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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:VPS53-UBR5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VPS53-UBR5
FusionPDB ID: 98493
FusionGDB2.0 ID: 98493
HgeneTgene
Gene symbol

VPS53

UBR5

Gene ID

55275

51366

Gene nameVPS53 subunit of GARP complexubiquitin protein ligase E3 component n-recognin 5
SynonymsHCCS1|PCH2E|hVps53L|pp13624DD5|EDD|EDD1|HYD
Cytomap

17p13.3

8q22.3

Type of geneprotein-codingprotein-coding
Descriptionvacuolar protein sorting-associated protein 53 homologVPS53, GARP complex subunitE3 ubiquitin-protein ligase UBR5E3 identified by differential displayE3 ubiquitin-protein ligase, HECT domain-containing 1HECT-type E3 ubiquitin transferase UBR5hyperplastic discs protein homologprogestin-induced protein
Modification date2020031320200315
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000291074, ENST00000437048, 
ENST00000446250, ENST00000571805, 
ENST00000576149, ENST00000401468, 
ENST00000574029, 
ENST00000519528, 
ENST00000220959, ENST00000518205, 
ENST00000520539, ENST00000521922, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 15 X 14=378014 X 17 X 10=2380
# samples 2419
** MAII scorelog2(24/3780*10)=-3.97727992349992
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(19/2380*10)=-3.64689024986436
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VPS53 [Title/Abstract] AND UBR5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VPS53 [Title/Abstract] AND UBR5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VPS53(526773)-UBR5(103277506), # samples:1
Anticipated loss of major functional domain due to fusion event.VPS53-UBR5 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.
VPS53-UBR5 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.
VPS53-UBR5 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.
VPS53-UBR5 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.
VPS53-UBR5 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
VPS53-UBR5 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
VPS53-UBR5 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
VPS53-UBR5 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
TgeneUBR5

GO:0000209

protein polyubiquitination

21118991|28689657

TgeneUBR5

GO:0006974

cellular response to DNA damage stimulus

12011095

TgeneUBR5

GO:0010628

positive regulation of gene expression

18076571

TgeneUBR5

GO:0050847

progesterone receptor signaling pathway

12011095

TgeneUBR5

GO:0070936

protein K48-linked ubiquitination

28689657



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/chr17:526773/chr8:103277506)
- 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 VPS53 (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 UBR5 (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)
ENST00000437048VPS53chr17526773-ENST00000520539UBR5chr8103277506-353112631472240697
ENST00000437048VPS53chr17526773-ENST00000220959UBR5chr8103277506-280412631472237696
ENST00000437048VPS53chr17526773-ENST00000518205UBR5chr8103277506-234212631472237696
ENST00000437048VPS53chr17526773-ENST00000521922UBR5chr8103277506-234212631472237696
ENST00000291074VPS53chr17526773-ENST00000520539UBR5chr8103277506-343111631342140668
ENST00000291074VPS53chr17526773-ENST00000220959UBR5chr8103277506-270411631342137667
ENST00000291074VPS53chr17526773-ENST00000518205UBR5chr8103277506-224211631342137667
ENST00000291074VPS53chr17526773-ENST00000521922UBR5chr8103277506-224211631342137667
ENST00000571805VPS53chr17526773-ENST00000520539UBR5chr8103277506-352112531372230697
ENST00000571805VPS53chr17526773-ENST00000220959UBR5chr8103277506-279412531372227696
ENST00000571805VPS53chr17526773-ENST00000518205UBR5chr8103277506-233212531372227696
ENST00000571805VPS53chr17526773-ENST00000521922UBR5chr8103277506-233212531372227696

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
ENST00000437048ENST00000520539VPS53chr17526773-UBR5chr8103277506-0.0007346650.9992654
ENST00000437048ENST00000220959VPS53chr17526773-UBR5chr8103277506-0.0019989370.99800104
ENST00000437048ENST00000518205VPS53chr17526773-UBR5chr8103277506-0.0038310130.99616903
ENST00000437048ENST00000521922VPS53chr17526773-UBR5chr8103277506-0.0038310130.99616903
ENST00000291074ENST00000520539VPS53chr17526773-UBR5chr8103277506-0.0003947750.99960524
ENST00000291074ENST00000220959VPS53chr17526773-UBR5chr8103277506-0.0012792830.9987207
ENST00000291074ENST00000518205VPS53chr17526773-UBR5chr8103277506-0.0025981060.99740195
ENST00000291074ENST00000521922VPS53chr17526773-UBR5chr8103277506-0.0025981060.99740195
ENST00000571805ENST00000520539VPS53chr17526773-UBR5chr8103277506-0.0007321530.9992679
ENST00000571805ENST00000220959VPS53chr17526773-UBR5chr8103277506-0.0019754240.9980246
ENST00000571805ENST00000518205VPS53chr17526773-UBR5chr8103277506-0.0037827560.9962172
ENST00000571805ENST00000521922VPS53chr17526773-UBR5chr8103277506-0.0037827560.9962172

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 VPS53-UBR5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VPS53chr17526773UBR5chr81032775061163343KRFSGCTLTDGTLENRKRHGSSRSVV
VPS53chr17526773UBR5chr81032775061163343KRFSGCTLTDGTLQENRKRHGSSRSV
VPS53chr17526773UBR5chr81032775061253372KRFSGCTLTDGTLENRKRHGSSRSVV
VPS53chr17526773UBR5chr81032775061253372KRFSGCTLTDGTLQENRKRHGSSRSV
VPS53chr17526773UBR5chr81032775061263372KRFSGCTLTDGTLENRKRHGSSRSVV
VPS53chr17526773UBR5chr81032775061263372KRFSGCTLTDGTLQENRKRHGSSRSV

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Potential FusionNeoAntigen Information of VPS53-UBR5 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.

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)

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Potential FusionNeoAntigen Information of VPS53-UBR5 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.
VPS53-UBR5_526773_103277506.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)
VPS53-UBR5chr17526773chr81032775061163DRB1-1103DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1103TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1111DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1141DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1141DGTLQENRKRHGSSR924
VPS53-UBR5chr17526773chr81032775061163DRB1-1141TDGTLQENRKRHGSS823
VPS53-UBR5chr17526773chr81032775061163DRB1-1155DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1155TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1163DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1163TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1176DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1176TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1185DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1185TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1324DGTLENRKRHGSSRS924
VPS53-UBR5chr17526773chr81032775061163DRB1-1324TDGTLENRKRHGSSR823
VPS53-UBR5chr17526773chr81032775061163DRB1-1363DGTLENRKRHGSSRS924

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Fusion breakpoint peptide structures of VPS53-UBR5

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VPS53-UBR5

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

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Vaccine Design for the FusionNeoAntigens of VPS53-UBR5

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

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
VPS53-UBR5chr17526773chr8103277506823TDGTLENRKRHGSSRACCGATGGGACCCTGGAAAACCGAAAGCGCCATGGCTCTAGTCGA
VPS53-UBR5chr17526773chr8103277506823TDGTLQENRKRHGSSACCGATGGGACCCTGCAGGAAAACCGAAAGCGCCATGGCTCTAGT
VPS53-UBR5chr17526773chr8103277506924DGTLENRKRHGSSRSGATGGGACCCTGGAAAACCGAAAGCGCCATGGCTCTAGTCGAAGT
VPS53-UBR5chr17526773chr8103277506924DGTLQENRKRHGSSRGATGGGACCCTGCAGGAAAACCGAAAGCGCCATGGCTCTAGTCGA

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Information of the samples that have these potential fusion neoantigens of VPS53-UBR5

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

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Potential target of CAR-T therapy development for VPS53-UBR5

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 VPS53-UBR5

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 VPS53-UBR5

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