To the best of our knowledge, this work represents the first computational study of the generation and maintenance mechanisms of AF induced by the three gain-of-function mutations—KCNH2 T895M, KCNH2 T436M, and KCNE3-V17M—on human atrial electrophysiological models at the cellular and tissue levels. The gene discussed is KCNE3; the disease is atrial fibrillation.