PIK3CA

The p110α catalytic subunit of class IA PI3K, encoded by PIK3CA, heterodimerizes with p85 regulatory subunits to convert PIP2 into PIP3 downstream of receptor tyrosine kinases, recruiting and activating AKT and mTOR. PIK3CA is one of the most frequently mutated genes in human cancer, with gain-of-function mutations clustering in its helical and kinase domains that render signaling constitutive. Beyond oncology, germline PIK3CA variants cause the overgrowth spectrum now named PROS, and p110α drives insulin action in metabolic tissues, which is why isoform-selective inhibitors such as alpelisib have entered clinical use.