AKR1A1 (Aldo-Keto Reductase Family 1 Member A1): A Key Enzyme in Drug Metabolism and Prostaglandin Synthesis
Comprehensive genomic and functional overview of AKR1A1, including gene structure, expression, disease associations, and mutation landscape.
Gene Information Card
| Symbol | AKR1A1 |
|---|---|
| Full Name | Aldo-Keto Reductase Family 1 Member A1 |
| Gene Type | protein-coding |
| Chromosomal Location | 1p33 |
| NCBI Gene ID | 10327 ncbi.nlm.nih.gov/gene/10327 |
| Ensembl ID | ENSG00000117448 |
| UniProt ID | P14550 |
| OMIM ID | 103830 |
| HGNC ID | 380 |
| Aliases | ALDR1, DD3, HEL-S-6, MGC1380, MGC15416, MGC15417 |
Description
AKR1A1 encodes aldo-keto reductase family 1 member A1, a cytosolic enzyme that catalyzes the reduction of various aldehydes and ketones to their corresponding alcohols. It plays a critical role in the metabolism of xenobiotics and endogenous compounds, including the reduction of the prostaglandin H2 to prostaglandin F2α. The enzyme is widely expressed and involved in detoxification pathways, particularly in the liver and kidney.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate Cancer | AKR1A1 expression is altered in prostate cancer; its role in prostaglandin metabolism may influence tumor progression. | COSMIC: mutations found in prostate cancer samples; expression data from GTEx and literature. |
| Breast Cancer | AKR1A1 may contribute to drug resistance via metabolism of chemotherapeutic agents; expression changes observed. | COSMIC: mutations and expression alterations in breast cancer; literature evidence. |
| Colorectal Cancer | AKR1A1 is involved in the metabolism of dietary aldehydes and may affect carcinogenesis. | COSMIC: mutations found in colorectal cancer; functional studies. |
| Diabetes | AKR1A1 participates in the polyol pathway, potentially contributing to diabetic complications. | Literature evidence; expression in tissues relevant to diabetes. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 42.3 | High |
| Kidney | 38.7 | High |
| Adrenal Gland | 25.1 | Medium |
| Small Intestine | 20.4 | Medium |
| Lung | 12.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 45.2 | Liver cancer cell line; high expression |
| A549 | 18.6 | Lung carcinoma; moderate expression |
| MCF7 | 22.3 | Breast cancer; moderate expression |
| HEK293 | 30.1 | Embryonic kidney; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | 0.01% (gnomAD) | Potential loss of start codon; may affect protein expression. |
| c.214C>T (p.Arg72Trp) | Missense | 0.02% (gnomAD) | Located in catalytic domain; may alter enzyme activity. |
| c.520G>A (p.Gly174Ser) | Missense | 0.005% (gnomAD) | Possible effect on substrate binding. |
| c.789delC (p.Pro264LeufsTer13) | Frameshift | Rare | Predicted to cause premature truncation; likely loss of function. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations leading to truncated protein or loss of enzymatic activity.
Gain of Function (GOF)
No evidence of gain-of-function mutations; all reported variants are either neutral or loss-of-function.
Dominant Negative (DN)
No evidence of dominant-negative effects; AKR1A1 is a monomeric enzyme, and mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • aldehyde reductase activity |
| • prostaglandin F synthase activity | • NADPH binding |
| • cytosol | • response to oxidative stress |
Pathways
• Prostaglandin synthesis
• Polyol pathway
• Xenobiotic metabolism
• Metabolism of aldehydes
Protein Summary
AKR1A1 is a 36 kDa monomeric enzyme belonging to the aldo-keto reductase superfamily. It uses NADPH as a cofactor to reduce a wide range of carbonyl compounds, including aldehydes, ketones, and prostaglandins. The enzyme is highly expressed in the liver and kidney, where it participates in detoxification and drug metabolism. Its crystal structure reveals a TIM-barrel fold with a conserved catalytic tetrad. AKR1A1 has been implicated in various cancers and metabolic disorders, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1A1 Knockout HEK293 Cell Line | EDJ-KQ2641 | Human | 10327 | Details Get a Quote |
| AKR1A1 Knockout A-549 Cell Line | EDJ-KQ23401 | Human | 10327 | Details Get a Quote |
| AKR1A1 Knockout HCT 116 Cell Line | EDJ-KQ23402 | Human | 10327 | Details Get a Quote |
| AKR1A1 Knockout HeLa Cell Line | EDJ-KQ23403 | Human | 10327 | Details Get a Quote |
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