Protein / target
Low affinity immunoglobulin gamma Fc region receptor III-A
Protein at a glance
Biological role
Low-affinity IgG receptor activity
Primary system
Immune system
Strongest disease association
autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity
Therapeutic maturity
Clinical-stage target
Druggability
Small molecule
Clinical development
2 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger (PubMed:11711607, PubMed:21768335, PubMed:22023369, PubMed:24412922, PubMed:25786175, PubMed:25816339, PubMed:28652325, PubMed:8609432, PubMed:9242542). Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation. Involved in the generation of memory-like adaptive NK cells capable to produce high amounts of IFNG and to efficiently eliminate virus-infected cells via ADCC (PubMed:24412922, PubMed:25786175). Regulates NK cell survival and proliferation, in particular by preventing NK cell progenitor apoptosis (PubMed:29967280, PubMed:9916693). Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation. The ITAM-dependent signaling coupled to receptor phosphorylation by PKC mediates robust intracellular calcium flux that leads to production of pro-inflammatory cytokines, whereas in the absence of receptor phosphorylation it mainly activates phosphatidylinositol 3-kinase signaling leading to cell degranulation (PubMed:1825220, PubMed:23024279, PubMed:2532305). Costimulates NK cells and trigger lysis of target cells independently of IgG binding (PubMed:10318937, PubMed:23006327). Mediates the antitumor activities of therapeutic antibodies. Upon ligation on monocytes triggers TNFA-dependent ADCC of IgG-coated tumor cells (PubMed:27670158). Mediates enhanced opsonization and ADCC in response to afucosylated IgGs (PubMed:34485821, PubMed:28566370)
Subcellular location
Domains and Gene Ontology detail (23)Hide
Domains & features
Gene Ontology
- Cexternal side of plasma membrane
- Cextracellular exosome
- Cextracellular space
- CFc-gamma receptor III complex
- Cplasma membrane
- FIgG binding
- FIgG receptor activity
- Fimmune receptor activity
- Flow-affinity IgG receptor activity
- Pantibody-dependent cellular cytotoxicity
- Pcalcium-mediated signaling
- Pcell surface receptor signaling pathway
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activat…
- ·antibody-dependent cellular cytotoxicity
- ·immune response
Kinase signalling
- ·Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG). Optimally activat…
- ·phosphatidylinositol 3-kinase/protein kinase B signal transduction
View underlying pathways (7)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Low affinity immunoglobulin gamma Fc region receptor III-A binding agent
Appears in clinical studies involving gastric cancer, gastric neoplasm, gastric adenocarcinoma, gastroesophageal junction adenocarcinoma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 510 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 2 total
gastric cancer · gastric neoplasm · gastric adenocarcinoma
metastatic colorectal cancer · non-small cell lung carcinoma · colorectal cancer
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (5)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.