Identified in a Danish patient with hyperphenylalaninaemia. They report that this variant had “a significant amount of normal PAH enzyme activity”.
This variant is the most common cause mild recessive non-PKU Hyperphenylalaninemia in N. Europe, accounting for 5% of cases.
This variant is reported as having mild PKU severity — when in combination with more severe mutations, mild PKU is likely. When homozygous, the authors predict mild PKU or mild hyperphenylalaninemia.
In contrast to Pey AL 2004, this study reports near normal activity (80%, std dev of 16%), but finds the variant forms more aggregates and less tetramers/dimers compared to wild-type (with chaperonin, Wild type is 27% vs 73%, Y414C was 41% vs. 59%) and a lower half-denaturation temperature (Tm 55C vs 59C).
This authors report that, in a eukaryotic recombinant system, the Y414C mutant protein has 28% of the wild-type activity.
They report the recombinant protein in E coli has 9% of wild-type activity and 18% after treatment with BH4.