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Center for Computational Systems Medicine
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FusionGeneSummary

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FusionProtFeature

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FusionGeneSequence

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FusionGenePPI

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RelatedDrugs

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RelatedDiseases

Fusion gene ID: 7458

FusionGeneSummary for CLOCK_UGT2A3

check button Fusion gene summary
Fusion gene informationFusion gene name: CLOCK_UGT2A3
Fusion gene ID: 7458
HgeneTgene
Gene symbol

CLOCK

UGT2A3

Gene ID

9575

79799

Gene nameclock circadian regulatorUDP glucuronosyltransferase family 2 member A3
SynonymsKAT13D|bHLHe8-
Cytomap

4q12

4q13.2

Type of geneprotein-codingprotein-coding
Descriptioncircadian locomoter output cycles protein kaputcircadian locomoter output cycles kaput proteinclass E basic helix-loop-helix protein 8clock homologUDP-glucuronosyltransferase 2A3UDP glucuronosyltransferase 2 family, polypeptide A3UDPGT 2A3
Modification date2018051920180523
UniProtAcc

O15516

Q6UWM9

Ensembl transtripts involved in fusion geneENST00000309964, ENST00000381322, 
ENST00000513440, ENST00000506923, 
ENST00000251566, ENST00000420231, 
ENST00000547910, 
Fusion gene scores* DoF score6 X 8 X 5=2404 X 1 X 3=12
# samples 84
** MAII scorelog2(8/240*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/12*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Context

PubMed: CLOCK [Title/Abstract] AND UGT2A3 [Title/Abstract] AND fusion [Title/Abstract]

Functional or gene categories assigned by FusionGDB annotation
* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneCLOCK

GO:0006473

protein acetylation

28985504

HgeneCLOCK

GO:0032922

circadian regulation of gene expression

24005054

HgeneCLOCK

GO:0045893

positive regulation of transcription, DNA-templated

23785138

HgeneCLOCK

GO:0051775

response to redox state

11441146

HgeneCLOCK

GO:0071479

cellular response to ionizing radiation

21659603

TgeneUGT2A3

GO:0052695

cellular glucuronidation

19858781


check button Fusion gene information from three resources
(ChiTars (NAR, 2018), tumorfusions (NAR, 2018), Gao et al. (Cell, 2018))
* All genome coordinats were lifted-over on hg19.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
Data typeSourceCancer typeSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
TCGARVBLCATCGA-GV-A3QH-01ACLOCKchr4

56412949

-UGT2A3chr4

69798477

-
TCGALDBLCATCGA-GV-A3QH-01ACLOCKchr4

56412649

-UGT2A3chr4

69798477

-
* LD: Li Ding group's fusion gene list
  RV: Roel Verhaak group's fusion gene list
  ChiTaRs fusion database

check button Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure.
* Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser.
ORFHenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrand
intron-3CDSENST00000309964ENST00000251566CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-5UTRENST00000309964ENST00000420231CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-intronENST00000309964ENST00000547910CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-3CDSENST00000381322ENST00000251566CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-5UTRENST00000381322ENST00000420231CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-intronENST00000381322ENST00000547910CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-3CDSENST00000513440ENST00000251566CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-5UTRENST00000513440ENST00000420231CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-intronENST00000513440ENST00000547910CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-3CDSENST00000506923ENST00000251566CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-5UTRENST00000506923ENST00000420231CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
5UTR-intronENST00000506923ENST00000547910CLOCKchr4

56412949

-UGT2A3chr4

69798477

-
intron-3CDSENST00000309964ENST00000251566CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-5UTRENST00000309964ENST00000420231CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-intronENST00000309964ENST00000547910CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-3CDSENST00000381322ENST00000251566CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-5UTRENST00000381322ENST00000420231CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-intronENST00000381322ENST00000547910CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-3CDSENST00000513440ENST00000251566CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-5UTRENST00000513440ENST00000420231CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-intronENST00000513440ENST00000547910CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-3CDSENST00000506923ENST00000251566CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-5UTRENST00000506923ENST00000420231CLOCKchr4

56412649

-UGT2A3chr4

69798477

-
intron-intronENST00000506923ENST00000547910CLOCKchr4

56412649

-UGT2A3chr4

69798477

-

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FusionProtFeatures for CLOCK_UGT2A3


check buttonMain function of each fusion partner protein. (from UniProt)
HgeneTgene
CLOCK

O15516

UGT2A3

Q6UWM9

Transcriptional activator which forms a core componentof the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes throughthe generation of approximately 24 hour circadian rhythms in geneexpression, which are translated into rhythms in metabolism andbehavior. It is derived from the Latin roots 'circa' (about) and'diem' (day) and acts as an important regulator of a wide array ofphysiological functions including metabolism, sleep, bodytemperature, blood pressure, endocrine, immune, cardiovascular,and renal function. Consists of two major components: the centralclock, residing in the suprachiasmatic nucleus (SCN) of the brain,and the peripheral clocks that are present in nearly every tissueand organ system. Both the central and peripheral clocks can bereset by environmental cues, also known as Zeitgebers (German for'timegivers'). The predominant Zeitgeber for the central clock islight, which is sensed by retina and signals directly to the SCN.The central clock entrains the peripheral clocks through neuronaland hormonal signals, body temperature and feeding-related cues,aligning all clocks with the external light/dark cycle. Circadianrhythms allow an organism to achieve temporal homeostasis with itsenvironment at the molecular level by regulating gene expressionto create a peak of protein expression once every 24 hours tocontrol when a particular physiological process is most activewith respect to the solar day. Transcription and translation ofcore clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2,PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythmgeneration, whereas delays imposed by post-translationalmodifications (PTMs) are important for determining the period(tau) of the rhythms (tau refers to the period of a rhythm and isthe length, in time, of one complete cycle). A diurnal rhythm issynchronized with the day/night cycle, while the ultradian andinfradian rhythms have a period shorter and longer than 24 hours,respectively. Disruptions in the circadian rhythms contribute tothe pathology of cardiovascular diseases, cancer, metabolicsyndromes 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 orARNTL2/BMAL2, form the positive limb of the feedback loop, act inthe form of a heterodimer and activate the transcription of coreclock genes and clock-controlled genes (involved in key metabolicprocesses), harboring E-box elements (5'-CACGTG-3') within theirpromoters. The core clock genes: PER1/2/3 and CRY1/2 which aretranscriptional repressors form the negative limb of the feedbackloop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2heterodimer inhibiting its activity and thereby negativelyregulating their own expression. This heterodimer also activatesnuclear receptors NR1D1/2 and RORA/B/G, which form a secondfeedback loop and which activate and repress ARNTL/BMAL1transcription, respectively. Regulates the circadian expression ofICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer ofthe transactivation potential of NF-kappaB. Plays an importantrole in the homeostatic regulation of sleep. The CLOCK-ARNTL/BMAL1heterodimer 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 alsogenes implicated in glucose and lipid metabolism. Promotesrhythmic chromatin opening, regulating the DNA accessibility ofother transcription factors. The CLOCK-ARNTL2/BMAL2 heterodimeractivates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. Thepreferred binding motif for the CLOCK-ARNTL/BMAL1 heterodimer is5'-CACGTGA-3', which contains a flanking Ala residue in additionto the canonical 6-nucleotide E-box sequence (PubMed:23229515).CLOCK specifically binds to the half-site 5'-CAC-3', while ARNTLbinds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-ARNTL/BMAL1 heterodimer also recognizes the non-canonical E-boxmotifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCKhas an intrinsic acetyltransferase activity, which enablescircadian chromatin remodeling by acetylating histones andnonhistone proteins, including its own partner ARNTL/BMAL1.Represses glucocorticoid receptor NR3C1/GR-induced transcriptionalactivity by reducing the association of NR3C1/GR to glucocorticoidresponse elements (GREs) via the acetylation of multiple lysineresidues located in its hinge region (PubMed:21980503). Theacetyltransferase activity of CLOCK is as important as itstranscription activity in circadian control. Acetylates metabolicenzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated byBMAL1, rhythmically interacts and acetylates argininosuccinatesynthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as wellas the circadian oscillation of arginine biosynthesis andsubsequent ureagenesis (PubMed:28985504).{ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630,ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503,ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515,ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054,ECO:0000269|PubMed:28985504}. UDP-glucuronosyltransferases catalyze phase IIbiotransformation reactions in which lipophilic substrates areconjugated with glucuronic acid to increase water solubility andenhance excretion. They are of major importance in the conjugationand subsequent elimination of potentially toxic xenobiotics andendogenous compounds (By similarity). {ECO:0000250}.

check buttonRetention analysis result of each fusion partner protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

.

* Minus value of BPloci means that the break pointn is located before the CDS.
- In-frame and retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note

- In-frame and not-retained protein feature among the 13 regional features.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note


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FusionGeneSequence for CLOCK_UGT2A3


check button For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences.
(nt: nucleotides, aa: amino acids)

* Fusion amino acid sequences.

* Fusion transcript sequences (only coding sequence (CDS) region).

* Fusion transcript sequences (Full-length transcript).

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FusionGenePPI for CLOCK_UGT2A3


check button Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in

ChiPPI page

.

check button Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)
HgeneHgene's interactorsTgeneTgene's interactors
CLOCKARNTL, ARNTL2, EP300, KAT2B, RXRA, RARA, SIRT1, TFAP4, SOX2, CIPC, CRY1, CRY2, DEC1, BHLHE41, NPAS2, PPP2R5D, PPP2R5E, CSNK2B, PPP2R1B, NR1D2, PER2, PPP1CA, PPP1CB, PPP1CC, RORB, CSNK1E, DBP, RORC, SRGAP3, TEKT4, CREBBP, EXOC1, PKN3, NCKAP5L, TFPT, CCHCR1, YEATS4, TUFT1, RABGAP1L, GOLGA5, PSMD9, VPS53, DZIP3, GRIPAP1, RCOR1, HMG20A, CCDC132, CCDC93, OIP5, PHF21A, PTRF, PHLDB3, GIT2, HAUS6, RPRD1A, MAX, RABGEF1, NUF2, THAP11, VPS51, TSSC1, KDM1A, RABEP1UGT2A3UGT2A2, UGT2B15, HBA2


check button - Retained PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenStill interaction with


check button - Lost PPIs in in-frame fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


check button - Retained PPIs, but lost function due to frame-shift fusion.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenInteraction lost with


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RelatedDrugs for CLOCK_UGT2A3


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.0 2018-04-02)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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RelatedDiseases for CLOCK_UGT2A3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCLOCKC0005586Bipolar Disorder5PSYGENET
HgeneCLOCKC0011570Mental Depression5PSYGENET
HgeneCLOCKC0011581Depressive disorder5PSYGENET
HgeneCLOCKC0041696Unipolar Depression5PSYGENET
HgeneCLOCKC0525045Mood Disorders5PSYGENET
HgeneCLOCKC1269683Major Depressive Disorder5PSYGENET
HgeneCLOCKC0085159Seasonal Affective Disorder3PSYGENET
HgeneCLOCKC3496069cocaine use2PSYGENET
HgeneCLOCKC0001957Alcohol Withdrawal Delirium1PSYGENET
HgeneCLOCKC0001973Alcoholic Intoxication, Chronic1PSYGENET
HgeneCLOCKC0036341Schizophrenia1PSYGENET
HgeneCLOCKC0600427Cocaine Dependence1PSYGENET