NOX3

Chr 6

NADPH oxidase 3

Also known as: GP91-3, MOX-2

NCBI Gene: 50508ENSG00000074771UniProt: Q9HBY0

This gene encodes a member of the NOX family of NADPH oxidases. These enzymes have the capacity to generate superoxide and other reactive oxygen species (ROS) and transport electrons across the plasma membrane. The ROS generated by family members have been implicated in numerous biological functions including host defense, posttranlational processing of proteins, cellular signaling, regulation of gene expression, and cell differentiation. The protein encoded by this gene is expressed predominantly in the inner ear and is involved in the biogenesis of otoconia/otolith, which are crystalline structures of the inner ear involved in the perception of gravity.[provided by RefSeq, May 2009]

127
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— NOX3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 93 VUS of 127 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.05LOEUF
pLI 0.000
Z-score 1.32
OE 0.76 (0.55–1.05)
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.
-0.23Z-score
OE missense 1.04 (0.95–1.13)
336 obs / 324.6 exp
Tolerant

Tolerant to missense variation

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.0.76 (0.55–1.05)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.95–1.13)
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.1.12
0≤1.21.6
LoF obs/exp: 26 / 34.4Missense obs/exp: 336 / 324.6Syn Z: -1.05

ClinVar Variant Classifications

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic2
VUS93
Likely Benign4
Benign1
27
Pathogenic
2
Likely Pathogenic
93
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
0
2
0
2
VUS
0
88
5
0
93
Likely Benign
0
4
0
0
4
Benign
0
0
0
1
1
Total092341127

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

View in ClinVar →

Protein Context — Lollipop Plot

NOX3 · 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
NADPH OXIDASE 3; NOX3
MIM #607105 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mammalian NADPH Oxidases.
Buvelot H et al.·Methods Mol Biol
2019Review
Genetic architecture of Meniere's disease.
Gallego-Martinez A et al.·Hear Res
2020Review
NADPH oxidases in vascular pathology.
Konior A et al.·Antioxid Redox Signal
2014Review
Targeting NADPH oxidases in vascular pharmacology.
Schramm A et al.·Vascul Pharmacol
2012Review
Nox/Duox Family of NADPH Oxidases: Lessons from Knockout Mouse Models.
Sirokmány G et al.·Trends Pharmacol Sci
2016Review
Therapeutic efficacy of dimethyl fumarate in relapsing-remitting multiple sclerosis associates with ROS pathway in monocytes.
Carlström KE et al.·Nat Commun
2019
Oxidant stress regulatory genetic variation in recipients and donors contributes to risk of primary graft dysfunction after lung transplantation.
Cantu E et al.·J Thorac Cardiovasc Surg
2015
The effects of palmitate on hepatic insulin resistance are mediated by NADPH Oxidase 3-derived reactive oxygen species through JNK and p38MAPK pathways.
Gao D et al.·J Biol Chem
2010
Oxidative stress-related genetic variation and antioxidant vitamin intake in intact and ruptured abdominal aortic aneurysm: a Swedish population-based retrospective cohort study.
Vats S et al.·Eur J Prev Cardiol
2024Cohort
The NOD2insC polymorphism is associated with worse outcome following ileal pouch-anal anastomosis for ulcerative colitis.
Tyler AD et al.·Gut
2013
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Nox3 expression and function in retinal ganglion cells and Amacrine cells.
Ueyama T et al.·Cell Mol Life Sci
2025🔓 Open Access
Epigallocatechin-3-gallate Restores X-irradiation-Induced Impairments in Cognitive Function and Hippocampal Neurogenesis by Suppressing the TLR4-NOX3/4 and ROS-NF-κB Pathways in Microglia.
Seong KJ et al.·Mol Neurobiol
2025
Diallyl trisulfide inhibits monosodium urate-induced NLRP3 inflammasome activation via NOX3/4-dependent mitochondrial oxidative stress in RAW 264.7 and bone marrow-derived macrophages.
Kim MY et al.·Phytomedicine
2023
Development and in vivo validation of small interfering RNAs targeting NOX3 to prevent sensorineural hearing loss.
Nacher-Soler G et al.·Front Neurol
2022🔓 Open Access
[Association between polymorphism of CASP and NOX3 with risk of noise-induced hearing loss].
Xin JR et al.·Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
2021
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Inflammatory Bowel Diseases

Markers of Oxidative Stress in Inflammatory Bowel Diseases: Risk Factors and Implications for a Dietetic Approach

ACTIVE NOT RECRUITING
NCT04513015Phase NAUniversità Politecnica delle MarcheStarted 2019-12-15
Antioxidant dietNormal dietetic scheme

External Resources

Links to major genomics databases and tools