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Center for Computational Systems Medicine
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Fusion Gene Summary

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Fusion Gene ORF analysis

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Fusion Genomic Features

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Fusion Protein Features

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Fusion Gene Sequence

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Fusion Gene PPI analysis

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Related Drugs

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Related Diseases

Fusion gene:USP28-CLYBL (FusionGDB2 ID:97305)

Fusion Gene Summary for USP28-CLYBL

check button Fusion gene summary
Fusion gene informationFusion gene name: USP28-CLYBL
Fusion gene ID: 97305
HgeneTgene
Gene symbol

USP28

CLYBL

Gene ID

57646

171425

Gene nameubiquitin specific peptidase 28citramalyl-CoA lyase
Synonyms-CLB
Cytomap

11q23.2

13q32.3

Type of geneprotein-codingprotein-coding
Descriptionubiquitin carboxyl-terminal hydrolase 28deubiquitinating enzyme 28ubiquitin carboxyl-terminal hydrolase 28 variant 1ubiquitin thioesterase 28ubiquitin thiolesterase 28ubiquitin-specific-processing protease 28citramalyl-CoA lyase, mitochondrial(3S)-malyl-CoA thioesterasebeta-methylmalate synthasecitrate lyase beta likecitrate lyase subunit beta-like protein, mitochondrialmalate synthase
Modification date2020031320200313
UniProtAcc.

Q8N0X4

Ensembl transtripts involved in fusion geneENST00000542033, ENST00000003302, 
ENST00000260188, ENST00000537706, 
ENST00000544967, ENST00000545540, 
ENST00000339105, ENST00000376354, 
ENST00000376355, ENST00000376360, 
ENST00000444838, 
Fusion gene scores* DoF score6 X 5 X 6=1808 X 7 X 7=392
# samples 613
** MAII scorelog2(6/180*10)=-1.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(13/392*10)=-1.59234203108675
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: USP28 [Title/Abstract] AND CLYBL [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointUSP28(113723223)-CLYBL(100425078), # samples:1
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)

check button Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
HgeneUSP28

GO:0006974

cellular response to DNA damage stimulus

17873522

HgeneUSP28

GO:0010212

response to ionizing radiation

16901786

HgeneUSP28

GO:0016579

protein deubiquitination

16901786|17558397|18662541

HgeneUSP28

GO:0034644

cellular response to UV

17873522

HgeneUSP28

GO:0042771

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

16901786

TgeneCLYBL

GO:0070207

protein homotrimerization

29056341

TgeneCLYBL

GO:0106064

regulation of cobalamin metabolic process

29056341


check buttonFusion gene breakpoints across USP28 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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

check button 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.
SourceDiseaseSampleHgeneHchrHbpHstrandTgeneTchrTbpTstrand
ChimerDB4STADTCGA-BR-7722-01AUSP28chr11

113723223

-CLYBLchr13

100425078

+


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Fusion Gene ORF analysis for USP28-CLYBL

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
5UTR-3CDSENST00000542033ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
5UTR-3CDSENST00000542033ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
5UTR-3CDSENST00000542033ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
5UTR-3CDSENST00000542033ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
5UTR-3CDSENST00000542033ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000003302ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000003302ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000003302ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000003302ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000003302ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000260188ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000260188ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000260188ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000260188ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000260188ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000537706ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000537706ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000537706ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000537706ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
Frame-shiftENST00000537706ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000544967ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000544967ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000544967ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000544967ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000544967ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000545540ENST00000339105USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000545540ENST00000376354USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000545540ENST00000376355USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000545540ENST00000376360USP28chr11

113723223

-CLYBLchr13

100425078

+
intron-3CDSENST00000545540ENST00000444838USP28chr11

113723223

-CLYBLchr13

100425078

+

check buttonORFfinder result based on the fusion transcript sequence of in-frame fusion genes.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)		BP loci
(transcript)		Predicted start
(transcript)		Predicted stop
(transcript)		Seq length
(amino acids)

check buttonDeepORF 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.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandNo-coding scoreCoding score

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Fusion Genomic Features for USP28-CLYBL


check buttonFusionAI 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.
HgeneHchrHbpHstrandTgeneTchrTbpTstrand1-pp (fusion gene breakpoint)
USP28chr11113723222-CLYBLchr13100425077+1.78E-091
USP28chr11113723222-CLYBLchr13100425077+1.78E-091

check buttonDistribution 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.

check buttonDistribution 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.
genomic feature of top 1%

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Fusion Protein Features for USP28-CLYBL


check button Four levels of functional features of fusion genes
Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:113723223/:100425078)
- 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.
FGviewer

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

Q8N0X4

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}.FUNCTION: Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (PubMed:29056341). The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:29056341, PubMed:24334609). Also displays malyl-CoA thioesterase activity (PubMed:29056341). Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341). Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341). {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341}.

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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Fusion Gene Sequence for USP28-CLYBL


check button 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 USP28-CLYBL


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


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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Related Drugs for USP28-CLYBL


check button Drugs targeting genes involved in this fusion gene.
(DrugBank Version 5.1.8 2021-05-08)
PartnerGeneUniProtAccDrugBank IDDrug nameDrug activityDrug typeDrug status

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Related Diseases for USP28-CLYBL


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource