Single/multiple amino acid substitutions in the JH7 domain naturally occurring in JAK3 deficiency patients or from JAK3-JAK1 or JAK3-JAK2 chimeras can prevent kinase–receptor interaction and IL-2-induced signaling (6, 7, 22, 24, 25). The gene discussed is JAK2; the disease is hyperinsulinemic hypoglycemia, familial, 4.