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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:TMEM66-TNKS (FusionGDB2 ID:92230)

Fusion Gene Summary for TMEM66-TNKS

check button Fusion gene summary
Fusion gene informationFusion gene name: TMEM66-TNKS
Fusion gene ID: 92230
HgeneTgene
Gene symbol

TMEM66

TNKS

Gene ID

51669

8658

Gene namestore-operated calcium entry associated regulatory factortankyrase
SynonymsFOAP-7|HSPC035|TMEM66|XTP3ARTD5|PARP-5a|PARP5A|PARPL|TIN1|TINF1|TNKS1|pART5
Cytomap

8p12

8p23.1

Type of geneprotein-codingprotein-coding
Descriptionstore-operated calcium entry-associated regulatory factorHBV X-transactivated gene 3 proteinHBV XAg-transactivated protein 3SARAF long isoformSARAF short isoformSOCE-associated regulatory factortesticular secretory protein Li 59transmembrane proteipoly [ADP-ribose] polymerase tankyrase-1ADP-ribosyltransferase diphtheria toxin-like 5TANK1TNKS-1TRF1-interacting ankyrin-related ADP-ribose polymerase 1poly [ADP-ribose] polymerase 5Aprotein poly-ADP-ribosyltransferase tankyrase-1tankyrase Itanky
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000256255, ENST00000521083, 
ENST00000536273, ENST00000545648, 
ENST00000518027, ENST00000522110, 
ENST00000310430, ENST00000518281, 
ENST00000520408, 
Fusion gene scores* DoF score5 X 4 X 4=808 X 9 X 6=432
# samples 59
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/432*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: TMEM66 [Title/Abstract] AND TNKS [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointTMEM66(29940363)-TNKS(9537461), # samples:2
Anticipated loss of major functional domain due to fusion event.TMEM66-TNKS seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
TMEM66-TNKS seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneTMEM66

GO:2001256

regulation of store-operated calcium entry

22464749

TgeneTNKS

GO:0000209

protein polyubiquitination

19759537|21478859

TgeneTNKS

GO:0006471

protein ADP-ribosylation

9822378|15133513|21270334

TgeneTNKS

GO:0018105

peptidyl-serine phosphorylation

17026964

TgeneTNKS

GO:0018107

peptidyl-threonine phosphorylation

17026964

TgeneTNKS

GO:0032212

positive regulation of telomere maintenance via telomerase

12782650|18221737

TgeneTNKS

GO:0045944

positive regulation of transcription by RNA polymerase II

19245366

TgeneTNKS

GO:0051973

positive regulation of telomerase activity

12782650

TgeneTNKS

GO:0070212

protein poly-ADP-ribosylation

9822378|16076287|25043379

TgeneTNKS

GO:0070213

protein auto-ADP-ribosylation

9822378|15133513|19759537|21478859

TgeneTNKS

GO:1904355

positive regulation of telomere capping

21531765

TgeneTNKS

GO:1904743

negative regulation of telomeric DNA binding

9822378


check buttonFusion gene breakpoints across TMEM66 (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 TNKS (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
ChimerDB4PRADTCGA-KK-A8I5-01ATMEM66chr8

29940363

-TNKSchr8

9537461

+
ChimerDB4PRADTCGA-KK-A8I5TMEM66chr8

29940363

-TNKSchr8

9537461

+


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Fusion Gene ORF analysis for TMEM66-TNKS

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-3UTRENST00000256255ENST00000518027TMEM66chr8

29940363

-TNKSchr8

9537461

+
5CDS-intronENST00000256255ENST00000522110TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000521083ENST00000310430TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000521083ENST00000518281TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000521083ENST00000520408TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000536273ENST00000310430TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000536273ENST00000518281TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000536273ENST00000520408TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000545648ENST00000310430TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000545648ENST00000518281TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3CDSENST00000545648ENST00000520408TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3UTRENST00000521083ENST00000518027TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3UTRENST00000536273ENST00000518027TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-3UTRENST00000545648ENST00000518027TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-intronENST00000521083ENST00000522110TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-intronENST00000536273ENST00000522110TMEM66chr8

29940363

-TNKSchr8

9537461

+
5UTR-intronENST00000545648ENST00000522110TMEM66chr8

29940363

-TNKSchr8

9537461

+
Frame-shiftENST00000256255ENST00000310430TMEM66chr8

29940363

-TNKSchr8

9537461

+
Frame-shiftENST00000256255ENST00000518281TMEM66chr8

29940363

-TNKSchr8

9537461

+
Frame-shiftENST00000256255ENST00000520408TMEM66chr8

29940363

-TNKSchr8

9537461

+

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 TMEM66-TNKS


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)
TMEM66chr829940362-TNKSchr89537460+9.49E-050.9999051
TMEM66chr829940362-TNKSchr89537460+9.49E-050.9999051
TMEM66chr829940362-TNKSchr89537460+9.49E-050.9999051
TMEM66chr829940362-TNKSchr89537460+9.49E-050.9999051

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 TMEM66-TNKS


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/:29940363/:9537461)
- 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 TMEM66-TNKS


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 TMEM66-TNKS


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 TMEM66-TNKS


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 TMEM66-TNKS


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