HBB and beta thalassemia: Both of these diseases are caused by mutations in the β-globin gene (HBB), which encodes two of the four hemoglobin chains, with beta-thalassemia being caused by various loss-of-function mutations that result in decreased expression or loss of function of the protein, and SCD being caused by a point mutation that results in the substitution of glutamate for valine in the active center, which affects the structure of hemoglobin and ultimately changes the shape of red blood cells.