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Center for Computational Systems Medicine
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Fusion Gene and Fusion Protein Summary

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Fusion Amino Acid Sequences (multiple BPs and multiple gene isoforms)

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Fusion Protein Breakpoint Sequences - (for the Screening of the FusionNeoAntigens)

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Potential FusionNeoAntigens in HLA I - (netMHCpan v4.1 + deepHLApan v1.1)

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Potential FusionNeoAntigens in HLA II - (netMHCIIpan v4.1)

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Fusion Breakpoint 14 AA Peptide Structure - (RoseTTAFold)

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D - (Glide)

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Vaccine Design for the FusionNeoAntigens (RNA/protein sequences)

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Potential target of CAR-T therapy development

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Information on the samples that have these potential fusion neoantigens

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Fusion Protein Targeting Drugs - (Manual Curation)

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Fusion Protein Related diseases - (Manual Curation)

Fusion Protein:VPS72-ROBO2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VPS72-ROBO2
FusionPDB ID: 98505
FusionGDB2.0 ID: 98505
HgeneTgene
Gene symbol

VPS72

ROBO2

Gene ID

6944

6092

Gene namevacuolar protein sorting 72 homologroundabout guidance receptor 2
SynonymsCFL1|Swc2|TCFL1|YL-1|YL1SAX3
Cytomap

1q21.3

3p12.3

Type of geneprotein-codingprotein-coding
Descriptionvacuolar protein sorting-associated protein 72 homologtranscription factor-like 1transformation suppressor gene YL-1roundabout homolog 2roundabout, axon guidance receptor, homolog 2
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000354473, ENST00000496809, 
ENST00000469233, ENST00000332191, 
ENST00000461745, ENST00000487694, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 5=36018 X 21 X 7=2646
# samples 922
** MAII scorelog2(9/360*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(22/2646*10)=-3.58823763275402
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VPS72 [Title/Abstract] AND ROBO2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VPS72 [Title/Abstract] AND ROBO2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VPS72(151156793)-ROBO2(77617464), # samples:3
Anticipated loss of major functional domain due to fusion event.VPS72-ROBO2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
VPS72-ROBO2 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF.
VPS72-ROBO2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF.
VPS72-ROBO2 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame 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
TgeneROBO2

GO:0007156

homophilic cell adhesion via plasma membrane adhesion molecules

12504588

TgeneROBO2

GO:0050772

positive regulation of axonogenesis

12504588

TgeneROBO2

GO:0050925

negative regulation of negative chemotaxis

11748139



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/chr1:151156793/chr3:77617464)
- 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 buttonRetention analysis results 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, are available here.

check buttonFusion gene breakpoints across VPS72 (5'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure

check buttonFusion gene breakpoints across ROBO2 (3'-gene)
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
all structure


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Fusion Amino Acid Sequences


check buttonFusion information from ORFfinder translation from full-length transcript sequence from FusionPDB.
HenstTenstHgeneHchrHbpHstrandTgeneTchrTbpTstrandSeq length
(transcript)
BP loci
(transcript)
Predicted start
(transcript)
Predicted stop
(transcript)
Seq length
(amino acids)
ENST00000354473VPS72chr1151156793-ENST00000487694ROBO2chr377617464+4342599372886949
ENST00000354473VPS72chr1151156793-ENST00000461745ROBO2chr377617464+6796599372886949
ENST00000354473VPS72chr1151156793-ENST00000332191ROBO2chr377617464+41315993730691010

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
ENST00000354473ENST00000487694VPS72chr1151156793-ROBO2chr377617464+0.0001602940.99983966
ENST00000354473ENST00000461745VPS72chr1151156793-ROBO2chr377617464+7.64E-050.9999236
ENST00000354473ENST00000332191VPS72chr1151156793-ROBO2chr377617464+0.0001685220.99983144

check button Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones.

Get the fusion protein sequences from here.

Fusion protein sequence information is available in the fasta format.
>FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP

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Fusion Protein Breakpoint Sequences for VPS72-ROBO2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VPS72chr1151156793ROBO2chr377617464599187EAKITEELNLRSLDISPPAQGVDHRQ

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Potential FusionNeoAntigen Information of VPS72-ROBO2 in HLA I

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
VPS72-ROBO2_151156793_77617464.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5)
Fusion geneHchrHbpTgeneTchrTbpHLA IFusionNeoAntigen peptideBinding scoreImmunogenic scoreNeoantigen start (at BP 13)Neoantigen end (at BP 13)
VPS72-ROBO2chr1151156793chr377617464599HLA-A30:08RSLDISPPA0.95020.87481019
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:27SLDISPPAQGV0.99690.66971122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:60SLDISPPAQGV0.99610.64611122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:67SLDISPPAQGV0.99580.59151122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:24SLDISPPAQGV0.99580.59151122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:30SLDISPPAQGV0.99580.59151122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:13SLDISPPAQGV0.99570.74471122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:11SLDISPPAQGV0.99540.60571122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:38SLDISPPAQGV0.99150.72261122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:19SLDISPPAQGV0.98680.65081122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:35SLDISPPAQGV0.9850.62881122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:29SLDISPPAQGV0.98070.6031122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:20SLDISPPAQGV0.97560.60131122
VPS72-ROBO2chr1151156793chr377617464599HLA-B73:01LRSLDISPPA0.99750.7271919
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:07SLDISPPAQGV0.99620.63421122
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:01SLDISPPAQGV0.99580.59151122
VPS72-ROBO2chr1151156793chr377617464599HLA-A30:01RSLDISPPA0.95140.94791019
VPS72-ROBO2chr1151156793chr377617464599HLA-A02:03SLDISPPAQGV0.99530.7381122

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Potential FusionNeoAntigen Information of VPS72-ROBO2 in HLA II

check button Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific.
VPS72-ROBO2_151156793_77617464.msa

check button Potential FusionNeoAntigen Information
* We used NetMHCIIpan v4.1 (%rank<0.5).
Fusion geneHchrHbpTgeneTchrTbpHLA IIFusionNeoAntigen peptideNeoantigen start (at BP 13)Neoantigen end (at BP 13)
VPS72-ROBO2chr1151156793chr377617464599DRB1-0413EAKITEELNLRSLDI015
VPS72-ROBO2chr1151156793chr377617464599DRB1-0422EAKITEELNLRSLDI015
VPS72-ROBO2chr1151156793chr377617464599DRB1-0444EAKITEELNLRSLDI015

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Fusion breakpoint peptide structures of VPS72-ROBO2

check button3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens
* The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA.
File nameBPseqHgeneTgeneHchrHbpTchrTbpAAlen
1913ELNLRSLDISPPAQVPS72ROBO2chr1151156793chr377617464599

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VPS72-ROBO2

check buttonVirtual screening between 25 HLAs (from PDB) and FusionNeoAntigens
* We used Glide to predict the interaction between HLAs and neoantigens.
HLA allelePDB IDFile nameBPseqDocking scoreGlide score
HLA-B14:023BVN1913ELNLRSLDISPPAQ-7.15543-7.26883
HLA-B14:023BVN1913ELNLRSLDISPPAQ-4.77435-5.80965
HLA-B52:013W391913ELNLRSLDISPPAQ-6.80875-6.92215
HLA-B52:013W391913ELNLRSLDISPPAQ-4.20386-5.23916
HLA-A11:014UQ21913ELNLRSLDISPPAQ-7.5194-8.5547
HLA-A11:014UQ21913ELNLRSLDISPPAQ-6.9601-7.0735
HLA-A24:025HGA1913ELNLRSLDISPPAQ-7.52403-7.63743
HLA-A24:025HGA1913ELNLRSLDISPPAQ-5.82433-6.85963
HLA-B27:056PYJ1913ELNLRSLDISPPAQ-3.28285-4.31815
HLA-B44:053DX81913ELNLRSLDISPPAQ-5.91172-6.94702
HLA-B44:053DX81913ELNLRSLDISPPAQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of VPS72-ROBO2

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptide sequenceFusionNeoAntigen RNA sequence
VPS72-ROBO2chr1151156793chr3776174641019RSLDISPPAGGTCACTGGATATCAGCCCACCAGCAC
VPS72-ROBO2chr1151156793chr3776174641122SLDISPPAQGVCACTGGATATCAGCCCACCAGCACAAGGAGTGG
VPS72-ROBO2chr1151156793chr377617464919LRSLDISPPATACGGTCACTGGATATCAGCCCACCAGCAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
VPS72-ROBO2chr1151156793chr377617464015EAKITEELNLRSLDIAGGCCAAGATCACAGAAGAGCTTAATTTACGGTCACTGGATATCA

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Information of the samples that have these potential fusion neoantigens of VPS72-ROBO2

check button These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens.
Cancer typeFusion geneHchrHbpHenstTchrTbpTenstSample
LUADVPS72-ROBO2chr1151156793ENST00000354473chr377617464ENST00000332191TCGA-91-A4BC-01A

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Potential target of CAR-T therapy development for VPS72-ROBO2

check button Predicted 3D structure. We used RoseTTAFold.

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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features


* Minus value of BPloci means that the break point is located before the CDS.
- In-frame and retained 'Transmembrane'.
PartnerGeneHbpTbpENSTStrandBPexonTotalExonProtein feature loci*BPlociTotalLenProtein featureProtein feature note
TgeneROBO2chr1:151156793chr3:77617464ENST000004617451126860_88001379.0TransmembraneHelical
TgeneROBO2chr1:151156793chr3:77617464ENST000004876941227860_88001395.0TransmembraneHelical

check button Subcellular localization prediction of the transmembrane domain retained fusion proteins
* We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image.
HgeneHchrHbpHenstTgeneTchrTbpTenstDeepLoc result

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Related Drugs to VPS72-ROBO2

check button Drugs used for this fusion-positive patient.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDrugSourcePMID

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Related Diseases to VPS72-ROBO2

check button Diseases that have this fusion gene.
(Manual curation of PubMed, 04-30-2022 + MyCancerGenome)
HgeneTgeneDiseaseSourcePMID

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