CLOCK - clock circadian regulator Gene

Also Known as KAT13D; bHLHe8

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 9575

About CLOCK

Cytogenetic location: 4q12 Genomic coordinates (GRCh38): 4:55,427,903-55,546,909 (from NCBI)

This gene has 11 transcripts (splice variants), 269 orthologues and 6 paralogues. Ubiquitous expression in testis (RPKM 7.8), thyroid (RPKM 6.2) and 24 other tissues.

Summary

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 protein forms a heterodimer with ARNTL (BMAL1) that binds E-box enhancer elements upstream of Period (PER1, PER2, PER3) and Cryptochrome (CRY1, CRY2) genes and activates transcription of these genes. PER and CRY proteins heterodimerize and repress their own transcription by interacting in a feedback loop with CLOCK/ARNTL complexes. Polymorphisms in this gene may be associated with behavioral changes in certain populations and with obesity and metabolic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

CLOCK Products (2)

mRNA	Protein	Name
NM_001267843.2	NP_001254772.1	circadian locomoter output cycles protein kaput
NM_004898.4	NP_004889.1	circadian locomoter output cycles protein kaput

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables DNA binding	IDA IDA: Inferred from direct assay	11441146	GOA
enables E-box binding	IDA IDA: Inferred from direct assay	18411297	GOA
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA IDA: Inferred from direct assay	18411297	GOA
enables histone acetyltransferase activity	IMP IMP: Inferred from mutant phenotype	21980503	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	11018023	GOA
enables sequence-specific double-stranded DNA binding	IDA IDA: Inferred from direct assay	28473536	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in DNA damage checkpoint signaling	IMP IMP: Inferred from mutant phenotype	21659603	GOA
involved in cellular response to ionizing radiation	IDA IDA: Inferred from direct assay	21659603	GOA
involved in circadian regulation of gene expression	IDA IDA: Inferred from direct assay	10864977	GOA
involved in circadian regulation of gene expression	IMP IMP: Inferred from mutant phenotype	21980503	GOA
involved in positive regulation of DNA-templated transcription	IDA IDA: Inferred from direct assay	10864977	GOA
involved in positive regulation of circadian rhythm	IDA IDA: Inferred from direct assay	12738229	GOA
involved in protein acetylation	IDA IDA: Inferred from direct assay	28985504	GOA
involved in regulation of hair cycle	IMP IMP: Inferred from mutant phenotype	24005054	GOA
involved in response to redox state	IDA IDA: Inferred from direct assay	11441146	GOA

Cellular Component GO Annotation	Evidence	References	Source
part of CLOCK-BMAL transcription complex	IPI IPI: Inferred from physical interaction	10864977	GOA
located in chromosome	IDA IDA: Inferred from direct assay	21659603	GOA
located in cytosol	IDA IDA: Inferred from direct assay	28985504	GOA
located in nucleus	IDA IDA: Inferred from direct assay	12738229	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

CLOCK Protein Structure

HLH

PAS

PAS_11

0
200
400
600
800
846 a.a.

Protein Preferred Names	Protein Names
circadian locomoter output cycles protein kaput	circadian locomoter output cycles kaput protein

CLOCK Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	CLOCK	O15516	BMAL2	Homo sapiens	Q8WYA1-3	Validated Y2H	32296183
Intra	CLOCK	O15516	BMAL1	Homo sapiens	O00327	Anti Tag CoIP	33961781
Intra	CLOCK	O15516	BMAL1	Homo sapiens	O00327	Y2H	11018023
Intra	CLOCK	O15516	BMAL1	Homo sapiens	O00327	Anti Bait CoIP	28388406

Cross: Cross-species interaction Intra: Intraspecies interaction

CLOCK Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P82175	CLOCK Antibody (YA1920)	WB, IHC-P, ICC/IF, FC	Human, Mouse, Rat
HY-P85104	CLOCK Antibody (YA4796)	WB, ICC/IF, ELISA	Human

Related Diseases

Diseases	Alias
Delayed Sleep Phase Disorder	Delayed Sleep Phase Syndrome Delayed Sleep Phase Syndrome, Susceptibility To DSPD Delayed Sleep Phase Disorder, Susceptibility To DSPS Sleep Phase, Delayed, Disorder Sleep Phase Syndrome, Delayed, Susceptibility To
Major Depressive Disorder	Seasonal Affective Disorder Unipolar Depression Depression MDD Depressive Disorder Unipolar Depression, Susceptibility To Major Depressive Disorder 1 Major Depressive Disorder, Response To Citalopram Therapy In Major Depressive Disorder 2 Winter Depression Single Major Depressive Episode Sad Clinical Depression Major Depression Depressive Syndrome Major Depressive Disorder And Accelerated Response To Antidepressant Drug Treatment Seasonal Affective Disorder, Susceptibility To Recurrent Major Depression Affective Disorder, Seasonal Depression In A Seasonal Pattern Depression Seasonal Major Depressive Disorder With A Seasonal Pattern Seasonal Depression Seasonal Mood Disorder Mental Depression Recurrent Major Depressive Episodes
Narcolepsy	Paroxysmal Sleep Gelineau Syndrome Narcoleptic Syndrome Narcolepsy-Cataplexy Syndrome Cataplexy And Narcolepsy Narcolepsy, Without Cataplexy Gelineau'S Syndrome Narcolepsy With Or Without Cataplexy Narcolepsy Nos
Bipolar Disorder	Bipolar Depression Manic Disorder Depression, Bipolar Bipolar Disorder Manic Phase Depressive-Manic Psych. Manic Bipolar Affective Disorder Manic Bipolar I Disorder Manic Depression Manic Depressive Disorder Mixed Bipolar Disorder Bipolar Affective Disorder Bipolar Affective Psychosis Bipolar Spectrum Disorder Manic Depressive Illness Depression Bipolar Bipolar Disorder, Mixed Major Affective Disorder Major Affective Disorder 1 Major Affective Disorder 2
Cluster Headache	Headache, Cluster
Bile Duct Cystadenoma	Cystadenoma Of The Bile Duct
Advanced Sleep Phase Syndrome	Fasps Familial Advanced Sleep-Phase Syndrome Advanced Sleep Phase Syndrome, Familial Familial Advanced Sleep Phase Syndrome Sleep Phase Syndrome, Advanced, Familial Advanced Sleep-Phase Syndrome, Familial
Restless Legs Syndrome	Wed Willis-Ekbom Disease Restless Leg Syndrome Ekbom Syndrome Wittmaack-Ekbom Syndrome Willis Ekbom Disease Ekbom'S Syndrome Rls Restless Legs Restless Legs Syndrome, Susceptibility To
Mood Disorder	Mood Disorders Episodic Mood Disorder
Smith-Magenis Syndrome	SMS Chromosome 17p11.2 Deletion Syndrome 17p11.2 Microdeletion Syndrome 17p11.2 Monosomy Chromosome 17p Deletion Syndrome Del(17) P11.2 17p- Syndrome Deletion 17p Syndrome Partial Monosomy 17p
Sleep Disorder	Sleep Disorders Non-Organic Sleep Disorder
Headache	Headache Disorder
Apnea, Obstructive Sleep	Obstructive Sleep Apnea Syndrome Obstructive Sleep Apnea Sleep Apnea, Obstructive Osa Osas Sleep Apnea/Hypopnea Syndrome Sahs Upper Airway Resistance Sleep Apnea Syndrome Apnea, Obstructive Obstructive Apnea Osahs Sleep Apnea Hypopnea Syndrome Sleep Apnea Syndrome, Obstructive Sleep Apnea Obstructive Sleep Apnea Syndromes Obstructive Sleep Apnoea Syndrome Obstructive Sleep Apnoea, Adult Osa - [Obstructive Sleep Apnoea] Obstructive Sleep Apnoea, Paediatric Obstructive Sleep Apnoea Hypopnoea Syndrome Osa Syndrome Sleep Apnoea Nos [Sas] - Sleep Apnoea Syndrome Sleep Apnoea Syndrome [Osahs] - Obstructive Sleep Apnoea-Hypopnea Syndrome [Sahs] - Sleep Apnoea-Hypopnea Syndrome
Colorectal Cancer	Colon Cancer Colorectal Carcinoma Colon Carcinoma Colorectal Cancer, Susceptibility To Carcinoma Of Colon CRC Colorectal Cancer With Chromosomal Instability, Somatic Colon Cancer, Somatic Colon Cancer, Susceptibility To Colonic Neoplasms Colorectal Neoplasms Colorectal Cancer, Somatic Colon Cancer, Advanced, Somatic Colonic Carcinoma Colorectal Carcinomas Colon Cancers Colorectal Cancers Cancer, Colorectal, Somatic Cancer, Colon Cancer, Colorectal, Susceptibility To Colorectal Neoplasm Colonic Neoplasm Malignant Tumor Of Colon
Schizophrenia	SCZD Schizophrenia With Or Without An Affective Disorder Schizophrenia 12 Schizophrenia, Susceptibility To Schizophrenia-1 Dementia Praecox Schizophrenia 1
Breast Cancer	Breast Carcinoma Male Breast Cancer Breast Cancer, Familial Malignant Neoplasm Of Breast Breast Cancer, Susceptibility To Breast Cancer, Early-Onset Malignant Tumor Of Breast Carcinoma Of Male Breast Breast Cancer, Invasive Ductal Breast Cancer, Protection Against Breast Cancer, Somatic Breast Cancer, Male Breast Cancer, Lobular, Somatic Breast Tumor Mammary Cancer Mammary Tumor Malignant Neoplasm Of Male Breast Mammary Carcinoma Male Breast Carcinoma Familial Cancer Of Breast Invasive Ductal Breast Carcinoma Breast Cancer Susceptibility Breast Cancer, Male, Susceptibility To Breast Cancer, Early-Onset, Susceptibility To Malignant Tumor Of The Breast Mammary Neoplasm Primary Breast Cancer Neoplasm Of Male Breast Carcinoma Of Breast Breast Cancer In Men Familial Breast Cancer Cancer Of Breast BC Breast Cancer Familial Breast Cancer Familial Male Breast Cancer, Familial Male Breast Male Carcinoma Breast Neoplasms Breast Neoplasms, Male Mammary Tumors Mammary Carcinomas Cancer, Breast Cancer, Breast, Susceptibility Invasive Breast Ductal Carcinoma Breast Neoplasm Susceptibility To Breast Cancer Mammary Neoplasms Animal Mammary Neoplasms Primary Malignant Neoplasm Of Breast Infiltrating Ductal Carcinoma Of Breast Infiltrating Duct Carcinoma Of Unspecified Site Infiltrating Ductular Carcinoma Of Unspecified Site Invasive Breast Carcinoma Of No Special Type Microinvasive Carcinoma Of Breast Carcinoma With Apocrine Differentiation
Body Mass Index Quantitative Trait Locus 11	OBESITY Obesity, Susceptibility To Leanness, Inherited Obesity, Susceptibility To, Bmiq11 Obesity, Mild, Early-Onset Obesity, Association With Obesity, Early-Onset, Susceptibility To Obesity, Severe Obesity, Severe, And Type Ii Diabetes Obesity, Late-Onset Obesity , Susceptibility To BMIQ11 Obesity Bmiq11 Obesity, Early-Onset Simple Obesity Nos Excess Fat Obesity, Not Elsewhere Classified, Body Mass Index Not Elsewhere Classified Adiposis

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (14)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-148765	CLK8	Inhibitor	98.06%	Unkown
HY-115672	KS15	Inhibitor	99.46%	Unkown
HY-115519	(E/Z)-GO289	Inhibitor	98.98%	Unkown
HY-134194	KL201		98.18%	Unkown
HY-119506	KL044		99.50%	Unkown
HY-145149	Duostatin 5		99.76%	Unkown
HY-RS02828	CLOCK Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS17250	Clock Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-W011425	NTPO		/	Unkown
HY-134193	KL101		/	Unkown
HY-145149S	Duostatin 5-13C,d3		/	Unkown
HY-184895	CM002	Activator	/	Unkown
HY-RS23704	Clock Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-W928636	5'-O-DMTr-2'-O-4'-C-locked-5-Me-rC(Bz)		/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Canis familiaris	CLOCK	VGNC	VGNC:39353
Bos taurus	CLOCK	VGNC	VGNC:27456
Rattus norvegicus	CLOCK	RGD	RGD:620271
Macaca mulatta	CLOCK	VGNC	VGNC:71262
Felis catus	CLOCK	VGNC	VGNC:60970
Mus musculus	CLOCK	MGD	MGI:99698
Others	CLOCK	NCBI