AKR1B1 (Aldo-Keto Reductase Family 1 Member B1)
A key enzyme in the polyol pathway, implicated in diabetic complications and oxidative stress.
Gene Information Card
| Symbol | AKR1B1 |
|---|---|
| Full Name | Aldo-Keto Reductase Family 1 Member B1 |
| Gene Type | protein-coding |
| Chromosomal Location | 7q33 |
| NCBI Gene ID | 231 ncbi.nlm.nih.gov/gene/231 |
| Ensembl ID | ENSG00000085662 |
| UniProt ID | P15121 |
| OMIM ID | 103880 |
| HGNC ID | 381 |
| Aliases | ALDR1, ADR, AR, ALR2 |
Description
AKR1B1 encodes aldose reductase, a member of the aldo/keto reductase superfamily. This enzyme catalyzes the reduction of glucose to sorbitol in the polyol pathway, playing a critical role in cellular osmoregulation and the pathogenesis of diabetic complications. It also metabolizes various aldehydes and is involved in detoxification and oxidative stress responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diabetic retinopathy | Increased flux through the polyol pathway leads to sorbitol accumulation, osmotic stress, and microvascular damage in the retina. | Multiple studies, including clinical trials of aldose reductase inhibitors (e.g., sorbinil) and genetic association studies. |
| Diabetic nephropathy | Aldose reductase activity contributes to renal tubular injury and fibrosis via sorbitol accumulation and altered redox balance. | Experimental animal models and human genetic studies linking AKR1B1 variants to nephropathy risk. |
| Diabetic neuropathy | Sorbitol accumulation in Schwann cells causes myelin damage and nerve conduction deficits. | Evidence from animal models and clinical trials of aldose reductase inhibitors. |
| Cataract | Polyol pathway activation in lens epithelial cells leads to osmotic swelling and opacification. | In vitro and in vivo studies, including transgenic mouse models. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | Medium |
| Liver | 8.7 | Low |
| Heart | 6.2 | Low |
| Brain | 5.1 | Low |
| Adipose tissue | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression |
| A549 | 10.5 | Moderate expression |
| HepG2 | 8.9 | Moderate expression |
| MCF7 | 6.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.95A>G (p.Asn32Ser) | Missense | Rare (MAF <0.01) | Reduced enzyme activity, possibly affecting polyol pathway flux. |
| c.103C>T (p.Arg35Cys) | Missense | Rare (MAF <0.01) | Altered substrate specificity, potential impact on detoxification. |
| c.561C>T (p.Ser187Leu) | Missense | Rare (MAF <0.01) | Decreased stability, leading to lower protein levels. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish aldose reductase activity, potentially impairing detoxification and increasing susceptibility to oxidative stress.
Gain of Function (GOF)
No clear gain-of-function mutations reported; increased expression or activity may exacerbate diabetic complications.
Dominant Negative (DN)
No evidence of dominant-negative effects; AKR1B1 functions as a monomer.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • aldose reductase activity |
| • NADPH binding | • carbohydrate metabolic process |
| • cellular response to oxidative stress | • polyol biosynthetic process |
Pathways
• Polyol pathway
• Metabolism of carbohydrates
• Glucose metabolism
Protein Summary
Aldose reductase (AKR1B1) is a monomeric enzyme that reduces glucose to sorbitol using NADPH as a cofactor. It is widely expressed, with highest levels in kidney and lens. The protein is involved in osmoregulation and detoxification of lipid peroxidation-derived aldehydes. Its activity is implicated in diabetic complications, making it a therapeutic target for aldose reductase inhibitors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1B1 Knockout HEK293 Cell Line | EDJ-KQ4040 | Human | 231 | Details Get a Quote |
| AKR1B10 Knockout HEK293 Cell Line | EDJ-KQ12322 | Human | 57016 | Details Get a Quote |
| AKR1B15 Knockout HEK293 Cell Line | EDJ-KQ12323 | Human | 441282 | Details Get a Quote |
| AKR1B10 Knockout A-549 Cell Line | EDJ-KQ41162 | Human | 57016 | Details Get a Quote |
| AKR1B10 Knockout HeLa Cell Line | EDJ-KQ41164 | Human | 57016 | Details Get a Quote |
| AKR1B15 Knockout A-549 Cell Line | EDJ-KQ41165 | Human | 441282 | Details Get a Quote |
| AKR1B1 Knockout A-549 Cell Line | EDJ-KQ26390 | Human | 231 | Details Get a Quote |
| AKR1B1 Knockout HCT 116 Cell Line | EDJ-KQ26391 | Human | 231 | Details Get a Quote |
| AKR1B1 Knockout HeLa Cell Line | EDJ-KQ26392 | Human | 231 | Details Get a Quote |
| AKR1B10 Knockout HCT 116 Cell Line | EDJ-KQ39906 | Human | 57016 | Details Get a Quote |
| AKR1B10 Knockout Hep-G2 Cell Line | EDJ-KZ535 | Human | 57016 | Details Get a Quote |
| AKR1B15 Knockout HeLa Cell Line | EDJ-KQ60419 | Human | 441282 | Details Get a Quote |
| AKR1B15 Knockout HCT 116 Cell Line | EDJ-KQ77247 | Human | 441282 | Details Get a Quote |
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