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	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	NR1D2	NO	yeast 2-hybrid	15604093
NR1D1	NR2E3	NO	in vitro;yeast 2-hybrid	15190009
NR1D1	NCOR1	NO	in vitro;in vivo;yeast 2-hybrid	8948627 , 9482666 , 15604093

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

View in gBrowse

Region: chr17:40092787..40100725 View in gBrowse