FCGR2A

Chr 1ADAR

Fc gamma receptor IIa

Also known as: CD32, CD32A, CDw32, FCG2, FCGR2, FCGR2A1, FcGR, FcgammaRIIa

NCBI Gene: 2212 ENSG00000143226 UniProt: P12318

This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

{Lupus nephritis, susceptibility to}MIM #152700

{Malaria, severe, susceptibility to}MIM #611162

{Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis}MIM #219700

Active trials

Pathogenic / LP

ClinVar variants

Pubs (1 yr)

0.4

Missense Z

1.35

LOEUF

Clinical Summary— FCGR2A

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

10 Pathogenic / Likely Pathogenic· 59 VUS of 92 total submissions

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

1.35LOEUF

pLI 0.000

Z-score 0.67

OE 0.79 (0.49–1.35)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.35Z-score

OE missense 0.92 (0.81–1.05)

161 obs / 174.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.79 (0.49–1.35)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.81–1.05)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18

0≤1.21.6

LoF obs/exp: 10 / 12.6Missense obs/exp: 161 / 174.1Syn Z: -1.16

0.82top 10%

GOF

0.74top 25%

LOF

0.2092th %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.