Gene and Protein Information
Species	TM	AA	Chromosomal Location	Gene Symbol	Gene Name	Reference
Human	1	254	1q23.3	FCGR3A	Fc gamma receptor IIIa
Mouse	1	249	1 78.53 cM	Fcgr4	Fc receptor, IgG, low affinity IV
Rat	1	249	13q24	Fcgr3a	Fc gamma receptor 3A
Gene and Protein Information Comments
Alternatively spliced transcript variants encoding different isoforms have been reported for the human gene.

Previous and Unofficial Names

Fc receptor, IgG, low affinity IV | Fc receptor | Fc gamma receptor IIIa | FCγRIIIa | FcRIIIA | low affinity immunoglobulin gamma Fc region receptor III-A

Database Links
Alphafold	P08637 (Hs), A0A0B4J1G0 (Mm)
ChEMBL Target	CHEMBL3856162 (Hs)
Ensembl Gene	ENSG00000203747 (Hs), ENSMUSG00000059089 (Mm), ENSRNOG00000024382 (Rn)
Entrez Gene	2214 (Hs), 246256 (Mm), 304966 (Rn)
Human Protein Atlas	ENSG00000203747 (Hs)
KEGG Gene	hsa:2214 (Hs), mmu:246256 (Mm), rno:304966 (Rn)
OMIM	146740 (Hs)
Pharos	P08637 (Hs)
RefSeq Nucleotide	NM_000569 (Hs), NM_144559 (Mm), NM_207603 (Rn)
RefSeq Protein	NP_000560 (Hs), NP_653142 (Mm), NP_997486 (Rn)
UniProtKB	P08637 (Hs), A0A0B4J1G0 (Mm)
Wikipedia	FCGR3A (Hs)

Download all structure-activity data for this target as a CSV file

Antibodies
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Antibody Sp. Action Value Parameter Reference AFM13 Hs Binding 9.1 – 9.4 pKd 2 ⤷ pKd 9.1 – 9.4 (Kd 8.4x10-10 – 3.9x10-10 M) [2] Description: Binding to CD16a 158V and 158F proteins by SPR. bemarituzumab Hs Binding 8.0 pKd 3 ⤷ pKd 8.0 (Kd 9.2x10-9 M) [3] Description: Binding affinity of FcγRIIIa (V158) for immobilised antibody by SPR.

Immunopharmacology Comments

The FCGR3A gene is expressed by natural killer (NK) cells. The protein product (CD16A or FcγRIIIa) is an integral peptide-tethered membrane glycoprotein. FcγRIIIa is a low-affinity receptor for IgG Fc and is involved in removing antigen-antibody complexes from the circulation and antibody-dependent responses. FcγRIIIa is being exploited for drug development, specifically as a NK cell-engager to mediate NK effector cell killing of cancer cells. For example, Affimed have developed AFM13, a tetravalent bispecific Fv peptide construct that simultaneously engages FcγRIIIa and CD30 on CD30-expressing malignant cells such as Hodgkin lymphoma cells, and AFM24 another tetravalent bispecific construct that targets epidermal growth factor receptor (EGFR) and FcγRIIIa to engage NK cells to destroy otherwise hard to treat EGFR-driven cancers. COVID-19: Analysis of blood from controls and COVID-19 patients was used to show that FcγRIIIa mediates phagocytosis of antibody-opsonised SARS-CoV-2 particles by human monocytes (and macrophages) [1]. Infection of monocytes via this receptor is inhibited by anti-FcγRIIIa antibodies in vitro. The infected monocytes proceed to undergo inflammasome-mediated pyroptosis. Although this cell death halts production of viable virus, it is proposed to contribute to the systemic inflammation that drives much of the pathology (e.g. acute lung injury and ARDS, vascular leak and multi-organ damage) that is observed in patients with severe COVID-19.

Immuno Process Associations

Immuno Process:  Inflammation

Immuno Process:  Immune regulation

Immuno Process:  Cellular signalling

General Comments
FcγRIIIa is an integral membrane glycoprotein anchored through a transmembrane peptide to the surface of natural killer (NK) cells. It is an important mediator of antibody-dependent phagocytosis, and appears to play a role in SARS-CoV-2 internalisation by monocytes in COVID-19 patients [1].