NQO1 Gene: NAD(P)H:Quinone Oxidoreductase 1
A key detoxifying enzyme in oxidative stress response and cancer susceptibility
Gene Information Card
| Symbol | NQO1 |
|---|---|
| Full Name | NAD(P)H:quinone oxidoreductase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 1728 ncbi.nlm.nih.gov/gene/1728 |
| Ensembl ID | ENSG00000181019 |
| UniProt ID | P15559 |
| OMIM ID | 125860 |
| HGNC ID | 2874 |
| Aliases | DHQU, DIA4, DT-diaphorase, NMOR1, QR1 |
Description
The NQO1 gene encodes NAD(P)H:quinone oxidoreductase 1, a cytosolic flavoenzyme that catalyzes the two-electron reduction of quinones and their derivatives, preventing the formation of reactive oxygen species and toxic semiquinones. NQO1 plays a critical role in cellular defense against oxidative stress and is involved in the metabolism of various xenobiotics and endogenous compounds. It also functions as a chaperone for tumor suppressor p53, influencing its stability and activity. NQO1 is widely expressed in many tissues and is induced by oxidative stress and electrophiles via the Nrf2 pathway. Polymorphisms, particularly the p.Pro187Ser variant, are associated with reduced enzyme activity and increased susceptibility to certain cancers and other diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Reduced NQO1 activity due to the p.Pro187Ser polymorphism leads to impaired detoxification of carcinogenic quinones, increasing DNA damage and cancer risk. | Multiple case-control studies; meta-analyses (e.g., lung, colorectal, breast cancer). |
| Alzheimer's disease | NQO1 deficiency may lead to increased oxidative stress in the brain, contributing to neurodegeneration. | Association studies; functional studies in cell models. |
| Parkinson's disease | Impaired detoxification of dopamine-derived quinones due to NQO1 variants may increase dopaminergic neuron vulnerability. | Case-control studies; neuropathological evidence. |
| Multiple sclerosis | NQO1 activity may influence oxidative damage in the central nervous system, affecting disease progression. | Genetic association studies. |
| Myelodysplastic syndrome (MDS) | NQO1 mutations or reduced activity may contribute to hematopoietic dysfunction and increased risk of MDS. | Clinical cohort studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 18.2 | High |
| Kidney | 12.5 | Medium |
| Colon | 10.8 | Medium |
| Lung | 8.4 | Medium |
| Brain | 5.1 | Low |
| Heart | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 25.3 | High expression; used for functional studies |
| A549 (lung) | 15.7 | Moderate expression; inducible by Nrf2 activators |
| MCF7 (breast) | 8.2 | Low expression; estrogen-responsive |
| HeLa (cervical) | 12.1 | Moderate expression |
| K562 (leukemia) | 6.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Pro187Ser (rs1800566) | Missense | ~20-25% allele frequency in Asian populations; ~5-10% in Caucasians | Reduced enzyme activity; increased cancer risk |
| p.Arg139Trp (rs1131341) | Missense | Rare | Loss of function; associated with reduced activity |
| p.Pro187Ser homozygous | Genotype | ~2-5% in Asians; <1% in Caucasians | Complete loss of NQO1 activity; higher susceptibility to toxicity |
Mutation functional classification
Loss of Function (LOF)
The p.Pro187Ser variant results in rapid degradation of the protein, leading to severely reduced or absent enzyme activity. This impairs detoxification of quinones and increases oxidative stress.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NQO1.
Dominant Negative (DN)
The p.Pro187Ser variant is recessive; heterozygotes have intermediate activity, but no dominant-negative effect has been observed.
View complete mutation data：
Gene Ontology (GO)
| • oxidoreductase activity | • NAD(P)H dehydrogenase (quinone) activity |
| • protein homodimerization activity | • response to oxidative stress |
| • xenobiotic metabolic process | • cellular response to DNA damage stimulus |
Pathways
• Quinone detoxification
• Nrf2-mediated oxidative stress response
• p53 signaling pathway
• Metabolism of xenobiotics by cytochrome P450
Protein Summary
NQO1 is a homodimeric flavoprotein that uses NADH or NADPH to reduce quinones to hydroquinones, bypassing the formation of reactive semiquinone intermediates. It is a major detoxifying enzyme in cells, protecting against oxidative stress and carcinogenesis. NQO1 also interacts with p53, stabilizing it and influencing its transcriptional activity. The protein is induced by various stressors via the antioxidant response element (ARE) and is highly expressed in many tumors, making it a target for cancer therapy and a biomarker.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NQO1 Knockout HEK293 Cell Line | EDJ-KQ14488 | Human | 1728 | Details Get a Quote |
| NQO1 Knockout A-549 Cell Line | EDJ-KQ44745 | Human | 1728 | Details Get a Quote |
| NQO1 Knockout HeLa Cell Line | EDJ-KQ44747 | Human | 1728 | Details Get a Quote |
| NQO1 Knockout HCT 116 Cell Line | EDJ-KQ43495 | Human | 1728 | Details Get a Quote |
| NQO1 Knockout 22Rv1 Cell Line | EDJ-KZ372 | Human | 1728 | Details Get a Quote |
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