 Adenylosuccinate lyase mutants can have considerably reduced activity whether the mutation is in or away from the active site.Disease-causing ASL mutants R396C and R396H are at the entrance to the active site and have lower Vmax than the wild-type ASL, but the mutants K246E and L311V which are away from the active site also cause decreased Vmax.ASL mutant R194C is away from the active site, and though it maintains a Vmax similar to wild-type ASL, it was shown to be the least conformationally stable of the five mutants "in vitro" and still causes disease.