580
Synonymous	-0.945	61	52.3	1.17	0.00000304	595
Loss of Function	2.33	2	9.93	0.201	4.22e-7	163

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the Fc region of complexed or aggregated immunoglobulins gamma. Low affinity receptor. Involved in a variety of effector and regulatory functions such as phagocytosis of immune complexes and modulation of antibody production by B- cells. Binding to this receptor results in down-modulation of previous state of cell activation triggered via antigen receptors on B-cells (BCR), T-cells (TCR) or via another Fc receptor. Isoform IIB1 fails to mediate endocytosis or phagocytosis. Isoform IIB2 does not trigger phagocytosis.;
Disease: DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:12115230, ECO:0000269|PubMed:20385827}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.840
RVIS EVS: 0.06
RVIS percentile EVS: 58.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.859

Gene Damage Prediction

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