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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:CDK2-ERBB3 (FusionGDB2 ID:HG1017TG2065)

Fusion Gene Summary for CDK2-ERBB3

check button Fusion gene summary
Fusion gene informationFusion gene name: CDK2-ERBB3
Fusion gene ID: hg1017tg2065
HgeneTgene
Gene symbol

CDK2

ERBB3

Gene ID

1017

2065

Gene namecyclin dependent kinase 2erb-b2 receptor tyrosine kinase 3
SynonymsCDKN2|p33(CDK2)ErbB-3|FERLK|HER3|LCCS2|MDA-BF-1|c-erbB-3|c-erbB3|erbB3-S|p180-ErbB3|p45-sErbB3|p85-sErbB3
Cytomap('CDK2')('ERBB3')

12q13.2

12q13.2

Type of geneprotein-codingprotein-coding
Descriptioncyclin-dependent kinase 2cdc2-related protein kinasecell division protein kinase 2p33 protein kinasereceptor tyrosine-protein kinase erbB-3human epidermal growth factor receptor 3proto-oncogene-like protein c-ErbB-3tyrosine kinase-type cell surface receptor HER3v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
Modification date2020031320200327
UniProtAcc..
Ensembl transtripts involved in fusion geneENST00000266970, ENST00000354056, 
ENST00000440311, ENST00000553376, 
ENST00000556656, 
Fusion gene scores* DoF score4 X 4 X 2=3228 X 12 X 14=4704
# samples 428
** MAII scorelog2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0		log2(28/4704*10)=-4.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: CDK2 [Title/Abstract] AND ERBB3 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCDK2(56360908)-ERBB3(56480315), # samples:2
Anticipated loss of major functional domain due to fusion event.CDK2-ERBB3 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
CDK2-ERBB3 seems lost the major protein functional domain in Tgene partner, which is a kinase 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
HgeneCDK2

GO:0006468

protein phosphorylation

12944431|28666995

HgeneCDK2

GO:0008284

positive regulation of cell proliferation

10767298

HgeneCDK2

GO:0016572

histone phosphorylation

11746698

HgeneCDK2

GO:0018105

peptidyl-serine phosphorylation

23184662

HgeneCDK2

GO:0060968

regulation of gene silencing

20935635

TgeneERBB3

GO:0007162

negative regulation of cell adhesion

7556068

TgeneERBB3

GO:0007165

signal transduction

10572067

TgeneERBB3

GO:0009968

negative regulation of signal transduction

11389077

TgeneERBB3

GO:0014065

phosphatidylinositol 3-kinase signaling

7556068

TgeneERBB3

GO:0042127

regulation of cell proliferation

11389077

TgeneERBB3

GO:0051048

negative regulation of secretion

10559227



check button Fusion gene information
* 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
ChimerDB4SARCTCGA-DX-A3LY-01BCDK2chr12

56360908

+ERBB3chr12

56480315

+


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Fusion Gene ORF analysis for CDK2-ERBB3

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-intronENST00000266970ENST00000411731CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000266970ENST00000415288CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000266970ENST00000450146CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000266970ENST00000549832CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000266970ENST00000553131CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000354056ENST00000411731CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000354056ENST00000415288CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000354056ENST00000450146CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000354056ENST00000549832CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000354056ENST00000553131CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000440311ENST00000411731CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000440311ENST00000415288CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000440311ENST00000450146CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000440311ENST00000549832CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000440311ENST00000553131CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000553376ENST00000411731CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000553376ENST00000415288CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000553376ENST00000450146CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000553376ENST00000549832CDK2chr12

56360908

+ERBB3chr12

56480315

+
5CDS-intronENST00000553376ENST00000553131CDK2chr12

56360908

+ERBB3chr12

56480315

+
Frame-shiftENST00000266970ENST00000267101CDK2chr12

56360908

+ERBB3chr12

56480315

+
Frame-shiftENST00000354056ENST00000267101CDK2chr12

56360908

+ERBB3chr12

56480315

+
Frame-shiftENST00000440311ENST00000267101CDK2chr12

56360908

+ERBB3chr12

56480315

+
Frame-shiftENST00000553376ENST00000267101CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-3CDSENST00000556656ENST00000267101CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-intronENST00000556656ENST00000411731CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-intronENST00000556656ENST00000415288CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-intronENST00000556656ENST00000450146CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-intronENST00000556656ENST00000549832CDK2chr12

56360908

+ERBB3chr12

56480315

+
intron-intronENST00000556656ENST00000553131CDK2chr12

56360908

+ERBB3chr12

56480315

+

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 CDK2-ERBB3


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)
CDK2chr1256360908+ERBB3chr1256480314+2.02E-060.999998
CDK2chr1256360908+ERBB3chr1256480314+2.02E-060.999998


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 CDK2-ERBB3


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/:56360908/:56480315)
- 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 CDK2-ERBB3


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 CDK2-ERBB3


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 CDK2-ERBB3


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 CDK2-ERBB3


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCDK2C0025202melanoma1CTD_human
HgeneCDK2C1168401Squamous cell carcinoma of the head and neck1CTD_human
TgeneC0036341Schizophrenia3PSYGENET
TgeneC1843478Lethal Congenital Contracture Syndrome 23CTD_human;GENOMICS_ENGLAND;ORPHANET
TgeneC0006142Malignant neoplasm of breast2CTD_human
TgeneC0678222Breast Carcinoma2CTD_human
TgeneC1257931Mammary Neoplasms, Human2CTD_human
TgeneC1458155Mammary Neoplasms2CTD_human
TgeneC4704874Mammary Carcinoma, Human2CTD_human
TgeneC0005586Bipolar Disorder1PSYGENET
TgeneC0011570Mental Depression1PSYGENET
TgeneC0016978gallbladder neoplasm1CTD_human
TgeneC0024121Lung Neoplasms1CTD_human
TgeneC0027627Neoplasm Metastasis1CTD_human
TgeneC0033578Prostatic Neoplasms1CTD_human
TgeneC0041696Unipolar Depression1PSYGENET
TgeneC0153452Malignant neoplasm of gallbladder1CTD_human
TgeneC0235874Disease Exacerbation1CTD_human
TgeneC0242379Malignant neoplasm of lung1CTD_human
TgeneC0376358Malignant neoplasm of prostate1CTD_human
TgeneC1269683Major Depressive Disorder1PSYGENET
TgeneC2931822Nasopharyngeal carcinoma1CTD_human
TgeneC4746575ERYTHROLEUKEMIA, FAMILIAL, SUSCEPTIBILITY TO1UNIPROT