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	NR1D1
Previous Symbol	THRAL
Symbol Alias	ear-1, hRev, Rev-ErbAalpha, THRA1
Approved Name	nuclear receptor subfamily 1, group D, member 1
Location	17q11.2
Position	chr17:40092787-40100725, -1
External Links	HGNC: 7962 Entrez Gene: 9572 Ensembl: ENSG00000126368 UCSC: uc002htz.3
No. of Studies	6 (Positive: 2; Negative: 4; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 6)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Kripke, D. F.,2009	SNP: rs2071427, rs2269457, rs2314339	Significant association was observed in the BP group.	Positive	Comment on Study
Byrne, E. M., 2014		P-value=0.31. Gene-based tests show no significant association between this gene and BD.	Negative	Comment on Study
Mansour, H. A.,2009		Gene-based tests:X<sup>2</sup>=2.973, P-value = 0.385 in dominant model, X<sup>2</sup>=3.107, P-value = 0.409 in recessive model, X<sup>2</sup>=2.316, P-value = 0.456 in additive model in BPI. No significant association was observed using neither single SNP-based analyses nor gene-based tests in BPI.	Negative	Comment on Study
Severino, G.,2009	SNP: rs12941497, rs939347 Haplotype: rs12941497 - rs939347(A-A), rs12941497 - rs939347(A-G), rs12941497 - rs939347(G-G)	In the case-control comparison, single marker analysis showed no association for any of the SNPs tested. Haplotype analysis showed a nominally significant association for two haplotypes of SNPs 1-2.Our results, indicating a nominal association of the REVERBa gene with BP, suggest a possible role of REV-ERBa in the pathogenesis of BP.	Positive	Comment on Study
Soria, V.,2010	SNP: rs2071427	No significant associations of NR1D1 gene were found in BPD patients.	Negative	Comment on Study
Kishi, T., 2008 (b)	SNP: rs2071427, rs3744805, rs939347	Our findings suggest that NR1D1 does not play a major role in the pathophysiology of mood disorders in the Japanese population.	Negative	Comment on Study

Gene functional annotation

Gene related GO terms (count: 44)

GO terms by PBA (count: 6)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0003714	transcription corepressor activity	molecular function	TAS[8622974]	21
GO:0003707	steroid hormone receptor activity	molecular function	IEA	10
GO:0030154	cell differentiation	biological process	IEA	31
GO:0030522	intracellular receptor signaling pathway	biological process	TAS[8622974]	8
GO:0004879	ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity	molecular function	TAS[8622974]	7
GO:0005634	nucleus	cellular component	ISS	283

GO terms by database search (count: 38)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0007623	circadian rhythm	biological process	TAS	40
GO:0030425	dendrite	cellular component	ISS	65
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	molecular function	IMP[8622974]	23
GO:0042752	regulation of circadian rhythm	biological process	ISS	12
GO:0045892	negative regulation of transcription, DNA-templated	biological process	IDA[15761026]; IMP[18006707]	43
GO:0032922	circadian regulation of gene expression	biological process	ISS	22
GO:0005978	glycogen biosynthetic process	biological process	ISS	4
GO:0005737	cytoplasm	cellular component	ISS	322
GO:0045893	positive regulation of transcription, DNA-templated	biological process	ISS	58
GO:0010871	negative regulation of receptor biosynthetic process	biological process	IMP[18511497]	1
GO:0045598	regulation of fat cell differentiation	biological process	ISS	4
GO:0010467	gene expression	biological process	TAS	41
GO:0044212	transcription regulatory region DNA binding	molecular function	IDA[18511497]	17
GO:2000188	regulation of cholesterol homeostasis	biological process	ISS	2
GO:0019216	regulation of lipid metabolic process	biological process	ISS	3
GO:0001046	core promoter sequence-specific DNA binding	molecular function	IDA[15761026]	10
GO:0000790	nuclear chromatin	cellular component	IDA[18511497]	7
GO:0035947	regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter	biological process	IMP[18006707]	1
GO:0001078	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription	molecular function	IDA[8622974]	14
GO:0005515	protein binding	molecular function	IPI[17892483]	563
GO:0070859	positive regulation of bile acid biosynthetic process	biological process	ISS	1
GO:0010498	proteasomal protein catabolic process	biological process	ISS	1
GO:0071222	cellular response to lipopolysaccharide	biological process	IMP[18511497]	12
GO:2000189	positive regulation of cholesterol homeostasis	biological process	IDA[18511497]	2
GO:0043197	dendritic spine	cellular component	ISS	21
GO:0034144	negative regulation of toll-like receptor 4 signaling pathway	biological process	IMP[18511497]	1
GO:0000977	RNA polymerase II regulatory region sequence-specific DNA binding	molecular function	IDA[19955433]	10
GO:0008270	zinc ion binding	molecular function	IEA	77
GO:0005654	nucleoplasm	cellular component	TAS	163
GO:0044321	response to leptin	biological process	ISS	1
GO:0001222	transcription corepressor binding	molecular function	IDA[15761026]; IMP[18006707]	3
GO:0020037	heme binding	molecular function	IDA[18006707]	6
GO:0060086	circadian temperature homeostasis	biological process	ISS	1
GO:0061469	regulation of type B pancreatic cell proliferation	biological process	ISS	1
GO:0061178	regulation of insulin secretion involved in cellular response to glucose stimulus	biological process	ISS	5
GO:0006367	transcription initiation from RNA polymerase II promoter	biological process	TAS	20
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[19955433]; IMP[18511497]	62
GO:0043401	steroid hormone mediated signaling pathway	biological process	IEA	10

Gene related KEGG pathways (count: 1)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
hsa04710	Circadian rhythm	11

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 3)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
NR1D1	NCOR1	NO	in vitro;in vivo;yeast 2-hybrid	8948627 , 9482666 , 15604093
NR1D1	NR1D2	NO	yeast 2-hybrid	15604093
NR1D1	NR2E3	NO	in vitro;yeast 2-hybrid	15190009

Related other genetic factors

Gene related SNPs (count: 9)

Literature-origin SNPs (count: 6)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs3744805	chr17:40092101 - 40092101(1)	3_prime_UTR_variant; downstream_gene_variant; intron_variant	1(0/1/0)
rs939347	chr17:40100440 - 40100440(1)	5_prime_UTR_variant	2(0/2/0)
rs2269457	chr17:40098436 - 40098436(1)	downstream_gene_variant; intron_variant	1(1/0/0)
rs2314339	chr17:40096959 - 40096959(1)	downstream_gene_variant; intron_variant	1(1/0/0)
rs2071427	chr17:40098239 - 40098239(1)	downstream_gene_variant; intron_variant	3(1/2/0)
rs12941497	chr17:40099341 - 40099341(1)	intron_variant	1(0/1/0)

LD-proxies (count: 3)

rs_ID	Location	Functional Annotation
rs4795424	chr17:40099932 - 40099932(1)	intron_variant
rs2071570	chr17:40100837 - 40100837(1)	upstream_gene_variant
rs883871	chr17:40096407 - 40096407(1)	downstream_gene_variant; intron_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 0)

Gene related regions (count: 5)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
17p12-q21.33	chr17:10800000-52100000	1 (0/1/0)
17q21	chr17:39800000-52100000	1 (0/1/0)
17q11-q23	chr17:25100000-64600000	1 (0/1/0)
17q11-25	chr17:25100000-83257441	1 (1/0/0)
Chr 17	chr17:0-83257441	3 (0/3/0)

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

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 2)

Reference	Description	Result Category
19839995	Gene-based tests:X<sup>2</sup>=4.633, P-value = 0.182 in recessive model in SZ/SZA, X<sup>2</sup>=2.144, P-value = 0.543 in dominant model in SZ/SZA, X<sup>2</sup>=0.572, P-value = 0.945 in additive model in SZ/SZA.No association was observed using neither single SNP-based analyses nor gene-based tests in SZ/SZA.	Negative
24687905	P-value=0.64. Gene-based tests show no significant association between this gene and SZ.	Negative

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

Reference	ID in SZGene	Result Category
19839995	885	Negative

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 2)

Reference	Description	Category in MDD
24687905	P-value=0.03. The NR1D1 gene was the only circadian gene to show nominal significancewith major depression(P=0.03).	Negative
20072116	No significant associations of NR1D1 gene were found in MDD patients.	Positive

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

Reference	Description	Category in MDD	Link in MK4MDD
18804497	No significant association was found with major depressive disorder	Neg	NR1D1

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Region: chr17:40092787..40100725 View in gBrowse