Bruton’s tyrosine kinase, a Tec family tyrosine kinase, an effector of PI3K activity, whose activation, in part, depends on the binding of PtdIns(3,4,5)P3 to the PH domain and is important for an enhanced intracellular Ca2+ signalling, caused AF in an off-target side effect, through atrial enlargement. The gene discussed is PIK3CA; the disease is atrial fibrillation.