BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

Search Gene with Disease Search Gene1 with Disease

Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

ADD to My Gene Set

Comment on Gene

View All Comments on Gene

Basic Info

Approved Symbol	NOS3
Symbol Alias	ECNOS, eNOS
Approved Name	nitric oxide synthase 3 (endothelial cell)
Name Alias	endothelial nitric oxide synthase
Location	7q36
Position	chr7:150990995-151014588, 1
External Links	HGNC: 7876 Entrez Gene: 4846 Ensembl: ENSG00000164867 UCSC: uc003wif.3
No. of Studies	2 (Positive: 1; Negative: 1; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 2)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Kittel-Schneider, S., 2014	SNP: rs2070744, rs1799983 Other variant: NOS3_Intron 4 VNTR_4a/b	None of the investigated polymorphisms in this gene was associated with BD.	Negative	Comment on Study
Reif, A., 2006 (b)	Haplotype: NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(c-a-g), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(c-a-t), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(c-b-g), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(c-b-t), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(c-c-t), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(t-a-g), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(t-b-g), NOS3_T-786C - NOS3_Intron4_VNTR - NOS3_G894T(t-b-t) Other variant: NOS3_G894T, NOS3_Intron4_VNTR, NOS3_T-786C	Our results thus suggest that the NOS-III genotype may convey a modest genetic risk to develop bipolar disorder.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 59)

GO terms by PBA (count: 3)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0005886	plasma membrane	cellular component	TAS	360
GO:0005634	nucleus	cellular component	ISS	283
GO:0005516	calmodulin binding	molecular function	IEA	20

GO terms by database search (count: 56)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0005737	cytoplasm	cellular component	IDA[9794441]	322
GO:0001525	angiogenesis	biological process	IEA	20
GO:0050661	NADP binding	molecular function	NAS[7488039]	5
GO:0007005	mitochondrion organization	biological process	ISS	8
GO:0005506	iron ion binding	molecular function	IEA	8
GO:0005856	cytoskeleton	cellular component	IEA	30
GO:0003785	actin monomer binding	molecular function	IPI[17502619]	4
GO:0001542	ovulation from ovarian follicle	biological process	IEA	3
GO:0005901	caveola	cellular component	IDA[17502619]	11
GO:0003100	regulation of systemic arterial blood pressure by endothelin	biological process	IMP[8999856]	1
GO:0090382	phagosome maturation	biological process	TAS	6
GO:0001701	in utero embryonic development	biological process	IEA	17
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	biological process	ISS	1
GO:0055114	oxidation-reduction process	biological process	IEA	43
GO:0034617	tetrahydrobiopterin binding	molecular function	IDA[7488039]	3
GO:0007263	nitric oxide mediated signal transduction	biological process	IBA	5
GO:0044281	small molecule metabolic process	biological process	TAS	117
GO:0004517	nitric-oxide synthase activity	molecular function	IDA[1378832]	2
GO:0006809	nitric oxide biosynthetic process	biological process	IDA[1378832]	8
GO:0031284	positive regulation of guanylate cyclase activity	biological process	IMP[17502619]; ISS	4
GO:0045909	positive regulation of vasodilation	biological process	NAS[18048451]	14
GO:0010544	negative regulation of platelet activation	biological process	NAS[7504210]	2
GO:0050999	regulation of nitric-oxide synthase activity	biological process	TAS	6
GO:0051926	negative regulation of calcium ion transport	biological process	IEA	3
GO:0050880	regulation of blood vessel size	biological process	ISS; NAS[7504210]	5
GO:0010181	FMN binding	molecular function	NAS[7488039]	2
GO:0003057	regulation of the force of heart contraction by chemical signal	biological process	IEA	1
GO:0008217	regulation of blood pressure	biological process	NAS[7504210]	12
GO:0030666	endocytic vesicle membrane	cellular component	TAS	8
GO:0014740	negative regulation of muscle hyperplasia	biological process	ISS	1
GO:0034405	response to fluid shear stress	biological process	IEP[10376603]	6
GO:0046870	cadmium ion binding	molecular function	NAS[7488039]	2
GO:0046209	nitric oxide metabolic process	biological process	TAS	5
GO:0005515	protein binding	molecular function	IPI[11149895]	563
GO:0005829	cytosol	cellular component	TAS	223
GO:0008285	negative regulation of cell proliferation	biological process	ISS	41
GO:0007596	blood coagulation	biological process	TAS	44
GO:0045766	positive regulation of angiogenesis	biological process	ISS	11
GO:0006527	arginine catabolic process	biological process	IDA[1378832]	2
GO:0014806	smooth muscle hyperplasia	biological process	ISS	1
GO:0048010	vascular endothelial growth factor receptor signaling pathway	biological process	TAS	12
GO:0050660	flavin adenine dinucleotide binding	molecular function	NAS[7488039]	5
GO:0031663	lipopolysaccharide-mediated signaling pathway	biological process	IEA	6
GO:0002028	regulation of sodium ion transport	biological process	IEA	9
GO:0051346	negative regulation of hydrolase activity	biological process	IEA	4
GO:0043542	endothelial cell migration	biological process	IMP[8999856]	3
GO:0003958	NADPH-hemoprotein reductase activity	molecular function	IBA	2
GO:0045776	negative regulation of blood pressure	biological process	IBA	10
GO:0009408	response to heat	biological process	NAS[18048451]	12
GO:0030324	lung development	biological process	IEA	9
GO:0051701	interaction with host	biological process	TAS	6
GO:0034618	arginine binding	molecular function	IDA[7488039]	2
GO:0043267	negative regulation of potassium ion transport	biological process	IEA	6
GO:0001974	blood vessel remodeling	biological process	ISS	8
GO:0020037	heme binding	molecular function	IDA[7488039]	6
GO:0000139	Golgi membrane	cellular component	TAS	36

Gene related KEGG pathways (count: 5)

KEGG pathways by PBA (count: 3)

ID	Name	No. of Genes in BDgene
hsa04730	Long-term depression	15
hsa04020	Calcium signaling pathway	53
hsa05222	Small cell lung cancer	8

KEGG pathways by database search (count: 2)

ID	Name	No. of Genes in BDgene	Brief Description
hsa00330	Arginine and proline metabolism	4
hsa04370	VEGF signaling pathway	11

Gene related BioCarta pathways (count: 5)

BioCarta pathways by PBA (count: 0)

BioCarta pathways by database search (count: 5)

ID	Name	No. of Genes in BDgene
vegfPathway	VEGF, Hypoxia, and Angiogenesis	4
hifPathway	Hypoxia-Inducible Factor in the Cardiovascular System	3
raccPathway	Ion Channels and Their Functional Role in Vascular Endothelium	2
no1Pathway	Actions of Nitric Oxide in the Heart	9
gcrPathway	Corticosteroids and cardioprotection	9

Gene related interactors from protein-protein interactions data in HPRD (count: 8)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
NOS3	NOSIP	NO	in vitro;in vivo;yeast 2-hybrid	11149895
NOS3	NOSTRIN	NO	in vitro;in vivo;yeast 2-hybrid	12446846
NOS3	SP1	NO	in vitro;in vivo	7541039
NOS3	NMT1	NO	in vivo	7512951
NOS3	PPP2R5A	NO	in vivo	12501214 , 11397791
NOS3	EDNRB	NO	in vitro	10510297
NOS3	CAV1	NO	in vitro	8910295
NOS3	AKT1	YES	in vitro	11696579 , 10376603

Related other genetic factors

Gene related SNPs (count: 2)

Literature-origin SNPs (count: 2)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs1799983	chr7:150999023 - 150999023(1)	missense_variant; upstream_gene_variant	1(0/1/0)
rs2070744	chr7:150992991 - 150992991(1)	intron_variant; upstream_gene_variant	1(0/1/0)

LD-proxies (count: 0)

Gene related CNVs (count: 0)

Gene related other variants (count: 4)

Variant Name	Variant Type	Location in Gene	No. of Studies (Positive/Negative/Trend)
NOS3_Intron 4 VNTR_4a/b	VNTR	Intron	1 (0/1/0)
NOS3_T-786C	point mutation		1 (0/1/0)
NOS3_Intron4_VNTR	VNTR	Intron4	1 (0/1/0)
NOS3_G894T	point mutation		1 (0/1/0)

Gene related regions (count: 3)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
Chr 7	chr7:0-159345973	3 (0/3/0)
7q34-qter	chr7:138500000-159345973	1 (0/1/0)
7q36	chr7:148200000-159345973	3 (0/0/3)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 0)

Overlap with SZ from candidate gene intersection analysis (count: 1)

Reference	ID in SZGene	Result Category
19412172	838	Negative

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 1)

Reference	Description	Category in MDD
15967063	MD was not found to be significantly associated with NOS3 after Bonferroni-adjustment in this study.	Positive

Overlap with MDD from candidate gene intersection analysis (count: 0)

View in gBrowse

Region: chr7:150990995..151014588 View in gBrowse