NOS2 Gene

Name nitric oxide synthase 2, inducible
Description Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
Summary
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In several studies, genetic polymorphisms in the NOS2 promoter region have been linked to enhanced basal NO production and protection against severe infections such as malaria and tuberculosis, while tightly controlled NOS2 expression underpins rapid, effective innate immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, NOS2 exerts a paradoxical influence on tumor biology. Elevated NOS2 expression and subsequent NO production have been implicated in promoting tumor angiogenesis, metastasis, and chemoresistance, yet in some settings NO also mediates cytotoxicity. Numerous observations across diverse malignancies—including colorectal, breast, glioma, melanoma, and cutaneous as well as head and neck carcinomas—associate high NOS2 levels with aggressive tumor behavior, activation of oncogenic signaling pathways (for example, via EGFR and mTOR‐linked mechanisms), and poor clinical outcomes. Moreover, genome‐wide association studies have identified NOS2 as a susceptibility locus in dermatologic disorders such as psoriasis, underscoring its involvement in both neoplastic and chronic inflammatory processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNOS2 is also central to neuroinflammatory and neurodegenerative processes. Studies in models of HIV‐associated dementia, Alzheimer’s disease, and Parkinson’s disease demonstrate that aberrant induction of NOS2 in glial cells and neurons contributes to nitrosative stress, neuronal injury, and consequent cognitive and motor deficits. In cultured astrocytes, specific cytokine combinations robustly stimulate NOS2 expression, further linking chronic neuroinflammation to pathological outcomes."}, {"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": "\nThe expression and activity of NOS2 are governed by complex regulatory networks that include transcriptional control, post‐translational modifications, and precise domain movements required for electron transfer. Multiple studies have demonstrated that NOS2 protein levels are modulated via ubiquitination and transcriptional repression (for example, through NF‑κB–repressing factors), while its catalytic efficiency depends on the proper orientation of bound cofactors. Such mechanistic insights underscore the importance of epigenetic and structural determinants in fine‐tuning NOS2 activity and NO production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrant NOS2 activity is implicated in diverse non‐neoplastic conditions spanning vascular and reproductive abnormalities, pulmonary disorders, and severe inflammatory syndromes. In the vasculature and placenta, NOS2‐derived NO influences endothelial function and trophoblast motility, affecting aortic homeostasis and contributing to disorders such as preeclampsia. In parallel, altered NOS2 expression in the lung is reflected by changes in exhaled NO levels in chronic obstructive pulmonary disease, while dysregulated NO signaling has been linked to catastrophic skin injury in toxic epidermal necrolysis and to systemic inflammatory conditions including chronic fatigue syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "42", "end_ref": "50"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J F Kun, B Mordmüller, D J Perkins, et al. 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Synonyms INOS, NOS2A, HEP-NOS
Proteins NOS2_HUMAN
NCBI Gene ID 4843
API
Download Associations
Predicted Functions View NOS2's ARCHS4 Predicted Functions.
Co-expressed Genes View NOS2's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View NOS2's ARCHS4 Predicted Functions.

Functional Associations

NOS2 has 10,418 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 111 datasets.

Click the + buttons to view associations for NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
Biocarta Pathways pathways involving NOS2 protein from the Biocarta Pathways dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CCLE Cell Line Gene Mutation Profiles cell lines with NOS2 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with NOS2 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 NOS2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of NOS2 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 NOS2 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 NOS2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing NOS2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with NOS2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of NOS2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with NOS2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with NOS2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with NOS2 gene/protein from the curated CTD Gene-Disease Associations dataset.
dbGAP Gene-Trait Associations traits associated with NOS2 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by NOS2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Curated Gene-Disease Association Evidence Scores 2025 diseases involving NOS2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with NOS2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 diseases associated with NOS2 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 NOS2 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 NOS2 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 NOS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with NOS2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
DrugBank Drug Targets interacting drugs for NOS2 protein from the curated DrugBank Drug Targets dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at NOS2 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 NOS2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of NOS2 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 NOS2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with NOS2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with NOS2 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 NOS2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with NOS2 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 NOS2 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 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 NOS2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving NOS2 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving NOS2 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Cellular Component Annotations 2015 cellular components containing NOS2 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing NOS2 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by NOS2 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by NOS2 gene from the curated GO Molecular Function Annotations 2023 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of NOS2 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 NOS2 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 NOS2 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
Guide to Pharmacology Chemical Ligands of Receptors ligands (chemical) binding NOS2 receptor from the curated Guide to Pharmacology Chemical Ligands of Receptors dataset.
GWAS Catalog SNP-Phenotype Associations phenotypes associated with NOS2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations dataset.
GWASdb SNP-Disease Associations diseases associated with NOS2 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with NOS2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
HMDB Metabolites of Enzymes interacting metabolites for NOS2 protein from the curated HMDB Metabolites of Enzymes dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of NOS2 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of NOS2 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 NOS2 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 NOS2 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for NOS2 from the curated Hub Proteins Protein-Protein Interactions dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with NOS2 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
HumanCyc Pathways pathways involving NOS2 protein from the HumanCyc Pathways dataset.
IMPC Knockout Mouse Phenotypes phenotypes of mice caused by NOS2 gene knockout from the IMPC Knockout Mouse Phenotypes dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for NOS2 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of NOS2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate NOS2 protein from the curated KEA Substrates of Kinases dataset.
Kinase Library Serine Threonine Kinome Atlas kinases that phosphorylate NOS2 protein from the Kinase Library Serine Threonine Atlas dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of NOS2 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 NOS2 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 NOS2 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 NOS2 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LOCATE Curated Protein Localization Annotations cellular components containing NOS2 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain NOS2 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by NOS2 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting NOS2 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 NOS2 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 NOS2 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Cancer Gene Co-expression Modules co-expressed genes for NOS2 from the MSigDB Cancer Gene Co-expression Modules dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of NOS2 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
MW Enzyme Metabolite Associations interacting metabolites for NOS2 protein from the MW Gene Metabolite Associations dataset.
NURSA Protein Complexes protein complexs containing NOS2 protein recovered by IP-MS from the NURSA Protein Complexes dataset.
OMIM Gene-Disease Associations phenotypes associated with NOS2 gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for NOS2 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of NOS2 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 NOS2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving NOS2 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving NOS2 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with NOS2 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
PhosphoSitePlus Substrates of Kinases kinases that phosphorylate NOS2 protein from the curated PhosphoSitePlus Substrates of Kinases dataset.
PID Pathways pathways involving NOS2 protein from the PID Pathways dataset.
Reactome Pathways 2014 pathways involving NOS2 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving NOS2 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles cell types and tissues with high or low DNA methylation of NOS2 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at NOS2 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of NOS2 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of NOS2 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Conserved microRNA Targets microRNAs regulating expression of NOS2 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of NOS2 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 NOS2 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 NOS2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with NOS2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
WikiPathways Pathways 2014 pathways involving NOS2 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving NOS2 protein from the WikiPathways Pathways 2024 dataset.