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PIK3CD gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PIK3CD gene

The PIK3CD gene provides instructions for making a protein essential for immune system function, and variants in this gene are linked to activated PIK3-delta syndrome.

Normal Function

The PIK3CD gene provides instructions for making the p110 delta (p110δ) protein, which is one subunit of an enzyme called phosphatidylinositol 3-kinase (PI3K). The version of PI3K containing this subunit, known as PI3K delta, is found in white blood cells, specifically lymphocytes such as B cells and T cells. These cells are responsible for recognizing and attacking foreign invaders like viruses and bacteria.

PI3K delta functions as a kinase, adding a phosphate group to other proteins through a process called phosphorylation. This triggers signaling cascades within cells. In lymphocytes, this signaling is critical for cell growth, division (proliferation), and maturation (differentiation), helping B and T cells develop into specialized types with distinct immune functions.

Health Conditions Related to Genetic Changes

Activated PIK3-delta syndrome

Variants in the PIK3CD gene cause a condition known as activated PIK3-delta syndrome type 1. Individuals with this condition typically experience recurrent bacterial respiratory infections and chronic viral infections.

  • Mechanism: These variants are classified as gain-of-function, meaning the resulting PI3K-delta enzyme is frequently overactive.
  • Impact on T cells: Overactive signaling causes T cells to mature and die prematurely.
  • Impact on B cells: The signaling blocks B cell maturation at an early stage, leading to immature cells that cannot respond to invaders and likely self-destruct.
  • Clinical consequences: The resulting lack of functional B and T cells impairs the body's ability to fight infections. Additionally, abnormal proliferation of lymphocytes can lead to enlarged lymph nodes (lymphadenopathy) and an increased risk of lymphoma, a form of blood cell cancer.

Autoimmune lymphoproliferative syndrome

The PIK3CD gene is also associated with autoimmune lymphoproliferative syndrome.

Genomic Location

The PIK3CD gene is located on chromosome 1.

Frequently Asked Questions

Live viral or bacterial vaccines (such as MMR, varicella, rotavirus, or BCG) are generally contraindicated or require extreme caution in patients with APDS due to underlying T-cell dysfunction, which can allow live vaccine strains to cause persistent, systemic infection. Inactivated or mRNA vaccines are safe but often fail to generate an adequate, protective antibody response due to impaired B-cell maturation. An immunologist must evaluate vaccine titers and determine an individualized vaccination and antibody-replacement strategy.
In addition to supportive immune therapies, targeted small-molecule inhibitors have been developed to address the specific biochemical defect. Leniolisib is an oral selective PI3K-delta inhibitor approved for APDS that directly downregulates the hyperactive p110-delta enzyme pathway, helping to restore normal lymphocyte development and reduce lymph node and spleen enlargement. Patients also frequently receive subcutaneous or intravenous immunoglobulin (SCIG/IVIG) replacement therapy and prophylactic antibiotics to prevent bacterial infections.
The gain-of-function mutation in PIK3CD causes the p110-delta subunit to become continuously overactive, leading to excessive cellular proliferation and preventing normal apoptosis (programmed cell death) of lymphocytes. This persistent, unregulated expansion of B and T cells, combined with chronic immune stimulation from recurrent viral infections like EBV, creates an environment where malignant transformation can occur. Routine clinical screening, including periodic imaging of persistently enlarging lymph nodes and routine blood counts, is essential to detect lymphoma early.
The earliest indicators typically include frequent, recurrent upper and lower respiratory tract infections (such as recurrent otitis media, chronic sinusitis, and repeated bouts of pneumonia) beginning in infancy or early childhood. Caregivers may also notice persistently enlarged lymph nodes (lymphadenopathy) in the neck or groin, chronic tonsillar enlargement that obstructs breathing, an enlarged spleen (splenomegaly), and recurrent or hard-to-clear herpesvirus infections, such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV).
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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