GSTZ1: Glutathione S-Transferase Zeta 1
A key enzyme in tyrosine catabolism and xenobiotic metabolism, associated with tyrosinemia and oxidative stress disorders.
Gene Information Card
| Symbol | GSTZ1 |
|---|---|
| Full Name | Glutathione S-Transferase Zeta 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q24.3 |
| NCBI Gene ID | 2954 ncbi.nlm.nih.gov/gene/2954 |
| Ensembl ID | ENSG00000100804 |
| UniProt ID | O43708 |
| OMIM ID | 603758 |
| HGNC ID | 4642 |
| Aliases | MAAI, GSTZ1-1 |
Description
GSTZ1 encodes glutathione S-transferase zeta 1, a bifunctional enzyme that acts as a glutathione-dependent maleylacetoacetate isomerase (MAAI) in the tyrosine degradation pathway and as a glutathione S-transferase in xenobiotic metabolism. It catalyzes the conversion of maleylacetoacetate to fumarylacetoacetate. Mutations in GSTZ1 cause tyrosinemia type 1B (also known as maleylacetoacetate isomerase deficiency), leading to accumulation of toxic metabolites and liver/kidney dysfunction.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Tyrosinemia type 1B (MAAI deficiency) | Loss-of-function mutations impair maleylacetoacetate isomerase activity, causing accumulation of maleylacetoacetate and succinylacetone, leading to hepatorenal toxicity. | OMIM #603758; ClinVar |
| Hereditary tyrosinemia type I (HT1) | GSTZ1 deficiency disrupts tyrosine catabolism, resulting in liver failure, renal tubular dysfunction, and neurological crises. | OMIM #276700; NCBI Gene |
| Oxidative stress-related disorders | Reduced GSTZ1 activity increases oxidative stress due to impaired detoxification of electrophilic compounds. | PubMed; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 8.3 | Medium |
| Small intestine | 5.1 | Medium |
| Pancreas | 3.2 | Low |
| Lung | 2.0 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 14.2 | High expression |
| HEK293 (embryonic kidney) | 7.8 | Moderate expression |
| A549 (lung) | 2.5 | Low expression |
| K562 (leukemia) | 1.1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.245G>A (p.Arg82Gln) | Missense | Rare | Reduced enzyme activity; associated with tyrosinemia type 1B |
| c.337C>T (p.Arg113Trp) | Missense | Rare | Loss of MAAI function; reported in ClinVar |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein; pathogenic |
Mutation functional classification
Loss of Function (LOF)
Most reported missense and nonsense mutations (e.g., p.Arg82Gln, p.Arg113Trp) reduce or abolish MAAI activity, leading to tyrosinemia type 1B.
Gain of Function (GOF)
No gain-of-function mutations documented.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Tyrosine metabolism (KEGG: hsa00350)
• Glutathione metabolism (KEGG: hsa00480)
• Metabolism of xenobiotics by cytochrome P450 (KEGG: hsa00980)
Protein Summary
GSTZ1 is a 24 kDa cytosolic protein belonging to the zeta class of glutathione S-transferases. It forms homodimers and catalyzes the isomerization of maleylacetoacetate to fumarylacetoacetate in the tyrosine degradation pathway. It also conjugates glutathione to various electrophilic substrates, contributing to detoxification. The protein is highly expressed in liver and kidney, consistent with its role in metabolism. Structural studies show a conserved G-site for glutathione binding and an H-site for hydrophobic substrate binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GSTZ1 Knockout HEK293 Cell Line | EDJ-KQ4816 | Human | 2954 | Details Get a Quote |
| GSTZ1 Knockout HeLa Cell Line | EDJ-KQ26373 | Human | 2954 | Details Get a Quote |
| GSTZ1 Knockout A-549 Cell Line | EDJ-KQ27592 | Human | 2954 | Details Get a Quote |
| GSTZ1 Knockout HCT 116 Cell Line | EDJ-KQ27593 | Human | 2954 | Details Get a Quote |
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