NOS1

nitric oxide synthase 1, the group of PDZ domain containing

Basic information

Region (hg38): 12:117208142-117452170

Previous symbols: [ "NOS" ]

Links

ENSG00000089250 ∙ NCBI:4842 ∙ OMIM:163731 ∙ HGNC:7872 ∙ Uniprot:P29475 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• idiopathic achalasia (Supportive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				34	15	49
missense			58	13	3	74
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				4	1	5
non coding			3	1	4	8
Total	0	0	61	48	22

Variants in NOS1

This is a list of pathogenic ClinVar variants found in the NOS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-117215301-G-A		NOS1-related disorder	Benign (Jun 17, 2019)
12-117215323-C-T		not specified	Uncertain significance (Apr 05, 2023)
12-117218048-A-G			Likely benign (May 01, 2023)
12-117218071-C-G			Likely benign (Dec 28, 2017)
12-117218073-A-G		not specified	Uncertain significance (Oct 13, 2023)
12-117218101-G-A		not specified	Uncertain significance (Mar 05, 2024)
12-117220098-C-T		not specified	Uncertain significance (Dec 19, 2023)
12-117220167-C-A		not specified	Uncertain significance (Jul 12, 2022)
12-117220186-G-T		NOS1-related disorder	Benign (Jan 03, 2024)
12-117220188-C-T		NOS1-related disorder • not specified	Uncertain significance (Sep 30, 2024)
12-117220198-G-T			Likely benign (Dec 31, 2019)
12-117220227-C-T		not specified	Uncertain significance (Oct 06, 2021)
12-117220234-C-T			Likely benign (Jan 03, 2019)
12-117222765-C-T		not specified	Uncertain significance (Jun 28, 2024)
12-117222782-T-C		not specified	Uncertain significance (Apr 06, 2022)
12-117222796-C-T			Likely benign (Jan 11, 2018)
12-117222832-G-A			Likely benign (Dec 28, 2017)
12-117225073-C-T		not specified	Uncertain significance (Feb 05, 2024)
12-117226709-G-A			Likely benign (Dec 26, 2017)
12-117226711-C-T		not specified	Uncertain significance (Mar 28, 2023)
12-117226750-G-A		not specified	Uncertain significance (Nov 13, 2023)
12-117227433-C-T		not specified	Uncertain significance (Oct 20, 2021)
12-117227439-C-T		not specified	Likely benign (Aug 12, 2021)
12-117227441-G-C			Uncertain significance (Mar 01, 2015)
12-117227508-T-C		not specified	Uncertain significance (Nov 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOS1	protein_coding	protein_coding	ENST00000338101	29	244029

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.25e-7	124790	0	10	124800	0.0000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.68	587	898	0.654	0.0000550	9621
Missense in Polyphen		177	373.88	0.47341		3849
Synonymous	-0.960	394	371	1.06	0.0000249	2894
Loss of Function	7.23	8	76.1	0.105	0.00000408	822

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.00	0.00
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.0000368	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Long-term depression - Homo sapiens (human);Phagosome - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Amyotrophic lateral sclerosis (ALS) - Homo sapiens (human);Circadian entrainment - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Salivary secretion - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Arginine biosynthesis - Homo sapiens (human);Hyperornithinemia with gyrate atrophy (HOGA);Creatine deficiency, guanidinoacetate methyltransferase deficiency;L-arginine:glycine amidinotransferase deficiency;Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome];Guanidinoacetate Methyltransferase Deficiency (GAMT Deficiency);Prolinemia Type II;Prolidase Deficiency (PD);Arginine and Proline Metabolism;Hyperprolinemia Type I;Hyperprolinemia Type II;Ornithine Aminotransferase Deficiency (OAT Deficiency);Arginine: Glycine Amidinotransferase Deficiency (AGAT Deficiency);Serotonin Transporter Activity;Effects of Nitric Oxide;Alzheimers Disease;Spinal Cord Injury;Quercetin and Nf-kB- AP-1 Induced Cell Apoptosis;Amyotrophic lateral sclerosis (ALS);Myometrial Relaxation and Contraction Pathways;Rac1-Pak1-p38-MMP-2 pathway;Association Between Physico-Chemical Features and Toxicity Associated Pathways;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;NO-cGMP-PKG mediated Neuroprotection;Phosphodiesterases in neuronal function;Monoamine Transport;nitric oxide signaling pathway;ROS, RNS production in phagocytes;Innate Immune System;Immune System;Ion homeostasis;citrulline-nitric oxide cycle;sumoylation as a mechanism to modulate ctbp-dependent gene responses;Cardiac conduction;Muscle contraction;Arginine Proline metabolism;Hemostasis;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.612

Intolerance Scores

• loftool: 0.306
• rvis_EVS: -1.01
• rvis_percentile_EVS: 8.21

Haploinsufficiency Scores

• pHI: 0.170
• hipred: Y
• hipred_score: 0.651
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.981

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nos1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; renal/urinary system phenotype; skeleton phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; respiratory system phenotype

Zebrafish Information Network

• Gene name: nos1
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: response to hypoxia;regulation of sodium ion transport;arginine catabolic process;nitric oxide biosynthetic process;striated muscle contraction;nitric oxide mediated signal transduction;myoblast fusion;response to heat;response to hormone;negative regulation of calcium ion transport into cytosol;peptidyl-cysteine S-nitrosylation;positive regulation of guanylate cyclase activity;response to lipopolysaccharide;multicellular organismal response to stress;positive regulation of histone acetylation;neurotransmitter biosynthetic process;vasodilation;exogenous drug catabolic process;negative regulation of potassium ion transport;cell redox homeostasis;negative regulation of blood pressure;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of neurogenesis;negative regulation of hydrolase activity;negative regulation of serotonin uptake;negative regulation of calcium ion transport;oxidation-reduction process;regulation of cardiac muscle contraction;regulation of ryanodine-sensitive calcium-release channel activity;cellular response to growth factor stimulus;positive regulation of the force of heart contraction;retrograde trans-synaptic signaling by nitric oxide;positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process;positive regulation of sodium ion transmembrane transport;regulation of calcium ion transmembrane transport via high voltage-gated calcium channel;regulation of cardiac conduction
• Cellular component: photoreceptor inner segment;nucleus;nucleoplasm;cytoplasm;mitochondrion;cytosol;cytoskeleton;plasma membrane;caveola;vesicle membrane;postsynaptic density;sarcoplasmic reticulum;Z disc;T-tubule;protein-containing complex;sarcolemma;dendritic spine;calyx of Held;membrane raft;synapse;perinuclear region of cytoplasm;ryanodine receptor complex
• Molecular function: NADPH-hemoprotein reductase activity;nitric-oxide synthase activity;protein binding;calmodulin binding;FMN binding;oxidoreductase activity;sodium channel regulator activity;heme binding;tetrahydrobiopterin binding;arginine binding;ion channel binding;cadmium ion binding;flavin adenine dinucleotide binding;NADP binding;scaffold protein binding