PIK3CD Gene: Function, Mutations, and Associated Diseases

PIK3CD encodes the p110δ catalytic subunit of class I phosphoinositide 3-kinase (PI3K), which is primarily expressed in leukocytes. This enzyme phosphorylates phosphatidylinositol (4,5)-bisphosphate to generate phosphatidylinositol (3,4,5)-trisphosphate, a key second messenger that activates downstream signaling pathways including AKT/mTOR, regulating cell growth, proliferation, survival, and immune cell function. Gain-of-function mutations cause activated PI3K-delta syndrome (APDS), an immunodeficiency disorder, while somatic alterations are implicated in B-cell lymphomas and other cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• PI3K/AKT signaling pathway (KEGG hsa04151)

• B cell receptor signaling pathway (KEGG hsa04662)

• Fc gamma R-mediated phagocytosis (KEGG hsa04666)

• T cell receptor signaling pathway (KEGG hsa04660)

• mTOR signaling pathway (KEGG hsa04150)

The p110δ catalytic subunit of PI3K is a 110 kDa protein that forms heterodimers with regulatory subunits (p85α, p85β, p55γ). It is selectively expressed in leukocytes and is essential for B-cell and T-cell development, activation, and function. The protein contains an N-terminal adaptor-binding domain (ABD), a Ras-binding domain (RBD), a C2 domain, a helical domain, and a C-terminal catalytic kinase domain. Gain-of-function mutations typically cluster in the helical or kinase domains, leading to increased lipid kinase activity and hyperactivation of downstream AKT signaling. The protein is a therapeutic target in B-cell malignancies and autoimmune diseases; inhibitors such as idelalisib are used clinically.