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Protein / target

NADPH oxidase 4

Encoded byNOX4Q9NPH5Homo sapiensSwiss-Prot
UniProt: Q9NPH5Ensembl: ENSG00000086991HGNC: HGNC:7891NCBI Gene: 50507
Clinical-stage
Therapeutic maturity
1
Clinical candidates
Small-molecule tractable
Druggability
Advanced Clinical
2
Research papers

Protein at a glance

Biological role

Superoxide-generating NAD(P)H oxidase

Strongest disease association

Hair color

Via encoding gene NOX4 · Genetic evidence · score 0.82

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

2 papers · latest 2023

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2.

View complete UniProt function annotation

NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2 (PubMed:14966267, PubMed:15356101, PubMed:15927447, PubMed:21343298, PubMed:25062272). Can also catalyze to a smaller extent, the reduction of oxygen to superoxide (PubMed:10869423, PubMed:11032835, PubMed:15155719, PubMed:15572675, PubMed:15927447, PubMed:16019190, PubMed:16179589, PubMed:16230378, PubMed:16324151, PubMed:25062272). May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity (PubMed:16019190). May regulate insulin signaling cascade (PubMed:14966267). May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB (PubMed:15356101, PubMed:15572675). May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation (PubMed:16324151). Promotes ferroptosis, reactive oxygen species production and reduced glutathione (GSH) levels by activating NLRP3 inflammasome activation and cytokine release (PubMed:39909992)

Subcellular location

CytoplasmEndoplasmic reticulum membraneCell membraneCell junction, focal adhesionNucleusNucleus, nucleolusCytoplasm, perinuclear region
Domains and Gene Ontology detail (37)

Domains & features

Ferric oxidoreductaseFAD-binding FR-type

Gene Ontology

  • Cendoplasmic reticulum
  • Cendoplasmic reticulum membrane
  • Cfocal adhesion
  • Cmembrane
  • Cmitochondrion
  • CNADPH oxidase complex
  • Cnucleolus
  • Cnucleus
  • Cperinuclear endoplasmic reticulum
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Felectron transfer activity

578 aa · 67 kDa · 9 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOImmune signallingUniProt · GOTranscriptional regulationUniProt · GOMetabolic enzyme activityGO
View supporting evidence

Cell proliferation & survival

  • ·negative regulation of cell population proliferation

Immune signalling

  • ·NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2 (PubMed:14966…
  • ·inflammatory response

Transcriptional regulation

  • ·NADPH oxidase that catalyzes predominantly the reduction of oxygen to H2O2 (PubMed:14966…
  • ·gene expression

Metabolic enzyme activity

  • ·homocysteine metabolic process
  • ·superoxide metabolic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene NOX4

Gene-level evidence surfaced through the gene NOX4that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Hair color
0.82Well supported

Genetic evidence dominant · Open Targets 0.50

Aneurysm
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.44

Alzheimer's Disease
0.62Moderately supported

Genetic evidence dominant · Open Targets 0.37

Glaucoma
0.52Moderately supported

Genetic evidence dominant · Open Targets 0.31

Protozoan Infections
0.50Moderately supported

Genetic evidence dominant · Open Targets 0.31

View evidence synthesis (5)
Hair colorWell supported
0.82
agreement 0.70–0.94
Genetic100%

Open Targets aggregate 0.50 · 1 independent evidence family

AneurysmModerately supported
0.72
agreement 0.58–0.86
Genetic95%Literature6%

Open Targets aggregate 0.44 · 2 independent evidence families

Alzheimer's DiseaseModerately supported
0.62
agreement 0.48–0.76
Genetic81%Literature19%

Open Targets aggregate 0.37 · 2 independent evidence families

GlaucomaModerately supported
0.52
agreement 0.38–0.66
Genetic96%Literature4%

Open Targets aggregate 0.31 · 2 independent evidence families

Protozoan InfectionsModerately supported
0.50
agreement 0.38–0.62
Genetic100%

Open Targets aggregate 0.31 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations
Hair color0.50
Aneurysm0.44
Neoplasms0.40
Leukemia, Myeloid, Acute0.38
Alzheimer's Disease0.37
Glaucoma0.31
Protozoan Infections0.31

Drug development

1 compounds recorded · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (1)
SETANAXIBPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and High-Quality Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Advanced ClinicalSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

2 papers · to 2023

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

NOX4 Inhibition Potentiates Immunotherapy by Overcoming Cancer-Associated Fibroblast-Mediated CD8 T-cell Exclusion from Tumors.278 cites

Ford K · Cancer research · 2020

Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.41 cites

Kang JY · Journal of extracellular vesicles · 2023

Recent

Engineered small extracellular vesicle-mediated NOX4 siRNA delivery for targeted therapy of cardiac hypertrophy.

Kang JY · Journal of extracellular vesicles · 2023

NOX4 Inhibition Potentiates Immunotherapy by Overcoming Cancer-Associated Fibroblast-Mediated CD8 T-cell Exclusion from Tumors.

Ford K · Cancer research · 2020

Europe PMC papers linked directly to this protein.