NOS2

Chr 17

nitric oxide synthase 2

Also known as: HEP-NOS, INOS, NOS, NOS2A

NCBI Gene: 4843UniProt: P35228

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]

Primary Disease Associations & Inheritance

{Malaria, resistance to}MIM #611162
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
1.8
Missense Z
0.76
LOEUF
4
Active trials
Clinical Summary— NOS2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.76LOEUF
pLI 0.000
Z-score 3.08
OE 0.56 (0.43–0.76)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.78Z-score
OE missense 0.81 (0.75–0.86)
534 obs / 663.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.43–0.76)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.75–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.92
0≤1.21.6
LoF obs/exp: 33 / 58.4Missense obs/exp: 534 / 663.3Syn Z: 0.99

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

NOS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Malaria, resistance to}

MIM #611162

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Tumor-derived exosomes drive immunosuppressive macrophages in a pre-metastatic niche through glycolytic dominant metabolic reprogramming.
Morrissey SM et al.·Cell Metab
2021
Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion.
Byndloss MX et al.·Science
2017
Targeting lipophagy in macrophages improves repair in multiple sclerosis.
Haidar M et al.·Autophagy
2022
DDX5 inhibits hyaline cartilage fibrosis and degradation in osteoarthritis via alternative splicing and G-quadruplex unwinding.
Liu Q et al.·Nat Aging
2024
Identification and multimodal characterization of a specialized epithelial cell type associated with Crohn's disease.
Li J et al.·Nat Commun
2024
Exosome-mediated genetic reprogramming of tumor-associated macrophages by exoASO-STAT6 leads to potent monotherapy antitumor activity.
Kamerkar S et al.·Sci Adv
2022
STING-dependent induction of neutrophilic asthma exacerbation in response to house dust mite.
Messaoud-Nacer Y et al.·Allergy
2025
Levistilide A ameliorates neuroinflammation via inhibiting JAK2/STAT3 signaling for neuroprotection and cognitive improvement in scopolamine-induced Alzheimer's disease mouse model.
Ni H et al.·Int Immunopharmacol
2023Functional
NO and hepatocellular cancer.
Wang R et al.·Br J Pharmacol
2020Review
MCM8-mediated mitophagy protects vascular health in response to nitric oxide signaling in a mouse model of Kawasaki disease.
Lin M et al.·Nat Cardiovasc Res
2023Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Inducible nitric oxide synthase deficiency promotes murine-beta-coronavirus induced demyelination
Kamble M et al.·Virol J
2023
Ferroptosis regulator NOS2 is closely associated with the prognosis and cell malignant behaviors of hepatoblastoma: a bioinformatic and in vitro study
Zhang L et al.·Front Oncol
2023
NOS2 as a prognostic biomarker for early-onset colorectal cancer based on public data and clinical validation analysis
Xing C et al.·Sci Rep
2025
Relationship between single nucleotide polymorphism of NOS2 gene and inheritance of allergic rhinitis in children
Wu X et al.·Front Genet
2023
Nonsynonymous SNPs within C7H15orf39 and NOS2 are associated with boar semen quality.
Wang T et al.·Anim Biotechnol
2022
A specific, non-immune system-related isoform of the human inducible nitric oxide synthase is expressed during differentiation of human stem cells into various cell types
Gather F et al.·Cell Commun Signal
2022
Disrupted NOS2 metabolism drives myoblast response to wasting-associated cytokines.
Arneson-Wissink PC et al.·Exp Cell Res
2021
Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density
Somasundaram V et al.·Redox Biol
2022
TRAF1 Inhibits Macrophage Killing of Sporothrix schenckii by Enhancing NOS2 Expression and Activity.
He C et al.·J Infect Dis
2025
Innate Resistance to Leishmania amazonensis Infection in Rat Is Dependent on NOS2
Chen YF et al.·Front Microbiol
2021
Top 10 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
COPD

Immuno-inflammatory Response of Erdosteine in COPD

NOT YET RECRUITING
NCT07329946Phase NAPierachille Santus, MD, PhDStarted 2026-02-28
ErdosteineStandard of Care (SOC)
CancerObesity

A Nutrition & Exercise Prehabilitation Intervention on Inflammatory Biomarkers in AI Cancer Patients

RECRUITING
NCT06644560Phase NAUniversity of ArizonaStarted 2025-11-13
Prehabilitation Intervention
Cerebral Aneurysm

Effect of Sirolimus on Molecular Alterations in Cerebral Aneurysms

RECRUITING
NCT04141020Phase PHASE2University of MiamiStarted 2021-10-27
Microsurgical clippingEndovascular treatmentSirolimus
HealthyObesity

A Study of Adipose Tissue in Adaptive Responses to Exercise

ACTIVE NOT RECRUITING
NCT06053125Phase NAMayo ClinicStarted 2023-11-09
Adipose Tissue BiopsyExercise

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients