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26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NOS1
nitric oxide synthase 1
Chromosome 12 · 12q24.22
NCBI Gene: 4842Ensembl: ENSG00000089250.20HGNC: HGNC:7872UniProt: A0PJJ7
402PubMed Papers
20Diseases
2Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Highly Studied
CLINICAL
Clinical Trials
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingsarcoplasmic reticulumplasma membranenitric-oxide synthase activitycervical carcinomaneurotic disordertype 2 diabetes mellituspreeclampsia
✦AI Summary

NOS1 encodes neuronal nitric oxide synthase (nNOS), the predominant nitric oxide (NO)-producing enzyme in the brain that catalyzes L-arginine to generate NO, functioning as a neurotransmitter with diverse signaling roles 1. NOS1 mediates multiple neuronal functions including learning, memory development, synaptic plasticity, and neuronal development through both canonical NO signaling and non-canonical roles such as cysteine S-nitrosylation of target proteins 1. The enzyme is transiently expressed by gonadotropin-releasing hormone (GnRH) neurons and critically regulates reproductive development; NOS1 loss-of-function mutations cause congenital hypogonadotropic hypogonadism with associated anosmia, hearing loss, and intellectual disability, reversible by nitric oxide treatment during minipuberty 2. In cardiac tissue, NOS1 translocates to the sarcolemma in ischemic cardiomyopathy and maintains myocardial homeostasis; BAT-derived lipokine 12,13-diHOME enhances cardiac function via NOS1-dependent calcium cycling regulation 34. Genetically, NOS1 polymorphisms associate with psychiatric disorders: the rs3782206 variant confers schizophrenia risk in Asian populations, while nNOS in ErbB4-positive GABAergic interneurons regulates hippocampal GABA transmission, with nNOS deletion inducing schizophrenia-relevant behavioral deficits 56. NOS1 exon18 polymorphism shows association with Parkinson's disease risk 7. Reduced prefrontal NO signaling, determined by NOS1 genetic variants, associates with cognitive and neuropsychiatric symptoms 8.

Sources cited
1
NOS1 produces nitric oxide and mediates functions in learning, memory, synaptic plasticity, and neuronal development
PMID: 35821897
2
NOS1 loss-of-function mutations cause congenital hypogonadotropic hypogonadism with anosmia, hearing loss, and intellectual disability; nitric oxide treatment during minipuberty rescues reproductive and behavioral phenotypes
PMID: 36197968
3
Cardiac NOS1 upregulation shows partial sarcolemmal translocation in ischemic cardiomyopathy and correlates with left ventricular systolic function
PMID: 27041589
4
BAT-derived 12,13-diHOME enhances cardiac function via NOS1-dependent regulation of calcium cycling and mitochondrial respiration
PMID: 33106031
5
NOS1 rs3782206 polymorphism shows strongest association with schizophrenia in Asian populations
PMID: 28795310
6
nNOS in ErbB4-positive GABAergic interneurons regulates hippocampal GABA transmission; nNOS deletion induces schizophrenia-relevant behavioral deficits including hyperactivity and impaired cognition
PMID: 38396027
7
NOS1 exon18 polymorphism associates with Parkinson's disease risk in multiple genetic models
PMID: 27749554
8
Reduced NO signaling driven by NOS1 genetic variants in prefrontal cortex associates with schizophrenia and cognitive deficits
PMID: 25612209
Disease Associationsⓘ20
cervical carcinomaOpen Targets
0.41Moderate
neurotic disorderOpen Targets
0.32Weak
type 2 diabetes mellitusOpen Targets
0.32Weak
preeclampsiaOpen Targets
0.31Weak
post-traumatic stress disorderOpen Targets
0.31Weak
ankylosing spondylitisOpen Targets
0.30Weak
viral pneumoniaOpen Targets
0.29Weak
sign or symptomOpen Targets
0.29Weak
myocardial infarctionOpen Targets
0.27Weak
placental retentionOpen Targets
0.27Weak
congestive heart failureOpen Targets
0.27Weak
ShockOpen Targets
0.26Weak
major depressive disorderOpen Targets
0.25Weak
skin diseaseOpen Targets
0.24Weak
amyotrophic lateral sclerosisOpen Targets
0.22Weak
insomniaOpen Targets
0.21Weak
poisoningOpen Targets
0.20Weak
retinopathyOpen Targets
0.18Weak
liver diseaseOpen Targets
0.17Weak
abortionOpen Targets
0.16Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets2
TILARGININEPhase II
Nitric oxide synthase inhibitor
sickle cell disease
TILARGININE ACETATEPhase III
Nitric oxide synthase inhibitor
myocardial infarction
Related Genes
CAMK2AProtein interaction100%CAMK2BProtein interaction100%CBSProtein interaction100%ITPR1Protein interaction100%ITPR3Protein interaction100%MAPK3Protein interaction99%
Tissue Expression6 tissues
Brain
100%
Lung
28%
Heart
6%
Liver
3%
Ovary
3%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
NOS1CAMK2ACAMK2BCBSITPR1ITPR3MAPK3
PROTEIN STRUCTURE
Preparing viewer…
PDB8BI9 · 1.44 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.40Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.31 [0.25–0.40]
RankingsWhere NOS1 stands among ~20K protein-coding genes
  • #723of 20,598
    Most Researched402 · top 5%
  • #1,995of 17,882
    Most Constrained (LOEUF)0.40 · top quartile
Genes detectedNOS1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
Association Between NOS1 Gene Polymorphisms and Schizophrenia in Asian and Caucasian Populations: A Meta-Analysis.
PMID: 28795310
Neuromolecular Med · 2017
1.00
2
The expanding roles of neuronal nitric oxide synthase (NOS1).
PMID: 35821897
PeerJ · 2022
0.90
3
A Novel Endocrine Role for the BAT-Released Lipokine 12,13-diHOME to Mediate Cardiac Function.
PMID: 33106031
Circulation · 2021
0.80
4
The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children, and the interactions with environmental factors.
PMID: 20609134
Pediatr Allergy Immunol · 2010
0.72
5
PMID: 36197968
Sci Transl Med · 2022
0.70