BDgene

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

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Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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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
raccPathway	Ion Channels and Their Functional Role in Vascular Endothelium	2
hifPathway	Hypoxia-Inducible Factor in the Cardiovascular System	3
no1Pathway	Actions of Nitric Oxide in the Heart	9
vegfPathway	VEGF, Hypoxia, and Angiogenesis	4
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	EDNRB	NO	in vitro	10510297
NOS3	NOSIP	NO	in vitro;in vivo;yeast 2-hybrid	11149895
NOS3	SP1	NO	in vitro;in vivo	7541039
NOS3	PPP2R5A	NO	in vivo	12501214 , 11397791
NOS3	CAV1	NO	in vitro	8910295
NOS3	AKT1	YES	in vitro	11696579 , 10376603
NOS3	NOSTRIN	NO	in vitro;in vivo;yeast 2-hybrid	12446846
NOS3	NMT1	NO	in vivo	7512951

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)

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Region: chr7:150990995..151014588 View in gBrowse