NOS2

nitric oxide synthase 2

Basic information

Region (hg38): 17:27756765-27800529

Previous symbols: [ "NOS2A" ]

Links

ENSG00000007171 ∙ NCBI:4843 ∙ OMIM:163730 ∙ HGNC:7873 ∙ Uniprot:P35228 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• schizophrenia (No Known Disease Relationship), mode of inheritance: Unknown

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOS2 gene.

• Inborn genetic diseases (49 variants)
• not provided (31 variants)
• not specified (12 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOS2 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				14	8	22
missense			46	8	1	55
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding				2	10	12
Total	0	0	46	24	19

Variants in NOS2

This is a list of pathogenic ClinVar variants found in the NOS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-27757300-C-T		NOS2-related disorder	Benign/Likely benign (Feb 25, 2019)
17-27757308-A-G		not specified	Uncertain significance (Nov 10, 2022)
17-27757313-A-T		not specified	Uncertain significance (Jan 05, 2022)
17-27758902-C-T			Benign/Likely benign (Mar 01, 2022)
17-27758905-G-A		NOS2-related disorder	Benign (Dec 31, 2019)
17-27758944-C-T		NOS2-related disorder	Likely benign (Feb 28, 2019)
17-27758954-G-A		not specified	Uncertain significance (Sep 22, 2023)
17-27758970-G-A		not specified	Likely benign (Apr 07, 2022)
17-27758979-G-A			Likely benign (Jun 05, 2018)
17-27759000-G-A		not specified	Uncertain significance (Jan 08, 2024)
17-27759004-G-T			Likely benign (Jun 28, 2018)
17-27759037-G-C		not specified	Uncertain significance (Jul 09, 2021)
17-27760049-C-T		not specified	Uncertain significance (Jun 21, 2023)
17-27760055-T-C		not specified	Uncertain significance (Oct 13, 2021)
17-27760058-G-A		not specified	Uncertain significance (Jan 23, 2024)
17-27760070-G-A		not specified	Uncertain significance (Feb 28, 2024)
17-27760097-T-G		not specified	Uncertain significance (Oct 22, 2021)
17-27760103-A-G		not specified	Uncertain significance (Nov 07, 2022)
17-27760137-G-T			Likely benign (Jun 26, 2018)
17-27760163-C-T		not specified	Uncertain significance (Dec 17, 2023)
17-27760173-G-A		not specified	Uncertain significance (May 16, 2023)
17-27760628-T-A		not specified	Uncertain significance (Aug 12, 2021)
17-27760720-C-G		not specified	Uncertain significance (Feb 17, 2024)
17-27761134-G-C		NOS2-related disorder	Likely benign (Oct 28, 2019)
17-27761177-T-C		not specified	Uncertain significance (Jun 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOS2	protein_coding	protein_coding	ENST00000313735	26	43734

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.03e-15	0.999	125668	0	80	125748	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	534	663	0.805	0.0000398	7523
Missense in Polyphen		171	266.89	0.64071		3084
Synonymous	0.989	253	274	0.924	0.0000173	2217
Loss of Function	3.08	33	58.4	0.565	0.00000282	673

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000636	0.000636
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000225	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000440	0.000431
Middle Eastern	0.000225	0.000217
South Asian	0.000398	0.000392
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body (PubMed:7531687, PubMed:7544004). In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2 (By similarity). As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on 'Cys-247' implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM (PubMed:25417112). Involved in inflammation, enhances the synthesis of proinflammatory mediators such as IL6 and IL8 (PubMed:19688109). {ECO:0000250|UniProtKB:P29477, ECO:0000269|PubMed:19688109, ECO:0000269|PubMed:25417112, ECO:0000269|PubMed:7531687, ECO:0000269|PubMed:7544004}.
• Pathway: Relaxin signaling pathway - Homo sapiens (human);Arginine and proline metabolism - Homo sapiens (human);Pertussis - Homo sapiens (human);Salmonella infection - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Peroxisome - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Doxorubicin Pathway (Cardiomyocyte Cell), Pharmacodynamics;Chagas disease (American trypanosomiasis) - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Leishmaniasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Pathways in cancer - Homo sapiens (human);Arginine biosynthesis - Homo sapiens (human);Effects of Nitric Oxide;Prolactin Signaling Pathway;AGE-RAGE pathway;Spinal Cord Injury;Rac1-Pak1-p38-MMP-2 pathway;Photodynamic therapy-induced HIF-1 survival signaling;Hepatitis C and Hepatocellular Carcinoma;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;NO-cGMP-PKG mediated Neuroprotection;Interleukin-4 and 13 signaling;Fibrin Complement Receptor 3 Signaling Pathway;no2-dependent il-12 pathway in nk cells;Type II interferon signaling (IFNG);mechanism of gene regulation by peroxisome proliferators via ppara;Metabolism of proteins;ROS, RNS production in phagocytes;Innate Immune System;Immune System;ATF-2 transcription factor network;citrulline-nitric oxide cycle;Peroxisomal protein import;Arginine Proline metabolism;Hemostasis;Nitric oxide stimulates guanylate cyclase;Platelet homeostasis;IL23-mediated signaling events;Signaling mediated by p38-alpha and p38-beta;Alpha9 beta1 integrin signaling events;HIF-1-alpha transcription factor network;IL12-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.950

Intolerance Scores

• loftool: 0.549
• rvis_EVS: -1.68
• rvis_percentile_EVS: 2.69

Haploinsufficiency Scores

• pHI: 0.170
• hipred: Y
• hipred_score: 0.782
• ghis: 0.524

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nos2
• Phenotype: digestive/alimentary 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); vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic system phenotype; reproductive system 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); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); neoplasm; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: response to hypoxia;positive regulation of leukocyte mediated cytotoxicity;innate immune response in mucosa;arginine catabolic process;protein targeting to peroxisome;superoxide metabolic process;nitric oxide biosynthetic process;nitric oxide mediated signal transduction;circadian rhythm;response to bacterium;response to hormone;negative regulation of gene expression;peptidyl-cysteine S-nitrosylation;cytokine-mediated signaling pathway;positive regulation of guanylate cyclase activity;prostaglandin secretion;response to lipopolysaccharide;cellular response to drug;regulation of cell population proliferation;negative regulation of protein catabolic process;defense response to bacterium;regulation of cellular respiration;cell redox homeostasis;negative regulation of blood pressure;regulation of insulin secretion;defense response to Gram-negative bacterium;positive regulation of killing of cells of other organism;oxidation-reduction process;cellular response to lipopolysaccharide;cellular response to interferon-gamma;interleukin-6 secretion;interleukin-8 secretion;regulation of cytokine production involved in inflammatory response
• Cellular component: nucleus;cytoplasm;peroxisome;peroxisomal matrix;cytosol;plasma membrane;vesicle membrane;cortical cytoskeleton;perinuclear region of cytoplasm
• Molecular function: NADPH-hemoprotein reductase activity;nitric-oxide synthase activity;signaling receptor binding;protein binding;calmodulin binding;FMN binding;oxidoreductase activity;heme binding;tetrahydrobiopterin binding;arginine binding;protein homodimerization activity;metal ion binding;flavin adenine dinucleotide binding;NADP binding