PTS

6-pyruvoyltetrahydropterin synthase (PTPS) is a Zn2+-dependent lyase that catalyzes the second step in de novo tetrahydrobiopterin (BH4) biosynthesis, converting 7,8-dihydroneopterin triphosphate (DHNTP) to 6-pyruvoyl-5,6,7,8-tetrahydropterin (6-PTP). The enzyme functions as a homohexamer (two trimers in head-to-head fashion) with active sites at subunit interfaces containing an intersubunit Cys-Asp-His catalytic triad. Phosphorylation at Ser-19 by cGMP-dependent protein kinase II (PKG2) is required for maximal enzyme activity. PTPS is primarily a cytosolic enzyme and is part of the GCH1-PTS-SPR pathway that supplies BH4, an essential cofactor for aromatic amino acid hydroxylases (PAH, TH, TPH1/2), nitric oxide synthases (NOS1/2/3), and alkylglycerol monooxygenase. Biallelic loss-of-function mutations cause PTPS deficiency (OMIM 261640), a form of BH4-deficient hyperphenylalaninemia with central neurotransmitter deficiency leading to progressive cognitive and motor deficits if untreated.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.