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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:CUL3-IRS1 (FusionGDB2 ID:HG8452TG3667)

Fusion Gene Summary for CUL3-IRS1

check button Fusion gene summary
Fusion gene informationFusion gene name: CUL3-IRS1
Fusion gene ID: hg8452tg3667
HgeneTgene
Gene symbol

CUL3

IRS1

Gene ID

8452

3667

Gene namecullin 3insulin receptor substrate 1
SynonymsCUL-3|PHA2EHIRS-1
Cytomap('CUL3')('IRS1')

2q36.2

2q36.3

Type of geneprotein-codingprotein-coding
Descriptioncullin-3insulin receptor substrate 1IRS-1
Modification date2020032720200313
UniProtAcc.

P35568

Ensembl transtripts involved in fusion geneENST00000264414, ENST00000409096, 
ENST00000409777, ENST00000432260, 
ENST00000344951, 
Fusion gene scores* DoF score12 X 12 X 7=10081 X 2 X 1=2
# samples 142
** MAII scorelog2(14/1008*10)=-2.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(2/2*10)=3.32192809488736
Context

PubMed: CUL3 [Title/Abstract] AND IRS1 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointCUL3(225422376)-IRS1(227600966), # samples:3
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
HgeneCUL3

GO:0000209

protein polyubiquitination

19261606

HgeneCUL3

GO:0006511

ubiquitin-dependent protein catabolic process

25401743|27561354

HgeneCUL3

GO:0006513

protein monoubiquitination

22358839

HgeneCUL3

GO:0006888

ER to Golgi vesicle-mediated transport

22358839

HgeneCUL3

GO:0016567

protein ubiquitination

17543862|19782033|19995937|20389280|23213400

HgeneCUL3

GO:0031145

anaphase-promoting complex-dependent catabolic process

10500095

HgeneCUL3

GO:0043161

proteasome-mediated ubiquitin-dependent protein catabolic process

19261606|19782033|20389280

HgeneCUL3

GO:0071630

nuclear protein quality control by the ubiquitin-proteasome system

27561354

TgeneIRS1

GO:0008286

insulin receptor signaling pathway

16516141|23401856

TgeneIRS1

GO:0014065

phosphatidylinositol 3-kinase signaling

7782332

TgeneIRS1

GO:0032868

response to insulin

16516141

TgeneIRS1

GO:0046326

positive regulation of glucose import

7493946

TgeneIRS1

GO:0046628

positive regulation of insulin receptor signaling pathway

7493946

TgeneIRS1

GO:0046676

negative regulation of insulin secretion

15572028



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
ChimerDB4BRCATCGA-E9-A1NE-01ACUL3chr2

225422375

-IRS1chr2

227600965

-
ChimerDB4BRCATCGA-E9-A1NE-01ACUL3chr2

225422376

-IRS1chr2

227600966

-
ChimerDB4BRCATCGA-E9-A1NECUL3chr2

225422375

-IRS1chr2

227600966

-


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Fusion Gene ORF analysis for CUL3-IRS1

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-3UTRENST00000264414ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-3UTRENST00000264414ENST00000305123CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-3UTRENST00000264414ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600966

-
5CDS-3UTRENST00000409096ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-3UTRENST00000409096ENST00000305123CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-3UTRENST00000409096ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600966

-
5CDS-3UTRENST00000409777ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-3UTRENST00000409777ENST00000305123CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-3UTRENST00000409777ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600966

-
5CDS-intronENST00000264414ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-intronENST00000264414ENST00000498335CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-intronENST00000264414ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600966

-
5CDS-intronENST00000409096ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-intronENST00000409096ENST00000498335CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-intronENST00000409096ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600966

-
5CDS-intronENST00000409777ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600965

-
5CDS-intronENST00000409777ENST00000498335CUL3chr2

225422376

-IRS1chr2

227600966

-
5CDS-intronENST00000409777ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600966

-
5UTR-3UTRENST00000432260ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600965

-
5UTR-3UTRENST00000432260ENST00000305123CUL3chr2

225422376

-IRS1chr2

227600966

-
5UTR-3UTRENST00000432260ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600966

-
5UTR-intronENST00000432260ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600965

-
5UTR-intronENST00000432260ENST00000498335CUL3chr2

225422376

-IRS1chr2

227600966

-
5UTR-intronENST00000432260ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600966

-
intron-3UTRENST00000344951ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600965

-
intron-3UTRENST00000344951ENST00000305123CUL3chr2

225422376

-IRS1chr2

227600966

-
intron-3UTRENST00000344951ENST00000305123CUL3chr2

225422375

-IRS1chr2

227600966

-
intron-intronENST00000344951ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600965

-
intron-intronENST00000344951ENST00000498335CUL3chr2

225422376

-IRS1chr2

227600966

-
intron-intronENST00000344951ENST00000498335CUL3chr2

225422375

-IRS1chr2

227600966

-

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 CUL3-IRS1


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)


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Fusion Protein Features for CUL3-IRS1


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/:225422376/:227600966)
- 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
.IRS1

P35568

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: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). {ECO:0000250, ECO:0000269|PubMed:16878150}.

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 CUL3-IRS1


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 CUL3-IRS1


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 CUL3-IRS1


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 CUL3-IRS1


check button Diseases associated with fusion partners.
(DisGeNet 4.0)
PartnerGeneDisease IDDisease name# pubmedsSource
HgeneCUL3C0025202melanoma1CTD_human
HgeneCUL3C0033578Prostatic Neoplasms1CTD_human
HgeneCUL3C0376358Malignant neoplasm of prostate1CTD_human
HgeneCUL3C1535926Neurodevelopmental Disorders1CTD_human
HgeneCUL3C3469606PSEUDOHYPOALDOSTERONISM, TYPE IIE1CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneC0011860Diabetes Mellitus, Non-Insulin-Dependent9CTD_human;UNIPROT
TgeneC2239176Liver carcinoma2CTD_human
TgeneC0002152Alloxan Diabetes1CTD_human
TgeneC0007621Neoplastic Cell Transformation1CTD_human
TgeneC0010054Coronary Arteriosclerosis1CTD_human
TgeneC0010068Coronary heart disease1CTD_human
TgeneC0011849Diabetes Mellitus1CTD_human
TgeneC0011853Diabetes Mellitus, Experimental1CTD_human
TgeneC0020459Hyperinsulinism1CTD_human
TgeneC0020473Hyperlipidemia1CTD_human
TgeneC0021655Insulin Resistance1CTD_human
TgeneC0028754Obesity1CTD_human
TgeneC0032927Precancerous Conditions1CTD_human
TgeneC0033578Prostatic Neoplasms1CTD_human
TgeneC0038433Streptozotocin Diabetes1CTD_human
TgeneC0282313Condition, Preneoplastic1CTD_human
TgeneC0376358Malignant neoplasm of prostate1CTD_human
TgeneC0920563Insulin Sensitivity1CTD_human
TgeneC1168401Squamous cell carcinoma of the head and neck1CTD_human
TgeneC1257963Endogenous Hyperinsulinism1CTD_human
TgeneC1257964Exogenous Hyperinsulinism1CTD_human
TgeneC1257965Compensatory Hyperinsulinemia1CTD_human
TgeneC1706412Lipidemias1CTD_human
TgeneC1956346Coronary Artery Disease1CTD_human