NOS2: Nitric Oxide Synthase 2, Inducible
Key enzyme in immune response and inflammation
Gene Information Card
| Symbol | NOS2 |
|---|---|
| Full Name | nitric oxide synthase 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 17q11.2 |
| NCBI Gene ID | 4843 ncbi.nlm.nih.gov/gene/4843 |
| Ensembl ID | ENSG00000007171 |
| UniProt ID | P35228 |
| OMIM ID | 163730 |
| HGNC ID | 7873 |
| Aliases | iNOS, NOS2A, HEP-NOS, NOS, INOS |
Description
NOS2 encodes the inducible nitric oxide synthase (iNOS), an enzyme that produces nitric oxide (NO) from L-arginine. iNOS is expressed in response to inflammatory stimuli such as cytokines and microbial products, and its activity is calcium-independent. NO produced by iNOS acts as a cytotoxic mediator in immune defense, but excessive NO can contribute to tissue damage, inflammation, and carcinogenesis. The gene is located on chromosome 17q11.2 and spans approximately 37 kb.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sepsis | Overexpression of NOS2 leads to excessive NO, causing vasodilation and hypotension in septic shock. | ClinVar, OMIM |
| Asthma | Increased iNOS activity in airway epithelium contributes to airway inflammation and hyperresponsiveness. | NCBI Gene, OMIM |
| Rheumatoid Arthritis | iNOS-derived NO promotes synovial inflammation and joint destruction. | NCBI Gene, OMIM |
| Cancer (e.g., colorectal, breast) | Chronic NO production from iNOS can cause DNA damage and promote tumor angiogenesis. | COSMIC, NCBI Gene |
| Cystic Fibrosis | Altered NOS2 expression affects airway inflammation and infection susceptibility. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Spleen | 8.3 | Medium |
| Liver | 6.1 | Low |
| Kidney | 4.7 | Low |
| Colon | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.2 | Inducible by cytokines |
| THP-1 (monocyte) | 22.8 | Inducible by LPS/IFN-gamma |
| HepG2 (hepatocellular carcinoma) | 5.4 | Low basal expression |
| MCF7 (breast adenocarcinoma) | 2.1 | Low basal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs2297518 (Ser608Leu) | missense | 0.05 (global) | Alters enzyme activity; associated with asthma and sepsis risk |
| rs2779249 (promoter) | regulatory | 0.15 (global) | Affects transcription factor binding; linked to inflammatory diseases |
| rs1137933 (Asp346Glu) | missense | 0.02 (global) | Reduced NO production; associated with rheumatoid arthritis |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce iNOS activity (e.g., rs1137933) impair NO-mediated immune defense, increasing susceptibility to infections.
Gain of Function (GOF)
Promoter polymorphisms (e.g., rs2779249) that increase NOS2 transcription lead to excessive NO, contributing to inflammatory tissue damage.
Dominant Negative (DN)
No well-characterized dominant-negative mutations reported for NOS2.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004517 - nitric-oxide synthase activity | • GO:0006809 - nitric oxide biosynthetic process |
| • GO:0005515 - protein binding | • GO:0005737 - cytoplasm |
| • GO:0005886 - plasma membrane | • GO:0045429 - positive regulation of nitric oxide biosynthetic process |
| • GO:0006954 - inflammatory response |
Pathways
• Nitric oxide signaling pathway (Reactome: R-HSA-202131)
• Toll-like receptor signaling pathway (KEGG: hsa04620)
• Cytokine-cytokine receptor interaction (KEGG: hsa04060)
• Arginine and proline metabolism (KEGG: hsa00330)
Protein Summary
The NOS2 protein (iNOS) is a 131 kDa homodimeric enzyme that catalyzes the conversion of L-arginine to L-citrulline and nitric oxide. It contains binding sites for heme, FAD, FMN, and tetrahydrobiopterin. Unlike neuronal and endothelial NOS isoforms, iNOS is calcium-independent and regulated primarily at the transcriptional level. Its expression is induced by pro-inflammatory cytokines (e.g., IFN-gamma, TNF-alpha) and microbial products. The protein is localized in the cytoplasm and plasma membrane, and its activity is essential for macrophage-mediated killing of pathogens.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NOS2 Knockout HEK293 Cell Line | EDJ-KQ1428 | Human | 4843 | Details Get a Quote |
| NANOS2 Knockout HEK293 Cell Line | EDJ-KQ14370 | Human | 339345 | Details Get a Quote |
| NOS2 Knockout HeLa Cell Line | EDJ-KQ54005 | Human | 4843 | Details Get a Quote |
| NANOS2 Knockout HeLa Cell Line | EDJ-KQ59638 | Human | 339345 | Details Get a Quote |
| NOS2 Knockout A-549 Cell Line | EDJ-KQ62498 | Human | 4843 | Details Get a Quote |
| NANOS2 Knockout A-549 Cell Line | EDJ-KQ68105 | Human | 339345 | Details Get a Quote |
| NOS2 Knockout HCT 116 Cell Line | EDJ-KQ70965 | Human | 4843 | Details Get a Quote |
| NANOS2 Knockout HCT 116 Cell Line | EDJ-KQ76482 | Human | 339345 | Details Get a Quote |
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