CR2Cancer

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Domain, Function and Classification > Gene Ontology > KEGG and Reactome Pathway

> Domain, Function and Classification

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Domain

PF00010 Helix-loop-helix DNA-binding domain
PF00989 PAS fold

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. CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner ARNTL/BMAL1. 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. 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. 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).

Classification

Class	Modification	Substrate	Product	PubMed
Histone modification write	Histone acetylation	H3, H4	#	#

> Gene Ontology [ TOP ]
Biological Process	GO:0000075 cell cycle checkpoint GO:0000077 DNA damage checkpoint GO:0002064 epithelial cell development GO:0002065 columnar/cuboidal epithelial cell differentiation GO:0002066 columnar/cuboidal epithelial cell development GO:0002067 glandular epithelial cell differentiation GO:0002068 glandular epithelial cell development GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0003309 type B pancreatic cell differentiation GO:0003323 type B pancreatic cell development GO:0006473 protein acetylation GO:0006475 internal protein amino acid acetylation GO:0007283 spermatogenesis GO:0007623 circadian rhythm GO:0009306 protein secretion GO:0009314 response to radiation GO:0009416 response to light stimulus GO:0009648 photoperiodism GO:0009755 hormone-mediated signaling pathway GO:0009914 hormone transport GO:0010212 response to ionizing radiation GO:0010498 proteasomal protein catabolic process GO:0010817 regulation of hormone levels GO:0015833 peptide transport GO:0016570 histone modification GO:0016573 histone acetylation GO:0018205 peptidyl-lysine modification GO:0018393 internal peptidyl-lysine acetylation GO:0018394 peptidyl-lysine acetylation GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0030518 intracellular steroid hormone receptor signaling pathway GO:0030522 intracellular receptor signaling pathway GO:0030856 regulation of epithelial cell differentiation GO:0031016 pancreas development GO:0031018 endocrine pancreas development GO:0031349 positive regulation of defense response GO:0031570 DNA integrity checkpoint GO:0031958 corticosteroid receptor signaling pathway GO:0032103 positive regulation of response to external stimulus GO:0032922 circadian regulation of gene expression GO:0033143 regulation of intracellular steroid hormone receptor signaling pathway GO:0033144 negative regulation of intracellular steroid hormone receptor signaling pathway GO:0035270 endocrine system development GO:0035883 enteroendocrine cell differentiation GO:0042303 molting cycle GO:0042633 hair cycle GO:0042634 regulation of hair cycle GO:0042886 amide transport GO:0042921 glucocorticoid receptor signaling pathway GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043401 steroid hormone mediated signaling pathway GO:0043543 protein acylation GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0048232 male gamete generation GO:0048511 rhythmic process GO:0048545 response to steroid hormone GO:0050708 regulation of protein secretion GO:0050727 regulation of inflammatory response GO:0050729 positive regulation of inflammatory response GO:0050796 regulation of insulin secretion GO:0051090 regulation of sequence-specific DNA binding transcription factor activity GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051775 response to redox state GO:0071214 cellular response to abiotic stimulus GO:0071383 cellular response to steroid hormone stimulus GO:0071396 cellular response to lipid GO:0071407 cellular response to organic cyclic compound GO:0071478 cellular response to radiation GO:0071479 cellular response to ionizing radiation GO:0090087 regulation of peptide transport GO:0090276 regulation of peptide hormone secretion GO:2000074 regulation of type B pancreatic cell development GO:2000322 regulation of glucocorticoid receptor signaling pathway GO:2000323 negative regulation of glucocorticoid receptor signaling pathway
Molecular Function	GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0000987 core promoter proximal region sequence-specific DNA binding GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0001076 transcription factor activity, RNA polymerase II transcription factor binding GO:0001159 core promoter proximal region DNA binding GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding GO:0001191 transcriptional repressor activity, RNA polymerase II transcription factor binding GO:0003682 chromatin binding GO:0004402 histone acetyltransferase activity GO:0008080 N-acetyltransferase activity GO:0016407 acetyltransferase activity GO:0016410 N-acyltransferase activity GO:0016746 transferase activity, transferring acyl groups GO:0016747 transferase activity, transferring acyl groups other than amino-acyl groups GO:0031490 chromatin DNA binding GO:0034212 peptide N-acetyltransferase activity GO:0043566 structure-specific DNA binding GO:0061733 peptide-lysine-N-acetyltransferase activity GO:0070888 E-box binding GO:0098811 transcriptional repressor activity, RNA polymerase II activating transcription factor binding
Cellular Component	GO:0005667 transcription factor complex GO:0033391 chromatoid body GO:0035770 ribonucleoprotein granule GO:0036464 cytoplasmic ribonucleoprotein granule

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04710 Circadian rhythm hsa04728 Dopaminergic synapse
Reactome	R-HSA-1368108: BMAL1 R-HSA-3247509: Chromatin modifying enzymes R-HSA-4839726: Chromatin organization R-HSA-400253: Circadian Clock R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism R-HSA-3214847: HATs acetylate histones R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1368071: NR1D1 (REV-ERBA) represses gene expression R-HSA-1989781: PPARA activates gene expression R-HSA-1368082: RORA activates gene expression R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04710 Circadian rhythm
hsa04728 Dopaminergic synapse

Reactome

R-HSA-1368108: BMAL1
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-400253: Circadian Clock
R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-3214847: HATs acetylate histones
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1368071: NR1D1 (REV-ERBA) represses gene expression
R-HSA-1989781: PPARA activates gene expression
R-HSA-1368082: RORA activates gene expression
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Mutation landscape in primary tumor tissue from TCGA > Mutation landscape in cancer cell line from CCLE > All mutations from COSMIC database V81 > Variations from text mining

> The Cancer Genome Atlas (TCGA) [ TOP ]

> Cancer Cell Line Encyclopedia (CCLE) [ TOP ]
There is no record.

> Catalogue of Somatic Mutations in Cancer (COSMIC)

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COSMIC ID	CDS change	AA change	Mutation Type	Anatomical Site
COSM5356131	c.1206+2T>C	p.?	Unknown	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM5666042	c.563A>T	p.K188I	Substitution - Missense	Soft_tissue
COSM1310145	c.392T>C	p.I131T	Substitution - Missense	Urinary_tract
COSM1430229	c.368_369insT	p.L123fs*14	Insertion - Frameshift	Large_intestine
COSM74177	c.1706A>T	p.Q569L	Substitution - Missense	Ovary
COSM4585110	c.1367C>T	p.P456L	Substitution - Missense	Bone
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM4585108	c.2434A>G	p.T812A	Substitution - Missense	Bone
COSM1186574	c.566A>G	p.N189S	Substitution - Missense	Lung
COSM3301666	c.2460A>G	p.Q820Q	Substitution - coding silent	Large_intestine
COSM5822608	c.2445G>A	p.Q815Q	Substitution - coding silent	Liver
COSM1618924	c.1397A>T	p.H466L	Substitution - Missense	Liver
COSM1157924	c.763G>A	p.V255I	Substitution - Missense	Pancreas
COSM734124	c.1709C>G	p.S570*	Substitution - Nonsense	Lung
COSM5026152	c.1285A>G	p.T429A	Substitution - Missense	Breast
COSM1671034	c.1662A>T	p.Q554H	Substitution - Missense	Large_intestine
COSM1671034	c.1662A>T	p.Q554H	Substitution - Missense	Large_intestine
COSM5060395	c.1875_1877delACA	p.Q626delQ	Deletion - In frame	Biliary_tract
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM215946	c.769T>G	p.L257V	Substitution - Missense	Central_nervous_system
COSM3714929	c.1408C>T	p.H470Y	Substitution - Missense	Upper_aerodigestive_tract
COSM3696684	c.875G>T	p.R292M	Substitution - Missense	Large_intestine
COSM734123	c.1291T>G	p.S431A	Substitution - Missense	Lung
COSM4755802	c.1412A>G	p.E471G	Substitution - Missense	Stomach
COSM1056166	c.2063A>G	p.Q688R	Substitution - Missense	Endometrium
COSM4918044	c.206A>T	p.D69V	Substitution - Missense	Liver
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM4965656	c.159C>T	p.L53L	Substitution - coding silent	Pancreas
COSM3604589	c.946G>A	p.D316N	Substitution - Missense	Skin
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM3767905	c.646A>T	p.I216L	Substitution - Missense	Liver
COSM5959203	c.1370C>T	p.T457M	Substitution - Missense	Thyroid
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM1056169	c.1159C>T	p.R387*	Substitution - Nonsense	Endometrium
COSM1430228	c.566_567insA	p.N189fs*23	Insertion - Frameshift	Large_intestine
COSM3301690	c.1079A>G	p.H360R	Substitution - Missense	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM3696682	c.1926G>A	p.G642G	Substitution - coding silent	Large_intestine
COSM3301663	c.2515G>A	p.D839N	Substitution - Missense	Bone
COSM1201428	c.2135A>C	p.K712T	Substitution - Missense	Large_intestine
COSM3696683	c.1319C>A	p.S440*	Substitution - Nonsense	Large_intestine
COSM4672880	c.263C>G	p.T88S	Substitution - Missense	Large_intestine
COSM1486016	c.1327_1328delAC	p.T443fs*28	Deletion - Frameshift	Breast
COSM5018175	c.2278_2280delCAG	p.Q760delQ	Deletion - In frame	Soft_tissue
COSM2151338	c.12C>T	p.T4T	Substitution - coding silent	Central_nervous_system
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM4755804	c.1140A>C	p.E380D	Substitution - Missense	Stomach
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM3696685	c.815C>T	p.P272L	Substitution - Missense	Large_intestine
COSM4386730	c.2520_2521insGA	p.S841fs*>7	Insertion - Frameshift	Lung
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM4650034	c.1789A>G	p.M597V	Substitution - Missense	Large_intestine
COSM5060395	c.1875_1877delACA	p.Q626delQ	Deletion - In frame	Stomach
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM5476533	c.2295G>A	p.Q765Q	Substitution - coding silent	Large_intestine
COSM4642903	c.1459T>C	p.S487P	Substitution - Missense	Large_intestine
COSM2151338	c.12C>T	p.T4T	Substitution - coding silent	Central_nervous_system
COSM4755803	c.1297T>C	p.S433P	Substitution - Missense	Stomach
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM4125215	c.569A>G	p.Q190R	Substitution - Missense	Stomach
COSM1671035	c.395T>C	p.I132T	Substitution - Missense	Haematopoietic_and_lymphoid_tissue
COSM3301698	c.474C>T	p.I158I	Substitution - coding silent	Large_intestine
COSM1137194	c.1539+1_1539+2GT>TC	p.?	Unknown	Kidney
COSM481353	c.1A>G	p.M1V	Substitution - Missense	Kidney
COSM1056168	c.1337C>G	p.S446*	Substitution - Nonsense	Endometrium
COSM5496493	c.1693-7T>C	p.?	Unknown	Biliary_tract
COSM2151519	c.416C>A	p.T139N	Substitution - Missense	Central_nervous_system
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Pancreas
COSM3767906	c.645T>A	p.F215L	Substitution - Missense	Liver
COSM138434	c.1714C>T	p.P572S	Substitution - Missense	Skin
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Liver
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM5018175	c.2278_2280delCAG	p.Q760delQ	Deletion - In frame	Bone
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM387435	c.2355T>A	p.F785L	Substitution - Missense	Lung
COSM5975173	c.2081C>T	p.T694I	Substitution - Missense	Upper_aerodigestive_tract
COSM5681321	c.796A>T	p.M266L	Substitution - Missense	Soft_tissue
COSM260147	c.662C>A	p.S221Y	Substitution - Missense	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM1201427	c.1438T>G	p.F480V	Substitution - Missense	Large_intestine
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Ovary
COSM1248469	c.1329G>A	p.T443T	Substitution - coding silent	Oesophagus
COSM1671034	c.1662A>T	p.Q554H	Substitution - Missense	Large_intestine
COSM2151519	c.416C>A	p.T139N	Substitution - Missense	Central_nervous_system
COSM1157924	c.763G>A	p.V255I	Substitution - Missense	Pancreas
COSM1056171	c.718A>G	p.T240A	Substitution - Missense	Endometrium
COSM4125218	c.53A>C	p.D18A	Substitution - Missense	Stomach
COSM1056175	c.55A>G	p.S19G	Substitution - Missense	Endometrium
COSM1056176	c.35C>T	p.S12L	Substitution - Missense	Endometrium
COSM734125	c.1895C>T	p.S632L	Substitution - Missense	Lung
COSM4403971	c.475C>T	p.P159S	Substitution - Missense	Skin
COSM4125213	c.1588T>G	p.L530V	Substitution - Missense	Stomach
COSM5466177	c.811G>T	p.E271*	Substitution - Nonsense	Large_intestine
COSM3946446	c.1540-3C>A	p.?	Unknown	Lung
COSM1248470	c.526G>C	p.E176Q	Substitution - Missense	Oesophagus
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM274574	c.618G>A	p.E206E	Substitution - coding silent	Large_intestine
COSM1633724	c.1833G>A	p.M611I	Substitution - Missense	Liver
COSM4585109	c.2157T>C	p.A719A	Substitution - coding silent	Bone
COSM3974948	c.2475A>G	p.Q825Q	Substitution - coding silent	Central_nervous_system
COSM140483	c.2342C>A	p.P781Q	Substitution - Missense	Skin
COSM343670	c.82G>A	p.E28K	Substitution - Missense	Lung
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM343669	c.94G>C	p.D32H	Substitution - Missense	Lung
COSM3993723	c.2375T>C	p.L792P	Substitution - Missense	Kidney
COSM4125216	c.438+2T>C	p.?	Unknown	Stomach
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM3301685	c.1304G>A	p.R435Q	Substitution - Missense	Oesophagus
COSM122202	c.1923T>G	p.S641R	Substitution - Missense	Upper_aerodigestive_tract
COSM3301682	c.1456A>C	p.N486H	Substitution - Missense	Soft_tissue
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Breast
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM5401337	c.220C>T	p.L74L	Substitution - coding silent	Skin
COSM1056172	c.514A>G	p.T172A	Substitution - Missense	Endometrium
COSM243736	c.890T>C	p.I297T	Substitution - Missense	Prostate
COSM5060396	c.1391G>A	p.R464K	Substitution - Missense	Stomach
COSM1056167	c.2017G>A	p.G673R	Substitution - Missense	Endometrium
COSM3604590	c.616G>A	p.E206K	Substitution - Missense	Skin
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM734126	c.1954C>G	p.Q652E	Substitution - Missense	Lung
COSM1730599	c.1234A>G	p.I412V	Substitution - Missense	Liver
COSM1430229	c.368_369insT	p.L123fs*14	Insertion - Frameshift	Large_intestine
COSM4125217	c.188G>A	p.G63D	Substitution - Missense	Stomach
COSM1736638	c.1007C>T	p.S336L	Substitution - Missense	Central_nervous_system
COSM5446285	c.2262_2264delGCA	p.Q760delQ	Deletion - In frame	Thyroid
COSM5749361	c.1868T>C	p.I623T	Substitution - Missense	Genital_tract
COSM42902	c.716G>A	p.R239H	Substitution - Missense	Large_intestine
COSM1056167	c.2017G>A	p.G673R	Substitution - Missense	Large_intestine
COSM4460889	c.1183C>T	p.L395F	Substitution - Missense	Skin
COSM481352	c.1267A>G	p.R423G	Substitution - Missense	Kidney
COSM1131106	c.1764T>C	p.N588N	Substitution - coding silent	Prostate
COSM5418634	c.290G>A	p.R97Q	Substitution - Missense	Haematopoietic_and_lymphoid_tissue
COSM5912055	c.1366C>T	p.P456S	Substitution - Missense	Skin
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Stomach
COSM310145	c.1371G>A	p.T457T	Substitution - coding silent	Lung
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM3380951	c.136C>T	p.R46C	Substitution - Missense	Pancreas
COSM4135815	c.1283C>G	p.P428R	Substitution - Missense	Ovary
COSM3825996	c.49G>T	p.D17Y	Substitution - Missense	Breast
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Large_intestine
COSM3714929	c.1408C>T	p.H470Y	Substitution - Missense	Upper_aerodigestive_tract
COSM160044	c.1945C>T	p.L649L	Substitution - coding silent	Breast
COSM4672878	c.2430G>C	p.Q810H	Substitution - Missense	Large_intestine
COSM4125214	c.1024C>T	p.L342L	Substitution - coding silent	Stomach
COSM3604593	c.346G>T	p.E116*	Substitution - Nonsense	Skin
COSM1618924	c.1397A>T	p.H466L	Substitution - Missense	Liver
COSM4672879	c.1975G>A	p.A659T	Substitution - Missense	Large_intestine
COSM1056170	c.859C>A	p.L287M	Substitution - Missense	Endometrium
COSM481349	c.1539+2T>C	p.?	Unknown	Kidney
COSM3825995	c.359G>T	p.G120V	Substitution - Missense	Breast
COSM734128	c.2482C>A	p.Q828K	Substitution - Missense	Lung
COSM5692896	c.570G>C	p.Q190H	Substitution - Missense	Soft_tissue
COSM481351	c.1539+1G>T	p.?	Unknown	Kidney
COSM1056174	c.66T>C	p.F22F	Substitution - coding silent	Endometrium
COSM5784091	c.102G>A	p.A34A	Substitution - coding silent	Breast
COSM1056173	c.312C>G	p.F104L	Substitution - Missense	Endometrium
COSM298619	c.1460C>T	p.S487F	Substitution - Missense	Large_intestine
COSM1430229	c.368_369insT	p.L123fs*14	Insertion - Frameshift	Large_intestine
COSM3702609	c.2211A>G	p.A737A	Substitution - coding silent	Liver
COSM252979	c.368delT	p.L123fs*1	Deletion - Frameshift	Lung
COSM3301698	c.474C>T	p.I158I	Substitution - coding silent	Large_intestine

> Text Mining based Variations

[ TOP ]

PMID	Variation	Cancer	Evidence
20551151	Mutation	Colorectal Carcinoma	CLOCK mutations occurred in 53% of MSI CRCs.

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Post-translational modification (PTM)

> Post-translational modification (PTM)

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Filter By:

Uniprot ID	Position	Amino Acid	Description	Upstream Enzyme	Affected By Mutation	Amino Acid Sequence Variant
O15516	42	S	Phosphoserine	-	No	None detected
O15516	408	S	Phosphoserine	-	No	None detected
O15516	427	S	Phosphoserine	GSK3-beta	No	None detected
O15516	431	S	Phosphoserine	-	Yes	p.S431A (cancer: LUSC)
O15516	451	T	Phosphothreonine	CDK5	No	None detected
O15516	461	T	Phosphothreonine	CDK5	No	None detected

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Expression analysis in primary tumor tissue from TCGA > Expression level in cancer cell line from CCLE > Expression level in human normal tissue from HPA > Text mining based expression change

> The Cancer Genome Atlas (TCGA)

[ TOP ]

Differential expression analysis for cancers with more than 10 normal samples

Cancer	Full Name	# N	# T	Median (N)	Median (T)	LogFC	Adj. P	Status
BLCA	Bladder urothelial carcinoma	19	408	3.983	3.116	-0.511	0.0627	NS
BRCA	Breast invasive carcinoma	112	1100	4.623	4.407	-0.168	0.153	NS
CESC	Cervical and endocervical cancers	3	306	2.57	3.42	NA	NA	NA
COAD	Colon adenocarcinoma	41	459	3.571	3.665	0.095	0.408	NS
ESCA	Esophageal carcinoma	11	185	5.572	4.997	-0.7	0.0056	Under
GBM	Glioblastoma multiforme	5	166	4.746	3.087	NA	NA	NA
HNSC	Head and Neck squamous cell carcinoma	44	522	4.779	3.934	-0.734	8.33e-06	Under
KIRC	Kidney renal clear cell carcinoma	72	534	4.743	4.05	-0.772	1.42e-09	Under
KIRP	Kidney renal papillary cell carcinoma	32	291	4.16	2.982	-1.14	2.68e-05	Under
LAML	Acute Myeloid Leukemia	0	173	NA	4.862	NA	NA	NA
LGG	Brain Lower Grade Glioma	0	530	NA	3.635	NA	NA	NA
LIHC	Liver hepatocellular carcinoma	50	373	2.113	1.675	-0.51	0.0158	NS
LUAD	Lung adenocarcinoma	59	517	3.82	3.956	0.165	0.132	NS
LUSC	Lung squamous cell carcinoma	51	501	3.834	3.796	0.002	0.99	NS
OV	Ovarian serous cystadenocarcinoma	0	307	NA	4.091	NA	NA	NA
PAAD	Pancreatic adenocarcinoma	4	179	3.174	3.675	NA	NA	NA
PCPG	Pheochromocytoma and Paraganglioma	3	184	3.429	3.285	NA	NA	NA
PRAD	Prostate adenocarcinoma	52	498	4.224	3.627	-0.615	0.000747	Under
READ	Rectum adenocarcinoma	10	167	3.971	3.66	-0.314	0.244	NS
SARC	Sarcoma	2	263	1.599	3.273	NA	NA	NA
SKCM	Skin Cutaneous Melanoma	1	472	2.635	3.595	NA	NA	NA
STAD	Stomach adenocarcinoma	35	415	4.824	4.992	-0.106	0.45	NS
TGCT	Testicular Germ Cell Tumors	0	156	NA	3.324	NA	NA	NA
THCA	Thyroid carcinoma	59	509	4.118	3.527	-0.553	0.00152	NS
THYM	Thymoma	2	120	2.21	1.062	NA	NA	NA
UCEC	Uterine Corpus Endometrial Carcinoma	35	546	3.097	3.241	0.013	0.942	NS

> Cancer Cell Line Encyclopedia (CCLE)

[ TOP ]

Tissue	Cell Line	Expression Level (Microarray)
Autonomic ganglia	CHP126	9
Autonomic ganglia	CHP212	7.9
Autonomic ganglia	IMR32	8.6
Autonomic ganglia	KELLY	7.7
Autonomic ganglia	KPNRTBM1	8.8
Autonomic ganglia	KPNSI9S	8
Autonomic ganglia	KPNYN	8.9
Autonomic ganglia	MHHNB11	8.8
Autonomic ganglia	NB1	9.4
Autonomic ganglia	NH6	8.8
Autonomic ganglia	SHSY5Y	8.7
Autonomic ganglia	SIMA	8.4
Autonomic ganglia	SKNAS	8.9
Autonomic ganglia	SKNBE2	8.5
Autonomic ganglia	SKNDZ	7.9
Autonomic ganglia	SKNFI	8.6
Autonomic ganglia	SKNSH	8.5
Biliary tract	HUCCT1	8.9
Biliary tract	HUH28	8.6
Biliary tract	SNU1079	8.3
Biliary tract	SNU1196	9.9
Biliary tract	SNU245	9.8
Biliary tract	SNU308	9
Biliary tract	SNU478	8.5
Bone	143B	8.7
Bone	A673	7.6
Bone	CADOES1	8.7
Bone	CAL78	10.7
Bone	G292CLONEA141B1	8.4
Bone	HOS	8.4
Bone	HS706T	9.6
Bone	HS737T	9.1
Bone	HS819T	8.8
Bone	HS821T	9.4
Bone	HS822T	9
Bone	HS863T	9.7
Bone	HS870T	9.3
Bone	HS888T	9.4
Bone	MG63	8.3
Bone	MHHES1	8.7
Bone	OUMS27	8
Bone	RDES	8.4
Bone	SJSA1	9.2
Bone	SKES1	8.4
Bone	SKNMC	8.7
Bone	SW1353	9.5
Bone	T173	9.4
Bone	TC71	8.5
Bone	U2OS	9.7
Breast	AU565	9
Breast	BT20	8.7
Breast	BT474	8.9
Breast	BT483	9.8
Breast	BT549	8.7
Breast	CAL120	9
Breast	CAL148	9.4
Breast	CAL51	8.9
Breast	CAL851	8.5
Breast	CAMA1	8.9
Breast	DU4475	8.6
Breast	EFM192A	10.1
Breast	EFM19	9.3
Breast	EVSAT	8.5
Breast	HCC1143	9.9
Breast	HCC1187	8.5
Breast	HCC1395	8.4
Breast	HCC1419	10
Breast	HCC1428	8.1
Breast	HCC1500	10.4
Breast	HCC1569	9
Breast	HCC1599	9.9
Breast	HCC1806	8.6
Breast	HCC1937	8.4
Breast	HCC1954	9.1
Breast	HCC202	9.2
Breast	HCC2157	9.1
Breast	HCC2218	8.7
Breast	HCC38	8.9
Breast	HCC70	8.5
Breast	HDQP1	8.4
Breast	HMC18	7.9
Breast	HS274T	9.6
Breast	HS281T	10
Breast	HS343T	9.9
Breast	HS578T	9
Breast	HS606T	8.7
Breast	HS739T	9.1
Breast	HS742T	9.4
Breast	JIMT1	8.9
Breast	KPL1	8.8
Breast	MCF7	9.1
Breast	MDAMB134VI	10.9
Breast	MDAMB157	9.3
Breast	MDAMB175VII	9
Breast	MDAMB231	9.1
Breast	MDAMB361	9.3
Breast	MDAMB415	8.9
Breast	MDAMB436	10
Breast	MDAMB453	9
Breast	MDAMB468	8.7
Breast	SKBR3	9.5
Breast	T47D	8.2
Breast	UACC812	9.6
Breast	UACC893	9.7
Breast	YMB1	9.6
Breast	ZR751	9.4
Breast	ZR7530	9.7
Central nervous system	1321N1	8.3
Central nervous system	42MGBA	8.9
Central nervous system	8MGBA	8.1
Central nervous system	A172	8.4
Central nervous system	AM38	8.2
Central nervous system	BECKER	9.1
Central nervous system	CAS1	8.7
Central nervous system	CCFSTTG1	9.3
Central nervous system	D283MED	8.2
Central nervous system	D341MED	8.3
Central nervous system	DAOY	7.6
Central nervous system	DBTRG05MG	8.7
Central nervous system	DKMG	9.4
Central nervous system	GAMG	8.6
Central nervous system	GB1	9.3
Central nervous system	GI1	8.1
Central nervous system	GMS10	8.7
Central nervous system	GOS3	8.9
Central nervous system	H4	9.1
Central nervous system	HS683	9.4
Central nervous system	KALS1	8.7
Central nervous system	KG1C	8.5
Central nervous system	KNS42	8.2
Central nervous system	KNS60	8.4
Central nervous system	KNS81	8.9
Central nervous system	KS1	8.8
Central nervous system	LN18	9.1
Central nervous system	LN229	9
Central nervous system	M059K	8.6
Central nervous system	MOGGCCM	8.6
Central nervous system	MOGGUVW	8.6
Central nervous system	NMCG1	9
Central nervous system	ONS76	8.2
Central nervous system	SF126	9.1
Central nervous system	SF295	9.2
Central nervous system	SNB19	10.3
Central nervous system	SNU1105	9.5
Central nervous system	SNU201	9.4
Central nervous system	SNU466	8.7
Central nervous system	SNU489	9.2
Central nervous system	SNU626	9
Central nervous system	SNU738	7.9
Central nervous system	SW1088	9.3
Central nervous system	SW1783	12.4
Central nervous system	T98G	8.4
Central nervous system	TM31	9.4
Central nervous system	U118MG	9.3
Central nervous system	U138MG	9.8
Central nervous system	U251MG	11
Central nervous system	U87MG	9.2
Central nervous system	YH13	8.6
Central nervous system	YKG1	8.6
Endometrium	AN3CA	8.2
Endometrium	COLO684	9.2
Endometrium	EFE184	8.7
Endometrium	EN	8.4
Endometrium	ESS1	8.5
Endometrium	HEC108	6.1
Endometrium	HEC151	8.1
Endometrium	HEC1A	8.4
Endometrium	HEC1B	8.4
Endometrium	HEC251	8.7
Endometrium	HEC265	8.5
Endometrium	HEC50B	8.3
Endometrium	HEC59	7.4
Endometrium	HEC6	8
Endometrium	ISHIKAWAHERAKLIO02ER	8.5
Endometrium	JHUEM1	9.2
Endometrium	JHUEM2	8.3
Endometrium	JHUEM3	9.5
Endometrium	KLE	8.6
Endometrium	MFE280	9.1
Endometrium	MFE296	8.8
Endometrium	MFE319	8.7
Endometrium	RL952	7.9
Endometrium	SNGM	8.2
Endometrium	SNU1077	8.3
Endometrium	SNU685	8.4
Endometrium	TEN	8.7
Haematopoietic and lymphoid	697	8.1
Haematopoietic and lymphoid	A3KAW	8.7
Haematopoietic and lymphoid	A4FUK	7.9
Haematopoietic and lymphoid	ALLSIL	8
Haematopoietic and lymphoid	AML193	7.9
Haematopoietic and lymphoid	AMO1	8
Haematopoietic and lymphoid	BCP1	7.9
Haematopoietic and lymphoid	BDCM	7.4
Haematopoietic and lymphoid	BL41	6.5
Haematopoietic and lymphoid	BL70	6.8
Haematopoietic and lymphoid	BV173	8.6
Haematopoietic and lymphoid	CA46	7.4
Haematopoietic and lymphoid	CI1	8.3
Haematopoietic and lymphoid	CMK115	7.6
Haematopoietic and lymphoid	CMK86	8.5
Haematopoietic and lymphoid	CMK	8.1
Haematopoietic and lymphoid	CMLT1	8.4
Haematopoietic and lymphoid	COLO775	8.1
Haematopoietic and lymphoid	DAUDI	7.5
Haematopoietic and lymphoid	DB	6.3
Haematopoietic and lymphoid	DEL	8.3
Haematopoietic and lymphoid	DND41	7.5
Haematopoietic and lymphoid	DOHH2	7.4
Haematopoietic and lymphoid	EB1	7.6
Haematopoietic and lymphoid	EB2	7.3
Haematopoietic and lymphoid	EHEB	8.7
Haematopoietic and lymphoid	EJM	9.1
Haematopoietic and lymphoid	EM2	8.5
Haematopoietic and lymphoid	EOL1	8.9
Haematopoietic and lymphoid	F36P	7.9
Haematopoietic and lymphoid	GA10	7.1
Haematopoietic and lymphoid	GDM1	7.6
Haematopoietic and lymphoid	GRANTA519	8.6
Haematopoietic and lymphoid	HDLM2	8.5
Haematopoietic and lymphoid	HDMYZ	8.4
Haematopoietic and lymphoid	HEL9217	6.8
Haematopoietic and lymphoid	HEL	7.2
Haematopoietic and lymphoid	HH	8.7
Haematopoietic and lymphoid	HL60	8.4
Haematopoietic and lymphoid	HPBALL	8.1
Haematopoietic and lymphoid	HS604T	9.1
Haematopoietic and lymphoid	HS611T	7.7
Haematopoietic and lymphoid	HS616T	9.1
Haematopoietic and lymphoid	HS751T	9.4
Haematopoietic and lymphoid	HT	6.2
Haematopoietic and lymphoid	HTK	8.8
Haematopoietic and lymphoid	HUNS1	8
Haematopoietic and lymphoid	HUT102	7
Haematopoietic and lymphoid	HUT78	6.7
Haematopoietic and lymphoid	JEKO1	8.1
Haematopoietic and lymphoid	JK1	7.9
Haematopoietic and lymphoid	JM1	8.1
Haematopoietic and lymphoid	JURKAT	7.9
Haematopoietic and lymphoid	JURLMK1	8.3
Haematopoietic and lymphoid	JVM2	8.1
Haematopoietic and lymphoid	JVM3	8.4
Haematopoietic and lymphoid	K562	8
Haematopoietic and lymphoid	KARPAS299	8.6
Haematopoietic and lymphoid	KARPAS422	6.9
Haematopoietic and lymphoid	KARPAS620	7.5
Haematopoietic and lymphoid	KASUMI1	8.6
Haematopoietic and lymphoid	KASUMI2	8.7
Haematopoietic and lymphoid	KASUMI6	8
Haematopoietic and lymphoid	KCL22	7.7
Haematopoietic and lymphoid	KE37	8.6
Haematopoietic and lymphoid	KE97	8.1
Haematopoietic and lymphoid	KG1	7.7
Haematopoietic and lymphoid	KHM1B	8.3
Haematopoietic and lymphoid	KIJK	7.5
Haematopoietic and lymphoid	KMH2	8.5
Haematopoietic and lymphoid	KMM1	8.2
Haematopoietic and lymphoid	KMS11	8.6
Haematopoietic and lymphoid	KMS12BM	7.3
Haematopoietic and lymphoid	KMS18	8.5
Haematopoietic and lymphoid	KMS20	8.9
Haematopoietic and lymphoid	KMS21BM	8.5
Haematopoietic and lymphoid	KMS26	7.2
Haematopoietic and lymphoid	KMS27	7.9
Haematopoietic and lymphoid	KMS28BM	8.2
Haematopoietic and lymphoid	KMS34	7.3
Haematopoietic and lymphoid	KO52	7.2
Haematopoietic and lymphoid	KOPN8	7.1
Haematopoietic and lymphoid	KU812	8.5
Haematopoietic and lymphoid	KYO1	7.5
Haematopoietic and lymphoid	L1236	7.4
Haematopoietic and lymphoid	L363	9
Haematopoietic and lymphoid	L428	8.4
Haematopoietic and lymphoid	L540	8.7
Haematopoietic and lymphoid	LAMA84	8.7
Haematopoietic and lymphoid	LOUCY	7
Haematopoietic and lymphoid	LP1	8.9
Haematopoietic and lymphoid	M07E	8.4
Haematopoietic and lymphoid	MC116	6.9
Haematopoietic and lymphoid	ME1	7
Haematopoietic and lymphoid	MEC1	8
Haematopoietic and lymphoid	MEC2	8.2
Haematopoietic and lymphoid	MEG01	7.8
Haematopoietic and lymphoid	MHHCALL2	8.4
Haematopoietic and lymphoid	MHHCALL3	8.8
Haematopoietic and lymphoid	MHHCALL4	8.4
Haematopoietic and lymphoid	MINO	8.2
Haematopoietic and lymphoid	MJ	6.4
Haematopoietic and lymphoid	MM1S	8.3
Haematopoietic and lymphoid	MOLM13	7.6
Haematopoietic and lymphoid	MOLM16	7.6
Haematopoietic and lymphoid	MOLM6	7.7
Haematopoietic and lymphoid	MOLP2	8.3
Haematopoietic and lymphoid	MOLP8	8
Haematopoietic and lymphoid	MOLT13	8.2
Haematopoietic and lymphoid	MOLT16	8.1
Haematopoietic and lymphoid	MOLT4	7.4
Haematopoietic and lymphoid	MONOMAC1	7.5
Haematopoietic and lymphoid	MONOMAC6	8.2
Haematopoietic and lymphoid	MOTN1	8.6
Haematopoietic and lymphoid	MUTZ5	7.8
Haematopoietic and lymphoid	MV411	8.2
Haematopoietic and lymphoid	NALM19	7.6
Haematopoietic and lymphoid	NALM1	8.7
Haematopoietic and lymphoid	NALM6	8.7
Haematopoietic and lymphoid	NAMALWA	8.2
Haematopoietic and lymphoid	NB4	8.2
Haematopoietic and lymphoid	NCIH929	8.7
Haematopoietic and lymphoid	NCO2	7.8
Haematopoietic and lymphoid	NOMO1	7.9
Haematopoietic and lymphoid	NUDHL1	8.1
Haematopoietic and lymphoid	NUDUL1	8.4
Haematopoietic and lymphoid	OCIAML2	7.8
Haematopoietic and lymphoid	OCIAML3	7.9
Haematopoietic and lymphoid	OCIAML5	8
Haematopoietic and lymphoid	OCILY10	6.5
Haematopoietic and lymphoid	OCILY19	8.2
Haematopoietic and lymphoid	OCILY3	8.2
Haematopoietic and lymphoid	OCIM1	8.3
Haematopoietic and lymphoid	OPM2	9.1
Haematopoietic and lymphoid	P12ICHIKAWA	7.8
Haematopoietic and lymphoid	P31FUJ	7.2
Haematopoietic and lymphoid	P3HR1	6.4
Haematopoietic and lymphoid	PCM6	8.7
Haematopoietic and lymphoid	PEER	6.7
Haematopoietic and lymphoid	PF382	8.4
Haematopoietic and lymphoid	PFEIFFER	7.2
Haematopoietic and lymphoid	PL21	8.4
Haematopoietic and lymphoid	RAJI	7.5
Haematopoietic and lymphoid	RCHACV	7.3
Haematopoietic and lymphoid	REC1	7.7
Haematopoietic and lymphoid	REH	7.7
Haematopoietic and lymphoid	RI1	7.4
Haematopoietic and lymphoid	RL	6.6
Haematopoietic and lymphoid	RPMI8226	7.6
Haematopoietic and lymphoid	RPMI8402	8
Haematopoietic and lymphoid	RS411	7.7
Haematopoietic and lymphoid	SEM	7.7
Haematopoietic and lymphoid	SET2	8.4
Haematopoietic and lymphoid	SIGM5	7.3
Haematopoietic and lymphoid	SKM1	7.6
Haematopoietic and lymphoid	SKMM2	9.2
Haematopoietic and lymphoid	SR786	8.7
Haematopoietic and lymphoid	ST486	8.3
Haematopoietic and lymphoid	SUDHL10	7.2
Haematopoietic and lymphoid	SUDHL1	8.2
Haematopoietic and lymphoid	SUDHL4	6.7
Haematopoietic and lymphoid	SUDHL5	7.4
Haematopoietic and lymphoid	SUDHL6	6.7
Haematopoietic and lymphoid	SUDHL8	7.4
Haematopoietic and lymphoid	SUPB15	8.4
Haematopoietic and lymphoid	SUPHD1	8.4
Haematopoietic and lymphoid	SUPM2	8.6
Haematopoietic and lymphoid	SUPT11	8.8
Haematopoietic and lymphoid	SUPT1	6.8
Haematopoietic and lymphoid	TALL1	7.7
Haematopoietic and lymphoid	TF1	8.1
Haematopoietic and lymphoid	THP1	7.8
Haematopoietic and lymphoid	TO175T	9.9
Haematopoietic and lymphoid	TOLEDO	8
Haematopoietic and lymphoid	U266B1	7.8
Haematopoietic and lymphoid	U937	7.3
Haematopoietic and lymphoid	UT7	8.8
Haematopoietic and lymphoid	WSUDLCL2	6.5
Kidney	769P	8.7
Kidney	786O	9.3
Kidney	A498	8.7
Kidney	A704	9.4
Kidney	ACHN	9.3
Kidney	BFTC909	8.7
Kidney	CAKI1	8.8
Kidney	CAKI2	9.3
Kidney	CAL54	8.7
Kidney	KMRC1	9.1
Kidney	KMRC20	8.8
Kidney	KMRC2	8.9
Kidney	KMRC3	8.6
Kidney	OSRC2	9
Kidney	RCC10RGB	8.8
Kidney	SNU1272	9
Kidney	SNU349	9.2
Kidney	TUHR10TKB	9.2
Kidney	TUHR14TKB	10.2
Kidney	TUHR4TKB	8.8
Kidney	VMRCRCW	8.4
Kidney	VMRCRCZ	8.5
Large intestine	C2BBE1	7.8
Large intestine	CCK81	8.3
Large intestine	CL11	10.9
Large intestine	CL14	8.5
Large intestine	CL34	9.9
Large intestine	CL40	11.4
Large intestine	COLO205	8.6
Large intestine	COLO320	8.9
Large intestine	COLO678	9.6
Large intestine	CW2	9.5
Large intestine	DLD1	8.9
Large intestine	GP2D	7.8
Large intestine	HCC56	9.1
Large intestine	HCT116	8.4
Large intestine	HCT15	9.4
Large intestine	HS675T	8.9
Large intestine	HS698T	10
Large intestine	HT115	9.8
Large intestine	HT29	8
Large intestine	HT55	9.5
Large intestine	KM12	8.7
Large intestine	LOVO	8.4
Large intestine	LS1034	10
Large intestine	LS123	9.7
Large intestine	LS180	8.4
Large intestine	LS411N	8.5
Large intestine	LS513	10.3
Large intestine	MDST8	8.3
Large intestine	NCIH508	8.1
Large intestine	NCIH716	8.8
Large intestine	NCIH747	9.3
Large intestine	OUMS23	7.7
Large intestine	RCM1	9.6
Large intestine	RKO	8.2
Large intestine	SKCO1	11.1
Large intestine	SNU1040	9.2
Large intestine	SNU1197	10.4
Large intestine	SNU175	9.6
Large intestine	SNU283	8.9
Large intestine	SNU407	9
Large intestine	SNU503	7.7
Large intestine	SNU61	9.2
Large intestine	SNU81	9.5
Large intestine	SNUC1	8.9
Large intestine	SNUC2A	7.4
Large intestine	SNUC4	8.9
Large intestine	SNUC5	9.1
Large intestine	SW1116	9.9
Large intestine	SW1417	8.8
Large intestine	SW1463	8.2
Large intestine	SW403	8.3
Large intestine	SW480	9.1
Large intestine	SW48	8.6
Large intestine	SW620	7.9
Large intestine	SW837	10
Large intestine	SW948	8.1
Large intestine	T84	9.3
Liver	ALEXANDERCELLS	8.7
Liver	C3A	8.2
Liver	HEP3B217	8.4
Liver	HEPG2	8
Liver	HLE	9.1
Liver	HLF	8.6
Liver	HUH1	7.9
Liver	HUH6	7.6
Liver	HUH7	7.6
Liver	JHH1	8.4
Liver	JHH2	8.4
Liver	JHH4	8.3
Liver	JHH5	7.6
Liver	JHH6	8.6
Liver	JHH7	7.7
Liver	LI7	8.9
Liver	PLCPRF5	8.5
Liver	SKHEP1	7.8
Liver	SNU182	8.3
Liver	SNU387	8.5
Liver	SNU398	7.8
Liver	SNU423	8.9
Liver	SNU449	8.2
Liver	SNU475	8.6
Liver	SNU761	8.8
Liver	SNU878	8.3
Liver	SNU886	7.9
Lung	A549	7.8
Lung	ABC1	8.3
Lung	BEN	8.7
Lung	CAL12T	8.1
Lung	CALU1	8.5
Lung	CALU3	8.5
Lung	CALU6	7.2
Lung	CHAGOK1	9.3
Lung	COLO668	8.4
Lung	COLO699	8.4
Lung	CORL105	8.1
Lung	CORL23	7.6
Lung	CORL24	8.8
Lung	CORL279	7.9
Lung	CORL311	8.8
Lung	CORL47	8.1
Lung	CORL51	9.4
Lung	CORL88	9.3
Lung	CORL95	9.1
Lung	CPCN	9.1
Lung	DMS114	8.3
Lung	DMS153	9.4
Lung	DMS273	8.9
Lung	DMS454	7.6
Lung	DMS53	8.2
Lung	DMS79	8.3
Lung	DV90	7.8
Lung	EBC1	10
Lung	EPLC272H	8.2
Lung	HARA	8.4
Lung	HCC1171	9.9
Lung	HCC1195	8
Lung	HCC15	8.1
Lung	HCC2279	8.5
Lung	HCC2935	8.9
Lung	HCC33	8
Lung	HCC366	9.5
Lung	HCC4006	9
Lung	HCC44	8.8
Lung	HCC78	9.3
Lung	HCC827	9.4
Lung	HCC95	7.6
Lung	HLC1	9.2
Lung	HLFA	8.7
Lung	HS229T	9.3
Lung	HS618T	8.9
Lung	IALM	8.7
Lung	KNS62	8.4
Lung	LC1F	8.9
Lung	LC1SQSF	8.7
Lung	LCLC103H	8.9
Lung	LCLC97TM1	9.3
Lung	LK2	8.7
Lung	LOUNH91	8.8
Lung	LU65	8.8
Lung	LU99	8.7
Lung	LUDLU1	7.7
Lung	LXF289	10.5
Lung	MORCPR	9.4
Lung	NCIH1048	8.4
Lung	NCIH1092	9.3
Lung	NCIH1105	8.6
Lung	NCIH1155	8.6
Lung	NCIH1184	8.4
Lung	NCIH1299	8.4
Lung	NCIH1339	9.6
Lung	NCIH1341	8.5
Lung	NCIH1355	9.3
Lung	NCIH1373	9
Lung	NCIH1385	9.8
Lung	NCIH1395	8.9
Lung	NCIH1435	9.9
Lung	NCIH1436	9.1
Lung	NCIH1437	9.2
Lung	NCIH146	8.3
Lung	NCIH1563	8.6
Lung	NCIH1568	8
Lung	NCIH1573	9
Lung	NCIH1581	8.4
Lung	NCIH1618	9.1
Lung	NCIH1623	9
Lung	NCIH1648	8.7
Lung	NCIH1650	8.9
Lung	NCIH1651	8
Lung	NCIH1666	9.1
Lung	NCIH1693	10.5
Lung	NCIH1694	9.1
Lung	NCIH1703	9
Lung	NCIH1734	8
Lung	NCIH1755	9
Lung	NCIH1781	8.4
Lung	NCIH1792	8.3
Lung	NCIH1793	8.7
Lung	NCIH1836	9.4
Lung	NCIH1838	10
Lung	NCIH1869	8.4
Lung	NCIH1876	9.2
Lung	NCIH1915	8.4
Lung	NCIH1930	9.1
Lung	NCIH1944	9.3
Lung	NCIH1963	8.9
Lung	NCIH196	8.8
Lung	NCIH1975	8.3
Lung	NCIH2009	9.7
Lung	NCIH2023	8.7
Lung	NCIH2029	9.6
Lung	NCIH2030	8
Lung	NCIH2066	8.5
Lung	NCIH2081	9.3
Lung	NCIH2085	9.6
Lung	NCIH2087	8.9
Lung	NCIH209	8.2
Lung	NCIH2106	7.4
Lung	NCIH2110	8.8
Lung	NCIH211	8.8
Lung	NCIH2122	8.8
Lung	NCIH2126	9.3
Lung	NCIH2141	8.7
Lung	NCIH2170	8.8
Lung	NCIH2171	7.5
Lung	NCIH2172	8.8
Lung	NCIH2196	8.2
Lung	NCIH2227	9.1
Lung	NCIH2228	8.5
Lung	NCIH226	8.9
Lung	NCIH2286	9.8
Lung	NCIH2291	9.3
Lung	NCIH2342	8.9
Lung	NCIH2347	9.3
Lung	NCIH23	10
Lung	NCIH2405	8.3
Lung	NCIH2444	8.7
Lung	NCIH292	9.7
Lung	NCIH322	9
Lung	NCIH3255	9.5
Lung	NCIH358	9.5
Lung	NCIH441	9.3
Lung	NCIH446	8.8
Lung	NCIH460	8.6
Lung	NCIH510	8.7
Lung	NCIH520	8.7
Lung	NCIH522	8.8
Lung	NCIH524	7.8
Lung	NCIH526	8.8
Lung	NCIH596	9.5
Lung	NCIH647	8.3
Lung	NCIH650	8.5
Lung	NCIH661	9.2
Lung	NCIH69	7.7
Lung	NCIH727	8.5
Lung	NCIH810	8.1
Lung	NCIH82	7.5
Lung	NCIH838	9
Lung	NCIH841	8.8
Lung	NCIH854	8.3
Lung	NCIH889	9.9
Lung	PC14	8.5
Lung	RERFLCAD1	9
Lung	RERFLCAD2	9
Lung	RERFLCAI	7.4
Lung	RERFLCKJ	8.9
Lung	RERFLCMS	8.4
Lung	RERFLCSQ1	8.2
Lung	SBC5	9.7
Lung	SCLC21H	8.9
Lung	SHP77	8.7
Lung	SKLU1	9.7
Lung	SKMES1	8.8
Lung	SQ1	9.1
Lung	SW1271	8.2
Lung	SW1573	9.1
Lung	SW900	9.5
Lung	VMRCLCD	8.7
Lung	VMRCLCP	9.6
Oesophagus	COLO680N	8.7
Oesophagus	ECGI10	8.8
Oesophagus	KYSE140	8.5
Oesophagus	KYSE150	8.5
Oesophagus	KYSE180	8.4
Oesophagus	KYSE270	7.5
Oesophagus	KYSE30	8.5
Oesophagus	KYSE410	8.8
Oesophagus	KYSE450	8.4
Oesophagus	KYSE510	8.4
Oesophagus	KYSE520	8.8
Oesophagus	KYSE70	9.3
Oesophagus	OE19	9.5
Oesophagus	OE33	9.8
Oesophagus	TE10	9.6
Oesophagus	TE11	8.9
Oesophagus	TE14	9.7
Oesophagus	TE15	8.9
Oesophagus	TE1	8.4
Oesophagus	TE4	8.4
Oesophagus	TE5	8.6
Oesophagus	TE6	8.9
Oesophagus	TE8	8.1
Oesophagus	TE9	8.7
Oesophagus	TT	9.3
Ovary	59M	8.1
Ovary	A2780	8.4
Ovary	CAOV3	9.7
Ovary	CAOV4	8.7
Ovary	COLO704	8.3
Ovary	COV318	8.7
Ovary	COV362	8.6
Ovary	COV434	9.2
Ovary	COV504	8.5
Ovary	COV644	9.2
Ovary	EFO21	9
Ovary	EFO27	7.7
Ovary	ES2	7.8
Ovary	FUOV1	7.5
Ovary	HEYA8	8
Ovary	HS571T	9
Ovary	IGROV1	7.8
Ovary	JHOC5	8
Ovary	JHOM1	8.4
Ovary	JHOM2B	10.1
Ovary	JHOS2	9.2
Ovary	JHOS4	8.7
Ovary	KURAMOCHI	8.5
Ovary	MCAS	8.8
Ovary	NIHOVCAR3	9.5
Ovary	OAW28	8.9
Ovary	OAW42	8.7
Ovary	OC314	7.3
Ovary	OC316	7
Ovary	ONCODG1	9.2
Ovary	OV56	8.8
Ovary	OV7	8.1
Ovary	OV90	8.7
Ovary	OVCAR4	8.6
Ovary	OVCAR8	9.6
Ovary	OVISE	8.2
Ovary	OVK18	8.3
Ovary	OVKATE	8.9
Ovary	OVMANA	9.5
Ovary	OVSAHO	8.9
Ovary	OVTOKO	8.1
Ovary	RMGI	8
Ovary	RMUGS	8.2
Ovary	SKOV3	9.4
Ovary	SNU119	8.9
Ovary	SNU840	8.9
Ovary	SNU8	8.8
Ovary	TOV112D	7.9
Ovary	TOV21G	8.1
Ovary	TYKNU	8
Pancreas	ASPC1	9
Pancreas	BXPC3	8.4
Pancreas	CAPAN1	8.8
Pancreas	CAPAN2	9.1
Pancreas	CFPAC1	9.4
Pancreas	DANG	7.6
Pancreas	HPAC	10.2
Pancreas	HPAFII	9.5
Pancreas	HS766T	8.7
Pancreas	HUPT3	9
Pancreas	HUPT4	8.7
Pancreas	KCIMOH1	8.4
Pancreas	KLM1	8.6
Pancreas	KP2	8.9
Pancreas	KP3	8.1
Pancreas	KP4	8.9
Pancreas	L33	8.4
Pancreas	MIAPACA2	9.1
Pancreas	PANC0203	9.1
Pancreas	PANC0213	9.1
Pancreas	PANC0327	9.3
Pancreas	PANC0403	10.7
Pancreas	PANC0504	9.8
Pancreas	PANC0813	9
Pancreas	PANC1005	8.7
Pancreas	PANC1	8.8
Pancreas	PATU8902	8
Pancreas	PATU8988S	8.7
Pancreas	PATU8988T	8.7
Pancreas	PK1	8.2
Pancreas	PK45H	9
Pancreas	PK59	9
Pancreas	PL45	9.1
Pancreas	PSN1	8.3
Pancreas	QGP1	8.6
Pancreas	SNU213	9
Pancreas	SNU324	9.7
Pancreas	SNU410	8.7
Pancreas	SU8686	9.3
Pancreas	SUIT2	9
Pancreas	SW1990	8.8
Pancreas	T3M4	9.5
Pancreas	TCCPAN2	7.6
Pancreas	YAPC	9.3
Pleura	ACCMESO1	8.9
Pleura	DM3	9.4
Pleura	ISTMES1	7.9
Pleura	ISTMES2	9.9
Pleura	JL1	8.8
Pleura	MPP89	9
Pleura	MSTO211H	9.1
Pleura	NCIH2052	8.4
Pleura	NCIH2452	8.7
Pleura	NCIH28	8.6
Prostate	22RV1	8.4
Prostate	DU145	8.6
Prostate	LNCAPCLONEFGC	8.3
Prostate	MDAPCA2B	8.2
Prostate	NCIH660	8.7
Prostate	PC3	9.9
Prostate	VCAP	8.2
Salivary gland	A253	8.2
Salivary gland	YD15	9.2
Skin	A101D	9.1
Skin	A2058	9.3
Skin	A375	8.3
Skin	C32	8.8
Skin	CHL1	7.8
Skin	CJM	9.5
Skin	COLO679	8.4
Skin	COLO741	8.7
Skin	COLO783	9
Skin	COLO792	8.7
Skin	COLO800	9.5
Skin	COLO818	8.9
Skin	COLO829	9.3
Skin	COLO849	8.8
Skin	G361	8.6
Skin	GRM	7.7
Skin	HMCB	8
Skin	HS294T	8.8
Skin	HS600T	9.3
Skin	HS688AT	9.2
Skin	HS695T	8.7
Skin	HS839T	9.4
Skin	HS852T	9.1
Skin	HS895T	9.5
Skin	HS934T	9.8
Skin	HS936T	8.9
Skin	HS939T	9.1
Skin	HS940T	9.5
Skin	HS944T	9.1
Skin	HT144	8.7
Skin	IGR1	9.6
Skin	IGR37	7.9
Skin	IGR39	8.7
Skin	IPC298	8.7
Skin	K029AX	7.8
Skin	LOXIMVI	7.9
Skin	MALME3M	9
Skin	MDAMB435S	8.9
Skin	MELHO	9.2
Skin	MELJUSO	8.6
Skin	MEWO	9.7
Skin	RPMI7951	9.5
Skin	RVH421	9
Skin	SH4	9.1
Skin	SKMEL1	9.2
Skin	SKMEL24	8.4
Skin	SKMEL28	9.1
Skin	SKMEL2	8.9
Skin	SKMEL30	8.6
Skin	SKMEL31	9.6
Skin	SKMEL3	8.2
Skin	SKMEL5	7.9
Skin	UACC257	8
Skin	UACC62	8.6
Skin	WM115	9.1
Skin	WM1799	9.5
Skin	WM2664	8.7
Skin	WM793	9.4
Skin	WM88	9.5
Skin	WM983B	9.1
Small intestine	HUTU80	8.7
Soft tissue	A204	8.9
Soft tissue	G401	8.4
Soft tissue	G402	8.8
Soft tissue	GCT	8.4
Soft tissue	HS729	9.2
Soft tissue	HT1080	8.8
Soft tissue	KYM1	9.5
Soft tissue	MESSA	8.6
Soft tissue	RD	8.3
Soft tissue	RH30	8
Soft tissue	RH41	9.3
Soft tissue	RKN	8.8
Soft tissue	S117	8.5
Soft tissue	SJRH30	9.2
Soft tissue	SKLMS1	9.5
Soft tissue	SKUT1	8.5
Soft tissue	TE125T	10
Soft tissue	TE159T	9.8
Soft tissue	TE441T	8.7
Soft tissue	TE617T	9.2
Stomach	2313287	7.6
Stomach	AGS	9.4
Stomach	AZ521	8.9
Stomach	ECC10	8.9
Stomach	ECC12	8.5
Stomach	FU97	8.4
Stomach	GCIY	8.1
Stomach	GSS	8.2
Stomach	GSU	9.7
Stomach	HGC27	8.3
Stomach	HS746T	8.5
Stomach	HUG1N	9.1
Stomach	IM95	8.4
Stomach	KATOIII	8.4
Stomach	KE39	8.9
Stomach	LMSU	10
Stomach	MKN1	8.2
Stomach	MKN45	7.8
Stomach	MKN74	8.4
Stomach	MKN7	9
Stomach	NCCSTCK140	7.8
Stomach	NCIN87	9.6
Stomach	NUGC2	7.9
Stomach	NUGC3	8.8
Stomach	NUGC4	7.7
Stomach	OCUM1	9
Stomach	RERFGC1B	8.1
Stomach	SH10TC	8.4
Stomach	SNU16	8.8
Stomach	SNU1	8.5
Stomach	SNU216	9
Stomach	SNU520	8.3
Stomach	SNU5	8.1
Stomach	SNU601	10.1
Stomach	SNU620	9.4
Stomach	SNU668	8.9
Stomach	SNU719	8.1
Stomach	TGBC11TKB	10.3
Thyroid	8305C	9
Thyroid	8505C	8.5
Thyroid	BCPAP	8.6
Thyroid	BHT101	9.3
Thyroid	CAL62	9.1
Thyroid	CGTHW1	10.6
Thyroid	FTC133	9.4
Thyroid	FTC238	8.2
Thyroid	ML1	9
Thyroid	SW579	10.2
Thyroid	TT2609C02	8.8
Thyroid	TT	10.3
Upper aerodigestive tract	BHY	8.8
Upper aerodigestive tract	BICR16	8.7
Upper aerodigestive tract	BICR18	8.4
Upper aerodigestive tract	BICR22	9.8
Upper aerodigestive tract	BICR31	8.7
Upper aerodigestive tract	BICR56	9.2
Upper aerodigestive tract	BICR6	8.5
Upper aerodigestive tract	CAL27	7.9
Upper aerodigestive tract	CAL33	9
Upper aerodigestive tract	DETROIT562	9.6
Upper aerodigestive tract	FADU	8.8
Upper aerodigestive tract	HS840T	9.3
Upper aerodigestive tract	HSC2	8.9
Upper aerodigestive tract	HSC3	8.7
Upper aerodigestive tract	HSC4	8
Upper aerodigestive tract	PECAPJ15	9.2
Upper aerodigestive tract	PECAPJ34CLONEC12	8.2
Upper aerodigestive tract	PECAPJ41CLONED2	9.2
Upper aerodigestive tract	PECAPJ49	8.6
Upper aerodigestive tract	SCC15	9.2
Upper aerodigestive tract	SCC25	8.9
Upper aerodigestive tract	SCC4	9.1
Upper aerodigestive tract	SCC9	9.7
Upper aerodigestive tract	SNU1076	9
Upper aerodigestive tract	SNU1214	8.2
Upper aerodigestive tract	SNU46	8.6
Upper aerodigestive tract	SNU899	9
Upper aerodigestive tract	YD10B	8.4
Upper aerodigestive tract	YD38	9.2
Upper aerodigestive tract	YD8	9
Urinary tract	5637	8.1
Urinary tract	639V	9.6
Urinary tract	647V	8.3
Urinary tract	BC3C	8.3
Urinary tract	BFTC905	8.8
Urinary tract	CAL29	8.9
Urinary tract	HS172T	9.8
Urinary tract	HT1197	9.1
Urinary tract	HT1376	8.5
Urinary tract	J82	8.4
Urinary tract	JMSU1	9.4
Urinary tract	KMBC2	8.2
Urinary tract	KU1919	9.5
Urinary tract	RT11284	8.3
Urinary tract	RT112	8.1
Urinary tract	RT4	8.1
Urinary tract	SCABER	8.9
Urinary tract	SW1710	9.4
Urinary tract	SW780	8.6
Urinary tract	T24	8.3
Urinary tract	TCCSUP	6.2
Urinary tract	UMUC1	8
Urinary tract	UMUC3	8.5
Urinary tract	VMCUB1	10.1

> The Human Protein Atlas (HPA)

[ TOP ]

Tissue	Expression Level (TPM)
Adipose tissue	6.7
Adrenal gland	8.6
Appendix	6.2
Bone marrow	0.9
Breast	7.6
Cerebral cortex	12.7
Cervix, uterine	12.9
Colon	5.5
Duodenum	5.4
Endometrium	11.9
Epididymis	7.1
Esophagus	11.1
Fallopian tube	9.3
Gallbladder	7.6
Heart muscle	5.3
Kidney	7.4
Liver	2.9
Lung	7.3
Lymph node	3.7
Ovary	8
Pancreas	1.1
Parathyroid gland	20.7
Placenta	8.6
Prostate	10.2
Rectum	6.8
Salivary gland	1.8
Seminal vesicle	8.8
Skeletal muscle	2.1
Skin	8.3
Small intestine	6.9
Smooth muscle	11
Spleen	6.6
Stomach	6.8
Testis	26.3
Thyroid gland	17.8
Tonsil	3.8
Urinary bladder	6

> Text Mining based Expression

[ TOP ]

PMID	Expression	Cancer	Evidence
28498393	Overexpression	Colorectal Carcinoma	Our results showed that the expression level of hClock significantly increased in human CRC tissues, which strongly associated with late TNM stage and positive lymph node metastasis. Moreover, a higher level of hClock expression was found in CRC cell lines with a higher metastatic potential.
27346616	Underexpression	Breast Carcinoma	The major findings from human studies indicate that expression of circadian genes is deregulated in breast cancer. Breast cancer etiology and prognosis-associated PERs, CRYs, CLOCK downregulation, and TIMELESS upregulation may be related to relevant gene methylation in tumor tissue.
27079271	altered expression	Tongue Carcinoma	In the in vitro systems, SCC9 tongue cancer cells displayed rhythmic expression of PFKFB3 and CLOCK that was distinct from control KC cells.
25622901	Overexpression	Hepatocellular Carcinoma	Moreover, immunohistochemistry staining and quantitative real-time polymerase chain reaction validated that the levels of CLOCK were elevated in HCC tissues, and the expression levels of HULC were positively associated with those of CLOCK in clinical HCC samples.
25485508	Loss of Expression	Breast Carcinoma	Stratification according to molecular subtype revealed prognostic relevance for PER1, PER3, CRY2 and NFIL3 in the ER+/HER2- subgroup, CLOCK and NPAS2 in the ER-/HER2- subtype, and ARNTL2 in HER2+ breast cancer. In conclusion, loss of clock genes is associated with worse prognosis in breast cancer.
24789043	Overexpression	Breast Carcinoma	Immunohistochemical analysis of human breast tumor samples revealed high expression of CLOCK in ERα-positive breast tumor samples.
23970287	Overexpression	Colorectal Carcinoma	Higher levels of hCLOCK expression were observed in human CRC tissues compared with the paired non-cancerous tissues.
23792158	Overexpression	Glioma	Here we show that the expression level of CLOCK is significantly increased in high-grade human glioma tissues and glioblastoma cell lines.
23784787	Underexpression	Head and Neck Squamous Cell Carcinoma	All the 9 CCGs were significantly downregulated in the PB of preoperative patients (p < .0001). Recovery of PER1 and CLOCK expression was observed in postoperative patients with good prognosis but not in patients that died within 1 year after surgery.
23254314	Underexpression	Pancreatic Ductal Adenocarcinoma	In the tumor tissue of PDA patients, compared to their matched adjacent tissue, expression levels of all circadian genes were lower, with statistical significance for Per1, Per2, Per3, Cry1, Cry2, Tipin, Tim, CK1ε, Bmal-ARNTL, and Clock (p<0.025).
22905804	altered expression	Glioma	Using reverse transcription polymerase chain reaction and immunohistochemistry techniques, we examined the expression of the most important clock genes, clock, in 67 gliomas.Our results revealed that asynchronized expression of the clock gene was found in cancerous tissues in comparison with paired non-cancerous tissues. The intensity of immunoactivity for Clock in highgrade gliomas was significantly higher than that of low-grade gliomas (r =-0.403, P50.012,< 0.05), non-tumor tissues around high-grade gliomas (r =-0.376, P =0.027< 0.05), while there was no difference in the intensity of immunoactivity for Clock between low-grade gliomas and the surrounding non-tumor tissues (P >0.05).
21454294	altered expression	Chronic Myeloid Leukemia	The expression of CLOCK and TIM did not show a time-dependent variation among the healthy and patients with CML.
21380491	Overexpression	Colorectal Carcinoma	Expression of the Clock gene and the CKIε gene in cancer tissue were significantly higher compared to that in adjacent normal mucosa.
20524973	Underexpression	Prostate Carcinoma	We found that Clock and Per2 protein levels were downregulated whereas Bmal1 protein levels were upregulated in PCa cells, compared to normal prostate cells.
20124474	overexpression (hypomethylation)	Breast Carcinoma	We also found that hypermethylation in the CLOCK promoter reduced the risk of breast cancer, and lower levels of CLOCK expression were documented in healthy controls relative to normal or tumor tissue from patients with breast cancer.
19296127	altered expression	Breast Carcinoma	Heterogeneous expression of CLOCK is associated significantly with 3-year survival. In conclusion, the expression pattern of circadian genes might be a biomarker for the prognosis of breast cancer.
19148895	Overexpression	Colorectal Carcinoma	Expression of CLOCK was significantly elevated in G(2) tumors of male patients (1.63-fold, P = 0.01).

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Somatic copy number alteration in primary tomur tissue

> The Cancer Genome Atlas (TCGA)

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Correlation between expression and SCNA as well as percentage of patients in different status.

Cancer	Full Name	# Sample	R	P	% Loss	% Neutral	% Gain	Status
BLCA	Bladder urothelial carcinoma	404	0.227	3.93e-06	28	57.9	14.1	Neutral
BRCA	Breast invasive carcinoma	1075	0.245	3.91e-16	22.2	64.6	13.2	Neutral
CESC	Cervical and endocervical cancers	292	0.311	5.83e-08	27.7	65.4	6.8	Neutral
COAD	Colon adenocarcinoma	449	0.374	2.36e-16	26.5	68.2	5.3	Neutral
ESCA	Esophageal carcinoma	183	0.386	6.56e-08	43.2	38.3	18.6	Loss
GBM	Glioblastoma multiforme	147	0.482	6.44e-10	12.9	76.9	10.2	Neutral
HNSC	Head and Neck squamous cell carcinoma	514	0.229	1.5e-07	21	63.2	15.8	Neutral
KIRC	Kidney renal clear cell carcinoma	525	0.148	0.000683	12	85.7	2.3	Neutral
KIRP	Kidney renal papillary cell carcinoma	288	0.005	0.93	8.3	88.5	3.1	Neutral
LAML	Acute Myeloid Leukemia	166	0.132	0.0892	1.2	97.6	1.2	Neutral
LGG	Brain Lower Grade Glioma	513	0.164	0.000198	12.7	82.7	4.7	Neutral
LIHC	Liver hepatocellular carcinoma	364	0.346	1.09e-11	31	63.2	5.8	Neutral
LUAD	Lung adenocarcinoma	512	0.408	5.77e-22	22.5	59.8	17.8	Neutral
LUSC	Lung squamous cell carcinoma	498	0.649	5.64e-61	40.6	35.9	23.5	Loss
OV	Ovarian serous cystadenocarcinoma	300	0.56	3.6e-26	36.3	40.7	23	Loss
PAAD	Pancreatic adenocarcinoma	177	0.164	0.0292	13.6	79.1	7.3	Neutral
PCPG	Pheochromocytoma and Paraganglioma	162	0.176	0.0247	7.4	90.1	2.5	Neutral
PRAD	Prostate adenocarcinoma	491	0.061	0.18	4.7	93.1	2.2	Neutral
READ	Rectum adenocarcinoma	164	0.333	1.31e-05	34.1	58.5	7.3	Loss
SARC	Sarcoma	255	0.339	2.94e-08	12.2	59.6	28.2	Neutral
SKCM	Skin Cutaneous Melanoma	367	0.292	1.19e-08	19.3	63.8	16.9	Neutral
STAD	Stomach adenocarcinoma	413	0.309	1.37e-10	34.9	58.6	6.5	Loss
TGCT	Testicular Germ Cell Tumors	150	0.394	5.98e-07	54.7	32.7	12.7	Loss
THCA	Thyroid carcinoma	497	0.113	0.012	0.4	98.6	1	Neutral
THYM	Thymoma	119	0.104	0.26	3.4	95	1.7	Neutral
UCEC	Uterine Corpus Endometrial Carcinoma	537	0.229	7.98e-08	14.7	81.4	3.9	Neutral

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Methylation level in the promoter region of CR

> Methylation level in the promoter region of CR

[ TOP ]

Correlation between expression and methylation as well as differential methylation analysis.

Cancer	Full Name	R	P	# N	# T	Delta beta (T vs N)	P value (T vs N)	Status
BLCA	Bladder urothelial carcinoma	-0.17	0.000437	17	408	0.007	1e-04	NS/NA
BRCA	Breast invasive carcinoma	-0.082	0.0154	83	785	0.001	0.00491	NS/NA
CESC	Cervical and endocervical cancers	-0.264	2.84e-06	3	306	NA	NA	NS/NA
COAD	Colon adenocarcinoma	-0.144	0.0107	19	297	0.011	2.64e-06	NS/NA
ESCA	Esophageal carcinoma	-0.261	0.000243	9	185	NA	NA	NS/NA
GBM	Glioblastoma multiforme	-0.41	0.000767	1	64	NA	NA	NS/NA
HNSC	Head and Neck squamous cell carcinoma	-0.206	1.48e-06	20	522	0.002	2.12e-11	NS/NA
KIRC	Kidney renal clear cell carcinoma	-0.124	0.0217	24	319	0.016	4.47e-17	NS/NA
KIRP	Kidney renal papillary cell carcinoma	-0.411	1.5e-13	23	275	0.021	7.11e-20	NS/NA
LAML	Acute Myeloid Leukemia	-0.11	0.152	0	170	NA	NA	NS/NA
LGG	Brain Lower Grade Glioma	-0.366	0	0	530	NA	NA	NS/NA
LIHC	Liver hepatocellular carcinoma	-0.379	1.33e-15	41	373	0.039	7.26e-35	NS/NA
LUAD	Lung adenocarcinoma	-0.115	0.0122	21	456	-0.001	0.218	NS/NA
LUSC	Lung squamous cell carcinoma	-0.246	1.39e-06	8	370	NA	NA	NS/NA
OV	Ovarian serous cystadenocarcinoma	-0.833	0.00827	0	9	NA	NA	NS/NA
PAAD	Pancreatic adenocarcinoma	-0.284	0.000103	4	179	NA	NA	NS/NA
PCPG	Pheochromocytoma and Paraganglioma	-0.147	0.0446	3	184	NA	NA	NS/NA
PRAD	Prostate adenocarcinoma	-0.31	3.46e-13	35	498	0.016	6.5e-27	NS/NA
READ	Rectum adenocarcinoma	-0.29	0.00339	2	99	NA	NA	NS/NA
SARC	Sarcoma	-0.272	8.17e-06	0	263	NA	NA	NS/NA
SKCM	Skin Cutaneous Melanoma	-0.265	5.75e-09	1	471	NA	NA	NS/NA
STAD	Stomach adenocarcinoma	-0.237	4.2e-06	0	372	NA	NA	NS/NA
TGCT	Testicular Germ Cell Tumors	-0.548	0	0	156	NA	NA	NS/NA
THCA	Thyroid carcinoma	-0.068	0.11	50	509	-0.001	0.216	NS/NA
THYM	Thymoma	-0.427	1.19e-06	2	120	NA	NA	NS/NA
UCEC	Uterine Corpus Endometrial Carcinoma	-0.099	0.0332	34	431	0.001	3.44e-05	NS/NA

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Primary tumor tissue from TCGA > Normal tumor tissue from HPA

>The Cancer Genome Atlas (TCGA) [ TOP ]
There is no record.

> The Human Protein Atlas (HPA)

[ TOP ]

Tissue	Level	Level Name
Adrenal gland	2	Medium
Appendix	2	Medium
Bone marrow	2	Medium
Breast	2	Medium
Bronchus	2	Medium
Caudate	2	Medium
Cerebellum	2	Medium
Cerebral cortex	2	Medium
Cervix, uterine	2	Medium
Colon	2	Medium
Duodenum	2	Medium
Endometrium	2	Medium
Epididymis	2	Medium
Esophagus	2	Medium
Fallopian tube	2	Medium
Gallbladder	2	Medium
Heart muscle	2	Medium
Hippocampus	2	Medium
Kidney	2	Medium
Liver	1	Low
Lung	2	Medium
Lymph node	2	Medium
Nasopharynx	2	Medium
Oral mucosa	2	Medium
Ovary	2	Medium
Pancreas	1	Low
Parathyroid gland	2	Medium
Placenta	2	Medium
Prostate	2	Medium
Rectum	2	Medium
Salivary gland	2	Medium
Seminal vesicle	2	Medium
Skeletal muscle	2	Medium
Skin	2	Medium
Small intestine	1	Low
Smooth muscle	2	Medium
Soft tissue	2	Medium
Spleen	1	Low
Stomach	2	Medium
Testis	2	Medium
Thyroid gland	2	Medium
Tonsil	2	Medium
Urinary bladder	2	Medium
Vagina	2	Medium

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Association between expresson and subtype > Overall survival analysis based on expression > Association between expresson and stage > Association between expresson and grade

> Subtype

[ TOP ]

Association between expresson and subtype.

Cancer	Full Name	# Patients	P Value (Kruskal-Wallis)	Association	Source
BLCA	Bladder urothelial carcinoma	128	0.821	NS	24476821
BRCA	Breast invasive carcinoma	521	5.02e-05	Significant	23000897
COAD	Colon adenocarcinoma	149	0.00328	Significant	22810696
GBM	Glioblastoma multiforme	157	0.249	NS	26824661
HNSC	Head and Neck squamous cell carcinoma	279	0.000691	Significant	25631445
KIRP	Kidney renal papillary cell carcinoma	161	0.0308	Significant	26536169
LGG	Brain Lower Grade Glioma	513	0.353	NS	26824661
LUAD	Lung adenocarcinoma	230	0.228	NS	25079552
LUSC	Lung squamous cell carcinoma	178	0.931	NS	22960745
OV	Ovarian serous cystadenocarcinoma	287	0.000343	Significant	21720365
PRAD	Prostate adenocarcinoma	333	0.0789	NS	26544944
READ	Rectum adenocarcinoma	67	0.276	NS	22810696
SKCM	Skin Cutaneous Melanoma	315	0.765	NS	26091043
STAD	Stomach adenocarcinoma	277	0.816	NS	25079317
THCA	Thyroid carcinoma	391	0.612	NS	25417114
UCEC	Uterine Corpus Endometrial Carcinoma	232	0.466	NS	23636398

> Overall survival

[ TOP ]

Overall survival analysis based on expression.

Cancer	Full Name	# Patients	Hazard Ratio	P Value (Log Rank Test)	Association
BLCA	Bladder urothelial carcinoma	405	1.222	0.344	NS
BRCA	Breast invasive carcinoma	1079	1.822	0.0135	Shorter
CESC	Cervical and endocervical cancers	291	2.018	0.0401	Shorter
COAD	Colon adenocarcinoma	439	0.466	0.0112	Longer
ESCA	Esophageal carcinoma	184	0.625	0.14	NS
GBM	Glioblastoma multiforme	158	0.875	0.602	NS
HNSC	Head and Neck squamous cell carcinoma	518	0.837	0.359	NS
KIRC	Kidney renal clear cell carcinoma	531	0.448	0.000342	Longer
KIRP	Kidney renal papillary cell carcinoma	287	1.265	0.623	NS
LAML	Acute Myeloid Leukemia	149	0.592	0.0765	NS
LGG	Brain Lower Grade Glioma	511	1.443	0.179	NS
LIHC	Liver hepatocellular carcinoma	365	1.329	0.225	NS
LUAD	Lung adenocarcinoma	502	1.226	0.337	NS
LUSC	Lung squamous cell carcinoma	494	1.46	0.049	Shorter
OV	Ovarian serous cystadenocarcinoma	303	1.155	0.476	NS
PAAD	Pancreatic adenocarcinoma	177	1.884	0.0227	Shorter
PCPG	Pheochromocytoma and Paraganglioma	179	590535412.58	0.0843	NS
PRAD	Prostate adenocarcinoma	497	0.959	0.974	NS
READ	Rectum adenocarcinoma	159	0.375	0.0819	NS
SARC	Sarcoma	259	1.73	0.0701	NS
SKCM	Skin Cutaneous Melanoma	459	0.951	0.803	NS
STAD	Stomach adenocarcinoma	388	1.037	0.871	NS
TGCT	Testicular Germ Cell Tumors	134	1.244	0.877	NS
THCA	Thyroid carcinoma	500	2.258	0.318	NS
THYM	Thymoma	119	5.114	0.12	NS
UCEC	Uterine Corpus Endometrial Carcinoma	543	1.145	0.635	NS

> Stage

[ TOP ]

Association between expresson and stage.

Cancer	Full Name	# Patients	R Value (Spearman)	P Value (Spearman)	Association
BLCA	Bladder urothelial carcinoma	406	-0.011	0.825	NS
BRCA	Breast invasive carcinoma	1071	0.003	0.921	NS
CESC	Cervical and endocervical cancers	167	0.075	0.333	NS
COAD	Colon adenocarcinoma	445	-0.046	0.338	NS
ESCA	Esophageal carcinoma	162	-0.108	0.169	NS
HNSC	Head and Neck squamous cell carcinoma	448	-0.034	0.468	NS
KIRC	Kidney renal clear cell carcinoma	531	-0.131	0.00251	Lower
KIRP	Kidney renal papillary cell carcinoma	260	0.04	0.525	NS
LIHC	Liver hepatocellular carcinoma	347	0.083	0.121	NS
LUAD	Lung adenocarcinoma	507	0.056	0.211	NS
LUSC	Lung squamous cell carcinoma	497	0.039	0.387	NS
OV	Ovarian serous cystadenocarcinoma	302	0.024	0.674	NS
PAAD	Pancreatic adenocarcinoma	176	0.02	0.791	NS
READ	Rectum adenocarcinoma	156	-0.028	0.731	NS
SKCM	Skin Cutaneous Melanoma	410	-0.022	0.662	NS
STAD	Stomach adenocarcinoma	392	0.064	0.208	NS
TGCT	Testicular Germ Cell Tumors	81	-0.196	0.0788	NS
THCA	Thyroid carcinoma	499	-0.011	0.814	NS
UCEC	Uterine Corpus Endometrial Carcinoma	501	-0.105	0.0186	Lower

> Grade

[ TOP ]

Association between expresson and grade.

Cancer	Full Name	# Patients	R Value (Spearman)	P Value (Spearman)	Association
CESC	Cervical and endocervical cancers	272	-0.164	0.00688	Lower
HNSC	Head and Neck squamous cell carcinoma	498	-0.09	0.0445	Lower
KIRC	Kidney renal clear cell carcinoma	525	-0.105	0.0158	Lower
LGG	Brain Lower Grade Glioma	514	0.008	0.857	NS
LIHC	Liver hepatocellular carcinoma	366	-0.083	0.111	NS
OV	Ovarian serous cystadenocarcinoma	296	0.053	0.36	NS
PAAD	Pancreatic adenocarcinoma	176	0.054	0.475	NS
STAD	Stomach adenocarcinoma	406	-0.069	0.165	NS
UCEC	Uterine Corpus Endometrial Carcinoma	534	-0.071	0.101	NS

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Targets inferred by reverse engineering method > Targets identified by ChIP-seq data

> Targets inferred by reverse engineering method [ TOP ]

> Targets identified by ChIP-seq data [ TOP ]

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Drugs from DrugBank database

> Drugs from DrugBank database [ TOP ]
There is no record for CLOCK.

Summary
Symbol	CLOCK
Name	clock circadian regulator
Aliases	KIAA0334; KAT13D; bHLHe8; clock (mouse) homolog; clock homolog (mouse); circadian locomoter output cycles ka ......
Location	4q12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Cancer Gene Databases	ONGene (Oncogene) , TSGene (Tumor suppressor gene) , NCG (Network of Cancer Genes)
Content	> Protein-Protein Interaction Network > miRNA Regulatory Relationship > Interactions from Text Mining

> Protein-Protein Interaction Network [ TOP ]

> miRNA Regulatory Relationship [ TOP ]

> Interactions from Text Mining

[ TOP ]

PMID	Cancer	Hierarchy	Gene	Relation to CR	Evidence
28498393	Colorectal Carcinoma	downstream	HIF-1α; ARNT; VEGF	Positive regulation	Finally, we found that overexpression of hClock enhanced the expression of angiogenesis-related genes such as HIF-1α, ARNT and VEGF, and promoted epithelial-mesenchymal (-like) transition (EMT) in CRC cells, both of which are considered to be critical for tumor progression.
27079271	Tongue Carcinoma	downstream	PFKFB3	Positive regulation	Furthermore, PFKFB3 expression in SCC9 cells was stimulated by CLOCK through binding and enhancing the transcription activity of PFKFB3 promoter.
25622901	Hepatocellular Carcinoma	upstream	HULC	Positive regulation	Taken together, our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis.
24789043	Breast Carcinoma	upstream	E2; ERα	Positive regulation	Subsequent experiments using ERα-positive human breast cancer cell lines showed that both protein and mRNA levels of CLOCK were up-regulated by E2 and ERα.
23970287	Colorectal Carcinoma	partner	ARNT; HIF-1α; VEGF	Positive correlation	A strong positive linear correlation was also found between hClock gene expression and ARNT, HIF-1α and VEGF expression in human CRCs.
23792158	Glioma	upstream	miR-124	Negative regulation	Further studies show that Clock is a direct target of miR-124, and either restoration of miR-124 or silencing of CLOCK can reduce the activation of NF-κB.
23792158	Glioma	downstream	NF-κB	Positive regulation	In conclusion, we suggest that as a target of glioma suppressor miR-124, CLOCK positively regulates glioma proliferation and migration by reinforcing NF-κB activity.