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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:SIRT1-WWP2 (FusionGDB2 ID:81991)

Fusion Gene Summary for SIRT1-WWP2

check button Fusion gene summary
Fusion gene informationFusion gene name: SIRT1-WWP2
Fusion gene ID: 81991
HgeneTgene
Gene symbol

SIRT1

WWP2

Gene ID

23411

11060

Gene namesirtuin 1WW domain containing E3 ubiquitin protein ligase 2
SynonymsSIR2|SIR2L1|SIR2alphaAIP2|WWp2-like
Cytomap

10q21.3

16q22.1

Type of geneprotein-codingprotein-coding
DescriptionNAD-dependent protein deacetylase sirtuin-1SIR2-like protein 1regulatory protein SIR2 homolog 1sirtuin type 1NEDD4-like E3 ubiquitin-protein ligase WWP2HECT-type E3 ubiquitin transferase WWP2atrophin-1 interacting protein 2
Modification date2020032920200327
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000212015, ENST00000432464, 
ENST00000406900, ENST00000403579, 
ENST00000497639, 		ENST00000542271, 
ENST00000544162, ENST00000568684, 
ENST00000356003, ENST00000569174, 
ENST00000359154, ENST00000448661, 
Fusion gene scores* DoF score3 X 1 X 3=913 X 14 X 9=1638
# samples 316
** MAII scorelog2(3/9*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0		log2(16/1638*10)=-3.35579154675365
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: SIRT1 [Title/Abstract] AND WWP2 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointSIRT1(69651312)-WWP2(69967873), # samples:1
Anticipated loss of major functional domain due to fusion event.SIRT1-WWP2 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
SIRT1-WWP2 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
SIRT1-WWP2 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
SIRT1-WWP2 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
* 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
HgeneSIRT1

GO:0000122

negative regulation of transcription by RNA polymerase II

12535671|15692560|20955178

HgeneSIRT1

GO:0000183

chromatin silencing at rDNA

18485871

HgeneSIRT1

GO:0001525

angiogenesis

20620956

HgeneSIRT1

GO:0002821

positive regulation of adaptive immune response

21890893

HgeneSIRT1

GO:0006343

establishment of chromatin silencing

15469825

HgeneSIRT1

GO:0006476

protein deacetylation

18203716|18662546|20027304|20955178

HgeneSIRT1

GO:0006974

cellular response to DNA damage stimulus

18203716

HgeneSIRT1

GO:0006979

response to oxidative stress

14976264

HgeneSIRT1

GO:0007179

transforming growth factor beta receptor signaling pathway

23960241

HgeneSIRT1

GO:0007346

regulation of mitotic cell cycle

15692560

HgeneSIRT1

GO:0016239

positive regulation of macroautophagy

18296641

HgeneSIRT1

GO:0016567

protein ubiquitination

21841822

HgeneSIRT1

GO:0016575

histone deacetylation

12006491|15469825|16079181|17172643

HgeneSIRT1

GO:0031648

protein destabilization

20955178

HgeneSIRT1

GO:0032088

negative regulation of NF-kappaB transcription factor activity

15152190

HgeneSIRT1

GO:0034983

peptidyl-lysine deacetylation

15469825

HgeneSIRT1

GO:0042542

response to hydrogen peroxide

19934257

HgeneSIRT1

GO:0043065

positive regulation of apoptotic process

15152190

HgeneSIRT1

GO:0043124

negative regulation of I-kappaB kinase/NF-kappaB signaling

17680780

HgeneSIRT1

GO:0043433

negative regulation of DNA-binding transcription factor activity

11672523|20955178

HgeneSIRT1

GO:0043518

negative regulation of DNA damage response, signal transduction by p53 class mediator

11672523

HgeneSIRT1

GO:0043536

positive regulation of blood vessel endothelial cell migration

23960241

HgeneSIRT1

GO:0045348

positive regulation of MHC class II biosynthetic process

21890893

HgeneSIRT1

GO:0045722

positive regulation of gluconeogenesis

30193097

HgeneSIRT1

GO:0045766

positive regulation of angiogenesis

23960241|25217442

HgeneSIRT1

GO:0045892

negative regulation of transcription, DNA-templated

11672523|20074560

HgeneSIRT1

GO:0045944

positive regulation of transcription by RNA polymerase II

12837246|21807113

HgeneSIRT1

GO:0046628

positive regulation of insulin receptor signaling pathway

21241768

HgeneSIRT1

GO:0051097

negative regulation of helicase activity

18203716

HgeneSIRT1

GO:0070301

cellular response to hydrogen peroxide

20027304

HgeneSIRT1

GO:0070932

histone H3 deacetylation

20027304

HgeneSIRT1

GO:0071356

cellular response to tumor necrosis factor

15152190

HgeneSIRT1

GO:2000480

negative regulation of cAMP-dependent protein kinase activity

20203304

HgeneSIRT1

GO:2000757

negative regulation of peptidyl-lysine acetylation

20100829

HgeneSIRT1

GO:2000773

negative regulation of cellular senescence

20203304

HgeneSIRT1

GO:2000774

positive regulation of cellular senescence

18687677

TgeneWWP2

GO:0016567

protein ubiquitination

18776082|26280536

TgeneWWP2

GO:0032410

negative regulation of transporter activity

18776082

TgeneWWP2

GO:0034765

regulation of ion transmembrane transport

17289006

TgeneWWP2

GO:0042391

regulation of membrane potential

17289006

TgeneWWP2

GO:0051865

protein autoubiquitination

24105792

TgeneWWP2

GO:1901016

regulation of potassium ion transmembrane transporter activity

17289006


check buttonFusion gene breakpoints across SIRT1 (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 WWP2 (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-A4PD-01ASIRT1chr10

69651312

+WWP2chr16

69967873

+


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Fusion Gene ORF analysis for SIRT1-WWP2

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
5CDS-3UTRENST00000212015ENST00000542271SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-3UTRENST00000212015ENST00000544162SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-3UTRENST00000212015ENST00000568684SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-3UTRENST00000432464ENST00000542271SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-3UTRENST00000432464ENST00000544162SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-3UTRENST00000432464ENST00000568684SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-intronENST00000212015ENST00000356003SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-intronENST00000212015ENST00000569174SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-intronENST00000432464ENST00000356003SIRT1chr10

69651312

+WWP2chr16

69967873

+
5CDS-intronENST00000432464ENST00000569174SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-3CDSENST00000406900ENST00000359154SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-3CDSENST00000406900ENST00000448661SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-3UTRENST00000406900ENST00000542271SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-3UTRENST00000406900ENST00000544162SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-3UTRENST00000406900ENST00000568684SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-intronENST00000406900ENST00000356003SIRT1chr10

69651312

+WWP2chr16

69967873

+
5UTR-intronENST00000406900ENST00000569174SIRT1chr10

69651312

+WWP2chr16

69967873

+
Frame-shiftENST00000212015ENST00000359154SIRT1chr10

69651312

+WWP2chr16

69967873

+
Frame-shiftENST00000212015ENST00000448661SIRT1chr10

69651312

+WWP2chr16

69967873

+
Frame-shiftENST00000432464ENST00000359154SIRT1chr10

69651312

+WWP2chr16

69967873

+
Frame-shiftENST00000432464ENST00000448661SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3CDSENST00000403579ENST00000359154SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3CDSENST00000403579ENST00000448661SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3CDSENST00000497639ENST00000359154SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3CDSENST00000497639ENST00000448661SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000403579ENST00000542271SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000403579ENST00000544162SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000403579ENST00000568684SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000497639ENST00000542271SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000497639ENST00000544162SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-3UTRENST00000497639ENST00000568684SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-intronENST00000403579ENST00000356003SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-intronENST00000403579ENST00000569174SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-intronENST00000497639ENST00000356003SIRT1chr10

69651312

+WWP2chr16

69967873

+
intron-intronENST00000497639ENST00000569174SIRT1chr10

69651312

+WWP2chr16

69967873

+

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 SIRT1-WWP2


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)
SIRT1chr1069651312+WWP2chr1669967872+4.47E-111
SIRT1chr1069651312+WWP2chr1669967872+4.47E-111

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 SIRT1-WWP2


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/:69651312/:69967873)
- 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
..
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: 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}.

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 SIRT1-WWP2


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 SIRT1-WWP2


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 SIRT1-WWP2


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 SIRT1-WWP2


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