NOX3
Chr 6NADPH oxidase 3
Also known as: GP91-3, MOX-2
This protein is a NADPH oxidase that generates superoxide and other reactive oxygen species, and plays a critical role in the biogenesis of otoconia/otoliths, the crystalline structures in the inner ear involved in gravity perception. Mutations cause autosomal recessive congenital hearing loss with vestibular dysfunction. The gene is highly constrained against loss-of-function variation, indicating that complete loss of NOX3 function is likely incompatible with normal inner ear development.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
133 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
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 |
| Total | 0 | 92 | 34 | 1 | 127 |
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.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools