Phosphatidylinositol 4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A)

Phosphatidylinositol 4-phosphate 3-kinase catalytic subunit type 2 alpha (PIK3C2A) is a member of the Class II phosphoinositide 3-kinase (PI3K) family that catalyzes the synthesis of PI3P and PI(3,4)P2 (UniProt O00443). Unlike Class I PI3Ks, PIK3C2A is primarily involved in intracellular membrane trafficking, specifically clathrin-mediated endocytosis and the formation of primary cilia (PubMed: 29109504). It plays a critical role in vascular signaling, insulin-stimulated glucose uptake, and the regulation of the cell cycle (PubMed: 22431513). Loss-of-function mutations in the PIK3C2A gene are the underlying cause of Galloway-Mowat syndrome, a rare disorder characterized by microcephaly and nephrotic syndrome (PubMed: 30478443). In oncology, PIK3C2A is often overexpressed in breast and prostate cancers, where it contributes to tumor cell survival and chemoresistance. While most clinical PI3K inhibitors target Class I isoforms, PIK3C2A is an emerging target for metabolic and malignant diseases. Therapeutic strategies include small molecule inhibition of the kinase domain or the targeting of PIK3C2A mRNA using RNA interference to modulate protein levels in disease states.

Other names

PI3-K-C2API3K-C2-alphaCPKPhosphoinositide-3-kinase-C2-alphaPI3K-C2A

Inhibition of the catalytic activity of the PIK3C2A enzyme to prevent the phosphorylation of phosphatidylinositol (PI) and PI4P, or the use of antisense oligonucleotides and siRNA to induce degradation of PIK3C2A mRNA, thereby reducing protein expression and downstream signaling (PubMed: 29109504).