NOX3 (NADPH Oxidase 3) Gene
Key regulator of reactive oxygen species in the inner ear and potential therapeutic target for hearing loss
Gene Information Card
| Symbol | NOX3 |
|---|---|
| Full Name | NADPH oxidase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 6q25.3 |
| NCBI Gene ID | 50508 ncbi.nlm.nih.gov/gene/50508 |
| Ensembl ID | ENSG00000174738 |
| UniProt ID | Q9HBY0 |
| OMIM ID | 607105 |
| HGNC ID | 7890 |
| Aliases | GP91-3, MOX-2, NOX-3, NADPH oxidase 3 |
Description
NOX3 encodes a member of the NOX family of NADPH oxidases, which catalyze the production of superoxide anion from molecular oxygen using NADPH as an electron donor. NOX3 is predominantly expressed in the inner ear, where it is essential for the formation of otoconia (calcium carbonate crystals) and normal vestibular function. It is also involved in the generation of reactive oxygen species (ROS) in response to cellular stress and has been implicated in age-related and noise-induced hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hearing loss, age-related | Increased ROS production from NOX3 contributes to cochlear hair cell damage | ClinVar, OMIM |
| Vestibular dysfunction | NOX3 mutations impair otoconia formation, leading to balance disorders | OMIM, PubMed |
| Noise-induced hearing loss | Upregulation of NOX3 in cochlea after noise exposure increases oxidative stress | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Inner ear (cochlea) | Not available (RNA-seq not standard) | High (by RT-PCR) |
| Brain | 0.2 | Low |
| Kidney | 0.1 | Low |
| Lung | 0.1 | Low |
| Testis | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.0 | No detectable expression |
| SH-SY5Y | 0.0 | No detectable expression |
| MCF7 | 0.0 | No detectable expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.910C>T (p.Arg304Trp) | Missense | Rare | Reduced superoxide production; associated with hearing loss |
| c.1225G>A (p.Gly409Ser) | Missense | Rare | Impaired protein stability; linked to vestibular dysfunction |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Loss of function; predicted null allele |
Mutation functional classification
Loss of Function (LOF)
Missense and start-loss mutations reduce or abolish NOX3 enzymatic activity, leading to impaired ROS production and otoconia defects.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NOX3.
Dominant Negative (DN)
No dominant-negative mutations have been described for NOX3.
View complete mutation data：
Gene Ontology (GO)
| • superoxide-generating NADPH oxidase activity (GO:0004601) | • NAD(P)H oxidase complex (GO:0043020) |
| • superoxide metabolic process (GO:0006801) | • oxidation-reduction process (GO:0055114) |
| • plasma membrane (GO:0005886) | • cytoplasm (GO:0005737) |
Pathways
• NADPH oxidase pathway (Reactome: R-HSA-5668599)
• ROS and RNS production in phagocytes (KEGG: hsa04621)
• Oxidative stress response (WikiPathways: WP408)
Protein Summary
NOX3 is a 568-amino acid transmembrane protein that forms a functional NADPH oxidase complex with p22phox (CYBA). It is localized primarily to the plasma membrane and endosomal compartments. The protein contains six transmembrane domains, a flavin adenine dinucleotide (FAD)-binding domain, and a NADPH-binding domain. NOX3-dependent ROS production is tightly regulated and is critical for the biogenesis of otoconia in the inner ear. Dysregulation of NOX3 activity contributes to oxidative damage in cochlear hair cells, linking it to hearing loss pathologies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NOX3 Knockout HEK293 Cell Line | EDJ-KQ10772 | Human | 50508 | Details Get a Quote |
| NOX3 Knockout HeLa Cell Line | EDJ-KQ56167 | Human | 50508 | Details Get a Quote |
| NOX3 Knockout A-549 Cell Line | EDJ-KQ64657 | Human | 50508 | Details Get a Quote |
| NOX3 Knockout HCT 116 Cell Line | EDJ-KQ73106 | Human | 50508 | Details Get a Quote |
