PTS

Chr 11AR

6-pyruvoyltetrahydropterin synthase

Also known as: PTPS

The encoded enzyme catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for enzymes involved in serotonin biosynthesis and nitric oxide synthase activity. Mutations cause autosomal recessive hyperphenylalaninemia due to BH4 deficiency. The pathogenic mechanism involves disrupted tetrahydrobiopterin synthesis leading to deficient cofactor availability for critical enzymatic processes.

OMIMResearchSummary from RefSeq, OMIM
LOFmechanismARLOEUF 1.691 OMIM phenotype
Clinical SummaryPTS
🧬
Gene-Disease Validity (ClinGen)
BH4-deficient hyperphenylalaninemia A · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

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 OE0.97 (0.571.69)
00.351.4
Missense OE0.96 (0.801.16)
00.61.4
Synonymous OE1.22
01.21.6
LoF obs/exp: 8 / 8.2Missense obs/exp: 76 / 79.1Syn Z: -0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePTS-related 6-pyruvoyltetrahydropterin synthase deficiencyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7035th %ile
GOF
0.4874th %ile
LOF
0.4332th %ile

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.

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Cancer, MetastaticCancerCancer of Pancreas

SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry

RECRUITING
NCT03452774Massive Bio, Inc.Started 2018-01-01
Clinical Trial Matching
Muscle Invasive Bladder Cancer

Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer

ACTIVE NOT RECRUITING
NCT02546661Phase PHASE1AstraZenecaStarted 2016-12-28
AZD4547MEDI4736Olaparib
Breast CancerPALB2-Mutated Breast CarcinomaHER2-negative Breast Cancer

Phase Ib Study of Axatilimab in Combination With Olaparib in BRCA1/2 and PALB2- Associated Metastatic HER2-negative Breast Cancer

RECRUITING
NCT06488378Phase PHASE1Dana-Farber Cancer InstituteStarted 2024-08-13
AxatilimabOlaparib
Recurrent Lung Non-Small Cell CarcinomaStage IV Lung Cancer AJCC v8

Ramucirumab Plus Pembrolizumab vs Usual Care for Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer Following Immunotherapy, Pragmatica-Lung Study

ACTIVE NOT RECRUITING
NCT05633602Phase PHASE3SWOG Cancer Research NetworkStarted 2023-03-14
ChemotherapyPembrolizumabRamucirumab
Colorectal Neuroendocrine Tumor G1Gastric Neuroendocrine Tumor G1Neuroendocrine Neoplasm

Octreotide Acetate and Recombinant Interferon Alfa-2b or Bevacizumab in Treating Patients With Metastatic or Locally Advanced, High-Risk Neuroendocrine Tumor

ACTIVE NOT RECRUITING
NCT00569127Phase PHASE3National Cancer Institute (NCI)Started 2007-12-01
BevacizumabLaboratory Biomarker AnalysisOctreotide Acetate
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
Infiltrating Bladder Urothelial CarcinomaStage II Bladder Urothelial CarcinomaStage III Bladder Urothelial Carcinoma

Gemcitabine and Cisplatin Without Cystectomy for Patients With Muscle Invasive Bladder Urothelial Cancer and Select Genetic Alterations

ACTIVE NOT RECRUITING
NCT03609216Phase PHASE2Alliance for Clinical Trials in OncologyStarted 2018-12-10
Gemcitabine HydrochlorideCisplatinPegfilgrastim
LeukemiaAcute Lymphoblastic Leukemia

Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19

ACTIVE NOT RECRUITING
NCT01044069Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2010-01-05
gene-modified T cells targeted
Chronic Lymphocytic Leukemia

CLL Therapy Approaches in Russia

ACTIVE NOT RECRUITING
NCT05140369AstraZenecaStarted 2021-10-29
GranulomaGranulomatous Disease, ChronicLeukocyte Disease

Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes

RECRUITING
NCT00001405National Institute of Allergy and Infectious Diseases (NIAID)Started 1994-02-27
Relapsed B-Cell Acute Lymphoblastic Leukemia

T-Lymphocytes Genetically Targeted to the B-Cell Specific Antigen CD19 in Pediatric and Young Adult Patients With Relapsed B-Cell Acute Lymphoblastic Leukemia

ACTIVE NOT RECRUITING
NCT01860937Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2013-05
leukapheresis or collection of PBMCscyclophosphamide based chemotherapy regimensmodified T cells
Stage IB Lung Non-Small Cell Carcinoma AJCC v7Stage II Lung Non-Small Cell Cancer AJCC v7Stage IIA Lung Cancer AJCC v8

Genetic Testing in Screening Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been or Will Be Removed by Surgery (The ALCHEMIST Screening Trial)

ACTIVE NOT RECRUITING
NCT02194738Phase NANational Cancer Institute (NCI)Started 2014-09-26
Biospecimen CollectionCarboplatinCisplatin
Clinical Literature
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