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	CRY2
Approved Name	cryptochrome circadian clock 2
Previous Name	cryptochrome 2 (photolyase-like)
Location	11p11.2
Position	chr11:45847118-45883248, 1
External Links	HGNC: 2385 Entrez Gene: 1408 Ensembl: ENSG00000121671 UCSC: uc010rgn.2
No. of Studies	5 (Positive: 3; Negative: 2; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 5)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Byrne, E. M., 2014	SNP: rs4132063	P-value=0.07. The most significant single SNP association with BPD was with rs4132063(P=0.0006), a SNP located upstream of CRY2.	Negative	Comment on Study
Nievergelt, C. M., 2006		Single SNP TDT analyses showed no evidence for association to BPAD.	Negative	Comment on Study
Mansour, H. A., 2006		No significant association was detected with Pittsburgh BD1 using CC test, but significant association (P<0.05) was detected in BD1 using TDT test.	Positive	Comment on Study
Sjoholm, L. K.,2010	SNP: rs10838524, rs10838527, rs3824872, rs7123390 Haplotype: rs10838524 - rs7123390 - rs10838527 - rs3824872(A-A-A-C), rs10838524 - rs7123390 - rs10838527 - rs3824872(A-G-A-A), rs10838524 - rs7123390 - rs10838527 - rs3824872(A-G-G-A), rs10838524 - rs7123390 - rs10838527 - rs3824872(G-A-A-C), rs10838524 - rs7123390 - rs10838527 - rs3824872(G-G-A-C)	In conclusion, this is the first report of genetic association between the circadian gene CRY2 and a severe form of human bipolar disorder.	Positive	Comment on Study
Mansour, H. A.,2009	SNP: rs1554338	Gene-based tests:X<sup>2</sup>=5.443, P-value = 0.119 in recessive model, X<sup>2</sup>=4.967, P-value = 0.133 in additive model, X<sup>2</sup>=1.486, P-value = 0.768 in dominant model in BPI. Significant association was observed using single SNP-based analyses while no association was observed using gene-based tests in BPI.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 30)

GO terms by PBA (count: 2)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0005634	nucleus	cellular component	IDA; ISS	283
GO:0003677	DNA binding	molecular function	IDA[12627958]	83

GO terms by database search (count: 28)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:2000118	regulation of sodium-dependent phosphate transport	biological process	IDA[9753616]	1
GO:0000989	transcription factor binding transcription factor activity	molecular function	IDA[15147242]	4
GO:2000323	negative regulation of glucocorticoid receptor signaling pathway	biological process	ISS	5
GO:0003684	damaged DNA binding	molecular function	IDA[12627958]	5
GO:0000719	photoreactive repair	biological process	IDA[12627958]	1
GO:0042593	glucose homeostasis	biological process	ISS	19
GO:0003697	single-stranded DNA binding	molecular function	IDA[12627958]	7
GO:0000976	transcription regulatory region sequence-specific DNA binding	molecular function	ISS	4
GO:0005515	protein binding	molecular function	IPI[17463251]	563
GO:0003904	deoxyribodipyrimidine photo-lyase activity	molecular function	IDA[8909283]	2
GO:0043153	entrainment of circadian clock by photoperiod	biological process	ISS	3
GO:0018298	protein-chromophore linkage	biological process	IEA	2
GO:0032922	circadian regulation of gene expression	biological process	ISS	22
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[12397359]	62
GO:0042754	negative regulation of circadian rhythm	biological process	ISS	3
GO:0003914	DNA (6-4) photolyase activity	molecular function	IDA[8909283]	2
GO:0042752	regulation of circadian rhythm	biological process	ISS	12
GO:0007623	circadian rhythm	biological process	ISS; TAS	40
GO:0032515	negative regulation of phosphoprotein phosphatase activity	biological process	IDA[9383998]	1
GO:0005737	cytoplasm	cellular component	IDA	322
GO:0005576	extracellular region	cellular component	IDA[9753616]	97
GO:0006351	transcription, DNA-templated	biological process	IEA	103
GO:0043130	ubiquitin binding	molecular function	IDA[11889036]	5
GO:0009882	blue light photoreceptor activity	molecular function	NAS[8909283]	2
GO:0009785	blue light signaling pathway	biological process	NAS[8909283]	2
GO:0019902	phosphatase binding	molecular function	IPI[9383998]	9
GO:0045892	negative regulation of transcription, DNA-templated	biological process	IDA[12397359]; ISS	43
GO:0071949	FAD binding	molecular function	ISS	3

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: 1)

BioCarta pathways by PBA (count: 0)

BioCarta pathways by database search (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
circadianPathway	Circadian Rhythms	6

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

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
CRY2	PPP5C	NO	in vitro	9383998
CRY2	PER3	YES	in vitro	14701732
CRY2	PER2	YES	in vivo	10428031

Related other genetic factors

Gene related SNPs (count: 19)

Literature-origin SNPs (count: 6)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs4132063	chr11:45820166 - 45820166(1)	intron_variant; non_coding_transcript_variant	1(0/1/0)
rs10838524	chr11:45848626 - 45848626(1)	intron_variant; non_coding_transcript_variant	1(1/0/0)
rs7123390	chr11:45869867 - 45869867(1)	downstream_gene_variant; intron_variant; upstream_gene_variant	1(0/1/0)
rs1554338	chr11:45885279 - 45885279(1)	downstream_gene_variant; upstream_gene_variant	1(1/0/0)
rs3824872	chr11:45884054 - 45884054(1)	downstream_gene_variant; upstream_gene_variant	1(1/0/0)
rs10838527	chr11:45881643 - 45881643(1)	3_prime_UTR_variant; downstream_gene_variant; upstream_gene_variant	1(1/0/0)

LD-proxies (count: 13)

rs_ID	Location	Functional Annotation
rs7121775	chr11:45842772 - 45842772(1)	upstream_gene_variant
rs11038689	chr11:45852713 - 45852713(1)	intron_variant; non_coding_transcript_variant
rs17787136	chr11:45873085 - 45873085(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant
rs2292910	chr11:45882062 - 45882062(1)	3_prime_UTR_variant; downstream_gene_variant; upstream_gene_variant
rs7121611	chr11:45842591 - 45842591(1)	upstream_gene_variant
rs11605924	chr11:45851540 - 45851540(1)	intron_variant; non_coding_transcript_variant
rs11038699	chr11:45875526 - 45875526(1)	intron_variant; non_coding_transcript_variant
rs2292912	chr11:45856137 - 45856137(1)	intron_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; upstream_gene_variant
rs7945565	chr11:45857441 - 45857441(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs7951225	chr11:45853841 - 45853841(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs11038695	chr11:45856910 - 45856910(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs11038696	chr11:45857042 - 45857042(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs11038698	chr11:45871621 - 45871621(1)	downstream_gene_variant; intron_variant; non_coding_transcript_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)
Chr 11	chr11:0-135086622	2 (0/2/0)
11q14.3-11q21	chr11:22000000-97400000	1 (0/0/1)
11p11.2	chr11:43400000-48800000	1 (0/1/0)
11p11	chr11:43400000-53400000	1 (1/0/0)
11p13-q13.3	chr11:31000000-70500000	1 (0/1/0)

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

Gene relationship with SZ

Overlap with SZ from cross-disorder studies (count: 3)

Reference	Description	Result Category
19839995	Gene-based tests:X<sup>2</sup>=1.267, P-value = 0.767 in additive model in SZ/SZA, X<sup>2</sup>=1.576, P-value = 0.788 in recessive model in SZ/SZA, X<sup>2</sup>=0.701, P-value = 0.954 in dominant 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=0.21. Gene-based tests show no significant association between this gene and SZ.	Negative
16507006	No significant association was detected with SZ/SZA using CC test, but significant association (P<0.05) was detected using TDT test.	Positive

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

Reference	ID in SZGene	Result Category
19839995	878	Negative

Gene relationship with MDD

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

Reference	Description	Category in MDD
24687905	P-value=0.68. Gene-based tests show no significant association between this gene and MDD.	Negative

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

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Region: chr11:45847118..45883248 View in gBrowse