GSR (Glutathione-Disulfide Reductase)
A key enzyme in glutathione metabolism, oxidative stress response, and redox homeostasis.
Gene Information Card
| Symbol | GSR |
|---|---|
| Full Name | Glutathione-Disulfide Reductase |
| Gene Type | Protein coding |
| Chromosomal Location | 8p12 |
| NCBI Gene ID | 2936 ncbi.nlm.nih.gov/gene/2936 |
| Ensembl ID | ENSG00000104687 |
| UniProt ID | P00390 |
| OMIM ID | 138300 |
| HGNC ID | 4623 |
| Aliases | GR, GRase, GSRD |
Description
The GSR gene encodes glutathione-disulfide reductase (EC 1.8.1.7), a homodimeric flavoprotein that catalyzes the reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH) using NADPH as a cofactor. This enzyme is essential for maintaining intracellular redox balance, protecting cells from oxidative damage, and regenerating the major cellular antioxidant glutathione.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glutathione reductase deficiency | Loss-of-function mutations impair GSSG reduction, leading to hemolytic anemia and increased oxidative stress in erythrocytes. | ClinVar, OMIM |
| Hemolytic anemia (nonspherocytic) | Deficient GSR activity reduces erythrocyte capacity to detoxify peroxides, causing hemolysis. | OMIM |
| Susceptibility to oxidative stress | Reduced GSR activity exacerbates damage from reactive oxygen species, linked to various disorders. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 28.5 | High |
| Kidney | 22.1 | High |
| Heart | 15.3 | Medium |
| Brain | 10.2 | Medium |
| Lung | 8.7 | Medium |
| Skeletal muscle | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 32.1 | High expression in liver-derived cell line |
| HEK 293 | 18.5 | Moderate expression |
| K-562 | 12.3 | Moderate expression in erythroleukemia cells |
| HeLa | 9.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.119G>A (p.Arg40Gln) | Missense | Rare | Reduced enzyme activity; associated with glutathione reductase deficiency |
| c.473C>T (p.Thr158Ile) | Missense | Rare | Impaired NADPH binding; decreased catalytic efficiency |
| c.688G>A (p.Gly230Ser) | Missense | Rare | Altered dimer stability; loss of function |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg40Gln, p.Thr158Ile) reduce or abolish enzymatic activity, leading to glutathione reductase deficiency and hemolytic anemia.
Gain of Function (GOF)
No gain-of-function mutations reported in GSR.
Dominant Negative (DN)
No dominant-negative mutations reported; GSR deficiency is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004362 – glutathione-disulfide reductase activity | • GO:0055114 – oxidation-reduction process |
| • GO:0006749 – glutathione metabolic process | • GO:0005737 – cytoplasm |
| • GO:0005829 – cytosol | • GO:0005634 – nucleus |
| • GO:0045454 – cell redox homeostasis |
Pathways
• Glutathione metabolism (Reactome: R-HSA-174403)
• Oxidative stress response (KEGG: hsa00480)
• Pentose phosphate pathway (NADPH regeneration)
Protein Summary
Glutathione-disulfide reductase (UniProt P00390) is a 52.4 kDa homodimeric flavoprotein. Each subunit contains FAD and NADPH binding domains. The enzyme catalyzes the reversible reduction of GSSG to GSH, a critical step in maintaining cellular redox balance. It is expressed ubiquitously with highest levels in liver and kidney. Defects in GSR cause glutathione reductase deficiency, a rare autosomal recessive disorder characterized by hemolytic anemia and increased susceptibility to oxidative stress.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSR Knockout HEK293 Cell Line | EDJ-KQ3546 | Human | 2936 | Details Get a Quote |
| GSR Knockout A-549 Cell Line | EDJ-KQ25398 | Human | 2936 | Details Get a Quote |
| GSR Knockout HCT 116 Cell Line | EDJ-KQ25399 | Human | 2936 | Details Get a Quote |
| GSR Knockout HeLa Cell Line | EDJ-KQ25400 | Human | 2936 | Details Get a Quote |
| GSR Knockout MDCK Cell Line | EDJ-KZ277 | Dog | 2936 | Details Get a Quote |
| GSR Knockout HAP1 Cell Line | EDC08032 | Human | 2936 | Details Get a Quote |
Displaying Records 1 To 6 Of 6 Records
