Gene Report

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Basic Info

Approved Symbol	TIMELESS
Symbol Alias	hTIM, TIM, TIM1
Approved Name	timeless circadian clock
Previous Name	timeless (Drosophila) homolog, "timeless homolog (Drosophila)"
Name Alias	Tof1 homolog (S. cerevisiae), "timeless circadian clock 1"
Location	12q13.3
Position	chr12:56416373-56449403, -1
External Links	HGNC: 11813 Entrez Gene: 8914 Ensembl: ENSG00000111602 UCSC: uc001slf.2
No. of Studies	3 (Positive: 0; Negative: 3; trend: 0)
Overlap with SZ?	YES
Overlap with MDD?	YES

Gene related studies (count: 3)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Byrne, E. M., 2014		P-value=0.27. It is notable that there are no SNPs in or near the TIMELESS gene that show evidence of association with risk to BPD, and similarly, the CLOCK gene harbors only one SNP that just reaches the nominal significance threshold (P=0.042), indicating that these genes are not strong candidates for influencing BPD risk in the population.	Negative	Comment on Study
Mansour, H. A.,2009		Gene-based tests:X<sup>2</sup>=3.072, P-value = 0.271 in recessive model, X<sup>2</sup>=0.332, P-value = 0.968 in additive model, X<sup>2</sup>=0.251, P-value = 0.993 in dominant model in BPI. No significant association was observed using neither single SNP-based analyses nor gene-based tests in BPI.	Negative	Comment on Study
Mansour, H. A., 2006	SNP: rs2279665, rs2291738, rs2291739, rs774026 Haplotype: rs2279665 - rs774026 - rs2291738 - rs2291739()	No significant association was detected in any sample using any test.	Negative	Comment on Study

Gene functional annotation

Gene related GO terms (count: 22)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0005634	nucleus	cellular component	IC[9856465]; IDA	283

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0044770	cell cycle phase transition	biological process	IMP[17102137]	3
GO:0006974	cellular response to DNA damage stimulus	biological process	ISS	14
GO:0009582	detection of abiotic stimulus	biological process	TAS[9856466]	3
GO:0000790	nuclear chromatin	cellular component	IDA[17102137]	7
GO:0005515	protein binding	molecular function	IPI[15798197]	563
GO:0051301	cell division	biological process	IEA	20
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IEA	62
GO:0046982	protein heterodimerization activity	molecular function	IEA	42
GO:0005730	nucleolus	cellular component	IDA	28
GO:0030324	lung development	biological process	IEA	9
GO:0045892	negative regulation of transcription, DNA-templated	biological process	IDA[9856465]	43
GO:0042803	protein homodimerization activity	molecular function	IEA	71
GO:0007623	circadian rhythm	biological process	ISS	40
GO:0009628	response to abiotic stimulus	biological process	TAS[9891984]	1
GO:0042752	regulation of circadian rhythm	biological process	IMP[23418588]	12
GO:0002009	morphogenesis of an epithelium	biological process	ISS	2
GO:0042127	regulation of cell proliferation	biological process	IMP[17102137]	14
GO:0006351	transcription, DNA-templated	biological process	IEA	103
GO:0048754	branching morphogenesis of an epithelial tube	biological process	IEA	3
GO:0007067	mitotic nuclear division	biological process	IEA	15
GO:0015630	microtubule cytoskeleton	cellular component	IDA	12

Gene related KEGG pathways (count: 0)

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 5)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
TIMELESS	PER2	YES	in vitro	9856465
TIMELESS	CRY2	YES	in vivo	15798197
TIMELESS	CRY1	YES	in vivo	10428031
TIMELESS	CHEK1	YES	in vivo	15798197
TIMELESS	PER1	YES	in vitro	9856465

Related other genetic factors

Gene related SNPs (count: 26)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs774026	chr12:56428214 - 56428214(1)	intron_variant; upstream_gene_variant	1(0/1/0)
rs2291738	chr12:56421497 - 56421497(1)	downstream_gene_variant; intron_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; splice_region_variant; upstream_gene_variant	1(1/0/0)
rs2279665	chr12:56433910 - 56433910(1)	synonymous_variant	1(1/0/0)
rs11171856	chr12:56448035 - 56448035(1)	downstream_gene_variant; intron_variant	1(1/0/0)
rs2291739	chr12:56420869 - 56420869(1)	downstream_gene_variant; missense_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant	2(1/1/0)

rs_ID	Location	Functional Annotation
rs7312888	chr12:56434764 - 56434764(1)	intron_variant
rs7977477	chr12:56434836 - 56434836(1)	intron_variant
rs774039	chr12:56432197 - 56432197(1)	intron_variant
rs6581094	chr12:56434451 - 56434451(1)	intron_variant
rs11171850	chr12:56437321 - 56437321(1)	intron_variant
rs3809125	chr12:56450565 - 56450565(1)	3_prime_UTR_variant; downstream_gene_variant; upstream_gene_variant
rs12299614	chr12:56437398 - 56437398(1)	intron_variant
rs11833581	chr12:56435034 - 56435034(1)	intron_variant
rs10876889	chr12:56435367 - 56435367(1)	intron_variant
rs774027	chr12:56428594 - 56428594(1)	missense_variant; upstream_gene_variant
rs703829	chr12:56429838 - 56429838(1)	intron_variant
rs812279	chr12:56420786 - 56420786(1)	downstream_gene_variant; intron_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant
rs774047	chr12:56422138 - 56422138(1)	missense_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; upstream_gene_variant
rs774035	chr12:56431965 - 56431965(1)	intron_variant
rs774036	chr12:56431995 - 56431995(1)	intron_variant
rs774033	chr12:56431527 - 56431527(1)	synonymous_variant
rs774034	chr12:56431953 - 56431953(1)	intron_variant
rs11610921	chr12:56440089 - 56440089(1)	intron_variant
rs10876890	chr12:56439967 - 56439967(1)	intron_variant
rs2371455	chr12:56450109 - 56450109(1)	3_prime_UTR_variant; downstream_gene_variant; upstream_gene_variant
rs11171852	chr12:56439440 - 56439440(1)	intron_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 0)

Gene related regions (count: 2)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
Chr 12	chr12:0-133275309	3 (0/3/0)
12q	chr12:38200000-133851895	1 (1/0/0)

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

Gene relationship with SZ

Reference	Description	Result Category
24687905	P-value=0.33. Gene-based tests show no significant association between this gene and SZ.	Negative
16507006	No significant association was detected in any sample using any test.	Negative
19839995	Gene-based tests:X<sup>2</sup>=3.823, P-value = 0.21 in recessive model in SZ/SZA, X<sup>2</sup>=3.599, P-value = 0.22 in additive model in SZ/SZA, X<sup>2</sup>=3.378, P-value = 0.298 in dominant model in SZ/SZA.No association was observed using neither single SNP-based analyses nor gene-based tests in SZ/SZA.	Negative

Reference	ID in SZGene	Result Category
16507006	142	Negative
19839995	142	Negative

Gene relationship with MDD

Reference	Description	Category in MDD
24687905	P-value=0.70. Gene-based tests show no significant association between this gene and MDD.	Negative

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Region: chr12:56416373..56449403 View in gBrowse