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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:TUBB6-ROBO1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TUBB6-ROBO1
FusionPDB ID: 95352
FusionGDB2.0 ID: 95352
HgeneTgene
Gene symbol

TUBB6

ROBO1

Gene ID

84617

6091

Gene nametubulin beta 6 class Vroundabout guidance receptor 1
SynonymsFPVEPD|HsT1601|TUBB-5DUTT1|SAX3
Cytomap

18p11.21

3p12.3

Type of geneprotein-codingprotein-coding
Descriptiontubulin beta-6 chainclass V beta-tubulintubulin beta MGC4083tubulin beta class Vtubulin, beta 6roundabout homolog 1deleted in U twenty twentyroundabout, axon guidance receptor, homolog 1
Modification date2020032020200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000317702, ENST00000586653, 
ENST00000590967, ENST00000591208, 
ENST00000591909, ENST00000592683, 
ENST00000466906, ENST00000467549, 
ENST00000436010, ENST00000464233, 
ENST00000495273, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 4 X 4=8015 X 14 X 5=1050
# samples 515
** MAII scorelog2(5/80*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1050*10)=-2.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TUBB6 [Title/Abstract] AND ROBO1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TUBB6 [Title/Abstract] AND ROBO1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TUBB6(12311052)-ROBO1(78685258), # samples:3
Anticipated loss of major functional domain due to fusion event.TUBB6-ROBO1 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.
TUBB6-ROBO1 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.
TUBB6-ROBO1 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.
TUBB6-ROBO1 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
TgeneROBO1

GO:0007156

homophilic cell adhesion via plasma membrane adhesion molecules

12504588

TgeneROBO1

GO:0021836

chemorepulsion involved in postnatal olfactory bulb interneuron migration

15207848

TgeneROBO1

GO:0050772

positive regulation of axonogenesis

12504588

TgeneROBO1

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/chr18:12311052/chr3:78685258)
- 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 TUBB6 (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 ROBO1 (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)
ENST00000317702TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-41025112342429731
ENST00000317702TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-41035112342429731
ENST00000317702TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-26555112342429731
ENST00000591909TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-3927336592254731
ENST00000591909TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-3928336592254731
ENST00000591909TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-2480336592254731
ENST00000586653TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-3920329522247731
ENST00000586653TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-3921329522247731
ENST00000586653TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-2473329522247731
ENST00000592683TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-3914323462241731
ENST00000592683TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-3915323462241731
ENST00000592683TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-2467323462241731
ENST00000590967TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-3908317402235731
ENST00000590967TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-3909317402235731
ENST00000590967TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-2461317402235731
ENST00000591208TUBB6chr1812311052+ENST00000464233ROBO1chr378685258-3899308312226731
ENST00000591208TUBB6chr1812311052+ENST00000436010ROBO1chr378685258-3900308312226731
ENST00000591208TUBB6chr1812311052+ENST00000495273ROBO1chr378685258-2452308312226731

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
ENST00000317702ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.000699060.99930096
ENST00000317702ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006990270.99930096
ENST00000317702ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0067368740.9932632
ENST00000591909ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.0006575730.9993424
ENST00000591909ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006575190.9993425
ENST00000591909ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0067721370.9932279
ENST00000586653ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.0006484460.99935156
ENST00000586653ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006483950.99935156
ENST00000586653ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0067329210.99326706
ENST00000592683ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.000639240.99936074
ENST00000592683ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006392850.99936074
ENST00000592683ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0069154210.99308455
ENST00000590967ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.0006496840.99935037
ENST00000590967ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006497280.99935025
ENST00000590967ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0069990410.993001
ENST00000591208ENST00000464233TUBB6chr1812311052+ROBO1chr378685258-0.0006378790.9993622
ENST00000591208ENST00000436010TUBB6chr1812311052+ROBO1chr378685258-0.0006379330.99936205
ENST00000591208ENST00000495273TUBB6chr1812311052+ROBO1chr378685258-0.0068005520.9931994

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 TUBB6-ROBO1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TUBB6chr1812311052ROBO1chr37868525830892PFGQLFRPDNFIFADCIANYNNQLDN
TUBB6chr1812311052ROBO1chr37868525831792PFGQLFRPDNFIFADCIANYNNQLDN
TUBB6chr1812311052ROBO1chr37868525832392PFGQLFRPDNFIFADCIANYNNQLDN
TUBB6chr1812311052ROBO1chr37868525832992PFGQLFRPDNFIFADCIANYNNQLDN
TUBB6chr1812311052ROBO1chr37868525833692PFGQLFRPDNFIFADCIANYNNQLDN
TUBB6chr1812311052ROBO1chr37868525851192PFGQLFRPDNFIFADCIANYNNQLDN

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Potential FusionNeoAntigen Information of TUBB6-ROBO1 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.
TUBB6-ROBO1_12311052_78685258.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)
TUBB6-ROBO1chr1812311052chr378685258511HLA-B39:06FRPDNFIFA0.99740.6072514
TUBB6-ROBO1chr1812311052chr378685258511HLA-B15:21IFADCIANY0.93310.84541120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:27FRPDNFIFA0.90540.9416514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:95FRPDNFIFA0.89650.5603514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:29FRPDNFIFA0.7860.8746514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:13FRPDNFIFA0.77470.8324514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:46FRPDNFIFA0.73960.78514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:10FRPDNFIFA0.73720.9317514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:80FRPDNFIFA0.71690.9125514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:67FRPDNFIFA0.71690.9125514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:67IFADCIANY0.5880.85641120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:80IFADCIANY0.5880.85641120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:10IFADCIANY0.54010.91331120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C12:16FRPDNFIFA0.00510.9472514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:01FRPDNFIFA0.90140.5201514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:17FRPDNFIFA0.8450.961514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C06:08FRPDNFIFA0.720.9902514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:02FRPDNFIFA0.71690.9125514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:02IFADCIANY0.5880.85641120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:22FRPDNFIFA0.54370.6652514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:17IFADCIANY0.52250.94991120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C07:04FRPDNFIFA0.50760.9083514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C14:03IFADCIANY0.02380.93591120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C14:02IFADCIANY0.02380.93591120
TUBB6-ROBO1chr1812311052chr378685258511HLA-C06:17FRPDNFIFA0.02130.993514
TUBB6-ROBO1chr1812311052chr378685258511HLA-C06:02FRPDNFIFA0.02130.993514

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Potential FusionNeoAntigen Information of TUBB6-ROBO1 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.
TUBB6-ROBO1_12311052_78685258.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)
TUBB6-ROBO1chr1812311052chr378685258511DRB1-1512IFADCIANYNNQLDN1126

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Fusion breakpoint peptide structures of TUBB6-ROBO1

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
8071RPDNFIFADCIANYTUBB6ROBO1chr1812311052chr378685258511

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TUBB6-ROBO1

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-B14:023BVN8071RPDNFIFADCIANY-7.89228-8.92758
HLA-B14:023BVN8071RPDNFIFADCIANY-6.88891-7.00231
HLA-B14:023BVN8071RPDNFIFADCIANY-6.41308-6.52648
HLA-B14:023BVN8071RPDNFIFADCIANY-5.79159-6.82689
HLA-B52:013W398071RPDNFIFADCIANY-5.96-6.0734
HLA-B52:013W398071RPDNFIFADCIANY-5.95743-6.07083
HLA-B52:013W398071RPDNFIFADCIANY-5.47012-6.50542
HLA-B52:013W398071RPDNFIFADCIANY-4.47032-5.50562
HLA-A11:014UQ28071RPDNFIFADCIANY-10.1899-10.3033
HLA-A11:014UQ28071RPDNFIFADCIANY-4.39665-5.43195
HLA-A11:014UQ28071RPDNFIFADCIANY-2.47279-3.50809
HLA-A24:025HGA8071RPDNFIFADCIANY-8.08878-9.12408
HLA-A24:025HGA8071RPDNFIFADCIANY-5.69412-5.80752
HLA-A24:025HGA8071RPDNFIFADCIANY-5.51884-5.63224
HLA-A24:025HGA8071RPDNFIFADCIANY-4.81054-5.84584
HLA-B44:053DX88071RPDNFIFADCIANY-7.18059-8.21589
HLA-B44:053DX88071RPDNFIFADCIANY-6.4458-6.5592
HLA-B44:053DX88071RPDNFIFADCIANY-6.08073-6.19413
HLA-B44:053DX88071RPDNFIFADCIANY-4.31241-5.34771

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Vaccine Design for the FusionNeoAntigens of TUBB6-ROBO1

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
TUBB6-ROBO1chr1812311052chr3786852581120IFADCIANYTCTTTGCTGATTGTATAGCAAATTATA
TUBB6-ROBO1chr1812311052chr378685258514FRPDNFIFATCCGGCCTGACAACTTCATCTTTGCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TUBB6-ROBO1chr1812311052chr3786852581126IFADCIANYNNQLDNTCTTTGCTGATTGTATAGCAAATTATAACAACCAACTGGATAACA

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Information of the samples that have these potential fusion neoantigens of TUBB6-ROBO1

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
BRCATUBB6-ROBO1chr1812311052ENST00000317702chr378685258ENST00000436010TCGA-A7-A5ZV-01A

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Potential target of CAR-T therapy development for TUBB6-ROBO1

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
TgeneROBO1chr18:12311052chr3:78685258ENST00000467549029898_91801552.0TransmembraneHelical

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 TUBB6-ROBO1

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 TUBB6-ROBO1

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