GSS (Glutathione Synthetase)
Key enzyme in glutathione biosynthesis, associated with metabolic disorders and hemolytic anemia
Gene Information Card
| Symbol | GSS |
|---|---|
| Full Name | Glutathione Synthetase |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 2937 ncbi.nlm.nih.gov/gene/2937 |
| Ensembl ID | ENSG00000100985 |
| UniProt ID | P48637 |
| OMIM ID | 601002 |
| HGNC ID | 4624 |
| Aliases | GSHS, GSH-S, HEL-S-64p, MGC14098 |
Description
The GSS gene encodes glutathione synthetase, the second enzyme in the glutathione biosynthesis pathway. This enzyme catalyzes the ATP-dependent condensation of gamma-glutamylcysteine and glycine to form glutathione, a critical antioxidant and detoxifying agent. Mutations in GSS cause glutathione synthetase deficiency, leading to metabolic acidosis, 5-oxoprolinuria, and hemolytic anemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glutathione synthetase deficiency | Impaired glutathione synthesis leads to accumulation of 5-oxoproline and metabolic acidosis | ClinVar, OMIM |
| Hemolytic anemia due to glutathione synthetase deficiency | Reduced glutathione increases oxidative stress in erythrocytes, causing hemolysis | ClinVar, OMIM |
| 5-Oxoprolinuria (pyroglutamic aciduria) | Deficient GSS activity results in gamma-glutamyl cycle disruption and 5-oxoproline accumulation | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 23.4 | High |
| Kidney | 18.7 | High |
| Heart | 12.1 | Medium |
| Brain | 8.5 | Medium |
| Lung | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 25.1 | Hepatocellular carcinoma cell line |
| HEK293 | 19.8 | Embryonic kidney cells |
| K562 | 14.5 | Chronic myelogenous leukemia |
| A549 | 11.2 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.656C>T (p.Pro219Leu) | Missense | Common | Reduced enzyme activity, associated with mild deficiency |
| c.847G>A (p.Glu283Lys) | Missense | Rare | Severe deficiency, metabolic crisis |
| c.374_375del (p.Leu125fs) | Frameshift | Rare | Loss of function, severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations reduce or abolish glutathione synthetase activity, leading to glutathione deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glutathione synthase activity (GO:0004363) | • glutathione biosynthetic process (GO:0006750) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • glutathione metabolic process (GO:0006749) |
Pathways
• Glutathione metabolism (KEGG: hsa00480)
• Gamma-glutamyl cycle (Reactome: R-HSA-174403)
Protein Summary
Glutathione synthetase (UniProt P48637) is a homodimeric enzyme of 474 amino acids per subunit. It catalyzes the second step of glutathione biosynthesis, using ATP to ligate gamma-glutamylcysteine and glycine. The protein is expressed in most tissues, with highest levels in liver and kidney. Defects cause glutathione synthetase deficiency, a rare autosomal recessive disorder characterized by hemolytic anemia, metabolic acidosis, and 5-oxoprolinuria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSS Knockout HEK293 Cell Line | EDJ-KQ2781 | Human | 2937 | Details Get a Quote |
| GSS Knockout HCT 116 Cell Line | EDJ-KQ22330 | Human | 2937 | Details Get a Quote |
| GSS Knockout A-549 Cell Line | EDJ-KQ23695 | Human | 2937 | Details Get a Quote |
| GSS Knockout HeLa Cell Line | EDJ-KQ23697 | Human | 2937 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
