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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:GSK3B-NCK1 (FusionGDB2 ID:35050)

Fusion Gene Summary for GSK3B-NCK1

check button Fusion gene summary
Fusion gene informationFusion gene name: GSK3B-NCK1
Fusion gene ID: 35050
HgeneTgene
Gene symbol

GSK3B

NCK1

Gene ID

2932

4690

Gene nameglycogen synthase kinase 3 betaNCK adaptor protein 1
Synonyms-NCK|NCKalpha|nck-1
Cytomap

3q13.33

3q22.3

Type of geneprotein-codingprotein-coding
Descriptionglycogen synthase kinase-3 betaGSK-3 betaGSK3beta isoformserine/threonine-protein kinase GSK3Bcytoplasmic protein NCK1NCK tyrosine kinaseSH2/SH3 adaptor protein NCK-alphamelanoma NCK proteinnon-catalytic region of tyrosine kinase
Modification date2020031520200327
UniProtAcc.

P16333

Ensembl transtripts involved in fusion geneENST00000264235, ENST00000316626, 
ENST00000473886, 
ENST00000288986, 
ENST00000481752, ENST00000469404, 
Fusion gene scores* DoF score31 X 22 X 12=81849 X 5 X 9=405
# samples 3612
** MAII scorelog2(36/8184*10)=-4.50673733341565
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/405*10)=-1.75488750216347
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: GSK3B [Title/Abstract] AND NCK1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointGSK3B(119812193)-NCK1(136646825), # 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
HgeneGSK3B

GO:0005977

glycogen metabolic process

8638126

HgeneGSK3B

GO:0006468

protein phosphorylation

11035810|16315267|20937854

HgeneGSK3B

GO:0006983

ER overload response

14744935

HgeneGSK3B

GO:0018105

peptidyl-serine phosphorylation

8638126|11104755|11955436|14744935|17139249

HgeneGSK3B

GO:0018107

peptidyl-threonine phosphorylation

11955436|17139249|25897075

HgeneGSK3B

GO:0031175

neuron projection development

19830702

HgeneGSK3B

GO:0031334

positive regulation of protein complex assembly

8638126

HgeneGSK3B

GO:0032091

negative regulation of protein binding

16890161

HgeneGSK3B

GO:0032436

positive regulation of proteasomal ubiquitin-dependent protein catabolic process

19364825

HgeneGSK3B

GO:0035556

intracellular signal transduction

14749367

HgeneGSK3B

GO:0043066

negative regulation of apoptotic process

14744935

HgeneGSK3B

GO:0046777

protein autophosphorylation

23184662

HgeneGSK3B

GO:0046827

positive regulation of protein export from nucleus

14744935

HgeneGSK3B

GO:1901215

negative regulation of neuron death

19830702

HgeneGSK3B

GO:1901216

positive regulation of neuron death

18508033

HgeneGSK3B

GO:2000300

regulation of synaptic vesicle exocytosis

17989287

TgeneNCK1

GO:0033137

negative regulation of peptidyl-serine phosphorylation

14676213|16835242

TgeneNCK1

GO:0036493

positive regulation of translation in response to endoplasmic reticulum stress

14676213

TgeneNCK1

GO:0045944

positive regulation of transcription by RNA polymerase II

10026169

TgeneNCK1

GO:0060548

negative regulation of cell death

18835251

TgeneNCK1

GO:0070262

peptidyl-serine dephosphorylation

16835242

TgeneNCK1

GO:1902237

positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway

14676213

TgeneNCK1

GO:1903676

positive regulation of cap-dependent translational initiation

11959995

TgeneNCK1

GO:1903679

positive regulation of cap-independent translational initiation

11959995

TgeneNCK1

GO:1903898

negative regulation of PERK-mediated unfolded protein response

14676213

TgeneNCK1

GO:1903912

negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation

14676213|16835242

TgeneNCK1

GO:1990441

negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress

16835242


check buttonFusion gene breakpoints across GSK3B (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 NCK1 (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
ChimerDB4COADTCGA-AA-3819GSK3Bchr3

119812193

-NCK1chr3

136646825

+


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Fusion Gene ORF analysis for GSK3B-NCK1

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-5UTRENST00000264235ENST00000288986GSK3Bchr3

119812193

-NCK1chr3

136646825

+
5CDS-5UTRENST00000264235ENST00000481752GSK3Bchr3

119812193

-NCK1chr3

136646825

+
5CDS-5UTRENST00000316626ENST00000288986GSK3Bchr3

119812193

-NCK1chr3

136646825

+
5CDS-5UTRENST00000316626ENST00000481752GSK3Bchr3

119812193

-NCK1chr3

136646825

+
5CDS-intronENST00000264235ENST00000469404GSK3Bchr3

119812193

-NCK1chr3

136646825

+
5CDS-intronENST00000316626ENST00000469404GSK3Bchr3

119812193

-NCK1chr3

136646825

+
intron-5UTRENST00000473886ENST00000288986GSK3Bchr3

119812193

-NCK1chr3

136646825

+
intron-5UTRENST00000473886ENST00000481752GSK3Bchr3

119812193

-NCK1chr3

136646825

+
intron-intronENST00000473886ENST00000469404GSK3Bchr3

119812193

-NCK1chr3

136646825

+

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 GSK3B-NCK1


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)
GSK3Bchr3119812193-NCK1chr3136646825+2.45E-060.9999975
GSK3Bchr3119812193-NCK1chr3136646825+2.45E-060.9999975

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 GSK3B-NCK1


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/:119812193/:136646825)
- 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
.NCK1

P16333

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: Adapter protein which associates with tyrosine-phosphorylated growth factor receptors, such as KDR and PDGFRB, or their cellular substrates. Maintains low levels of EIF2S1 phosphorylation by promoting its dephosphorylation by PP1. Plays a role in the DNA damage response, not in the detection of the damage by ATM/ATR, but for efficient activation of downstream effectors, such as that of CHEK2. Plays a role in ELK1-dependent transcriptional activation in response to activated Ras signaling. Modulates the activation of EIF2AK2/PKR by dsRNA. May play a role in cell adhesion and migration through interaction with ephrin receptors. {ECO:0000269|PubMed:10026169, ECO:0000269|PubMed:16835242, ECO:0000269|PubMed:17803907, ECO:0000269|PubMed:18835251, ECO:0000269|PubMed:23358419, ECO:0000269|PubMed:9430661}.

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 GSK3B-NCK1


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 GSK3B-NCK1


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 GSK3B-NCK1


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 GSK3B-NCK1


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