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

Gene ID: 2214, updated on 10-Dec-2024

Summary

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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

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See FCGR3A in Genome Data Viewer
Location:
1q23.3
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (161541759..161550737, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (160804385..160813363, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (161511549..161520527, complement)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1482 Neighboring gene ribosomal protein S23 pseudogene 10 Neighboring gene tRNA-Asn (anticodon GTT) 1-1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:161518401-161518900 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:161547932-161548874 Neighboring gene Fc gamma receptor IIc (gene/pseudogene) Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:161559016-161559516 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:161562499-161562705 Neighboring gene heat shock protein family A (Hsp70) member 7 (pseudogene)

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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Related articles in PubMed

  1. Association of Fcγ receptor IIIA variant with a subset of anti-topoisomerase I-positive patients in systemic sclerosis: a descriptive pilot study. Magnant J, et al. Rheumatol Int, 2012 Jul. PMID 21785957
  2. A genetic variant of FcγRIIIa is strongly associatedwith humoral immunity to cyclin B1 in African American patients with prostate cancer. Pandey JP, et al. Immunogenetics, 2013 Feb. PMID 23114687
  3. Association of the FCGR3A-158F/V gene polymorphism with the response to rituximab treatment in Spanish systemic autoimmune disease patients. Robledo G, et al. DNA Cell Biol, 2012 Dec. PMID 23075294
  4. Association of Fcγ receptor IIIa genotype with the rate of HIV infection after gp120 vaccination. Forthal DN, et al. Blood, 2012 Oct 4. PMID 22915639, Free PMC Article
  5. Correlation between CD16a binding and immuno effector functionality of an antigen specific immunoglobulin Fc fragment (Fcab). Kainer M, et al. Arch Biochem Biophys, 2012 Oct 15. PMID 22634259

See all (491) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Fcgamma-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis.
    Title: Fcγ-receptor-IIIA bioactivity of circulating and synovial immune complexes in rheumatoid arthritis.
  2. FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population.
    Title: FCGR3A F158V alleles frequency differs in multiple myeloma patients from healthy population.
  3. Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.
    Title: Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
Submit: New GeneRIF Correction See all GeneRIFs (340)

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

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
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
EBI GWAS Catalog

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 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

  1. NG_009066.1 RefSeqGene

    Range
    5001..13865
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_60

mRNA and Protein(s)

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    161541759..161550737 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    UniProtKB/TrEMBL
    A0A1W2PQB1

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

    UniProtKB/TrEMBL
    A0A1W2PQB1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    160804385..160813363 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P08637.2 GenPept UniProtKB/Swiss-Prot:P08637

Gene LinkOut

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