PTS

Chr 11AR

6-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]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperphenylalaninemia, BH4-deficient, AMIM #261640
AR

Clinical highlights

Gene-disease validity (ClinGen)
BH4-deficient hyperphenylalaninemia A · ARDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
12
Active trials
1881
Pubs (1 yr)
P/LP submissions
P/LP missense
1.69
LOEUF
LOF
Mechanism· G2P
📖
GeneReview available — PTS
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.69LOEUF
pLI 0.000
Z-score 0.07
OE 0.97 (0.571.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
0.13Z-score
OE missense 0.96 (0.801.16)
76 obs / 79.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.97 (0.571.69)
00.351.4
Missense OE?0.96 (0.801.16)
00.61.4
Synonymous OE?1.22
01.21.6
LoF obs/exp: 8 / 8.2Missense obs/exp: 76 / 79.1Syn Z: -0.93

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PTS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Chronic Lymphocytic Leukemia

CLL Therapy Approaches in Russia

ACTIVE NOT RECRUITING
NCT05140369AstraZenecaStarted 2021-10-29
Breast CancerER-positive Breast CancerHER2-negative Breast Cancer

Levels of Circulating Tumor DNA as a Predictive Marker for Early Switch in Treatment for Patients With Metastatic (Stage IV) Breast Cancer

ACTIVE NOT RECRUITING
NCT05826964Phase PHASE2University of MiamiStarted 2023-06-12
AI+CDK4/6iSERD+CDK4/6imTOR inhibitor + AI
Locally Advanced Pancreatic AdenocarcinomaStage III Pancreatic Cancer AJCC v8

Testing the Addition of a New Anti-cancer Drug, M3814 (Peposertib), to the Usual Radiotherapy in Patients With Locally Advanced Pancreatic Cancer

RECRUITING
NCT04172532Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2021-01-11
Biopsy ProcedureBiospecimen CollectionComputed Tomography
Malignant Solid Neoplasm

Immune Checkpoint Inhibitor Toxicity Risk Prediction in Solid Tumors

RECRUITING
NCT04871542SWOG Cancer Research NetworkStarted 2021-09-13
Biospecimen CollectionQuestionnaire Administration
Intracranial MeningiomaRecurrent MeningiomaNF2 Gene Mutation

Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas

RECRUITING
NCT02523014Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2015-09-28
VismodegibFAK Inhibitor GSK2256098Capivasertib
Chronic Granulomatous Disease (CGD)X-Linked Severe Combined Immune Deficiency (XSCID)Leukocyte Adhesion Deficiency 1 (LAD)

Evaluation of Patients With Immune Function Abnormalities

RECRUITING
NCT00128973National Institute of Allergy and Infectious Diseases (NIAID)Started 2005-09-19
Breast Cancer

S1207 Hormone Therapy With or Without Everolimus in Treating Patients With Breast Cancer

ACTIVE NOT RECRUITING
NCT01674140Phase PHASE3SWOG Cancer Research NetworkStarted 2013-09-12
anastrozoleeverolimusexemestane
Recurrent GlioblastomaRecurrent Malignant GliomaRecurrent WHO Grade II Glioma

Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma

ACTIVE NOT RECRUITING
NCT02208362Phase PHASE1City of Hope Medical CenterStarted 2015-05-18
Arm 1: IL13Ra2-specific CAR Tcm cellsArm 2: IL13Ra2-specific CAR Tcm cellsArm 3: IL13Ra2-specific CAR Tcm cells
Amyotrophic Lateral Sclerosis (ALS)

Identification of Early Markers for ALS

RECRUITING
NCT07213440Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2024-09-30
lumbar puncture
Breast Carcinoma In SituInvasive Breast CarcinomaStage I Breast Cancer AJCC v7

Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer

ACTIVE NOT RECRUITING
NCT02954874Phase PHASE3National Cancer Institute (NCI)Started 2017-01-18
Biospecimen CollectionLaboratory Biomarker AnalysisPatient Observation
Hodgkin LymphomaNon-Hodgkin Lymphoma

Evaluating the Impact of Social and Genetic Factors on Outcomes in Adolescent and Young Adult Cancer Survivors

RECRUITING
NCT06002828ECOG-ACRIN Cancer Research GroupStarted 2023-10-13
Biospecimen CollectionQuality-of-Life AssessmentQuestionnaire Administration
ALK Gene RearrangementALK Gene TranslocationALK Positive

Crizotinib 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 RECRUITING
NCT02201992Phase PHASE3ECOG-ACRIN Cancer Research GroupStarted 2015-03-23
Clinical ObservationCrizotinibLaboratory Biomarker Analysis