FCGR3A

Chr 1AR

Fc gamma receptor IIIa

Also known as: CD16-II, CD16A, FCG3, FCGR3, FCRIIIA, FcGRIIIA, IGFR3, IMD20

NCBI Gene: 2214ENSG00000203747UniProt: P08637OMIM: 146740

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]

OMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 1.501 OMIM phenotype
Clinical Summary— FCGR3A
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 VUS of 76 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.50LOEUF
pLI 0.000
Z-score 0.41
OE 0.86 (0.52–1.50)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-1.04Z-score
OE missense 1.24 (1.10–1.40)
186 obs / 150.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.86 (0.52–1.50)
0≤0.351.4
Missense OE?1.24 (1.10–1.40)
0≤0.61.4
Synonymous OE?0.96
0≤1.21.6
LoF obs/exp: 9 / 10.4Missense obs/exp: 186 / 150.2Syn Z: 0.26

This gene — mechanism propensity

DN
0.82top 10%
GOF
0.6930th %ile
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

76 submitted variants in ClinVar

ClinVar

Classification Summary

VUS50
Likely Benign10
Benign6
50
VUS
10
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
1
47
1
1
50
Likely Benign
0
9
0
1
10
Benign
0
4
1
1
6
Total1602366

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap FCGR3A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

FCGR3A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients