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	NOS1
Previous Symbol	NOS
Symbol Alias	nNOS
Approved Name	nitric oxide synthase 1 (neuronal)
Location	12q24.22
Position	chr12:117208142-117452170, -1
External Links	HGNC: 7872 Entrez Gene: 4842 Ensembl: ENSG00000089250 UCSC: uc001twn.2
No. of Studies	8 (Positive: 2; Negative: 5; trend: 1)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 8)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Kittel-Schneider, S., 2014	Other variant: NOS1_Exon 1c_A/G, NOS1_Exon 1f_L/S	None of the investigated polymorphisms in this gene was associated with BD.	Negative	Comment on Study
Okumura, T., 2010	SNP: rs41279104	We did not detect a significant association between NOS1 and BP.	Negative	Comment on Study
Fallin, M. D.,2005		9 SNP typed, Median D'=0.49, Median r<sup>2</sup> =0.07, 4 LD blocks, 0.2 block coverage, there exists SNP or haplotype nominal P-value < 0.01 in SZ and SNP or haplotype P-value > 0.01 and <0.05 in BP.. This gene is highly suggestive to SZ/SZA and suggestive to BP.	Trend	Comment on Study
Yosifova, A.,2009	SNP: rs2293051, rs2682826, rs3782206, rs3782219, rs3782221, rs532967, rs561712, rs816363	Significant association of SNP in this gene with BD in our population was observed.	Positive	Comment on Study
Schanze, D.,2011	SNP: rs6490121	In a German population, we found none of the GWA risk alleles associated with psychosis.	Negative	Comment on Study
Silberberg, G.,2010	SNP: rs41279104 Other variant: NOS1_promoter_VNTR	Polymorphisms at the promoters of NOS1_1d and NOS1_1f, previously shown to be functional in vitro, revealed no significant allelic or genotypic differences among clinical groups and showed no effect on these transcripts' expression.	Negative	Comment on Study
Reif, A., 2006 (a)	Other variant: NOS1_promoter_VNTR, NOS1_SNP1, NOS1_exon13_SNP2, NOS1_exon15_IVS15+38C/T, NOS1_exon16_2607C/T, NOS1_exon17_2712C/T, NOS1_exon17_IVS17+15A/G, NOS1_exon18_SNP3, NOS1_exon19_IVS19+13T/G, NOS1_exon20_137244A/G, NOS1_exon21_3258C/T, NOS1_exon27_4063G/A, NOS1_exon27_4065G/A, NOS1_exon27_4154G/A, NOS1_exon27_IVS27+14T/G, NOS1_exon27_IVS27+9C/A, NOS1_exon27_SNP5, NOS1_exon29_SNP4, NOS1_exon7_IVS7-15C/G	No significant association was detected.	Negative	Comment on Study
Buttenschon, H. N., 2004	SNP: rs2682826	rs2682826, allelic P-value = 0.980, genotypic P-value = 0.045 in Danish sample.. The allele and genotype frequencies were very similaramongcases and controls in the total and in the British sample. In the Danish sample, we believe that the slight difference in genotype frequencies is due to chance. it is still possible that other polymorphisms in the NOS1 gene could have a role in the genetic susceptibility to schizophrenia or bipolar disorder.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 64)

GO terms by PBA (count: 2)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0045202	synapse	cellular component	ISS	29
GO:0005516	calmodulin binding	molecular function	IEA	20

GO terms by database search (count: 62)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0071363	cellular response to growth factor stimulus	biological process	ISS	8
GO:1990425	ryanodine receptor complex	cellular component	TAS[21536106]	1
GO:0001666	response to hypoxia	biological process	IEP[16276418]	24
GO:0043234	protein complex	cellular component	ISS	27
GO:0051926	negative regulation of calcium ion transport	biological process	ISS	3
GO:0042738	exogenous drug catabolic process	biological process	ISS	1
GO:0005515	protein binding	molecular function	IPI[11149895]	563
GO:0055117	regulation of cardiac muscle contraction	biological process	TAS[9892689]	6
GO:1901206	positive regulation of adrenergic receptor signaling pathway involved in heart process	biological process	IEA	1
GO:0002028	regulation of sodium ion transport	biological process	ISS	9
GO:0005506	iron ion binding	molecular function	IEA	8
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	biological process	ISS	91
GO:0051612	negative regulation of serotonin uptake	biological process	ISS	1
GO:0051346	negative regulation of hydrolase activity	biological process	ISS	4
GO:0018119	peptidyl-cysteine S-nitrosylation	biological process	ISS	1
GO:0045893	positive regulation of transcription, DNA-templated	biological process	ISS	58
GO:0020037	heme binding	molecular function	ISS	6
GO:0034617	tetrahydrobiopterin binding	molecular function	NAS[7488039]	3
GO:0007520	myoblast fusion	biological process	TAS[7545544]	4
GO:1902514	regulation of generation of L-type calcium current	biological process	TAS[21536106]	1
GO:0043197	dendritic spine	cellular component	IEA	21
GO:0005739	mitochondrion	cellular component	ISS	75
GO:1902307	positive regulation of sodium ion transmembrane transport	biological process	ISS	1
GO:0003958	NADPH-hemoprotein reductase activity	molecular function	IBA	2
GO:0007596	blood coagulation	biological process	TAS	44
GO:0006941	striated muscle contraction	biological process	ISS	2
GO:0044325	ion channel binding	molecular function	ISS; TAS[21536106]	14
GO:0016491	oxidoreductase activity	molecular function	IBA	2
GO:0007263	nitric oxide mediated signal transduction	biological process	IBA	5
GO:0043267	negative regulation of potassium ion transport	biological process	ISS	6
GO:0010181	FMN binding	molecular function	ISS	2
GO:0090382	phagosome maturation	biological process	TAS	6
GO:0035066	positive regulation of histone acetylation	biological process	ISS	3
GO:0006809	nitric oxide biosynthetic process	biological process	IBA; ISS[7545544]	8
GO:0005829	cytosol	cellular component	TAS	223
GO:0031284	positive regulation of guanylate cyclase activity	biological process	IBA	4
GO:0045909	positive regulation of vasodilation	biological process	IDA[18048451]; IMP[18391107]	14
GO:0005737	cytoplasm	cellular component	TAS[17892502]	322
GO:0048471	perinuclear region of cytoplasm	cellular component	ISS[17027776]	50
GO:0042136	neurotransmitter biosynthetic process	biological process	TAS[7545544]	10
GO:0098735	positive regulation of the force of heart contraction	biological process	ISS	2
GO:0045121	membrane raft	cellular component	ISS	22
GO:0033555	multicellular organismal response to stress	biological process	IMP[18391107]	1
GO:0009408	response to heat	biological process	IDA[18048451]	12
GO:0050661	NADP binding	molecular function	ISS	5
GO:0060314	regulation of ryanodine-sensitive calcium-release channel activity	biological process	TAS[21536106]	2
GO:0001917	photoreceptor inner segment	cellular component	ISS[17027776]	3
GO:0016529	sarcoplasmic reticulum	cellular component	IDA[9892689]	6
GO:0097110	scaffold protein binding	molecular function	ISS	5
GO:0050660	flavin adenine dinucleotide binding	molecular function	ISS	5
GO:0005856	cytoskeleton	cellular component	ISS	30
GO:0006527	arginine catabolic process	biological process	IC[7545544]	2
GO:0004517	nitric-oxide synthase activity	molecular function	IBA; IDA[1689048]; ISS	2
GO:0010523	negative regulation of calcium ion transport into cytosol	biological process	TAS[17568574]	2
GO:0055114	oxidation-reduction process	biological process	IEA	43
GO:0046870	cadmium ion binding	molecular function	ISS	2
GO:0034618	arginine binding	molecular function	TAS[17029414]	2
GO:0051701	interaction with host	biological process	TAS	6
GO:0045776	negative regulation of blood pressure	biological process	IBA	10
GO:0042383	sarcolemma	cellular component	IDA[7545544]	12
GO:1901205	negative regulation of adrenergic receptor signaling pathway involved in heart process	biological process	TAS[21536106]	1
GO:0017080	sodium channel regulator activity	molecular function	ISS	4

Gene related KEGG pathways (count: 4)

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: 1)

ID	Name	No. of Genes in BDgene	Brief Description
hsa00330	Arginine and proline metabolism	4

Gene related BioCarta pathways (count: 1)

BioCarta pathways by PBA (count: 0)

BioCarta pathways by database search (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
ctbp1Pathway	SUMOylation as a mechanism to modulate CtBP-dependent gene responses	1

Gene related interactors from protein-protein interactions data in HPRD (count: 29)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
NOS1	NOS1AP	NO	in vitro;in vivo;yeast 2-hybrid	9459447
NOS1	ADRB1	NO	in vivo	12184796
NOS1	PRKACA	NO	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	ADRA1D	NO	in vivo	12184796
NOS1	HSP90AA1	YES	in vitro;in vivo	11284722 , 9880522
NOS1	DLG4	NO	in vitro;in vivo;yeast 2-hybrid	8625413 , 10488080 , 9459447
NOS1	ATP2B4	NO	in vitro;in vivo	11591728
NOS1	ADRA1B	YES	in vivo	12184796
NOS1	SNTA1	NO	in vitro;in vivo	11747091 , 10221915
NOS1	DLG2	YES	in vitro;yeast 2-hybrid	8625413 , 8922396
NOS1	CAMK2A	YES	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	DLGAP2	NO	in vitro	10824095
NOS1	PFKM	NO	in vitro	10187848
NOS1	DYNLL1	NO	in vitro;in vivo;yeast 2-hybrid	8864115 , 9837926 , 9808772
NOS1	HMOX1	NO	in vivo	11849436
NOS1	PTPN6	NO	in vitro;in vivo	11511520
NOS1	CAMK4	NO	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	BDKRB2	YES	in vivo	10681501
NOS1	NOSIP	NO	in vivo	15548660
NOS1	CTBP1	NO	in vitro;in vivo	11590170
NOS1	PRKCA	NO	in vitro	10400690 , 10874031 , 12630910 , 1375933
NOS1	CAMK1	NO	in vitro;in vivo	10400690 , 10874031 , 12630910 , 1375933 , 15251453
NOS1	PTPRN	NO	in vitro;in vivo	11043403
NOS1	ADRB2	YES	in vivo	12184796
NOS1	ZDHHC23	NO	in vitro;in vivo	15105416
NOS1	CAV3	YES	in vitro	9353265
NOS1	ARG1	NO	in vivo	11849441
NOS1	RASD1	NO	in vivo	11086993
NOS1	VAC14	YES	in vitro;in vivo	17161399

Related other genetic factors

Gene related SNPs (count: 40)

Literature-origin SNPs (count: 10)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs3782219	chr12:117350435 - 117350435(1)	intron_variant; non_coding_transcript_variant	1(0/1/0)
rs3782221	chr12:117358076 - 117358076(1)	intron_variant; non_coding_transcript_variant	1(0/1/0)
rs3782206	chr12:117307284 - 117307284(1)	intron_variant	1(0/1/0)
rs561712	chr12:117314264 - 117314264(1)	intron_variant	1(0/1/0)
rs41279104	chr12:117439680 - 117439680(1)	intron_variant; non_coding_transcript_variant	2(0/2/0)
rs2682826	chr12:117215033 - 117215033(1)	3_prime_UTR_variant; downstream_gene_variant	2(1/1/0)
rs816363	chr12:117222662 - 117222662(1)	intron_variant	1(0/1/0)
rs6490121	chr12:117270390 - 117270390(1)	intron_variant	1(0/1/0)
rs2293051	chr12:117280881 - 117280881(1)	intron_variant	1(0/1/0)
rs532967	chr12:117294534 - 117294534(1)	intron_variant	1(1/0/0)

LD-proxies (count: 30)

rs_ID	Location	Functional Annotation
rs4766845	chr12:117349749 - 117349749(1)	intron_variant; non_coding_transcript_variant
rs4767533	chr12:117355725 - 117355725(1)	intron_variant; non_coding_transcript_variant
rs482555	chr12:117343586 - 117343586(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant
rs527590	chr12:117344113 - 117344113(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant
rs7310618	chr12:117309501 - 117309501(1)	intron_variant
rs11068445	chr12:117307124 - 117307124(1)	intron_variant
rs12579387	chr12:117325646 - 117325646(1)	intron_variant
rs9658307	chr12:117310637 - 117310637(1)	intron_variant
rs2293052	chr12:117277815 - 117277815(1)	intron_variant
rs3825102	chr12:117282380 - 117282380(1)	intron_variant
rs1607817	chr12:117274381 - 117274381(1)	intron_variant
rs816361	chr12:117217326 - 117217326(1)	intron_variant
rs816293	chr12:117324894 - 117324894(1)	intron_variant
rs567581	chr12:117319707 - 117319707(1)	intron_variant
rs816353	chr12:117246975 - 117246975(1)	intron_variant; upstream_gene_variant
rs570234	chr12:117333177 - 117333177(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2682825	chr12:117249121 - 117249121(1)	intron_variant; upstream_gene_variant
rs845820	chr12:117250894 - 117250894(1)	intron_variant; upstream_gene_variant
rs1093329	chr12:117258359 - 117258359(1)	intron_variant
rs1093330	chr12:117258729 - 117258729(1)	intron_variant
rs7309163	chr12:117291469 - 117291469(1)	intron_variant
rs4767529	chr12:117284007 - 117284007(1)	intron_variant
rs530393	chr12:117313453 - 117313453(1)	intron_variant
rs539291	chr12:117297336 - 117297336(1)	intron_variant
rs553715	chr12:117316051 - 117316051(1)	intron_variant
rs478597	chr12:117313620 - 117313620(1)	intron_variant
rs549098	chr12:117316522 - 117316522(1)	intron_variant
rs551846	chr12:117316255 - 117316255(1)	intron_variant
rs499813	chr12:117310595 - 117310595(1)	intron_variant
rs9658350	chr12:117286623 - 117286623(1)	intron_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 21)

Variant Name	Variant Type	Location in Gene	No. of Studies (Positive/Negative/Trend)
NOS1_Exon 1f_L/S		Exon 1f	1 (0/1/0)
NOS1_exon20_137244A/G	point mutation	exon20	1 (0/0/1)
NOS1_Exon 1c_A/G	point mutation	Exon 1c	1 (0/1/0)
NOS1_exon21_3258C/T	point mutation	exon21	1 (0/0/1)
NOS1_exon27_4063G/A	point mutation	exon27	1 (0/0/1)
NOS1_exon27_4065G/A	point mutation	exon27	1 (0/0/1)
NOS1_exon27_4154G/A	point mutation	exon27	1 (0/0/1)
NOS1_exon27_IVS27+14T/G	point mutation	exon27	1 (0/0/1)
NOS1_exon27_IVS27+9C/A	point mutation	exon27	1 (0/0/1)
NOS1_exon27_SNP5	point mutation	exon27	1 (0/0/1)
NOS1_exon13_SNP2	point mutation	exon13	1 (0/0/1)
NOS1_exon15_IVS15+38C/T	point mutation	exon15	1 (0/0/1)
NOS1_exon16_2607C/T	point mutation	exon16	1 (0/0/1)
NOS1_exon17_2712C/T	point mutation	exon17	1 (0/0/1)
NOS1_exon17_IVS17+15A/G	point mutation	exon17	1 (0/0/1)
NOS1_exon18_SNP3	point mutation	exon18	1 (0/0/1)
NOS1_exon19_IVS19+13T/G	point mutation	exon19	1 (0/0/1)
NOS1_SNP1	point mutation		1 (0/1/0)
NOS1_promoter_VNTR	VNTR	promoter	2 (0/2/0)
NOS1_exon7_IVS7-15C/G	point mutation	exon7	1 (0/0/1)
NOS1_exon29_SNP4	point mutation	exon29	1 (0/0/1)

Gene related regions (count: 5)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
12q24.2	chr12:113900000-120300000	1 (0/1/0)
Chr 12	chr12:0-133275309	3 (0/3/0)
12q24	chr12:108600000-133275309	4 (1/1/2)
12q23-q24	chr12:95800000-133275309	3 (2/0/1)
12q	chr12:38200000-133851895	1 (1/0/0)

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

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 4)

Reference	Description	Result Category
16380905	This gene is highly suggestive to SZ/SZA and suggestive to BP.	Positive
16389274	Collectively these findings suggest that regulatory polymorphisms of NOS1 contribute to the genetic risk for SCZ, and modulate prefrontal brain functioning.	Positive
20645313	Polymorphisms at the promoters of NOS1_1d and NOS1_1f, previously shown to be functional in vitro, revealed no significant allelic or genotypic differences among clinical groups and showed no effect on these transcripts' expression.	Negative
21302348	In a German population, we found none of the GWA risk alleles associated with psychosis.	Negative

Overlap with SZ from candidate gene intersection analysis (count: 12)

Reference	ID in SZGene	Result Category
18544180	138	Positive
16380905	138	Positive
18677311	138	Positive
16389274	138	Positive
19513863	138	Negative
19805695	138	Positive
19158809	138	Negative
19844207	138	Negative
20605417	138	Positive
20645313	138	Negative
12140778	138	Positive
14623375	138	Negative

Gene relationship with MDD

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

Reference	Description	Category in MDD
20016223	We did not detect a significant association between NOS1 and MDD.	Negative

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

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Region: chr12:117208142..117452170 View in gBrowse