A rare missense mutation (R274H) in AKT2 found in diabetes patients results in the loss of kinase activity.469 Although other missense mutations (such as R208K and R467W) do not cause a loss of kinase activity in vitro,470 functional loss mutations in AKT can impede the normal activation of its downstream targets, mTORC1 and GSK-3β, leading to reduced glycogen synthesis and impaired glucose uptake.471 Furthermore, dysregulation of AKT signaling is associated with increased lipolysis in adipocytes, which exacerbates insulin resistance and hyperglycemia.472. The gene discussed is AKT1; the disease is Insulin resistance.