NQO2

Chr 6ADSomatic

N-ribosyldihydronicotinamide:quinone dehydrogenase 2

Also known as: DHQV, DIA6, NMOR2, QR2

NCBI Gene: 4835ENSG00000124588UniProt: P16083

This gene encodes a member of the thioredoxin family of enzymes. It is a cytosolic and ubiquitously expressed flavoprotein that catalyzes the two-electron reduction of quinone substrates and uses dihydronicotinamide riboside as a reducing coenzyme. Mutations in this gene have been associated with neurodegenerative diseases and several cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

Primary Disease Associations & Inheritance

{?Breast cancer susceptibility}MIM #114480
ADSomatic
93
ClinVar variants
52
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NQO2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 37 VUS of 93 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.48LOEUF
pLI 0.000
Z-score 0.38
OE 0.88 (0.54–1.48)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.47Z-score
OE missense 0.88 (0.76–1.03)
118 obs / 133.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.54–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.76–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.10
0≤1.21.6
LoF obs/exp: 10 / 11.4Missense obs/exp: 118 / 133.4Syn Z: -0.58

ClinVar Variant Classifications

93 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic47
Likely Pathogenic5
VUS37
Likely Benign2
Benign2
47
Pathogenic
5
Likely Pathogenic
37
VUS
2
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
47
0
47
Likely Pathogenic
0
0
5
0
5
VUS
0
32
5
0
37
Likely Benign
0
1
1
0
2
Benign
0
1
1
0
2
Total03459093

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NQO2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{?Breast cancer susceptibility}

MIM #114480

Disorder with associated gene

Autosomal dominantSomatic mutation
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Null association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility and prognosis of Esophageal cancer in north Indian population and meta-analysis.
Umar M et al.·Cancer Epidemiol
2012Meta-analysis
FRK exerts oncogenic effects by targeting NQO2 via exosomal miR-9-3p to regulate mitochondrial function.
Huang H et al.·FASEB J
2024
Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis.
Malik MA et al.·Mol Biol Rep
2012Meta-analysis
CB 1954: from the Walker tumor to NQO2 and VDEPT.
Knox RJ et al.·Curr Pharm Des
2003Review
Melatonin Receptor Expression in Primary Uveal Melanoma.
Hagström A et al.·Int J Mol Sci
2024
Identification of Colorectal Cancer-Related RNA Markers from Whole Blood Using Integrated Bioinformatics Analysis.
Han J et al.·Int J Mol Sci
2025
NAD(P)H:quinone oxidoreductase 1 and nrh:quinone oxidoreductase 2 activity and expression in bladder and ovarian cancer and lower NRH:quinone oxidoreductase 2 activity associated with an NQO2 exon 3 single-nucleotide polymorphism.
Jamieson D et al.·Clin Cancer Res
2007
Melatonin as a major skin protectant: from free radical scavenging to DNA damage repair.
Fischer TW et al.·Exp Dermatol
2008Review
NRF2 Pathway Activation as a Molecular Toxicology Mechanism in Oxidative Stress and Lipid Metabolic Disorders.
Arif Asghar M et al.·J Biochem Mol Toxicol
2025Meta-analysis
Genetic variants in metabolizing genes NQO1, NQO2, MTHFR and risk of prostate cancer: a study from North India.
Mandal RK et al.·Mol Biol Rep
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
NQO1 and NQO2 Gene Polymorphisms Related to Methamphetamine-Associated Psychosis in the Makassar Population, Indonesia.
Ludong DH et al.·Noro Psikiyatr Ars
2026
Dentin bonding agents and camphorquinone-induced cytotoxicity, 8-isoprostane and prostaglandin production is associated with CYP450, NQO1, NQO2, GST, and GSH peroxidase in human dental pulp cells.
Chang MC et al.·Dent Mater
2026
Synthesis of novel 4/5-substituted 3-arylidene-2-oxindole derivatives and their biological evaluation as NQO2 ligands and NLRP3 downregulators.
Bezsonova EN et al.·Bioorg Med Chem Lett
2025
Astragalin induces immunogenic cell death in liver cancer by targeting NQO2 to promote ROS-mediated endoplasmic reticulum stress pathway.
Zheng L et al.·Free Radic Biol Med
2025
The induction of quinone oxidoreductases NQO1 and NQO2 by clozapine: Potential implications for clozapine-induced agranulocytosis.
Rashid MH et al.·Toxicol Lett
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools