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Aliases for CLOCK Gene

Aliases for CLOCK Gene

  • Clock Circadian Regulator 2 3 5
  • Class E Basic Helix-Loop-Helix Protein 8 3 4
  • EC 2.3.1.48 4 56
  • BHLHe8 3 4
  • Circadian Locomoter Output Cycles Kaput Protein 3
  • Circadian Locomoter Output Cycles Protein Kaput 3
  • Clock (Mouse) Homolog 2
  • Clock Homolog (Mouse) 2
  • Clock Homolog 3
  • KIAA0334 4
  • KAT13D 3
  • HCLOCK 4

External Ids for CLOCK Gene

Previous GeneCards Identifiers for CLOCK Gene

  • GC04M056102
  • GC04M056260
  • GC04M056214
  • GC04M056139
  • GC04M055988
  • GC04M056294
  • GC04M052247

Summaries for CLOCK Gene

Entrez Gene Summary for CLOCK Gene

  • 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]

GeneCards Summary for CLOCK Gene

CLOCK (Clock Circadian Regulator) is a Protein Coding gene. Diseases associated with CLOCK include Cataract 7 and Delayed Sleep Phase Disorder. Among its related pathways are Circadian rhythm pathway and Melatonin metabolism and effects. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and signal transducer activity. An important paralog of this gene is NPAS2.

UniProtKB/Swiss-Prot for CLOCK Gene

  • Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots circa (about) and diem (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for timegivers). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5-CACGTG-3) within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK NPAS2-ARNTL/BMAL1 ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5-CACGTGA-3, which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5-CAC-3, while ARNTL binds to the half-site 5-GTGA-3 (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5-AACGTGA-3 and 5-CATGTGA-3 (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504).

Gene Wiki entry for CLOCK Gene

Additional gene information for CLOCK Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CLOCK Gene

Genomics for CLOCK Gene

GeneHancer (GH) Regulatory Elements for CLOCK Gene

Promoters and enhancers for CLOCK Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH04I055543 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 559.8 +0.8 761 4.8 SMAD1 ZFP64 ARID4B SIN3A FEZF1 DMAP1 ZNF2 YY1 POLR2B ZNF766 CLOCK ENSG00000272969 RN7SKP30 TMEM165 CEP135 AASDH SRP72 NMU SRD5A3
GH04I055489 Promoter 0.5 EPDnew 570.5 +57.7 57701 0.1 CLOCK ENSG00000238585 GC04M055502 GC04M055433 PIR52615
GH04I055509 Promoter 0.5 EPDnew 550.3 +37.1 37143 0.1 CLOCK GC04M055502 ENSG00000238585 RN7SKP30
GH04I055394 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 15.1 +149.8 149848 4.7 HDGF PKNOX1 FOXA2 ARNT ARID4B SIN3A DMAP1 YBX1 ZNF2 YY1 TMEM165 GC04P055398 SRD5A3-AS1 CEP135 RN7SKP30 CLOCK AASDH SRD5A3 NMU ENSG00000272969
GH04I055436 Enhancer 1 ENCODE dbSUPER 19.8 +108.8 108822 2.8 HDAC1 PKNOX1 ATF1 FOXA2 TCF12 CREM ZBTB2 ZEB2 ZNF592 MTA1 RN7SKP30 TMEM165 CLOCK SRD5A3-AS1 GC04M055433 PIR52615 GC04M055502 ENSG00000238585
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around CLOCK on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the CLOCK gene promoter:

Genomic Locations for CLOCK Gene

Genomic Locations for CLOCK Gene
chr4:55,427,901-55,547,138
(GRCh38/hg38)
Size:
119,238 bases
Orientation:
Minus strand
chr4:56,294,070-56,413,305
(GRCh37/hg19)

Genomic View for CLOCK Gene

Genes around CLOCK on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLOCK Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLOCK Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLOCK Gene

Proteins for CLOCK Gene

  • Protein details for CLOCK Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15516-CLOCK_HUMAN
    Recommended name:
    Circadian locomoter output cycles protein kaput
    Protein Accession:
    O15516
    Secondary Accessions:
    • A0AV01
    • A2I2N9
    • O14516
    • Q9UIT8

    Protein attributes for CLOCK Gene

    Size:
    846 amino acids
    Molecular mass:
    95304 Da
    Quaternary structure:
    • Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (By similarity). Interacts with KMT2A; in a circadian manner (By similarity). Forms a heterodimer with ARNTL/BMAL1 (PubMed:21613214, PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and for phosphorylation of both CLOCK and ARNTL/BMAL1 (By similarity). Interacts with NR3C1 in a ligand-dependent fashion (PubMed:21980503). Interacts with ESR1 and estrogen stimulates this interaction (PubMed:23160374). Interacts with the complex p35/CDK5 (PubMed:24235147). Interacts with RELA/p65 (By similarity). Interacts with KAT2B, CREBBP, EP300 (PubMed:14645221). Interacts with ID1 and ID3 (By similarity). Interacts with ID2 (PubMed:20861012). Interacts with MTA1 (By similarity). Interacts with MGEA5 (By similarity). Interacts with SIRT1 (By similarity). Interacts with CIPC (By similarity). Interacts with EZH2 (By similarity). Interacts with EIF4E, PIWIL1 and DDX4 (By similarity). Interacts with PER2 and CRY1 and the interaction with PER and CRY proteins requires translocation to the nucleus. Interacts with Interacts with PER1 and CRY2 (By similarity). Interaction of the CLOCK-ARNTL/BMAL1 heterodimer with PER or CRY inhibits transcription activation (PubMed:21613214). Interaction of the CLOCK-ARNTL/BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (PubMed:21613214). The CLOCK-ARNTL/BMAL1 heterodimer interacts with GSK3B. Interacts with KDM5A (PubMed:21960634). Interacts with MYBBP1A (By similarity). Interacts with THRAP3 (By similarity). Interacts with MED1; this interaction requires the presence of THRAP3 (By similarity). Interacts with NCOA2 (By similarity). The CLOCK-ARNTL/BMAL1 heterodimer interacts with PASD1 (PubMed:25936801). Interacts with ASS1 and IMPDH2; in a circadian manner (PubMed:28985504). Interacts with NDUFA9 (PubMed:28985504).
    Miscellaneous:
    • CLOCK-ARNTL/BMAL1 double mutations within the PAS domains result in synergistic desensitization to high levels of CRY on repression of CLOCK-ARNTL/BMAl1 transcriptional activity of PER1 and disrupt circadian rhythmicity.
    SequenceCaution:
    • Sequence=BAA20792.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for CLOCK Gene

neXtProt entry for CLOCK Gene

Selected DME Specific Peptides for CLOCK Gene

O15516:
  • LEALDGFF
  • VTTFTQDRQIRFSQGQQLVTKLVTAPVACGAVMVPSTM
  • QPSQAQLTQ
  • SHHQQHQSQQQQQLSRHRTDSL
  • LQSTSTQ
  • QRRSSFSSQS
  • KSQDSGS
  • HLPAHEKM
  • KAKRVSRNKSEKKRRDQFNVLIKELGSMLPGNAR
  • PINMQGQVVPTNQIQSGMN
  • GSVQLSSGNS
  • QQQSSQEQQL
  • SYEDRVC

Post-translational modifications for CLOCK Gene

  • O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-ARNTL/BMAL1 heterodimer thereby increasing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2/3 and CRY1/2.
  • Phosphorylation is dependent on the CLOCK-ARNTL/BMAL1 heterodimer formation. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver. May be phosphorylated by CSNK1D and CKSN1E.
  • Sumoylation enhances its transcriptional activity and interaction with ESR1, resulting in up-regulation of ESR1 activity. Estrogen stimulates sumoylation. Desumoylation by SENP1 negatively regulates its transcriptional activity. Sumoylation stimulates cell proliferation and increases the proportion of S phase cells in breast cancer cell lines.
  • Ubiquitinated, leading to its proteasomal degradation.

Domains & Families for CLOCK Gene

Gene Families for CLOCK Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Transcription factors

Suggested Antigen Peptide Sequences for CLOCK Gene

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with CLOCK: view

No data available for UniProtKB/Swiss-Prot for CLOCK Gene

Function for CLOCK Gene

Molecular function for CLOCK Gene

GENATLAS Biochemistry:
CLOCK gene,homolog to murine Clock,regulator of circadian rhythms,with two major transcripts 8 and 10kb,predominantly expressed in the suprachiasmatic nuclei and cerebellum
UniProtKB/Swiss-Prot CatalyticActivity:
Acetyl-CoA + [protein]-L-lysine = CoA + [protein]-N(6)-acetyl-L-lysine.
UniProtKB/Swiss-Prot EnzymeRegulation:
There is conflicting data about the effect of NAD cofactors on activity. PubMed:11441146 suggests that the redox state of the cell can modulate the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer; NADH and NADPH enhance the DNA-binding activity of the heterodimer. PubMed:23229515 reports that NADH and NADPH have no significant effect on DNA-binding activity of the CLOCK-ARNTL/BMAL1 heterodimer.
UniProtKB/Swiss-Prot Function:
Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots circa (about) and diem (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for timegivers). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5-CACGTG-3) within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK NPAS2-ARNTL/BMAL1 ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress ARNTL/BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is 5-CACGTGA-3, which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5-CAC-3, while ARNTL binds to the half-site 5-GTGA-3 (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5-AACGTGA-3 and 5-CATGTGA-3 (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504).

Enzyme Numbers (IUBMB) for CLOCK Gene

Phenotypes From GWAS Catalog for CLOCK Gene

Gene Ontology (GO) - Molecular Function for CLOCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding IDA 18411297
GO:0000982 transcription factor activity, RNA polymerase II proximal promoter sequence-specific DNA binding ISS --
GO:0001046 core promoter sequence-specific DNA binding IEA --
GO:0001047 core promoter binding ISS --
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding ISS --
genes like me logo Genes that share ontologies with CLOCK: view
genes like me logo Genes that share phenotypes with CLOCK: view

Animal Models for CLOCK Gene

MGI Knock Outs for CLOCK:

miRNA for CLOCK Gene

miRTarBase miRNAs that target CLOCK
Targeted motifs for CLOCK Gene
HOMER Transcription Factor Regulatory Elements motif CLOCK
  • Consensus sequence: GHCACGTG Submotif: canonical Cell Type: Liver GEO ID: GSE39860

Clone Products

  • Addgene plasmids for CLOCK

No data available for Human Phenotype Ontology and Transcription Factor Targets for CLOCK Gene

Localization for CLOCK Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLOCK Gene

Nucleus. Cytoplasm. Cytoplasm, cytosol. Note=Shuffling between the cytoplasm and the nucleus is under circadian regulation and is ARNTL/BMAL1-dependent. Phosphorylated form located in the nucleus while the nonphosphorylated form found only in the cytoplasm. Sequestered to the cytoplasm in the presence of ID2 (By similarity). Localizes to sites of DNA damage in a H2AX-independent manner. {ECO:0000250 UniProtKB:O08785, ECO:0000269 PubMed:21659603}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CLOCK gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 1
peroxisome 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for CLOCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 14645221
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IPI,IEA 9576906
GO:0005694 chromosome IDA 21659603
GO:0005737 cytoplasm IEA --
genes like me logo Genes that share ontologies with CLOCK: view

Pathways & Interactions for CLOCK Gene

genes like me logo Genes that share pathways with CLOCK: view

SIGNOR curated interactions for CLOCK Gene

Is activated by:

Gene Ontology (GO) - Biological Process for CLOCK Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000077 DNA damage checkpoint IMP 21659603
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA,ISS --
GO:0006357 regulation of transcription by RNA polymerase II TAS 10198158
GO:0006366 transcription by RNA polymerase II IEA --
genes like me logo Genes that share ontologies with CLOCK: view

Drugs & Compounds for CLOCK Gene

(7) Drugs for CLOCK Gene - From: PharmGKB, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Lithium Approved Pharma 0
Salbutamol Approved, Vet_approved Pharma Partial agonist, Agonist 0
Coenzyme A Investigational Nutra 0

(3) Additional Compounds for CLOCK Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
acetyl-coa
  • Ac-CoA
  • Ac-Coenzyme A
  • Ac-S-CoA
  • Ac-S-Coenzyme A
  • Acetyl coenzyme-A
72-89-9
genes like me logo Genes that share compounds with CLOCK: view

Transcripts for CLOCK Gene

Clone Products

  • Addgene plasmids for CLOCK

Alternative Splicing Database (ASD) splice patterns (SP) for CLOCK Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7a · 7b · 7c ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13a · 13b ^ 14a · 14b · 14c ^ 15
SP1: - -
SP2: - -
SP3:
SP4: -
SP5:
SP6:

Relevant External Links for CLOCK Gene

GeneLoc Exon Structure for
CLOCK
ECgene alternative splicing isoforms for
CLOCK

Expression for CLOCK Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for CLOCK Gene

Protein differential expression in normal tissues from HIPED for CLOCK Gene

This gene is overexpressed in Platelet (61.6) and Retina (6.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for CLOCK Gene



Protein tissue co-expression partners for CLOCK Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of CLOCK Gene:

CLOCK

SOURCE GeneReport for Unigene cluster for CLOCK Gene:

Hs.436975

mRNA Expression by UniProt/SwissProt for CLOCK Gene:

O15516-CLOCK_HUMAN
Tissue specificity: Hair follicles (at protein level). Expressed in all tissues examined including spleen, thymus, prostate, testis, ovary, small intestine, colon, leukocytes, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highest levels in testis and skeletal muscle. Low levels in thymus, lung and liver. Expressed in all brain regions with highest levels in cerebellum. Highly expressed in the suprachiasmatic nucleus (SCN).

Evidence on tissue expression from TISSUES for CLOCK Gene

  • Nervous system(4.6)
  • Liver(4.5)
  • Lung(4.3)
  • Muscle(2.5)
  • Heart(2.4)
  • Kidney(2)
genes like me logo Genes that share expression patterns with CLOCK: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLOCK Gene

Orthologs for CLOCK Gene

This gene was present in the common ancestor of animals.

Orthologs for CLOCK Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLOCK 33 34
  • 99.41 (n)
dog
(Canis familiaris)
Mammalia CLOCK 33 34
  • 92.83 (n)
cow
(Bos Taurus)
Mammalia CLOCK 33 34
  • 92.34 (n)
oppossum
(Monodelphis domestica)
Mammalia CLOCK 34
  • 91 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Clock 33 16 34
  • 90.84 (n)
rat
(Rattus norvegicus)
Mammalia Clock 33
  • 89.46 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia CLOCK 34
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves CLOCK 33 34
  • 80.81 (n)
lizard
(Anolis carolinensis)
Reptilia CLOCK 34
  • 82 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia clock 33
  • 74.73 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.566 33
zebrafish
(Danio rerio)
Actinopterygii clock 33 34
  • 65.57 (n)
clock3 34
  • 61 (a)
OneToMany
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.11889 33
fruit fly
(Drosophila melanogaster)
Insecta Clk 35 34
  • 50 (a)
Species where no ortholog for CLOCK was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CLOCK Gene

ENSEMBL:
Gene Tree for CLOCK (if available)
TreeFam:
Gene Tree for CLOCK (if available)

Paralogs for CLOCK Gene

Paralogs for CLOCK Gene

(7) SIMAP similar genes for CLOCK Gene using alignment to 3 proteins:

genes like me logo Genes that share paralogs with CLOCK: view

Variants for CLOCK Gene

Sequence variations from dbSNP and Humsavar for CLOCK Gene

SNP ID Clin Chr 04 pos Variation AA Info Type
rs1000057798 -- 55,486,337(-) G/A genic_upstream_transcript_variant, intron_variant
rs1000070451 -- 55,440,593(-) C/A/G intron_variant
rs1000071144 -- 55,484,065(-) A/G genic_upstream_transcript_variant, intron_variant
rs1000088900 -- 55,433,483(-) G/C 3_prime_UTR_variant
rs1000121491 -- 55,433,152(-) T/C 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for CLOCK Gene

Variant ID Type Subtype PubMed ID
dgv841e201 CNV deletion 23290073
esv1694176 CNV insertion 17803354
esv2661534 CNV deletion 23128226
esv2727633 CNV deletion 23290073
esv3563876 CNV deletion 23714750
esv5988 CNV gain 19470904
nsv10496 CNV loss 18304495
nsv1073334 CNV deletion 25765185
nsv1074714 CNV deletion 25765185
nsv1119001 CNV deletion 24896259
nsv1123796 CNV deletion 24896259
nsv1136856 CNV deletion 24896259
nsv474606 CNV novel sequence insertion 20440878
nsv955700 CNV deletion 24416366

Variation tolerance for CLOCK Gene

Residual Variation Intolerance Score: 21.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.27; 70.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLOCK Gene

Human Gene Mutation Database (HGMD)
CLOCK
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLOCK

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLOCK Gene

Disorders for CLOCK Gene

MalaCards: The human disease database

(10) MalaCards diseases for CLOCK Gene - From: HGMD, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cataract 7
  • ctrct7
delayed sleep phase disorder
  • delayed sleep phase disorder, susceptibility to
cluster headache
major depressive disorder
  • mdd
advanced sleep phase syndrome
  • familial advanced sleep-phase syndrome
- elite association - COSMIC cancer census association via MalaCards
Search CLOCK in MalaCards View complete list of genes associated with diseases

Additional Disease Information for CLOCK

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CLOCK: view

No data available for UniProtKB/Swiss-Prot and Genatlas for CLOCK Gene

Publications for CLOCK Gene

  1. Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei. (PMID: 10198158) Steeves TD … Takahashi JS (Genomics 1999) 2 3 4 22 58
  2. Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population). (PMID: 19888304) Garaulet M … Ordovas JM (European journal of human genetics : EJHG 2010) 3 22 44 58
  3. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. (PMID: 20065968) Garaulet M … Ordovas JM (International journal of obesity (2005) 2010) 3 22 44 58
  4. Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. (PMID: 20072116) Soria V … Urretavizcaya M (Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2010) 3 22 44 58
  5. Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population. (PMID: 19224106) Kishi T … Iwata N (European archives of psychiatry and clinical neuroscience 2009) 3 22 44 58

Products for CLOCK Gene

Sources for CLOCK Gene

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