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	Fusion Gene Summary
	Fusion Gene ORF analysis
	Fusion Genomic Features
	Fusion Protein Features
	Fusion Gene Sequence
	Fusion Gene PPI analysis
	Related Drugs
	Related Diseases

Fusion gene:CLOCK-UGT2A3 (FusionGDB2 ID:17278)

Fusion Gene Summary for CLOCK-UGT2A3

Fusion gene summary

Fusion gene information	Fusion gene name: CLOCK-UGT2A3
	Fusion gene ID: 17278
		Hgene	Tgene
	Gene symbol	CLOCK	UGT2A3
	Gene ID	9575	79799
	Gene name	clock circadian regulator	UDP glucuronosyltransferase family 2 member A3
	Synonyms	KAT13D\|bHLHe8	-
	Cytomap	4q12	4q13.2
	Type of gene	protein-coding	protein-coding
	Description	circadian locomoter output cycles protein kaputcircadian locomoter output cycles kaput proteinclass E basic helix-loop-helix protein 8clock homolog	UDP-glucuronosyltransferase 2A3UDP glucuronosyltransferase 2 family, polypeptide A3UDPGT 2A3
	Modification date	20200313	20200313
	UniProtAcc	O15516	.
	Ensembl transtripts involved in fusion gene	ENST00000506923, ENST00000513440, ENST00000309964, ENST00000381322,	ENST00000251566, ENST00000420231, ENST00000547910,
Fusion gene scores	* DoF score	10 X 13 X 6=780	4 X 4 X 3=48
	# samples	14	7
	** MAII score	log2(14/780*10)=-2.47804729680464 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0	log2(7/48*10)=0.54432051622381 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]
Most frequent breakpoint	CLOCK(56412949)-UGT2A3(69798477), # samples:2
Anticipated loss of major functional domain due to fusion event.

* DoF score (Degree of Frequency) = # partners X # break points X # cancer types
** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10)

Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Partner	Gene	GO ID	GO term	PubMed ID
Hgene	CLOCK	GO:0006473	protein acetylation	28985504
Hgene	CLOCK	GO:0032922	circadian regulation of gene expression	24005054
Hgene	CLOCK	GO:0045893	positive regulation of transcription, DNA-templated	23785138
Hgene	CLOCK	GO:0051775	response to redox state	11441146
Hgene	CLOCK	GO:0071479	cellular response to ionizing radiation	21659603
Tgene	UGT2A3	GO:0052695	cellular glucuronidation	19858781

Fusion gene breakpoints across CLOCK (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene breakpoints across UGT2A3 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0)
* 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.

Source	Disease	Sample	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
ChimerDB4	BLCA	TCGA-GV-A3QH-01A	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
ChimerDB4	BLCA	TCGA-GV-A3QH-01A	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
ChimerDB4	BLCA	TCGA-GV-A3QH-01A	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
ChimerDB4	BLCA	TCGA-GV-A3QH-01A	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
ChimerDB4	BLCA	TCGA-GV-A3QH	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-

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Fusion Gene ORF analysis for CLOCK-UGT2A3

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.

ORF	Henst	Tenst	Hgene	Hchr	Hbp	Hstrand	Tgene	Tchr	Tbp	Tstrand
5UTR-3CDS	ENST00000506923	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-3CDS	ENST00000506923	ENST00000251566	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
5UTR-3CDS	ENST00000513440	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-3CDS	ENST00000513440	ENST00000251566	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
5UTR-5UTR	ENST00000506923	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-5UTR	ENST00000506923	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-5UTR	ENST00000506923	ENST00000420231	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
5UTR-5UTR	ENST00000513440	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-5UTR	ENST00000513440	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-5UTR	ENST00000513440	ENST00000420231	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
5UTR-intron	ENST00000506923	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-intron	ENST00000506923	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000506923	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000506923	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-intron	ENST00000506923	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-intron	ENST00000506923	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000506923	ENST00000547910	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
5UTR-intron	ENST00000513440	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-intron	ENST00000513440	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000513440	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000513440	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
5UTR-intron	ENST00000513440	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
5UTR-intron	ENST00000513440	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
5UTR-intron	ENST00000513440	ENST00000547910	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000309964	ENST00000251566	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000309964	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000309964	ENST00000251566	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000381322	ENST00000251566	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000381322	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000381322	ENST00000251566	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000506923	ENST00000251566	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-3CDS	ENST00000513440	ENST00000251566	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000309964	ENST00000420231	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000309964	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000309964	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-5UTR	ENST00000309964	ENST00000420231	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000381322	ENST00000420231	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000381322	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000381322	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-5UTR	ENST00000381322	ENST00000420231	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000506923	ENST00000420231	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-5UTR	ENST00000513440	ENST00000420231	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000309964	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-intron	ENST00000309964	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000309964	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000309964	ENST00000547910	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000309964	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000309964	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-intron	ENST00000309964	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000309964	ENST00000547910	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000381322	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-intron	ENST00000381322	ENST00000251566	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000381322	ENST00000420231	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000381322	ENST00000547910	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000381322	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000381322	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4	69809096	-
intron-intron	ENST00000381322	ENST00000547910	CLOCK	chr4	56412949	-	UGT2A3	chr4_ctg9_hap1	510728	-
intron-intron	ENST00000381322	ENST00000547910	CLOCK	chr4	56412948	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000506923	ENST00000547910	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-
intron-intron	ENST00000513440	ENST00000547910	CLOCK	chr4	56412649	-	UGT2A3	chr4	69798477	-

ORFfinder result based on the fusion transcript sequence of in-frame fusion genes.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

Seq length
(transcript)

BP loci
(transcript)

Predicted start
(transcript)

Predicted stop
(transcript)

Seq length
(amino acids)

DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated.

Henst

Tenst

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

No-coding score

Coding score

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Fusion Genomic Features for CLOCK-UGT2A3

FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints.

Hgene

Hchr

Hbp

Hstrand

Tgene

Tchr

Tbp

Tstrand

1-p

p (fusion gene breakpoint)

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page.

Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page.

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Fusion Protein Features for CLOCK-UGT2A3

Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:56412949/:69798477)
- FGviewer provides the online visualization of the retention search of the protein functional features across DNA, RNA, protein, and pathological levels.
- How to search
1. Put your fusion gene symbol.
2. Press the tab key until there will be shown the breakpoint information filled.
4. Go down and press 'Search' tab twice.
4. Go down to have the hyperlink of the search result.
5. Click the hyperlink.
6. See the FGviewer result for your fusion gene.

Main function of each fusion partner protein. (from UniProt)

Hgene	Tgene
CLOCK O15516	.
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). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250\|UniProtKB:O08785, 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}.	FUNCTION: Transcriptional activator which is required for calcium-dependent dendritic growth and branching in cortical neurons. Recruits CREB-binding protein (CREBBP) to nuclear bodies. Component of the CREST-BRG1 complex, a multiprotein complex that regulates promoter activation by orchestrating a calcium-dependent release of a repressor complex and a recruitment of an activator complex. In resting neurons, transcription of the c-FOS promoter is inhibited by BRG1-dependent recruitment of a phospho-RB1-HDAC1 repressor complex. Upon calcium influx, RB1 is dephosphorylated by calcineurin, which leads to release of the repressor complex. At the same time, there is increased recruitment of CREBBP to the promoter by a CREST-dependent mechanism, which leads to transcriptional activation. The CREST-BRG1 complex also binds to the NR2B promoter, and activity-dependent induction of NR2B expression involves a release of HDAC1 and recruitment of CREBBP (By similarity). {ECO:0000250}.

Retention 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.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

- In-frame and not-retained protein feature among the 13 regional features.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Protein feature

Protein feature note

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Fusion Gene Sequence for CLOCK-UGT2A3

For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones.

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Fusion Gene PPI Analysis for CLOCK-UGT2A3

Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in
ChiPPI page.

Protein-protein interactors with each fusion partner protein in wild-type (BIOGRID-3.4.160)

Hgene

Hgene's interactors

Tgene

Tgene's interactors

- Retained PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Still interaction with

- Lost PPIs in in-frame fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

- Retained PPIs, but lost function due to frame-shift fusion.

Partner

Gene

Hbp

Tbp

ENST

Strand

BPexon

TotalExon

Protein feature loci

*BPloci

TotalLen

Interaction lost with

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Related Drugs for CLOCK-UGT2A3

Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)

Partner

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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Related Diseases for CLOCK-UGT2A3

Diseases associated with fusion partners.
(DisGeNet 4.0)

Partner

Gene

Disease ID

Disease name

# pubmeds

Source