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Protein / target

NADPH oxidase 2

Encoded byCYBBP04839Homo sapiensSwiss-Prot
UniProt: P04839Ensembl: ENSG00000165168HGNC: HGNC:2578NCBI Gene: 1536
Small-molecule tractable
Druggability
Structure with Ligand
1
Research papers

Protein at a glance

Biological role

Superoxide-generating NAD(P)H oxidase

Strongest disease association

Granulomatous Disease, Chronic

Via encoding gene CYBB · Genetic evidence · score 0.95

Research activity

Emerging research

1 papers · latest 2024

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

Catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)).

View complete UniProt function annotation

Catalytic subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)) (PubMed:15338276, PubMed:36241643, PubMed:36413210, PubMed:38355798). In the activated complex, electrons are first transferred from NADPH to flavin adenine dinucleotide (FAD) and subsequently transferred via two heme molecules to molecular oxygen, producing superoxide through an outer-sphere reaction (Probable) (PubMed:38355798). Activation of the NADPH oxidase complex is initiated by the assembly of cytosolic subunits of the NADPH oxidase complex with the core NADPH oxidase complex to form a complex at the plasma membrane or phagosomal membrane (PubMed:19028840, PubMed:38355798). This activation process is initiated by phosphorylation dependent binding of the cytosolic NCF1/p47-phox subunit to the C-terminus of CYBA/p22-phox (By similarity). NADPH oxidase complex assembly is impaired through interaction with NRROS (By similarity)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (39)

Domains & features

Ferric oxidoreductaseFAD-binding FR-type

Gene Ontology

  • Cdendrite
  • Cendoplasmic reticulum membrane
  • Cmonoatomic ion channel complex
  • CNADPH oxidase complex
  • Cneuronal cell body
  • Cnuclear envelope
  • Cperinuclear endoplasmic reticulum
  • Cphagocytic vesicle membrane
  • Cplasma membrane
  • Cspecific granule membrane
  • Ctertiary granule membrane
  • FFAD binding

570 aa · 65 kDa

Biological roles

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

Ion channel gatingGOImmune signallingGO
View supporting evidence

Ion channel gating

  • ·monoatomic ion channel complex
  • ·monoatomic ion transmembrane transport

Immune signalling

  • ·inflammatory response
  • ·innate immune response

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 CYBB

Gene-level evidence surfaced through the gene CYBB that 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.

Granulomatous Disease, Chronic
0.97Well supported

Genetic evidence dominant · Open Targets 0.86

Genetic Diseases, Inborn
0.32Limited support

Genetic evidence dominant · Open Targets 0.19

Neurodegenerative Diseases
0.25Preliminary

Pathway evidence dominant · Open Targets 0.35 · no direct causal or clinical evidence

Diabetes Mellitus
0.23Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

Lupus Erythematosus, Systemic
0.22Preliminary

Literature evidence dominant · Open Targets 0.11 · no direct causal or clinical evidence

View evidence synthesis (5)
Granulomatous Disease, ChronicWell supported
0.97
agreement 0.87–1.00
Genetic65%Somatic mutation24%Animal model7%Literature4%Genetic literaturedup

Open Targets aggregate 0.86 · 4 independent evidence families · 1 not counted as duplicate

Genetic Diseases, InbornLimited support
0.32
agreement 0.18–0.46
Genetic97%Literature4%

Open Targets aggregate 0.19 · 2 independent evidence families

Neurodegenerative DiseasesPreliminary
0.25
agreement 0.07–0.43
Pathway88%Literature12%

Open Targets aggregate 0.35 · 2 independent evidence families · no direct causal or clinical evidence

Diabetes MellitusPreliminary
0.23
agreement 0.09–0.38
Literature50%Animal model49%RNA expression1%

Open Targets aggregate 0.11 · 3 independent evidence families · no direct causal or clinical evidence

Lupus Erythematosus, SystemicPreliminary
0.22
agreement 0.05–0.40
Literature52%Animal model48%

Open Targets aggregate 0.11 · 2 independent evidence families · no direct causal or clinical evidence

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
Granulomatous Disease, Chronic0.86
Neurodegenerative Diseases0.35
Genetic Diseases, Inborn0.19
Kartagener Syndrome0.12
Diabetes Mellitus0.11
Lupus Erythematosus, Systemic0.11
Neoplasms0.11

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

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 (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (10)
SM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Research activity

1 papers · to 2024

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

Most cited

Microglial CR3 promotes neuron ferroptosis via NOX2-mediated iron deposition in rotenone-induced experimental models of Parkinson's disease.22 cites

Wang Q · Redox biology · 2024

Recent

Microglial CR3 promotes neuron ferroptosis via NOX2-mediated iron deposition in rotenone-induced experimental models of Parkinson's disease.

Wang Q · Redox biology · 2024

Europe PMC papers linked directly to this protein.