HAGH (Hydroxyacylglutathione Hydrolase)
Glyoxalase II: Detoxification of Methylglyoxal and Role in Cellular Metabolism
Gene Information Card
| Symbol | HAGH |
|---|---|
| Full Name | Hydroxyacylglutathione Hydrolase |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 3029 ncbi.nlm.nih.gov/gene/3029 |
| Ensembl ID | ENSG00000103174 |
| UniProt ID | Q16775 |
| OMIM ID | 138760 |
| HGNC ID | 4806 |
| Aliases | GLX2, GLXII, HAGH1 |
Description
The HAGH gene encodes hydroxyacylglutathione hydrolase, also known as glyoxalase II. This enzyme catalyzes the second step of the glyoxalase system, converting S-D-lactoylglutathione to D-lactate and glutathione, thereby detoxifying methylglyoxal, a cytotoxic byproduct of glycolysis. The gene is located on chromosome 16p13.3 and is expressed ubiquitously.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glyoxalase II deficiency | Loss of HAGH function leads to accumulation of S-D-lactoylglutathione and methylglyoxal, causing hemolytic anemia and neurological symptoms. | OMIM #138760; ClinVar |
| Hemolytic anemia (nonspherocytic) | Deficiency in HAGH impairs methylglyoxal detoxification, resulting in red blood cell damage. | OMIM #138760; PubMed studies |
| Diabetes complications (potential) | Altered glyoxalase activity may contribute to diabetic nephropathy and retinopathy. | NCBI Gene; literature review |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Liver | 10.8 | Medium |
| Heart | 8.5 | Medium |
| Brain | 6.2 | Low |
| Lung | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.7 | High expression |
| HepG2 | 11.2 | Moderate expression |
| K562 | 9.8 | Moderate expression |
| A549 | 7.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.239G>A (p.Arg80Gln) | Missense | Rare | Reduced enzyme activity; associated with glyoxalase II deficiency |
| c.457C>T (p.Arg153Trp) | Missense | Rare | Loss of function; reported in hemolytic anemia |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish hydrolase activity, leading to methylglyoxal accumulation and cellular toxicity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • hydroxyacylglutathione hydrolase activity | • zinc ion binding |
| • lactoylglutathione lyase activity | • cellular response to methylglyoxal |
| • glutathione metabolic process | • carbohydrate metabolic process |
Pathways
• Glyoxalase system (R-HSA-71406)
• Methylglyoxal detoxification (R-HSA-71406)
• Glutathione conjugation (R-HSA-156590)
Protein Summary
Hydroxyacylglutathione hydrolase (glyoxalase II) is a 260-amino-acid zinc-dependent enzyme that hydrolyzes S-D-lactoylglutathione to D-lactate and glutathione. It is a homodimer localized in the cytoplasm and mitochondria. The enzyme is essential for detoxifying methylglyoxal, a reactive dicarbonyl produced during glycolysis. Deficiency leads to hemolytic anemia and neurological impairment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HAGH Knockout HEK293 Cell Line | EDJ-KQ3338 | Human | 3029 | Details Get a Quote |
| HAGH Knockout A-549 Cell Line | EDJ-KQ24980 | Human | 3029 | Details Get a Quote |
| HAGH Knockout HeLa Cell Line | EDJ-KQ24981 | Human | 3029 | Details Get a Quote |
| HAGH Knockout HCT 116 Cell Line | EDJ-KQ23589 | Human | 3029 | Details Get a Quote |
| HAGHL Knockout HEK293 Cell Line | EDJ-KQ51824 | Human | 84264 | Details Get a Quote |
| HAGHL Knockout HeLa Cell Line | EDJ-KQ57564 | Human | 84264 | Details Get a Quote |
| HAGHL Knockout A-549 Cell Line | EDJ-KQ66061 | Human | 84264 | Details Get a Quote |
| HAGHL Knockout HCT 116 Cell Line | EDJ-KQ74483 | Human | 84264 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
