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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:VWA8-RB1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VWA8-RB1
FusionPDB ID: 98628
FusionGDB2.0 ID: 98628
HgeneTgene
Gene symbol

VWA8

RB1

Gene ID

23078

5925

Gene namevon Willebrand factor A domain containing 8RB transcriptional corepressor 1
SynonymsKIAA0564|P7BP2OSRC|PPP1R130|RB|p105-Rb|p110-RB1|pRb|pp110
Cytomap

13q14.11

13q14.2

Type of geneprotein-codingprotein-coding
Descriptionvon Willebrand factor A domain-containing protein 8PEX7-binding protein 2retinoblastoma-associated proteinGOS563 exon 17 substitution mutation causes premature stopexon 17 tumor GOS561 substitution mutation causes premature stopprepro-retinoblastoma-associated proteinprotein phosphatase 1, regulatory subunit 130retinoblas
Modification date2020031320200329
UniProtAcc

A3KMH1

Main function of 5'-partner protein: FUNCTION: Exhibits ATPase activity in vitro. {ECO:0000250|UniProtKB:Q8CC88}.

RB1CC1

Main function of 5'-partner protein: 1594
Ensembl transtripts involved in fusion geneENST idsENST00000281496, ENST00000379310, 
ENST00000478987, 
ENST00000484879, 
ENST00000267163, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 12 X 6=93613 X 16 X 11=2288
# samples 1327
** MAII scorelog2(13/936*10)=-2.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(27/2288*10)=-3.08305573972756
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VWA8 [Title/Abstract] AND RB1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VWA8 [Title/Abstract] AND RB1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VWA8(42439872)-RB1(48916735), # samples:2
Anticipated loss of major functional domain due to fusion event.VWA8-RB1 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.
VWA8-RB1 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.
VWA8-RB1 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.
VWA8-RB1 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
TgeneRB1

GO:0043550

regulation of lipid kinase activity

16286473

TgeneRB1

GO:0045892

negative regulation of transcription, DNA-templated

10783144|12065415|19223331

TgeneRB1

GO:2000679

positive regulation of transcription regulatory region DNA binding

25100735



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/chr13:42439872/chr13:48916735)
- 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 VWA8 (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 RB1 (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)
ENST00000379310VWA8chr1342439872-ENST00000267163RB1chr1348916735+593214946940161315
ENST00000281496VWA8chr1342439872-ENST00000267163RB1chr1348916735+596815301240521346

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
ENST00000379310ENST00000267163VWA8chr1342439872-RB1chr1348916735+0.0001584250.9998416
ENST00000281496ENST00000267163VWA8chr1342439872-RB1chr1348916735+0.0001639120.9998361

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 VWA8-RB1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VWA8chr1342439872RB1chr13489167351494474DTLGYNIEPIMLYQGGYIQKKKELWG
VWA8chr1342439872RB1chr13489167351530505DTLGYNIEPIMLYQGGYIQKKKELWG

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Potential FusionNeoAntigen Information of VWA8-RB1 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 VWA8-RB1 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.
VWA8-RB1_42439872_48916735.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)
VWA8-RB1chr1342439872chr13489167351530DRB1-1501IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1501NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1501EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1502IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1503IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1504IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1504NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1504EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1505IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1505NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1505EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1506IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1506NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1506EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1507IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1507NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1507EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1508IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1509IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1509NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1509EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1510IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1510EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1510NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1511IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1512IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1512NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1512EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1513IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1513NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1513EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1514IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1515IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1516IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1516NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1516EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1518IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1518NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1518EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1519IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1520IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1520NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1520EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1521IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1521EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1521NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1522IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1522NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1522EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1523IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1524IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1524NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1524EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1526IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1528IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1528NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1528EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1529IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1530IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1531IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1532IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1532NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1532EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1533IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1533NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1533EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1535IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1535NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1535EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1536IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1536NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1536EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1537IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1537NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1537EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1538IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1539IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1540IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1540NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1540EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1541IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1541NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1541EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1542IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1542NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1542EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1543IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1543NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1543EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1544IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1545IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1545NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1545EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1546IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1546NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1546EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1547IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1548IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1548NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1548EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB1-1549IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB1-1549NIEPIMLYQGGYIQK520
VWA8-RB1chr1342439872chr13489167351530DRB1-1549EPIMLYQGGYIQKKK722
VWA8-RB1chr1342439872chr13489167351530DRB5-0202IEPIMLYQGGYIQKK621
VWA8-RB1chr1342439872chr13489167351530DRB5-0204IEPIMLYQGGYIQKK621

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Fusion breakpoint peptide structures of VWA8-RB1

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 VWA8-RB1

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 VWA8-RB1

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
VWA8-RB1chr1342439872chr1348916735520NIEPIMLYQGGYIQKATAGAACCTATTATGCTCTATCAGGGAGGTTATATTCAAAAGAAA
VWA8-RB1chr1342439872chr1348916735621IEPIMLYQGGYIQKKGAACCTATTATGCTCTATCAGGGAGGTTATATTCAAAAGAAAAAG
VWA8-RB1chr1342439872chr1348916735722EPIMLYQGGYIQKKKCCTATTATGCTCTATCAGGGAGGTTATATTCAAAAGAAAAAGGAA

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Information of the samples that have these potential fusion neoantigens of VWA8-RB1

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 VWA8-RB1

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 VWA8-RB1

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 VWA8-RB1

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