PLCG2 (P16885) variants and mutations

PLCG2 (also known as P16885) is a human protein-coding gene encoding a 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 protein. It generates IP3 and diacylglycerol downstream of immune receptors, triggering intracellular calcium release and protein-kinase-C signaling in B cells and myeloid cells. Gain-of-function variants cause autoinflammatory and antibody-deficiency syndromes, while somatic mutations can mediate resistance to BTK inhibitors. This analysis covers 1,789 PLCG2 variants and mutations. Of these, 83% have computational variant effect predictions. Disease context includes PLCG2-associated antibody deficiency and immune dysregulation, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, and familial cold autoinflammatory syndrome 3. Example PLCG2 variants include S2S, T3N, and T3P.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.

Notable PLCG2 variants

Examples include S2S, T3N, T3P, T3A, T3S, T3I, T3T, T4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.