PLCG2
Chr 16ADphospholipase C gamma 2
Also known as: APLAID, FCAS3, PLC-IV, PLC-gamma-2
The encoded phospholipase C gamma 2 enzyme catalyzes the conversion of phosphatidylinositol 4,5-bisphosphate to the second messengers IP3 and diacylglycerol, which are crucial for transmitting signals from growth factor and immune system receptors across cell membranes. Mutations cause autoinflammation, antibody deficiency, and immune dysregulation syndrome as well as familial cold autoinflammatory syndrome 3, both inherited in an autosomal dominant pattern. This gene is highly constrained against loss-of-function mutations, indicating that protein function is essential for normal cellular processes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
100 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 0 | 0 | 0 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 3 | 38 | 6 | 0 | 47 |
Likely Benign | 0 | 0 | 24 | 29 | 53 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 3 | 38 | 30 | 29 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PLCG2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools