GLS2: Glutaminase 2 (Liver/Mitochondrial)
Key enzyme in glutamine metabolism, tumor suppression, and redox homeostasis
Gene Information Card
| Symbol | GLS2 |
|---|---|
| Full Name | Glutaminase 2 (liver, mitochondrial) |
| Gene Type | Protein coding |
| Chromosomal Location | 12q13.3 |
| NCBI Gene ID | 27165 ncbi.nlm.nih.gov/gene/27165 |
| Ensembl ID | ENSG00000135423 |
| UniProt ID | Q9UI32 |
| OMIM ID | 606365 |
| HGNC ID | 29570 |
| Aliases | GA, LGA, hLGA, GLS2L, glutaminase liver isoform |
Description
GLS2 encodes the mitochondrial glutaminase 2 (liver-type) enzyme, which catalyzes the hydrolysis of glutamine to glutamate and ammonia. It is a key regulator of glutamine metabolism, redox balance, and energy production. GLS2 is transcriptionally regulated by p53 and acts as a tumor suppressor in several cancers, particularly hepatocellular carcinoma. Its expression is associated with reduced cell proliferation and increased oxidative stress resistance.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of GLS2 expression reduces glutamine catabolism, promoting tumor growth and oxidative stress | PMID: 20010871, 20581835 |
| Colorectal cancer | Epigenetic silencing of GLS2 leads to altered glutamine metabolism and increased proliferation | PMID: 23542689 |
| Breast cancer | Reduced GLS2 expression correlates with poor prognosis and altered redox homeostasis | PMID: 24755471 |
| Glioma | GLS2 downregulation supports glutamine-dependent growth and metabolic reprogramming | PMID: 25944712 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Brain | 8.2 | Low |
| Kidney | 6.1 | Low |
| Pancreas | 4.3 | Low |
| Small intestine | 3.9 | Low |
| Spleen | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Hepatocellular carcinoma cell line |
| HEK293 | 7.8 | Embryonic kidney cells |
| MCF7 | 2.1 | Breast cancer cell line |
| A549 | 1.5 | Lung carcinoma cell line |
| U87MG | 0.9 | Glioblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.820C>T (p.Arg274Trp) | Missense | Rare | Reduced enzyme activity |
| c.1042G>A (p.Gly348Arg) | Missense | Rare | Unknown functional impact |
| c.1195C>T (p.Arg399Trp) | Missense | Rare | Potential loss of function |
| c.1462G>A (p.Glu488Lys) | Missense | Rare | Unknown functional impact |
Mutation functional classification
Loss of Function (LOF)
Missense variants such as p.Arg274Trp are predicted to reduce catalytic activity, consistent with tumor suppressor role.
Gain of Function (GOF)
No gain-of-function mutations reported in GLS2.
Dominant Negative (DN)
No dominant-negative mutations reported in GLS2.
View complete mutation data：
Gene Ontology (GO)
| • glutaminase activity (GO:0004359) | • mitochondrion (GO:0005739) |
| • glutamine metabolic process (GO:0006541) | • oxidation-reduction process (GO:0055114) |
| • negative regulation of apoptotic process (GO:0043066) | • apoptotic process (GO:0006915) |
Pathways
• Glutamine metabolism (Reactome: R-HSA-8964539)
• p53-dependent G1 DNA damage response (Reactome: R-HSA-69580)
• Metabolism of amino acids and derivatives (Reactome: R-HSA-71291)
Protein Summary
Glutaminase 2 (GLS2) is a mitochondrial enzyme that converts glutamine to glutamate and ammonia. It is predominantly expressed in liver and brain, and its expression is regulated by p53. GLS2 plays a critical role in maintaining redox homeostasis by supporting glutathione synthesis. Loss of GLS2 expression is observed in multiple cancers and is associated with tumor progression and poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GLS2 Knockout HEK293 Cell Line | EDJ-KQ8704 | Human | 27165 | Details Get a Quote |
| GLS2 Knockout HeLa Cell Line | EDJ-KQ34929 | Human | 27165 | Details Get a Quote |
| GLS2 Knockout A-549 Cell Line | EDJ-KQ64506 | Human | 27165 | Details Get a Quote |
| GLS2 Knockout HCT 116 Cell Line | EDJ-KQ72964 | Human | 27165 | Details Get a Quote |
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