PLCG2: Phospholipase C Gamma 2
Key signaling enzyme in immune cell activation and calcium regulation
Gene Information Card
| Symbol | PLCG2 |
|---|---|
| Full Name | phospholipase C gamma 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 16q23.3 |
| NCBI Gene ID | 5336 ncbi.nlm.nih.gov/gene/5336 |
| Ensembl ID | ENSG00000197943 |
| UniProt ID | P16885 |
| OMIM ID | 600220 |
| HGNC ID | 9066 |
| Aliases | PLC-gamma-2, PLC-IV, PLCgamma2 |
Description
PLCG2 encodes phospholipase C gamma 2, a key enzyme in intracellular signal transduction. It is primarily expressed in hematopoietic cells and catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to generate second messengers inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), leading to calcium mobilization and protein kinase C activation. PLCG2 is critical for B cell receptor, Fc receptor, and T cell receptor signaling, regulating immune cell activation, proliferation, and differentiation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| PLAID (PLCγ2-associated antibody deficiency and immune dysregulation) | Autosomal dominant gain-of-function mutations in PLCG2 cause constitutive activation of phospholipase C, leading to aberrant calcium signaling, cold-induced urticaria, and antibody deficiency. | OMIM #614468; PMID: 22236195 |
| APLAID (autoinflammatory PLCγ2-associated antibody deficiency and immune dysregulation) | Autosomal dominant gain-of-function mutations in PLCG2 result in recurrent infections, autoinflammation, and skin blistering due to enhanced PLC activity. | OMIM #614878; PMID: 22236196 |
| Familial cold autoinflammatory syndrome 3 (FCAS3) | Gain-of-function PLCG2 mutations cause cold-induced urticaria, fever, and arthralgia. | OMIM #614468; ClinVar |
| Chronic lymphocytic leukemia (CLL) | Somatic mutations and altered expression of PLCG2 are associated with B cell receptor signaling dysregulation and ibrutinib resistance. | COSMIC; PMID: 25605293 |
| Common variable immunodeficiency (CVID) | Rare PLCG2 variants may contribute to impaired B cell function and hypogammaglobulinemia. | ClinVar; PMID: 22236195 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 48.2 | High |
| Lymph node | 42.1 | High |
| Bone marrow | 35.6 | High |
| Blood | 30.4 | High |
| Lung | 12.3 | Medium |
| Small intestine | 8.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (B lymphocyte) | 62.5 | High expression |
| Jurkat (T lymphocyte) | 45.3 | High expression |
| THP-1 (monocyte) | 28.1 | Moderate expression |
| HEK293 (embryonic kidney) | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2120C>A (p.Ser707Tyr) | Missense | Rare (germline) | Gain-of-function; associated with PLAID/APLAID |
| c.2419G>A (p.Glu807Lys) | Missense | Rare (germline) | Gain-of-function; associated with FCAS3 |
| c.3425G>A (p.Arg1142His) | Missense | Somatic (CLL) | Altered BCR signaling; ibrutinib resistance |
| c.3496C>T (p.Arg1166Trp) | Missense | Somatic (CLL) | Gain-of-function; ibrutinib resistance |
Mutation functional classification
Loss of Function (LOF)
Rare; not well characterized in human disease. Knockout studies in mice show impaired B cell development and antibody responses.
Gain of Function (GOF)
Common mechanism in PLAID, APLAID, and FCAS3. Mutations in the SH2 domain or catalytic region lead to constitutive PLC activity, increased IP3 production, and elevated calcium flux.
Dominant Negative (DN)
Not reported for PLCG2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• B cell receptor signaling pathway (KEGG hsa04662)
• Fc gamma R-mediated phagocytosis (KEGG hsa04666)
• Calcium signaling pathway (KEGG hsa04020)
• Phospholipase C signaling (Reactome R-HSA-1855204)
Protein Summary
Phospholipase C gamma 2 (PLCγ2) is a 1265-amino acid protein containing pleckstrin homology (PH), Src homology 2 (SH2), Src homology 3 (SH3), and catalytic domains. It is activated by tyrosine phosphorylation downstream of immune receptors such as BCR and FcRs. Upon activation, PLCγ2 hydrolyzes PIP2 to IP3 and DAG, triggering calcium release from endoplasmic reticulum and activation of PKC, NF-κB, and MAPK pathways. PLCγ2 is essential for B cell maturation, antibody production, and innate immune responses. Dysregulation due to gain-of-function mutations leads to autoinflammatory and immunodeficiency syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLCG2 Knockout HEK293 Cell Line | EDJ-KQ583 | Human | 5336 | Details Get a Quote |
| PLCG2 Knockout A-549 Cell Line | EDJ-KQ19003 | Human | 5336 | Details Get a Quote |
| PLCG2 Knockout HCT 116 Cell Line | EDJ-KQ19004 | Human | 5336 | Details Get a Quote |
| PLCG2 Knockout HeLa Cell Line | EDJ-KQ54152 | Human | 5336 | Details Get a Quote |
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