PTS
Chr 11AR6-pyruvoyltetrahydropterin synthase
Also known as: PTPS
The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008]
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene — mechanism propensity
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
374 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 17 | 15 | 9 | 0 | 41 |
Likely Pathogenic | 33 | 36 | 2 | 1 | 72 |
VUS | 1 | 58 | 9 | 2 | 70 |
Likely Benign | 0 | 1 | 92 | 56 | 149 |
Benign | 0 | 0 | 14 | 1 | 15 |
Conflicting | — | 19 | |||
| Total | 51 | 110 | 126 | 60 | 366 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →13 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap PTS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
PTS · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer
ACTIVE NOT RECRUITINGTesting the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma
ACTIVE NOT RECRUITINGCrizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
ACTIVE NOT RECRUITINGOctreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor
ACTIVE NOT RECRUITINGNivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
ACTIVE NOT RECRUITINGEarly Post-Traumatic Seizures Prevention Trial (E-PTS Trial)
RECRUITINGPrecursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19
ACTIVE NOT RECRUITINGOral Arsenic With ATRA for Newly Diagnosed Patients With Acute Promyelocytic Leukemia
RECRUITINGPhysician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery
ACTIVE NOT RECRUITINGComparing Combinations of Targeted Drugs for Advanced Non-Small Cell Lung Cancer That Has EGFR and MET Gene Changes (A Lung-MAP Treatment Trial)
RECRUITINGCAR-T Long Term Follow Up (LTFU) Study
RECRUITINGInvestigator Grant (IG) 2022 27746
RECRUITINGExternal Resources
Links to major genomics databases and tools