NOX4 Gene

Name NADPH oxidase 4
Description This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
Summary
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In these contexts, NOX4‐generated hydrogen peroxide (H₂O₂) appears essential for the activation of downstream signaling cascades that consolidate tissue scarring and epithelial injury."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vascular and endothelial cells, NOX4 is widely expressed and differentially localized—including at internal membranes, the endoplasmic reticulum, and even the nucleus—thereby tailoring ROS production to specific subcellular compartments. By constitutively generating H₂O₂, NOX4 modulates key receptor‐mediated events such as insulin and TLR4 signaling, regulates protein tyrosine phosphatase activity, and functions as an oxygen sensor owing to its unique kinetic profile. Its interactions with the regulatory subunit p22phox, as well as its responsiveness to hypoxic, inflammatory, and metabolic cues, underscore a pivotal role in modulating endothelial cell adhesion, smooth muscle cell proliferation, pulmonary vascular remodeling, and cardiac physiology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer and senescence contexts, NOX4‐derived ROS serve a dual role by promoting both prosurvival signaling and oncogene‐induced DNA damage responses that culminate in cellular senescence. In pancreatic, melanoma, and breast cancers, NOX4 modulates key pathways—such as the AKT–ASK1 axis and Ras‐dependent signaling—to inhibit apoptosis and support tumor growth, drug resistance, and metabolic reprogramming. In addition, paracrine signals from senescent cells can upregulate NOX4, thereby reinforcing a proinflammatory secretory phenotype that further contributes to tumor progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in fibrosis, vascular regulation, and cancer, NOX4 orchestrates cellular stress responses by linking endoplasmic reticulum signaling to mitochondrial dysfunction and autophagy. Its localization within the nucleus and ER facilitates the oxidation of key modulators—including protein tyrosine phosphatases and kinases—to fine‐tune the unfolded protein response and Ras/ERK pathway activation. These mechanisms also contribute to neurodegenerative processes, as exemplified by NOX4‐mediated ferroptosis in Alzheimer’s disease and TGF–β–induced hepatocyte apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Louise Hecker, Ragini Vittal, Tamara Jones, et al. 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Synonyms KOX, KOX-1, RENOX
Proteins NOX4_HUMAN
NCBI Gene ID 50507
API
Download Associations
Predicted Functions View NOX4's ARCHS4 Predicted Functions.
Co-expressed Genes View NOX4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View NOX4's ARCHS4 Predicted Functions.

Functional Associations

NOX4 has 8,424 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 108 datasets.

Click the + buttons to view associations for NOX4 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by NOX4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of NOX4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of NOX4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of NOX4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of NOX4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of NOX4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of NOX4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of NOX4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of NOX4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with NOX4 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of NOX4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of NOX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of NOX4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of NOX4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing NOX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing NOX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with NOX4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with NOX4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of NOX4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with NOX4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with NOX4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with NOX4 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by NOX4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with NOX4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with NOX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with NOX4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with NOX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with NOX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at NOX4 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of NOX4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of NOX4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing NOX4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with NOX4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with NOX4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of NOX4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with NOX4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing NOX4 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of NOX4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving NOX4 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving NOX4 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving NOX4 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing NOX4 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing NOX4 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing NOX4 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by NOX4 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by NOX4 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by NOX4 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of NOX4 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of NOX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of NOX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with NOX4 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWASdb SNP-Disease Associations diseases associated with NOX4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with NOX4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of NOX4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HMDB Metabolites of Enzymes interacting metabolites for NOX4 protein from the curated HMDB Metabolites of Enzymes dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of NOX4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of NOX4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HuBMAP ASCT+B Annotations cell types associated with NOX4 gene from the HuBMAP ASCT+B dataset.
HuBMAP ASCT+B Augmented with RNA-seq Coexpression cell types associated with NOX4 gene from the HuBMAP ASCT+B Augmented with RNA-seq Coexpression dataset.
HuBMAP Azimuth Cell Type Annotations cell types associated with NOX4 gene from the HuBMAP Azimuth Cell Type Annotations dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with NOX4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by NOX4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for NOX4 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of NOX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of NOX4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with NOX4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of NOX4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of NOX4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of NOX4 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of NOX4 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain NOX4 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by NOX4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting NOX4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of NOX4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by NOX4 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of NOX4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of NOX4 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for NOX4 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of NOX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of NOX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving NOX4 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving NOX4 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with NOX4 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
PID Pathways pathways involving NOX4 protein from the PID Pathways dataset.
Reactome Pathways 2024 pathways involving NOX4 protein from the Reactome Pathways 2024 dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of NOX4 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of NOX4 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of NOX4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of NOX4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of NOX4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of NOX4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of NOX4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of NOX4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of NOX4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with NOX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with NOX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving NOX4 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving NOX4 protein from the WikiPathways Pathways 2024 dataset.