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PLCG2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PLCG2 gene

The PLCG2 gene provides instructions for making an enzyme critical for immune system signaling, cell growth, and the body's response to infection.

Normal Function

The PLCG2 gene provides instructions for making an enzyme called phospholipase C gamma 2 (PLCγ2). This enzyme relays signals from outside the cell to the inside, directing cellular functions such as growth, maturation, and migration. It is particularly important in immune system cells, including B cells, natural killer (NK) cells, and mast cells.

When foreign invaders are detected, PLCγ2 triggers B cells to produce antibodies and NK cells to destroy invaders. In mast cells, the enzyme triggers inflammation and plays a role in allergic reactions.

Health Conditions Related to Genetic Changes

PLCG2-associated antibody deficiency and immune dysregulation (PLAID)

Mutations in the PLCG2 gene can cause PLAID, characterized by hives or rashes when exposed to cool temperatures. These germline mutations delete small pieces of DNA, altering the region of the enzyme that controls activation. At low temperatures, the enzyme is constantly turned on, triggering rashes. At normal body temperatures, the enzyme's activity is reduced, impairing B-cell and NK-cell function and leading to recurrent infections.

Other disorders

  • APLAID (Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation): Caused by mutations that change single amino acids in the enzyme. The enzyme is constantly turned on at normal body temperatures, causing uncontrolled inflammation and recurrent infections. Unlike PLAID, this is not associated with cold-induced allergic reactions.
  • Ibrutinib resistance: Somatic mutations in the PLCG2 gene can arise in cancer cells during a person's lifetime. These mutations increase the activity of the PLCγ2 protein, allowing cancerous cells to multiply even when the drug ibrutinib is used to block signaling.

Frequently Asked Questions

The diagnosis is confirmed by sequencing the PLCG2 gene from a blood sample. A positive result indicates a germline mutation that either keeps the enzyme constantly active (PLAID) or causes uncontrolled inflammation (APLAID). Knowing the mutation type helps guide treatment—antihistamines and cold avoidance for PLAID, or immunosuppressive therapy for APLAID.
Patients may present with chronic hives that flare when exposed to cold temperatures, along with a history of frequent upper respiratory infections, sinusitis, or pneumonia. In APLAID, the rash is not cold‑triggered but patients still experience recurrent infections and may have systemic inflammation such as fevers or joint pain. A detailed history and physical exam can raise suspicion for a PLCG2‑related disorder.
First‑line treatment includes non‑sedating antihistamines taken daily. For severe cases, add a leukotriene receptor antagonist or a low‑dose systemic steroid during flare periods. Patients should avoid cold exposure by wearing insulated clothing, using heated rooms, and applying topical barrier creams. Regular monitoring of symptom severity helps adjust medication doses.
Somatic PLCG2 mutations increase the enzyme’s activity, allowing malignant B cells to bypass the B‑cell receptor blockade that ibrutinib targets. When resistance develops, clinicians may switch to other Bruton's tyrosine kinase inhibitors (e.g., acalabrutinib), use B‑cell receptor‑independent agents such as venetoclax, or consider targeted therapies like PI3K inhibitors. Clinical trials may also offer access to novel agents that bypass PLCG2‑mediated pathways.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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