NOXO1

Chr 16

NADPH oxidase organizer 1

Also known as: P41NOX, P41NOXA, P41NOXB, P41NOXC, SH3PXD5, SNX28

NCBI Gene: 124056ENSG00000196408UniProt: Q8NFA2OMIM: 611256

The protein is an NADPH oxidase organizer that potentiates superoxide-generating activity of NOX1 and NOX3 and is required for biogenesis of otoconia, the crystalline structures in the inner ear that detect gravity. Mutations cause autosomal recessive hearing loss with vestibular dysfunction due to absent or malformed otoconia. The gene shows low constraint to loss-of-function variants, consistent with a recessive inheritance pattern affecting primarily inner ear development and function.

OMIMResearchSummary from RefSeq, UniProt
GOFmechanismLOEUF 1.62
Clinical Summary— NOXO1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 103 VUS of 162 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.62LOEUF
pLI 0.000
Z-score -0.21
OE 1.06 (0.71–1.62)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.81Z-score
OE missense 1.15 (1.04–1.28)
252 obs / 218.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.06 (0.71–1.62)
0≤0.351.4
Missense OE1.15 (1.04–1.28)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 15 / 14.1Missense obs/exp: 252 / 218.3Syn Z: -1.31
DN
0.5674th %ile
GOF
0.6930th %ile
LOF
0.4037th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

162 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic1
VUS103
Likely Benign10
42
Pathogenic
1
Likely Pathogenic
103
VUS
10
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
42
0
42
Likely Pathogenic
0
0
1
0
1
VUS
1
86
16
0
103
Likely Benign
1
8
0
1
10
Benign
0
0
0
0
0
Total294591156

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

View in ClinVar →

Protein Context — Lollipop Plot

NOXO1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Overexpression of a Novel Noxo1 Mutant Increases Ros Production and Noxo1 Relocalisation.
Benssouina FZ et al.·Int J Mol Sci
2023
The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.
Rezende F et al.·Redox Biol
2018
Integrative bioinformatics analysis reveals that microplastics promote chronic rhinosinusitis with nasal polyps through NOXO1-mediated oxidative stress and myoepithelial cell reprogramming.
Gao Y et al.·Comput Biol Chem
2026
Escherichia coli LF82 differentially regulates ROS production and mucin expression in intestinal epithelial T84 cells: implication of NOX1.
Elatrech I et al.·Inflamm Bowel Dis
2015
Binding of EBP50 to Nox organizing subunit p47phox is pivotal to cellular reactive species generation and altered vascular phenotype.
Al Ghouleh I et al.·Proc Natl Acad Sci U S A
2016
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients