FCGR3A

protein-coding

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

Gene summary

This gene encodes a receptor for the Fc portion of immunoglobulin G, and it is involved in the removal of antigen-antibody complexes from the circulation, as well as other responses, including antibody dependent cellular mediated cytotoxicity and antibody dependent enhancement of virus infections. This gene (FCGR3A) is highly similar to another nearby gene (FCGR3B) located on chromosome 1. The receptor encoded by this gene is expressed on natural killer (NK) cells as an integral membrane glycoprotein anchored through a transmembrane peptide, whereas FCGR3B is expressed on polymorphonuclear neutrophils (PMN) where the receptor is anchored through a phosphatidylinositol (PI) linkage. Mutations in this gene are associated with immunodeficiency 20, and have been linked to susceptibility to recurrent viral infections, susceptibility to systemic lupus erythematosus, and alloimmune neonatal neutropenia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]

Previous symbols:

FCGR3
FCG3

MANE transcript

NM_000569.8

Inheritance

ClinVar variants

U:50B:21

Top phenotype

Immunodeficiency 20

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr1:161,541,759-161,550,968

External References & Databases

Ensembl (ENSG00000203747)

Transcript & Mutation Effects

hg38 • Region Span ~9.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicityMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014313

Submitter: PanelApp Australia

autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicitySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014313

Submitter: Orphanet

Clinical Genomic Database (CGD)

Immunodeficiency 20AR

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described as affected by early-onset severe herpes viral infections (eg, EBV, HPV), and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial

Refs: 8608639; 8874200; 23006327

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FCGR3A variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 10

Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicityTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000569.8. 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	13 clinvar		14
missense			46 clinvar	7 clinvar	1 clinvar	54
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	50	20	1	71

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000569.8	RefSeq	NP_000560.7	5	MANE Select
ENST00000443193.6	Ensembl	ENSP00000392047.2	5	MANE Select
NM_001127592.2	RefSeq	NP_001121064.2	5	Standard
NM_001127593.1	RefSeq	NP_001121065.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fc gamma R-mediated phagocytosis - Homo sapiens (human)
Systemic lupus erythematosus - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Staphylococcus aureus infection - Homo sapiens (human)
Tuberculosis - Homo sapiens (human)

Biological Process

immune response
Fc-gamma receptor signaling pathway involved in phagocytosis
regulation of immune response

Molecular Function

IgG binding

Cellular Component

plasma membrane
external side of plasma membrane
integral component of membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367969
Coding exons: 5
Length: 89369
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.04	186	150	1.24	0.00000765	1850
Missense (PolyPhen)		52	44.001	1.1818		614
Synonymous	0.262	56	58.6	0.956	0.00000295	555
Loss of Function	0.407	9	10.4	0.864	4.45e-7	121

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.000066	0.000065	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the Fc region of IgG. Binds complexed or aggregated IgG and also monomeric IgG. Mediates antibody-dependent cellular cytotoxicity (ADCC) and other antibody-dependent responses, such as phagocytosis. {ECO:0000269|PubMed:21768335, ECO:0000269|PubMed:22023369}.;
Disease: DISEASE: Immunodeficiency 20 (IMD20) [MIM:615707]: A rare autosomal recessive primary immunodeficiency characterized by functional deficiency of NK cells. Affected individuals typically present with severe herpes viral infections, particularly Epstein Barr virus (EBV), and human papillomavirus (HPV). {ECO:0000269|PubMed:23006327, ECO:0000269|PubMed:8608639, ECO:0000269|PubMed:8609432, ECO:0000269|PubMed:8874200}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.147

Intolerance Scores

LoFtool: 0.990
RVIS EVS: 0.44
RVIS percentile EVS: 77.8

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00307

Gene Damage Prediction

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