• Gene id: 9575

Gene Summary

• Gene Symbol: CLOCK   Gene   UCSC   Ensembl
• Aliases: KAT13D, bHLHe8
• Gene name: clock circadian regulator
• Alternate names: circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput protein, class E basic helix-loop-helix protein 8, clock homolog,
• Gene location: 4q12 (55547137: 55427900)     Exons: 28     NC_000004.12
• Gene summary(Entrez): The protein encoded by this gene plays a central role in the regulation of circadian rhythms. The protein encodes a transcription factor of the basic helix-loop-helix (bHLH) family and contains DNA binding histone acetyltransferase activity. The encoded p
• OMIM: 601851

SNPs

rs3817444

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55509814A>C
NC_000004.12   g.55509814A>G
NC_000004.11   g.56375981A>C
NC_000004.11   g.56375981A>G|SEQ=[A/C/G]|GENE=CLOCK

rs3749474

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55434518C>T
NC_000004.11   g.56300685C>T
NM_004898.4   c.*897G>A
NM_004898.3   c.*897G>A
XM_011534409.2   c.*897G>A
XM_005265787.2   c.*897G>A
XM_005265787.1   c.*897G>A
XM_011534410.2   c.*897G>A
XM_011534411.2   c.*897G>A
NM_001267843.1   c.*897G>A
XM  

rs1801260

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55435202A>G
NC_000004.11   g.56301369A>G
NM_004898.4   c.*213T>C
NM_004898.3   c.*213T>C
XM_011534409.2   c.*213T>C
XM_005265787.2   c.*213T>C
XM_005265787.1   c.*213T>C
XM_011534410.2   c.*213T>C
XM_011534411.2   c.*213T>C
NM_001267843.1   c.*213T>C
XM  

rs11932595

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55457430A>G
NC_000004.12   g.55457430A>T
NC_000004.11   g.56323597A>G
NC_000004.11   g.56323597A>T|SEQ=[A/G/T]|GENE=CLOCK

rs6811520

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55449011T>C
NC_000004.11   g.56315178T>C|SEQ=[T/C]|GENE=CLOCK
TMEM165   55858

rs6850524

Strand:    Allele origin:   Allele change:   Mutation type: snv

NC_000004.12   g.55515830C>A
NC_000004.12   g.55515830C>G
NC_000004.12   g.55515830C>T
NC_000004.11   g.56381997C>A
NC_000004.11   g.56381997C>G
NC_000004.11   g.56381997C>T|SEQ=[C/A/G/T]|GENE=CLOCK

Protein Summary

• Protein general information: O15516  
  • Name: Circadian locomoter output cycles protein kaput (hCLOCK) (EC 2.3.1.48) (Class E basic helix loop helix protein 8) (bHLHe8)
  • Length: 846  
  • Mass: 95,304
• Sequence:

  MLFTVSCSKMSSIVDRDDSSIFDGLVEEDDKDKAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNARKMDKSTVLQ
  KSIDFLRKHKEITAQSDASEIRQDWKPTFLSNEEFTQLMLEALDGFFLAIMTDGSIIYVSESVTSLLEHLPSDLV
  DQSIFNFIPEGEHSEVYKILSTHLLESDSLTPEYLKSKNQLEFCCHMLRGTIDPKEPSTYEYVKFIGNFKSLNSV
  SSSAHNGFEGTIQRTHRPSYEDRVCFVATVRLATPQFIKEMCTVEEPNEEFTSRHSLEWKFLFLDHRAPPIIGYL
  PFEVLGTSGYDYYHVDDLENLAKCHEHLMQYGKGKSCYYRFLTKGQQWIWLQTHYYITYHQWNSRPEFIVCTHTV
  VSYAEVRAERRRELGIEESLPETAADKSQDSGSDNRINTVSLKEALERFDHSPTPSASSRSSRKSSHTAVSDPSS
  TPTKIPTDTSTPPRQHLPAHEKMVQRRSSFSSQSINSQSVGSSLTQPVMSQATNLPIPQGMSQFQFSAQLGAMQH
  LKDQLEQRTRMIEANIHRQQEELRKIQEQLQMVHGQGLQMFLQQSNPGLNFGSVQLSSGNSSNIQQLAPINMQGQ
  VVPTNQIQSGMNTGHIGTTQHMIQQQTLQSTSTQSQQNVLSGHSQQTSLPSQTQSTLTAPLYNTMVISQPAAGSM
  VQIPSSMPQNSTQSAAVTTFTQDRQIRFSQGQQLVTKLVTAPVACGAVMVPSTMLMGQVVTAYPTFATQQQQSQT
  LSVTQQQQQQSSQEQQLTSVQQPSQAQLTQPPQQFLQTSRLLHGNPSTQLILSAAFPLQQSTFPQSHHQQHQSQQ
  QQQLSRHRTDSLPDPSKVQPQ

• Structural information:
  • Protein Domains: bHLH. (34-84)
    PAS (107-177)
    PAS (262-332)
    PAC. (336-379)
  • Interpro: IPR011598  IPR036638  IPR001067  IPR001610  IPR000014   IPR035965  IPR013767  
  • Prosite: PS50888 PS50112
  • CDD: cd00083 cd00130
  • PDB: 4H10
  • PDBsum: 4H10
  • DIP: 46009
  • STRING: ENSP00000308741
• Other Databases: GeneCards:  CLOCK  Malacards:  CLOCK

Gene ontology

GO accession	Term name	Evidence code	Go category
GO:0000077	DNA damage checkpoint	IMP	biological process
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	IDA	molecular function
GO:0000982	transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding	ISS	molecular function
GO:0001046	core promoter sequence-specific DNA binding	IEA	molecular function
GO:0001047	core promoter binding	ISS	molecular function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	ISS	molecular function
GO:0004402	histone acetyltransferase activity	IMP	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IDA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005667	transcription factor complex	IPI	cellular component
GO:0005694	chromosome	IDA	cellular component
GO:0006355	regulation of transcription, DNA-templated	ISS	biological process
GO:0006357	regulation of transcription from RNA polymerase II promoter	TAS	biological process
GO:0006366	transcription from RNA polymerase II promoter	IEA	biological process
GO:0007165	signal transduction	TAS	biological process
GO:0007283	spermatogenesis	ISS	biological process
GO:0007623	circadian rhythm	TAS	biological process
GO:0009648	photoperiodism	TAS	biological process
GO:0009649	entrainment of circadian clock	IEA	biological process
GO:0016573	histone acetylation	IEA	biological process
GO:0031490	chromatin DNA binding	ISS	molecular function
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	IMP	biological process
GO:0032922	circadian regulation of gene expression	IDA	biological process
GO:0033391	chromatoid body	ISS	cellular component
GO:0042634	regulation of hair cycle	IMP	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	ISS	biological process
GO:0043231	intracellular membrane-bounded organelle	IDA	cellular component
GO:0043565	sequence-specific DNA binding	ISS	molecular function
GO:0045892	negative regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IGI	biological process
GO:0046983	protein dimerization activity	IEA	molecular function
GO:0050729	positive regulation of inflammatory response	IEA	biological process
GO:0050796	regulation of insulin secretion	ISS	biological process
GO:0051092	positive regulation of NF-kappaB transcription factor activity	ISS	biological process
GO:0051775	response to redox state	IDA	biological process
GO:0070888	E-box binding	IDA	molecular function
GO:0070888	E-box binding	IDA	molecular function
GO:0071479	cellular response to ionizing radiation	IDA	biological process
GO:2000074	regulation of type B pancreatic cell development	ISS	biological process
GO:2000323	negative regulation of glucocorticoid receptor signaling pathway	ISS	biological process
GO:0000077	DNA damage checkpoint	IMP	biological process
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	IDA	molecular function
GO:0000982	transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding	IEA	molecular function
GO:0000982	transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding	ISS	molecular function
GO:0001046	core promoter sequence-specific DNA binding	IEA	molecular function
GO:0001047	core promoter binding	IEA	molecular function
GO:0001047	core promoter binding	ISS	molecular function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	IEA	molecular function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular function
GO:0003677	DNA binding	IEA	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IEA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	IEA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	ISS	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	TAS	molecular function
GO:0004402	histone acetyltransferase activity	IEA	molecular function
GO:0004402	histone acetyltransferase activity	IEA	molecular function
GO:0004402	histone acetyltransferase activity	IMP	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IEA	cellular component
GO:0005634	nucleus	IDA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005667	transcription factor complex	IEA	cellular component
GO:0005667	transcription factor complex	IEA	cellular component
GO:0005667	transcription factor complex	IPI	cellular component
GO:0005694	chromosome	IDA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0005737	cytoplasm	IEA	cellular component
GO:0006351	transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006355	regulation of transcription, DNA-templated	ISS	biological process
GO:0006355	regulation of transcription, DNA-templated	IEA	biological process
GO:0006357	regulation of transcription from RNA polymerase II promoter	TAS	biological process
GO:0006366	transcription from RNA polymerase II promoter	IEA	biological process
GO:0006974	cellular response to DNA damage stimulus	IEA	biological process
GO:0007165	signal transduction	TAS	biological process
GO:0007283	spermatogenesis	IEA	biological process
GO:0007283	spermatogenesis	ISS	biological process
GO:0007623	circadian rhythm	IEA	biological process
GO:0007623	circadian rhythm	TAS	biological process
GO:0007623	circadian rhythm	TAS	biological process
GO:0009416	response to light stimulus	IEA	biological process
GO:0009648	photoperiodism	TAS	biological process
GO:0009649	entrainment of circadian clock	IEA	biological process
GO:0016573	histone acetylation	IEA	biological process
GO:0016740	transferase activity	IEA	molecular function
GO:0016746	transferase activity, transferring acyl groups	IEA	molecular function
GO:0031490	chromatin DNA binding	IEA	molecular function
GO:0031490	chromatin DNA binding	ISS	molecular function
GO:0032922	circadian regulation of gene expression	IEA	biological process
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	IMP	biological process
GO:0032922	circadian regulation of gene expression	IDA	biological process
GO:0033391	chromatoid body	IEA	cellular component
GO:0033391	chromatoid body	ISS	cellular component
GO:0042634	regulation of hair cycle	IMP	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	IEA	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	ISS	biological process
GO:0043231	intracellular membrane-bounded organelle	IDA	cellular component
GO:0043565	sequence-specific DNA binding	IEA	molecular function
GO:0043565	sequence-specific DNA binding	ISS	molecular function
GO:0045892	negative regulation of transcription, DNA-templated	IEA	biological process
GO:0045892	negative regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IEA	biological process
GO:0045893	positive regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IEA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IGI	biological process
GO:0046983	protein dimerization activity	IEA	molecular function
GO:0048511	rhythmic process	IEA	biological process
GO:0050729	positive regulation of inflammatory response	IEA	biological process
GO:0050796	regulation of insulin secretion	IEA	biological process
GO:0050796	regulation of insulin secretion	ISS	biological process
GO:0051092	positive regulation of NF-kappaB transcription factor activity	IEA	biological process
GO:0051092	positive regulation of NF-kappaB transcription factor activity	ISS	biological process
GO:0051775	response to redox state	IDA	biological process
GO:0070888	E-box binding	IEA	molecular function
GO:0070888	E-box binding	IDA	molecular function
GO:0070888	E-box binding	IDA	molecular function
GO:0071479	cellular response to ionizing radiation	IDA	biological process
GO:2000074	regulation of type B pancreatic cell development	IEA	biological process
GO:2000074	regulation of type B pancreatic cell development	ISS	biological process
GO:2000323	negative regulation of glucocorticoid receptor signaling pathway	IEA	biological process
GO:2000323	negative regulation of glucocorticoid receptor signaling pathway	ISS	biological process
GO:0000077	DNA damage checkpoint	IMP	biological process
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding	IDA	molecular function
GO:0000982	transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding	ISS	molecular function
GO:0001047	core promoter binding	ISS	molecular function
GO:0001190	transcriptional activator activity, RNA polymerase II transcription factor binding	ISS	molecular function
GO:0003677	DNA binding	IDA	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	ISS	molecular function
GO:0003700	transcription factor activity, sequence-specific DNA binding	TAS	molecular function
GO:0004402	histone acetyltransferase activity	IMP	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005515	protein binding	IPI	molecular function
GO:0005634	nucleus	IDA	cellular component
GO:0005654	nucleoplasm	IDA	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005654	nucleoplasm	TAS	cellular component
GO:0005667	transcription factor complex	IPI	cellular component
GO:0005694	chromosome	IDA	cellular component
GO:0006355	regulation of transcription, DNA-templated	ISS	biological process
GO:0006357	regulation of transcription from RNA polymerase II promoter	TAS	biological process
GO:0007165	signal transduction	TAS	biological process
GO:0007283	spermatogenesis	ISS	biological process
GO:0007623	circadian rhythm	TAS	biological process
GO:0007623	circadian rhythm	TAS	biological process
GO:0009648	photoperiodism	TAS	biological process
GO:0031490	chromatin DNA binding	ISS	molecular function
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	ISS	biological process
GO:0032922	circadian regulation of gene expression	IMP	biological process
GO:0032922	circadian regulation of gene expression	IDA	biological process
GO:0033391	chromatoid body	ISS	cellular component
GO:0042634	regulation of hair cycle	IMP	biological process
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process	ISS	biological process
GO:0043231	intracellular membrane-bounded organelle	IDA	cellular component
GO:0043565	sequence-specific DNA binding	ISS	molecular function
GO:0045892	negative regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	ISS	biological process
GO:0045893	positive regulation of transcription, DNA-templated	IDA	biological process
GO:0045944	positive regulation of transcription from RNA polymerase II promoter	IGI	biological process
GO:0050796	regulation of insulin secretion	ISS	biological process
GO:0051092	positive regulation of NF-kappaB transcription factor activity	ISS	biological process
GO:0051775	response to redox state	IDA	biological process
GO:0070888	E-box binding	IDA	molecular function
GO:0070888	E-box binding	IDA	molecular function
GO:0071479	cellular response to ionizing radiation	IDA	biological process
GO:2000074	regulation of type B pancreatic cell development	ISS	biological process
GO:2000323	negative regulation of glucocorticoid receptor signaling pathway	ISS	biological process

KEGG pathways

Pathway id	Pathway name
hsa04728	Dopaminergic synapse
hsa04710	Circadian rhythm

Diseases

Associated diseases	References
Cancer	GAD: 19934327
Cancer (prostate)	GAD: 19934327
Fatty liver	GAD: 17696255
Metabolic syndrome	GAD: 19470168
Obesity	GAD: 18314271
Insomnia	GAD: 12898572
Sleep disorders	GAD: 15331141
Affective disorder	GAD: 15572273
Anorexia nervosa	GAD: 17516548
Autism	GAD: 17264841
Bipolar disorder	GAD: 14582141
Major depressive disorder	GAD: 19347611
Schizophrenia	GAD: 17116390
Psychological disorders	GAD: 15475734
Depression	GAD: 11927173
Ovarian endometriosis	INFBASE: 23006437
Male factor infertility	MIK: 22999556
Endometriosis	GAD: 18379422
Aberrant CpGs in Low Motility Sperm	MIK: 21674046
Spermatogenic defects	MIK: 29126923
Male infertility	MIK: 23527142
Teratozoospermia	MIK: 17327269

PubMed references

PMID	Condition	Mutation	Ethnicity	Population details	Infertility_type	Associated_genes
23527142	Male infertility	CLOCK (rs11932595, rs6811520, rs6850524)	Sloveni an, Ser bian Ca ucasian	961 (517 patients with idiopathic infertility, 444 control group of fertile men)	Male infertility
22999556	Idiopathic infertility	rs3749474, rs3817444, rs1801260		478 men with idiopathic infertility	Male infertility	CLOCK
29126923	Involved in spermatogenesis, Male infertility				Male infertility
26264441	Male infertility				Male infertility
23735500	Male infertility				Male infertility
17327269	Teratozoospermia			19 (6 controls, 13 cases)	Male infertility	GSE6872 analyzed by GEO2R (cutoff 1.5 fold)
21674046	Aberrant CpGs in Low Motility Sperm			18	Male infertility	GSE26881