OPLAH Gene: 5-Oxoprolinase, ATP-Hydrolysing
Essential enzyme in the gamma-glutamyl cycle for glutathione metabolism
Gene Information Card
| Symbol | OPLAH |
|---|---|
| Full Name | 5-oxoprolinase, ATP-hydrolysing |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 26873 ncbi.nlm.nih.gov/gene/26873 |
| Ensembl ID | ENSG00000120907 |
| UniProt ID | O14841 |
| OMIM ID | 613347 |
| HGNC ID | 8148 |
| Aliases | OPLAH, 5-oxoprolinase, OPLAH1 |
Description
The OPLAH gene encodes 5-oxoprolinase, an ATP-hydrolysing enzyme that catalyzes the conversion of 5-oxoproline (pyroglutamic acid) to glutamate in the gamma-glutamyl cycle. This cycle is critical for glutathione synthesis, recycling, and amino acid transport. Deficiency of OPLAH leads to 5-oxoprolinuria (pyroglutamic aciduria), a metabolic disorder characterized by accumulation of 5-oxoproline and metabolic acidosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 5-Oxoprolinuria (Pyroglutamic Aciduria) | Loss-of-function mutations in OPLAH impair conversion of 5-oxoproline to glutamate, causing accumulation of 5-oxoproline and metabolic acidosis. | ClinVar, OMIM #613347 |
| Glutathione synthetase deficiency (indirect) | Secondary 5-oxoprolinuria can occur due to defects in glutathione synthetase, but primary OPLAH deficiency is a direct cause. | OMIM #266130 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.5 | Medium |
| Liver | 10.2 | Medium |
| Small intestine | 8.1 | Medium |
| Brain | 4.3 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | High expression in embryonic kidney cells |
| HepG2 | 11.5 | Hepatocellular carcinoma cell line |
| K-562 | 6.2 | Chronic myelogenous leukemia |
| HeLa | 5.0 | Cervical adenocarcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.875G>A (p.Arg292Gln) | Missense | Rare | Reduced enzyme activity; associated with 5-oxoprolinuria |
| c.1522C>T (p.Arg508*) | Nonsense | Rare | Loss of function; premature stop codon |
| c.1873_1874del (p.Leu625Valfs*2) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most reported OPLAH mutations are loss-of-function, leading to 5-oxoprolinuria.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • 5-oxoprolinase (ATP-hydrolysing) activity (GO:0017168) | • glutathione biosynthetic process (GO:0006750) |
| • cytoplasm (GO:0005737) | • ATP binding (GO:0005524) |
| • glutamine metabolic process (GO:0006542) |
Pathways
• Gamma-glutamyl cycle (Reactome: R-HSA-174403)
• Glutathione metabolism (KEGG: hsa00480)
Protein Summary
The OPLAH protein (5-oxoprolinase) is a homodimeric enzyme that requires ATP and magnesium for activity. It catalyzes the ATP-dependent hydrolysis of 5-oxoproline to glutamate, a key step in the gamma-glutamyl cycle. The enzyme is expressed in tissues with high glutathione turnover, such as kidney and liver. Deficiency leads to accumulation of 5-oxoproline, causing metabolic acidosis and 5-oxoprolinuria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OPLAH Knockout HEK293 Cell Line | EDJ-KQ8618 | Human | 26873 | Details Get a Quote |
| OPLAH Knockout A-549 Cell Line | EDJ-KQ34764 | Human | 26873 | Details Get a Quote |
| OPLAH Knockout HCT 116 Cell Line | EDJ-KQ34765 | Human | 26873 | Details Get a Quote |
| OPLAH Knockout HeLa Cell Line | EDJ-KQ34766 | Human | 26873 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
