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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:ROS1-FBXO9 (FusionGDB2 ID:75413)

Fusion Gene Summary for ROS1-FBXO9

check button Fusion gene summary
Fusion gene informationFusion gene name: ROS1-FBXO9
Fusion gene ID: 75413
HgeneTgene
Gene symbol

ROS1

FBXO9

Gene ID

6098

26268

Gene nameROS proto-oncogene 1, receptor tyrosine kinaseF-box protein 9
SynonymsMCF3|ROS|c-ros-1FBX9|NY-REN-57|VCIA1|dJ341E18.2
Cytomap

6q22.1

6p12.1

Type of geneprotein-codingprotein-coding
Descriptionproto-oncogene tyrosine-protein kinase ROSROS proto-oncogene 1 , receptor tyrosine kinasec-ros oncogene 1 , receptor tyrosine kinaseproto-oncogene c-Ros-1transmembrane tyrosine-specific protein kinasev-ros avian UR2 sarcoma virus oncogene homolog 1F-box only protein 9F-box protein Fbx9cross-immune reaction antigen 1renal carcinoma antigen NY-REN-57
Modification date2020031420200313
UniProtAcc.

Q9UK97

Ensembl transtripts involved in fusion geneENST00000368507, ENST00000368508, 
ENST00000461222, ENST00000244426, 
ENST00000323557, ENST00000370939, 
Fusion gene scores* DoF score3 X 4 X 1=127 X 8 X 5=280
# samples 49
** MAII scorelog2(4/12*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(9/280*10)=-1.63742992061529
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Context

PubMed: ROS1 [Title/Abstract] AND FBXO9 [Title/Abstract] AND fusion [Title/Abstract]

Most frequent breakpointROS1(117724302)-FBXO9(52962520), # samples:1
Anticipated loss of major functional domain due to fusion event.ROS1-FBXO9 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
ROS1-FBXO9 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
ROS1-FBXO9 seems lost the major protein functional domain in Hgene 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
HgeneROS1

GO:0001558

regulation of cell growth

16885344

HgeneROS1

GO:0006468

protein phosphorylation

16885344

HgeneROS1

GO:0032006

regulation of TOR signaling

16885344

TgeneFBXO9

GO:0016567

protein ubiquitination

23263282

TgeneFBXO9

GO:0031146

SCF-dependent proteasomal ubiquitin-dependent protein catabolic process

23263282


check buttonFusion gene breakpoints across ROS1 (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 FBXO9 (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
ChimerDB4LUADTCGA-64-1680-01AROS1chr6

117724302

-FBXO9chr6

52962520

+


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Fusion Gene ORF analysis for ROS1-FBXO9

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-intronENST00000368507ENST00000461222ROS1chr6

117724302

-FBXO9chr6

52962520

+
5CDS-intronENST00000368508ENST00000461222ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368507ENST00000244426ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368507ENST00000323557ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368507ENST00000370939ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368508ENST00000244426ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368508ENST00000323557ROS1chr6

117724302

-FBXO9chr6

52962520

+
Frame-shiftENST00000368508ENST00000370939ROS1chr6

117724302

-FBXO9chr6

52962520

+

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 ROS1-FBXO9


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)
ROS1chr6117724301-FBXO9chr652962519+0.0046010060.99539906
ROS1chr6117724301-FBXO9chr652962519+0.0046010060.99539906

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 ROS1-FBXO9


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/:117724302/:52962520)
- 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
.FBXO9

Q9UK97

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: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of TTI1 and TELO2 in a CK2-dependent manner, thereby directly regulating mTOR signaling. SCF(FBXO9) recognizes and binds mTORC1-bound TTI1 and TELO2 when they are phosphorylated by CK2 following growth factor deprivation, leading to their degradation. In contrast, the SCF(FBXO9) does not mediate ubiquitination of TTI1 and TELO2 when they are part of the mTORC2 complex. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation, while mTORC2 is activated due to the relief of feedback inhibition by mTORC1. {ECO:0000269|PubMed:23263282}.

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 ROS1-FBXO9


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 ROS1-FBXO9


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 ROS1-FBXO9


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 ROS1-FBXO9


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