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Last update 08 May 2025

OPLAH

Last update 08 May 2025

Basic Info

Synonyms

5-Opase, 5-oxo-L-prolinase, 5-oxoprolinase

+ [4]

Introduction

Catalyzes the cleavage of 5-oxo-L-proline to form L-glutamate coupled to the hydrolysis of ATP to ADP and inorganic phosphate.

Drugs associated with OPLAH

CN114574486

Patent Mining

Target

OPLAH

Mechanism-

Active Org.

Dalian Institute of Chemical Physics Chinese Academy of Sci

Originator Org.

Dalian Institute of Chemical Physics Chinese Academy of Sci

Active Indication

Prostatic Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with OPLAH

100 Translational Medicine associated with OPLAH

0 Patents (Medical) associated with OPLAH

125

Literatures (Medical) associated with OPLAH

01 Jun 2025·Pediatric Blood & Cancer

Amino Acid Stress Response Genes Contribute to a 25‐Fold Increased Risk of L‐Asparaginase–Induced Hypersensitivity

Article

Author: Scott, Erika N. ; Trueman, Jessica N. ; Chang, Wan‐Chun ; Anderson, Spencer J. ; Córdova‐Delgado, Miguel ; Raack, Edward J. ; Carleton, Bruce C. ; Rassekh, S. Rod. ; Loucks, Catrina M. ; Ross, Colin J. D.

ABSTRACTBackgroundL‐asparaginase is essential in treating pediatric acute lymphoblastic leukemia (ALL) but is limited by hypersensitivity reactions in up to 70% of patients, leading to severe, dose‐limiting complications and compromised event‐free survival.ProcedureThis study conducted a genome‐wide association study (GWAS) in a discovery cohort of 221 pediatric cancer patients who experienced l‐asparaginase–induced hypersensitivity reactions (≥CTCAE grade 2) and 705 controls without hypersensitivity despite equivalent exposure. Results were replicated in an independent cohort of 41 cases and 139 controls.ResultsSignificant associations were identified between hypersensitivity and four genes crucial for amino acid stress response: CYP1B1 (rs59569490; odds ratio [OR] = 8.5; 95% confidence interval [CI], 3.9–18.5; p = 1.5 × 10−10), SEC16B (rs115461320; OR = 4.2; 95% CI, 2.5–7.9; p = 1.2 × 10−6), OPLAH (rs11993268; OR = 4.8; 95% CI, 2.4–9.9; p = 2.0 × 10−6), and SORCS2 (rs11940340; OR = 6.7; 95% CI, 2.8–15.7; p = 5.7 × 10−7). Variants in SEC16B, OPLAH, and SORCS2 remained significant in the analysis of the replication cohort (p < 0.05). Patients who carried risk alleles in two or more of these genes experienced an 86.4% increased incidence of hypersensitivity reactions in the discovery cohort (OR = 25.2; 95% CI, 7.4–86.2; p = 1.0 × 10−10), which was replicated in the independent cohort with a 100% incidence in carriers (p = 0.04).ConclusionsThe cumulative incidence of these large effect variants highlights their significance for the identification of patients at high risk of l‐asparaginase–induced hypersensitivity. Successfully identifying patients at increased risk of hypersensitivity reactions can inform personalized treatment strategies and limit these harmful dose‐limiting reactions in pediatric ALL.

01 Jan 2024·Molecular Syndromology

Is 5-Oxoprolinase Deficiency More than Just a Benign Condition?

Article

Author: Kasapkara, Çiğdem Seher ; Kıreker Köylü, Oya ; Ceylan, Nesrin ; Ceylaner, Serdar ; Yürek, Burak ; Engin Erdal, Ayşenur

Introduction: Inherited 5-oxoprolinase (OPLAH) deficiency is a rare inborn condition characterized by 5-oxoprolinuria. The inherited condition of 5-oxoprolinuria, or pyroglutamic aciduria, is primarily caused by mutations in the genes that encode glutathione synthetase (GSS) and 5-oxoprolinase (OPLAH), which are enzymes involved in the gamma-glutamyl cycle in glutathione metabolism. We report a 3-year-old male patient with epilepsy and speech difficulty diagnosed as primary 5-oxoprolinuria due to a novel OPLAH gene mutation. Case Presentation: A 3-year-old boy who was delivered at full term in an uncomplicated birth to consanguineous parents presented with epilepsy at the age of 2 years. He did not speak fluently. He was using 5–10 words with decreased language fluency. His past medical history revealed postnatal macrocephaly, hydrocephalus, and well-controlled epilepsy with levetiracetam. Progressive cerebral atrophy, hypomyelination, ventriculomegaly, and corpus callosum hypoplasia were striking features in brain MRI. A urine sample was sent for organic acid analysis by gas chromatography-mass spectrometry (GC-MS); quantitation of 5-oxoproline by stable isotope dilution gave a value of 177.9 mmol/mol creatinine (reference values 25.8–92.2). Molecular genetic analysis of the OPLAH gene revealed a novel homozygous variant (OPLAH (NM_017570.5): c.1909C>T p.Arg637Trp). Conclusion: We conclude that inherited 5-oxoprolinase deficiency is not a benign biochemical condition, and patients with 5-oxoprolinuria should be screened for it. The nature of this inherited metabolic disorder must be determined through long-term observation. We wish to emphasize the significance of molecular genetic analysis in symptomatic patients with persistently elevated levels of 5-oxoproline in the urine, as measured by organic acid analysis.

01 Jan 2023·Cancer Genomics - Proteomics

OPLAH Protein Expression Stratifies the Prognosis of Patients With Squamous Cell Carcinoma of the Esophagus

Article

Author: Tanaka, Chie ; Kishida, Takayoshi ; Sasahara, Masahiro ; Inokawa, Yoshikuni ; Hayashi, Masamichi ; Shimizu, Dai ; Sato, Yusuke ; Kanda, Mitsuro ; Motoyama, Satoru ; Nakamura, Shunsuke ; Kodera, Yasuhiro ; Ueda, Sei ; Hattori, Norifumi

BACKGROUND/AIMSquamous cell carcinoma is one of the major subtypes of esophageal carcinoma, and the 5-year overall survival rate of esophageal squamous cell carcinoma patients who underwent curative treatment remains below 40%. We aimed to detect and validate the prognosticators of esophageal squamous cell carcinoma in patients who underwent radical esophagectomy.MATERIALS AND METHODSComprehensive analysis of transcriptome and clinical data from The Cancer Genome Atlas revealed OPLAH as one of the differentially expressed genes between esophageal squamous cell carcinoma tissues and normal esophageal mucosa. OPLAH expression changes were significantly associated with a patient prognosis. OPLAH protein levels were further evaluated by immunohisto-chemistry in esophageal squamous cell carcinoma tissues (n=177) as well as in serum samples (n=54) using ELISA.RESULTSOPLAH mRNA was significantly overexpressed in esophageal squamous cell carcinoma tissues compared to normal esophageal mucosa, and patients with high OPLAH mRNA expression have a significantly poorer prognosis, according to The Cancer Genome Atlas data. The high staining intensity of OPLAH protein in esophageal squamous cell carcinoma tissue clearly stratified patient prognosis. According to multivariable analysis, high OPLAH protein expression was an independent prognostic factor for survival after surgery. Pre-neoadjuvant chemotherapy serum OPLAH protein concentrations were significantly associated with clinical tumor depth and node positivity and, consequently, with advanced clinical stage. The serum OPLAH protein concentration was significantly decreased by neoadjuvant chemotherapy.CONCLUSIONOPLAH protein expression in cancerous tissue and serum may have clinical utility towards stratifying prognosis of patients with esophageal squamous cell carcinoma.

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OPLAH

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