Certain PKU-associated mutants have been demonstrated to result in protein-folding defects (e.g. R261Q, p. L249P)18,33, impairment of PAH catalytic activity (e.g. H170Q, P275L, A300S)34 or to affect conformational stability (e.g. G46S, R408W, I65S)34–36. Here, PAH is linked to phenylketonuria.