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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:UNC5C-VTA1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: UNC5C-VTA1
FusionPDB ID: 96853
FusionGDB2.0 ID: 96853
HgeneTgene
Gene symbol

UNC5C

VTA1

Gene ID

8633

51534

Gene nameunc-5 netrin receptor Cvesicle trafficking 1
SynonymsUNC5H3C6orf55|DRG-1|DRG1|HSPC228|LIP5|My012|SBP1
Cytomap

4q22.3

6q24.1-q24.2

Type of geneprotein-codingprotein-coding
Descriptionnetrin receptor UNC5Cprotein unc-5 homolog 3protein unc-5 homolog Cunc-5 homolog 3unc-5 homolog Cunc5 (C.elegans homolog) cvacuolar protein sorting-associated protein VTA1 homologLYST-interacting protein 5SKD1-binding protein 1Vps20-associated 1 homologdopamine-responsive gene 1 proteinhomolog of mouse SKD1-binding protein 1vesicle (multivesicular body) trafficking 1
Modification date2020031320200313
UniProtAcc

UNC5CL

Main function of 5'-partner protein: 518
.
Ensembl transtripts involved in fusion geneENST idsENST00000453304, ENST00000504962, 
ENST00000506749, 
ENST00000491881, 
ENST00000367621, ENST00000367630, 
ENST00000452973, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 7 X 3=14710 X 12 X 6=720
# samples 713
** MAII scorelog2(7/147*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/720*10)=-2.46948528330122
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: UNC5C [Title/Abstract] AND VTA1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: UNC5C [Title/Abstract] AND VTA1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)UNC5C(96256560)-VTA1(142519575), # samples:1
Anticipated loss of major functional domain due to fusion event.UNC5C-VTA1 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.
UNC5C-VTA1 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.
UNC5C-VTA1 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.
UNC5C-VTA1 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
HgeneUNC5C

GO:1990791

dorsal root ganglion development

28483977



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/chr4:96256560/chr6:142519575)
- 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 UNC5C (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 VTA1 (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)
ENST00000453304UNC5Cchr496256560-ENST00000367630VTA1chr6142519575+7145695221098358
ENST00000453304UNC5Cchr496256560-ENST00000367621VTA1chr6142519575+1523695221098358
ENST00000453304UNC5Cchr496256560-ENST00000452973VTA1chr6142519575+1626695221017331
ENST00000506749UNC5Cchr496256560-ENST00000367630VTA1chr6142519575+7145695221098358
ENST00000506749UNC5Cchr496256560-ENST00000367621VTA1chr6142519575+1523695221098358
ENST00000506749UNC5Cchr496256560-ENST00000452973VTA1chr6142519575+1626695221017331
ENST00000504962UNC5Cchr496256560-ENST00000367630VTA1chr6142519575+7139689161092358
ENST00000504962UNC5Cchr496256560-ENST00000367621VTA1chr6142519575+1517689161092358
ENST00000504962UNC5Cchr496256560-ENST00000452973VTA1chr6142519575+1620689161011331

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
ENST00000453304ENST00000367630UNC5Cchr496256560-VTA1chr6142519575+0.0011386680.9988613
ENST00000453304ENST00000367621UNC5Cchr496256560-VTA1chr6142519575+0.0034868660.9965132
ENST00000453304ENST00000452973UNC5Cchr496256560-VTA1chr6142519575+0.003031840.9969682
ENST00000506749ENST00000367630UNC5Cchr496256560-VTA1chr6142519575+0.0011386680.9988613
ENST00000506749ENST00000367621UNC5Cchr496256560-VTA1chr6142519575+0.0034868660.9965132
ENST00000506749ENST00000452973UNC5Cchr496256560-VTA1chr6142519575+0.003031840.9969682
ENST00000504962ENST00000367630UNC5Cchr496256560-VTA1chr6142519575+0.0011357720.9988643
ENST00000504962ENST00000367621UNC5Cchr496256560-VTA1chr6142519575+0.0034884780.9965115
ENST00000504962ENST00000452973UNC5Cchr496256560-VTA1chr6142519575+0.0032700340.99672997

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 UNC5C-VTA1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
UNC5Cchr496256560VTA1chr6142519575689224KDHIVDERVDETSDIEENEDAGAASL
UNC5Cchr496256560VTA1chr6142519575695224KDHIVDERVDETSDIEENEDAGAASL

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Potential FusionNeoAntigen Information of UNC5C-VTA1 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.
UNC5C-VTA1_96256560_142519575.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)
UNC5C-VTA1chr496256560chr6142519575695HLA-C08:15RVDETSDI0.99960.8818715
UNC5C-VTA1chr496256560chr6142519575695HLA-C08:02RVDETSDI0.99960.8818715

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Potential FusionNeoAntigen Information of UNC5C-VTA1 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.
UNC5C-VTA1_96256560_142519575.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)
UNC5C-VTA1chr496256560chr6142519575695DRB4-0101KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0101DHIVDERVDETSDIE116
UNC5C-VTA1chr496256560chr6142519575695DRB4-0103KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0103DHIVDERVDETSDIE116
UNC5C-VTA1chr496256560chr6142519575695DRB4-0104KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0104DHIVDERVDETSDIE116
UNC5C-VTA1chr496256560chr6142519575695DRB4-0106KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0106DHIVDERVDETSDIE116
UNC5C-VTA1chr496256560chr6142519575695DRB4-0107KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0107DHIVDERVDETSDIE116
UNC5C-VTA1chr496256560chr6142519575695DRB4-0108KDHIVDERVDETSDI015
UNC5C-VTA1chr496256560chr6142519575695DRB4-0108DHIVDERVDETSDIE116

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Fusion breakpoint peptide structures of UNC5C-VTA1

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
2108ERVDETSDIEENEDUNC5CVTA1chr496256560chr6142519575695

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of UNC5C-VTA1

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-B14:023BVN2108ERVDETSDIEENED-7.94671-8.06011
HLA-B14:023BVN2108ERVDETSDIEENED-3.49164-4.52694
HLA-B52:013W392108ERVDETSDIEENED-4.98615-5.09955
HLA-B52:013W392108ERVDETSDIEENED-3.36084-4.39614
HLA-A24:025HGA2108ERVDETSDIEENED-5.97793-6.09133
HLA-A24:025HGA2108ERVDETSDIEENED-5.06167-6.09697
HLA-B44:053DX82108ERVDETSDIEENED-9.16206-9.27546
HLA-B44:053DX82108ERVDETSDIEENED-4.83147-5.86677

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Vaccine Design for the FusionNeoAntigens of UNC5C-VTA1

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
UNC5C-VTA1chr496256560chr6142519575715RVDETSDIGAGTAGATGAAACTTCCGATATTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
UNC5C-VTA1chr496256560chr6142519575015KDHIVDERVDETSDIAGGACCACATAGTAGATGAAAGAGTAGATGAAACTTCCGATATTG
UNC5C-VTA1chr496256560chr6142519575116DHIVDERVDETSDIEACCACATAGTAGATGAAAGAGTAGATGAAACTTCCGATATTGAAG

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Information of the samples that have these potential fusion neoantigens of UNC5C-VTA1

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
UCECUNC5C-VTA1chr496256560ENST00000453304chr6142519575ENST00000367621TCGA-EY-A2OO

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Potential target of CAR-T therapy development for UNC5C-VTA1

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

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 UNC5C-VTA1

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 UNC5C-VTA1

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