DefinitionThis section has been translated automatically.
The PAH gene (PAH stands for phenylalanine hydroxylase) is a protein-coding gene located on chromosome 12q23.2. The metabolic pathways influenced by this enzyme include biogenic amine synthesis and tyrosine catabolism. It is therefore also a regulator of melanogenesis. An important paralog of this gene is TPH2.
General informationThis section has been translated automatically.
The PAH gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded enzyme phenylalanine hydroxylase hydroxylates phenylalanine to tyrosine and is therefore the rate-limiting step in phenylalanine catabolism.
Clinic: A deficiency in this enzyme activity leads to the autosomal recessive disease phenylketonuria. These patients have a light skin color, light blond hair and blue eyes.
More than a thousand PAH gene mutations are now known, with large regional differences in the mutation spectrum.
Iranian collective: A total of 129 different PAH gene mutations, including IVS10-11G > A (c.1066-11G > A) (19.23 %), p.R261Q (c.782G > A) (7.63 %), p.P281L (c.842C > T) (6.24 %), IVS2 + 5G > C (c.168 + 5G > C) (5.75 %), p.R243* (c.727 C > T) (3.59%), IVS9 + 5G > A (c.969 + 5G > A) (2.84%), p.R176* (c.526C > T) (2.42%), p.Lys363Nfs*37 (c.1089 delG) (2.13%), IVS11 + 1G > C (c.1199 + 1G > C) (2.07%) and p.L48S (c.143 T > C) (2.04%) were identified (Alibakhshi R et al. 2021).
Chinese collective: A total of 174 different PAH variants were identified: While single-base variants were distributed across the 13 exons, they were particularly concentrated in exons 7 (33.3%), 11 (14.2%), 6 (13.2%), 12 (11.0%), 3 (10.4%) and 5 (4.4%). The predominant variant was p.Arg243Gln (17.7%), followed by Ex6-96A > G (8.3%), p.Val399 = (6.4%), p.Arg53His (4.7%), p.Tyr356* (4.7%), p.Arg241Cys (4.6%), p.Arg413Pro (4.6%), p.Arg111* (4.4%), and c.442-1G > A (3.4%) (Liu N et al.(2017).
LiteratureThis section has been translated automatically.
- Alibakhshi R et al. (2021) Spectrum of PAH gene mutations in 1547 phenylketonuria patients from Iran: a comprehensive systematic review. Metab Brain Dis 36:767-780.
- Liu N et al.(2017) Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China. BMC Med Genet 18:108.
