FCGR3A Fc gamma receptor IIIa [Homo sapiens (human)] - Gene

Summary

Official Symbol: FCGR3Aprovided by HGNC
Official Full Name: Fc gamma receptor IIIaprovided by HGNC
Primary source: HGNC:HGNC:3619
See related: Ensembl:ENSG00000203747 MIM:146740; AllianceGenome:HGNC:3619
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD16; FCG3; CD16A; FCGR3; IGFR3; IMD20; FCR-10; FCRIII; CD16-II; FCGRIII; FCRIIIA; FcGRIIIA
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]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression: Biased expression in spleen (RPKM 154.1), lung (RPKM 70.6) and 10 other tissues See more
Orthologs: all
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Genomic context

Location:: 1q23.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (161541759..161550737, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (160804385..160813363, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (161511549..161520527, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association of NK cell subsets and cytotoxicity with FCGR3A gene polymorphism in functional NK cell deficiency.
Title: Association of NK cell subsets and cytotoxicity with FCGR3A gene polymorphism in functional NK cell deficiency.
Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis.
Title: Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis.
Multiplex interrogation of the NK cell signalome reveals global downregulation of CD16 signaling during lentivirus infection through an IL-18/ADAM17-dependent mechanism.
Title: Multiplex interrogation of the NK cell signalome reveals global downregulation of CD16 signaling during lentivirus infection through an IL-18/ADAM17-dependent mechanism.
Association between the functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to biologics in rheumatoid arthritis patients: A meta-analysis.
Title: Association between the functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to biologics in rheumatoid arthritis patients: A meta-analysis.
Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status.
Title: Analysis of FCGR3A-p.176Val variants in women with recurrent pregnancy loss and the association with CD16a expression and anti-HLA antibody status.
FcgammaRIIIA activation-mediated up-regulation of glycolysis alters MDSCs modulation in CD4[+] T cell subsets of Sjogren syndrome.
Title: FcγRIIIA activation-mediated up-regulation of glycolysis alters MDSCs modulation in CD4(+) T cell subsets of Sjögren syndrome.
The weaker-binding Fc gamma receptor IIIa F158 allotype retains sensitivity to N-glycan composition and exhibits a destabilized antibody-binding interface.
Title: The weaker-binding Fc γ receptor IIIa F158 allotype retains sensitivity to N-glycan composition and exhibits a destabilized antibody-binding interface.
FCGR3A gene duplication, FcgammaRIIb-232TT and FcgammaRIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1.
Title: FCGR3A gene duplication, FcγRIIb-232TT and FcγRIIIb-HNA1a associate with an increased risk of vertical acquisition of HIV-1.
High-affinity FcgammaRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19.
Title: High-affinity FcγRIIIa genetic variants and potent NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) responses contributing to severe COVID-19.
FcgammaRIIIa receptor interacts with androgen receptor and PIP5K1alpha to promote growth and metastasis of prostate cancer.
Title: FcγRIIIa receptor interacts with androgen receptor and PIP5K1α to promote growth and metastasis of prostate cancer.

Submit: New GeneRIF Correction See all GeneRIFs (337)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity MedGen: C3810342 OMIM: 615707 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genetic predictors of risk and resilience in psychiatric disorders: a cross-disorder genome-wide association study of functional impairment in major depressive disorder, bipolar disorder, and schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 is vertically transmitted more readily by mothers who are heterozygous for high-affinity and low-affinity FCGR3A	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	NK cells that respond with IFN-gamma and TNF-alpha cytokine production to HIV-1 gp120 peptides have reduced CD16 and NKp46 expression and have increased levels of CD57	PubMed
	env	IgG2 and IgG4 bind more poorly to enzymatically deglycosylated recombinant gp120 (rgp120) than to unchanged rgp120	PubMed
Nef	nef	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Nef may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1	PubMed
Tat	tat	HIV-1 Tat upregulates the expression of CCR2, CD16, and TLR4 in monocyte-derived macrophages	PubMed
	tat	HIV-1 Tat inhibits the rise in intracellular free calcium concentration in Natural Killer (NK) cells upon cross-linking of the adhesion molecule CD11a and the activation molecule CD16, indicating Tat is involved in the impairment of NK cell function	PubMed
Vpr	vpr	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1	PubMed
Vpu	vpu	The ability of HIV-1 Vpu to antagonize tetherin is important for the antibody opsonization of HIV-infected cells, which in turn increases FCGRIII (CD16) signaling	PubMed
	vpu	Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of FCGR3A against production of infectious wild-type HIV-1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC20248P1 (e-PCR)
- UniSTS:271891

WI-16134 (e-PCR)
- UniSTS:2862

NoName (e-PCR)
- UniSTS:480827

RH79714 (e-PCR)
- UniSTS:86623

RH11453 (e-PCR)
- UniSTS:65438

PMC26659P2 (e-PCR)
- UniSTS:272344

GDB:190042 (e-PCR)
- UniSTS:155612

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables IgG binding	IEA Inferred from Electronic Annotation more info
enables IgG receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables immune receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables low-affinity IgG receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Fc-gamma receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in antibody-dependent cellular cytotoxicity	IBA Inferred from Biological aspect of Ancestor more info
involved_in antibody-dependent cellular cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in calcium-mediated signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in macrophage activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell activation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in natural killer cell degranulation	IDA Inferred from Direct Assay more info	PubMed
involved_in natural killer cell mediated cytotoxicity	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of natural killer cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of Fc-gamma receptor III complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: low affinity immunoglobulin gamma Fc region receptor III-A

Names: CD16a antigen; Fc fragment of IgG receptor IIIa; Fc fragment of IgG, low affinity III, receptor for (CD16); Fc fragment of IgG, low affinity IIIa, receptor (CD16a); Fc gamma receptor III-A; Fc-gamma RIII-alpha; Fc-gamma receptor III-2 (CD 16); Fc-gamma receptor IIIb (CD16); FcgammaRIIIA; IgG Fc receptor III-A; igG Fc receptor III-2; immunoglobulin G Fc receptor III; low affinity immunoglobulin gamma Fc region receptor III-A/III-B recombinant; low affinity immunoglobulin gamma Fc region receptor III-B; low affinity immunoglobulin gamma receptor III-a Fc fragment; neutrophil-specific antigen NA

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009066.1 RefSeqGene

Range

5001..13865

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_60

mRNA and Protein(s)

NM_000569.8 → NP_000560.7 low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) retains an intron in its 5' UTR and 5' coding region compared to variant 3. Variants 1, 3, 4 and 6 encode the same isoform (c).

Source sequence(s)

AK302126, BC033678

Consensus CDS

CCDS44266.1

UniProtKB/Swiss-Prot

A2N6W9, P08637, Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0

UniProtKB/TrEMBL

A0A8V8TPL1

Related

ENSP00000392047.2, ENST00000443193.6

Conserved Domains (2) summary

cd05752
Location:26 → 104

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:108 → 190

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains
NM_001127592.2 → NP_001121064.2 low affinity immunoglobulin gamma Fc region receptor III-A isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) retains an intron in its 5' UTR and 5' coding region, and uses an alternate in-frame splice site in its 5' coding region compared to variant 3. The encoded isoform (2) is longer than isoform c. This isoform (b) lacks a predicted signal peptide compared to isoform c.

Source sequence(s)

AK302126, BC036723, DA944383, M24853

UniProtKB/TrEMBL

A0A1W2PQB1
NM_001127593.1 → NP_001121065.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

See identical proteins and their annotated locations for NP_001121065.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes isoform c. Variants 1, 3, 4 and 6 encode the same isoform (c).

Source sequence(s)

AL590385, BC036723, DA957430, M24853

Consensus CDS

CCDS44266.1

UniProtKB/Swiss-Prot

A2N6W9, P08637, Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0

UniProtKB/TrEMBL

A0A8V8TPL1

Related

ENSP00000416607.1, ENST00000436743.7

Conserved Domains (2) summary

cd05752
Location:26 → 104

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:108 → 190

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains
NM_001127595.2 → NP_001121067.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

See identical proteins and their annotated locations for NP_001121067.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 3. Variants 1, 3, 4 and 6 encode the same isoform (c).

Source sequence(s)

BC036723, DA933259, DA957430, M24853

Consensus CDS

CCDS44266.1

UniProtKB/Swiss-Prot

A2N6W9, P08637, Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0

UniProtKB/TrEMBL

A0A8V8TPL1

Related

ENSP00000356944.3, ENST00000367967.8

Conserved Domains (2) summary

cd05752
Location:26 → 104

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:108 → 190

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains
NM_001127596.2 → NP_001121068.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform d precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate in-frame splice site in the 5' coding region compared to variant 3. The encoded isoform (d) is shorter than isoform c.

Source sequence(s)

BC036723, DA674960, DA957430, M24853

Consensus CDS

CCDS91089.1

UniProtKB/TrEMBL

A0A8V8TPL1, H0Y755

Related

ENSP00000514361.1, ENST00000699400.1

Conserved Domains (2) summary

cd05752
Location:25 → 103

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:107 → 189

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains
NM_001329120.2 → NP_001316049.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR compared to variant 3. Variants 1, 3, 4 and 6 encode the same isoform (c).

Source sequence(s)

AL590385, BC036723

Consensus CDS

CCDS44266.1

UniProtKB/Swiss-Prot

A2N6W9, P08637, Q53FJ0, Q53FL6, Q5EBR4, Q65ZM6, Q6PIJ0

UniProtKB/TrEMBL

A0A8V8TPL1

Related

ENSP00000514358.1, ENST00000699397.1

Conserved Domains (2) summary

cd05752
Location:26 → 104

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:108 → 190

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains
NM_001329122.1 → NP_001316051.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (7) retains an intron in its 5' UTR and 5' coding region, and lacks an alternate in-frame exon in its 3' coding region compared to variant 3. The encoded isoform is longer than isoform c. This isoform (e) lacks a predicted signal peptide compared to isoform c.

Source sequence(s)

AL590385, BC036723
NM_001386450.1 → NP_001373379.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform d precursor

Status: REVIEWED

Source sequence(s)

AL590385

Consensus CDS

CCDS91089.1

UniProtKB/TrEMBL

A0A8V8TPL1, H0Y755

Conserved Domains (2) summary

cd05752
Location:25 → 103

Ig1_FcgammaR_like; First immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

cd05753
Location:107 → 189

Ig2_FcgammaR_like; Second immunoglobulin (Ig)-like domain of Fcgamma-receptors (FcgammaRs), and similar domains

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

161541759..161550737 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047449444.1 → XP_047305400.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform X2
XM_047449443.1 → XP_047305399.1 low affinity immunoglobulin gamma Fc region receptor III-A isoform X1