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FLASH GENE

Symbol

FCGR3A

contributors: mct/npt - updated : 04-09-2017

HGNC name	Fc fragment of IgG, low affinity IIIa, receptor for (CD16)
HGNC id	3619

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	IMD20 Immunodeficiency 20
Location	1q23.3      Physical location : 161.511.552 - 161.520.413
Synonym name	cell differentiation antigen CD16,50-65kD, low affinity Fc gamma RIII receptor, glycosyl-phosphatidylinositol (GPI) linked membrane glycoprotein, identified by monoclonal antibodies BW209/2, 3G8, CLB/FcGran1, B73.1 (see IGFCR@)
	immunoglobulin G Fc receptor III
	neutrophil-specific antigen NA
Synonym symbol(s)	CD16, FCG3, FCGR3, IGFR3, FC3A, FCR-10, FCRIII, FCRIIIA, IGFR3, CD16a

DNA

TYPE	functioning gene
STRUCTURE	8.86 kb     5 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	alternative promoter
	Binding site   transcription factor
motif	repetitive sequence   other
text structure	three alternative promoter, Pmed1/2 and Pprox in the 5'UTR (Pmed1 containing binding sites for Sp1 and NK element-recognizing factor)
	only FCGR3A, FCGR2C and FCGR3B show CNV

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000569 5 - 2406 NP_000560 - 290 - 1990 2139735 NM_001127592 5 - 2338 NP_001121064 - 289 - 1990 2139735 NM_001127593 6 - 2204 NP_001121065 - 254 - 1990 2139735 NM_001127595 6 - 2186 NP_001121067 - 254 - 1990 2139735 NM_001127596 6 - 2183 NP_001121068 - 253 - 1990 2139735

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune spleen       predominantly Reproductive male system prostate       Respiratory lung         Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Lymphoid/Immune macrophage Lymphoid/Immune natural killer Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal sequence, two Ig-like extracellular domain
	a single transmembrane (TM) domain (TM1)
	a protein kinase C (PKC) phosphorylation consensus motif [RSSTR], pecifically phosphorylated by PKCs
	a short cytoplasmic tail whose expression at the cell surface depends on association with the signaling adaptor molecules CD247 and/or FCER1G

HOMOLOGY

Homologene

FAMILY

CATEGORY

immunity/defense , antigen , receptor

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	mediating antibody-dependent cellular cytotoxicity and other antibody-dependent responses, such as phagocytosis
	plays a prominent role in the elimination of tumor cells by antibody-based cancer therapies
	is involved in the pathogenesis of coronary heart disease (CHD) by activating monocytes and stimulating inflammation
	role for FCGR3B in the removal of soluble immune complexes within the vasculature that may serve to maintain homeostasis
	FCGR3A and PRF1 may participate in the pathogenesis and progression of primary biliary cirrhosis (PBC)
	shedding of FCGR3A/CD16A was at least partially ADAM17 dependent, and it may be considered as a marker of FCGR3A/CD16A-independent NK cell activation highly correlated with degranulation
	FCGR3A, FCGR3B are IgG Fc receptors expressed by human natural killer (NK) cells and neutrophils, respectively
	association of the adaptor modules FCER1G or CD247 with FCGR3A not only is required for progression of this receptor through the secretory pathway and cell surface expression but also protects the FCGR3A protein from degradation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	over-activation of ADAM17 in NK cells may be detrimental to their effector functions by down-regulating surface expression of FCGR3A and SELL
	MMP25 is a proteinase responsible for FCGR3A downmodulation
	FCGR3A cleavage by ADAM17, but non-cleavable version of FCGR3A can be expressed in engineered NK cells (
	expression of the FCGR3A depends on a noncovalent association with the signaling dimers FCER1G and/or CD247
	FCGR3A requires association with adaptor modules for cell surface expression but shows no preference for assembly with either CD247 or FCER1G

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

IMD20

Susceptibility

to systemic lupus erythematosus (SLE) to viral infections, recurrent and neutropenia, alloimmune neonatal to Takayasu arteritis to HIV infection and progression to immune thrombocytopenia (ITP)

Variant & Polymorphism other	genetic association between Takayasu arteritis and the FCGR2A/FCGR3A locus
	homozygous for the high activity allele of FCGR3A (158VV) were predominantly found among HIV progressors and this group was also skewed toward higher allele frequencies for the V158 variant
	FCGR3A (158V/F) polymorphism, known to increase the affinity of FCGR3A to IgG, was over-represented in ITP patients

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS