In addition to promoting phosphorylation-dependent eNOS activation, Rap1 is required for Ca2+-dependent eNOS activation, as endothelium-specific deletion of Rap1 leads to a significant impairment of acetylcholine induced-Ca2+-dependent vasodilation and is sufficient to induce hypertension in vivo [128,143]. The gene discussed is RAP1A; the disease is Hypertension.