AKR1B10 (Aldo-Keto Reductase Family 1 Member B10)
A multifunctional aldo-keto reductase involved in lipid metabolism, detoxification, and cancer biology.
Gene Information Card
| Symbol | AKR1B10 |
|---|---|
| Full Name | aldo-keto reductase family 1 member B10 |
| Gene Type | protein coding |
| Chromosomal Location | 7q33 |
| NCBI Gene ID | 57016 ncbi.nlm.nih.gov/gene/57016 |
| Ensembl ID | ENSG00000198074 |
| UniProt ID | O60218 |
| OMIM ID | 604594 |
| HGNC ID | 382 |
| Aliases | ARL-1, ALDRLn, AKR1B11, HSI |
Description
The AKR1B10 gene encodes a member of the aldo/keto reductase superfamily. This cytosolic enzyme catalyzes the NADPH-dependent reduction of a variety of carbonyl substrates, including aldehydes and ketones. AKR1B10 plays a significant role in the metabolism of lipid peroxidation-derived aldehydes, the reduction of retinal to retinol, and the detoxification of dietary and environmental xenobiotics. Its expression is highly upregulated in several cancers, particularly hepatocellular carcinoma and lung squamous cell carcinoma, where it is thought to contribute to tumorigenesis through modulation of retinoid signaling and lipid metabolism. Conversely, its expression is often downregulated in colon cancer, suggesting a context-dependent role in tumor biology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular Carcinoma | Overexpression of AKR1B10 promotes tumor cell survival and proliferation by reducing toxic lipid aldehydes and inactivating retinoic acid, thereby supporting a pro-tumorigenic environment. | High expression levels are consistently found in HCC tissues compared to normal liver, correlating with poor prognosis (PMID: 12835555). |
| Lung Cancer (Squamous Cell Carcinoma) | AKR1B10 is highly expressed in lung squamous cell carcinoma, where it may contribute to carcinogen detoxification and resistance to chemotherapy. | Multiple studies show significant upregulation in lung SCC tissues and cell lines (PMID: 12835555). |
| Colorectal Cancer | In contrast to HCC, AKR1B10 expression is frequently downregulated in colorectal cancer, potentially due to promoter hypermethylation. Loss of its detoxifying function may increase susceptibility to carcinogens. | Reduced expression is observed in a majority of colorectal tumors compared to adjacent normal mucosa (PMID: 17234600). |
| Breast Cancer | AKR1B10 expression is elevated in estrogen receptor-positive breast cancers and is associated with tamoxifen resistance, potentially through its role in lipid metabolism. | Studies have shown increased expression in breast cancer cell lines and tissues, with functional links to therapy resistance (PMID: 28202525). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 42.3 | High |
| Colon | 35.1 | High |
| Liver | 28.7 | Medium |
| Adrenal Gland | 22.5 | Medium |
| Lung | 12.4 | Low |
| Kidney | 8.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (Liver) | 85.2 | High expression; used as a model for HCC. |
| A549 (Lung) | 45.7 | High expression; relevant for lung cancer studies. |
| MCF7 (Breast) | 38.9 | Moderate-high expression; associated with ER+ breast cancer. |
| Caco-2 (Colon) | 5.3 | Low expression; reflects downregulation in colorectal cancer. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.561C>A (p.Asp187Glu) | Missense | Rare (<0.1%) | Reported in a single case of colorectal cancer; functional impact is unknown, but may alter substrate specificity. |
| c.958G>A (p.Val320Met) | Missense | Rare (<0.1%) | Found in a lung cancer sample; predicted to be possibly damaging by in silico tools, but no functional studies have been performed. |
| c.1037C>T (p.Pro346Leu) | Missense | Rare (<0.1%) | Observed in a hepatocellular carcinoma case; potential effect on protein stability or catalytic activity is not yet characterized. |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations have been reported in AKR1B10. However, epigenetic silencing via promoter methylation is a common mechanism of reduced expression in colorectal cancer.
Gain of Function (GOF)
Gene amplification and transcriptional upregulation are the primary mechanisms of increased AKR1B10 activity in cancers like HCC and lung SCC. Specific gain-of-function mutations have not been identified.
Dominant Negative (DN)
No dominant-negative mutations have been described for AKR1B10.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • aldehyde reductase activity |
| • retinal reductase activity | • NADP binding |
| • protein homodimerization activity | • cytosol |
| • carbohydrate metabolic process | • retinol metabolic process |
| • xenobiotic metabolic process | • cellular response to oxidative stress |
Pathways
• Retinol metabolism
• Metabolism of xenobiotics by cytochrome P450
• Fructose and mannose metabolism
• Biosynthesis of unsaturated fatty acids
Protein Summary
The AKR1B10 protein is a 316-amino acid monomeric enzyme that adopts the typical (α/β)8 TIM barrel fold of the aldo-keto reductase superfamily. It requires NADPH as a cofactor for its catalytic activity. The enzyme efficiently reduces a broad range of substrates, including aliphatic and aromatic aldehydes, and is particularly efficient at reducing all-trans-retinal to all-trans-retinol, a key step in the regulation of retinoic acid biosynthesis. It also plays a crucial role in protecting cells from lipid peroxidation by reducing reactive aldehydes like 4-hydroxynonenal (4-HNE). Its substrate specificity and tissue-specific expression pattern are critical to its physiological and pathological roles.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AKR1B10 Knockout HEK293 Cell Line | EDJ-KQ12322 | Human | 57016 | 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 |
| 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 |
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