PLCG2

Chr 16AD

phospholipase C gamma 2

Also known as: APLAID, FCAS3, PLC-IV, PLC-gamma-2

NCBI Gene: 5336 ENSG00000197943 UniProt: P16885 OMIM: 600220

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a transmembrane signaling enzyme that catalyzes the conversion of 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate to 1D-myo-inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) using calcium as a cofactor. IP3 and DAG are second messenger molecules important for transmitting signals from growth factor receptors and immune system receptors across the cell membrane. Mutations in this gene have been found in autoinflammation, antibody deficiency, and immune dysregulation syndrome and familial cold autoinflammatory syndrome 3. [provided by RefSeq, Mar 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Autoinflammation, antibody deficiency, and immune dysregulation syndromeMIM #614878

Familial cold autoinflammatory syndrome 3MIM #614468

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· G2P