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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:WWP1-ITGB4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: WWP1-ITGB4
FusionPDB ID: 99514
FusionGDB2.0 ID: 99514
HgeneTgene
Gene symbol

WWP1

ITGB4

Gene ID

11059

3691

Gene nameWW domain containing E3 ubiquitin protein ligase 1integrin subunit beta 4
SynonymsAIP5|Tiul1|hSDRP1CD104|GP150
Cytomap

8q21.3

17q25.1

Type of geneprotein-codingprotein-coding
DescriptionNEDD4-like E3 ubiquitin-protein ligase WWP1HECT-type E3 ubiquitin transferase WWP1Nedd-4-like ubiquitin-protein ligaseTGIF-interacting ubiquitin ligase 1WW domain-containing protein 1atrophin-1 interacting protein 5integrin beta-4CD104 antigen
Modification date2020032220200329
UniProtAcc.

P16144

Main function of 5'-partner protein: FUNCTION: Integrin alpha-6/beta-4 is a receptor for laminin. Plays a critical structural role in the hemidesmosome of epithelial cells. Is required for the regulation of keratinocyte polarity and motility. ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000269|PubMed:12482924, ECO:0000269|PubMed:19403692, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.
Ensembl transtripts involved in fusion geneENST idsENST00000265428, ENST00000517970, 
ENST00000341922, ENST00000349423, 
ENST00000523863, 
ENST00000584558, 
ENST00000200181, ENST00000339591, 
ENST00000449880, ENST00000450894, 
ENST00000579662, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 12 X 9=19448 X 8 X 7=448
# samples 199
** MAII scorelog2(19/1944*10)=-3.35495689527483
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/448*10)=-2.31550182572793
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: WWP1 [Title/Abstract] AND ITGB4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: WWP1 [Title/Abstract] AND ITGB4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)WWP1(87414432)-ITGB4(73750657), # samples:1
Anticipated loss of major functional domain due to fusion event.WWP1-ITGB4 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.
WWP1-ITGB4 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.
WWP1-ITGB4 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.
WWP1-ITGB4 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
TgeneITGB4

GO:0009611

response to wounding

19403692

TgeneITGB4

GO:0031581

hemidesmosome assembly

12482924



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/chr8:87414432/chr17:73750657)
- 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 WWP1 (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 ITGB4 (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)
ENST00000517970WWP1chr887414432+ENST00000579662ITGB4chr1773750657+223110313072181624
ENST00000517970WWP1chr887414432+ENST00000339591ITGB4chr1773750657+260310313072340677
ENST00000517970WWP1chr887414432+ENST00000200181ITGB4chr1773750657+244510313072181624
ENST00000517970WWP1chr887414432+ENST00000450894ITGB4chr1773750657+244210313072181624
ENST00000517970WWP1chr887414432+ENST00000449880ITGB4chr1773750657+260410313072340677
ENST00000265428WWP1chr887414432+ENST00000579662ITGB4chr1773750657+1934734101884624
ENST00000265428WWP1chr887414432+ENST00000339591ITGB4chr1773750657+2306734102043677
ENST00000265428WWP1chr887414432+ENST00000200181ITGB4chr1773750657+2148734101884624
ENST00000265428WWP1chr887414432+ENST00000450894ITGB4chr1773750657+2145734101884624
ENST00000265428WWP1chr887414432+ENST00000449880ITGB4chr1773750657+2307734102043677

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
ENST00000517970ENST00000579662WWP1chr887414432+ITGB4chr1773750657+0.0195287540.98047125
ENST00000517970ENST00000339591WWP1chr887414432+ITGB4chr1773750657+0.0182043370.9817956
ENST00000517970ENST00000200181WWP1chr887414432+ITGB4chr1773750657+0.0183248240.9816752
ENST00000517970ENST00000450894WWP1chr887414432+ITGB4chr1773750657+0.018190130.98180985
ENST00000517970ENST00000449880WWP1chr887414432+ITGB4chr1773750657+0.0182525220.98174745
ENST00000265428ENST00000579662WWP1chr887414432+ITGB4chr1773750657+0.0205732430.97942674
ENST00000265428ENST00000339591WWP1chr887414432+ITGB4chr1773750657+0.017913570.9820864
ENST00000265428ENST00000200181WWP1chr887414432+ITGB4chr1773750657+0.0185576680.9814423
ENST00000265428ENST00000450894WWP1chr887414432+ITGB4chr1773750657+0.0184705760.9815294
ENST00000265428ENST00000449880WWP1chr887414432+ITGB4chr1773750657+0.0179502480.98204976

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 WWP1-ITGB4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
WWP1chr887414432ITGB4chr17737506571031241APKPLASEPADDTEHLVNGRMDFAFP
WWP1chr887414432ITGB4chr1773750657734241APKPLASEPADDTEHLVNGRMDFAFP

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Potential FusionNeoAntigen Information of WWP1-ITGB4 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.
WWP1-ITGB4_87414432_73750657.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)
WWP1-ITGB4chr887414432chr1773750657734HLA-B18:01TEHLVNGRM0.9740.83771221
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:08EPADDTEHL0.96020.7118716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:01EPADDTEHL0.94940.8023716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:03EPADDTEHL0.92530.8337716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:02EPADDTEHL0.75380.8675716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:04EPADDTEHL0.75380.8675716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:03SEPADDTEHL0.71350.7946616
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:02SEPADDTEHL0.63570.8206616
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:04SEPADDTEHL0.63570.8206616
WWP1-ITGB4chr887414432chr1773750657734HLA-C05:09PADDTEHLV0.99980.9462817
WWP1-ITGB4chr887414432chr1773750657734HLA-C08:15PADDTEHLV0.99820.9725817
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:12EPADDTEHL0.75380.8675716
WWP1-ITGB4chr887414432chr1773750657734HLA-B39:10EPADDTEHL0.4590.7851716
WWP1-ITGB4chr887414432chr1773750657734HLA-B39:08SEPADDTEHL0.8560.5796616
WWP1-ITGB4chr887414432chr1773750657734HLA-B39:10SEPADDTEHL0.74310.6746616
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:12SEPADDTEHL0.63570.8206616
WWP1-ITGB4chr887414432chr1773750657734HLA-C05:09SEPADDTEHLV0.99980.8504617
WWP1-ITGB4chr887414432chr1773750657734HLA-C05:01PADDTEHLV0.99980.9462817
WWP1-ITGB4chr887414432chr1773750657734HLA-C04:03PADDTEHLV0.99980.8466817
WWP1-ITGB4chr887414432chr1773750657734HLA-C08:02PADDTEHLV0.99820.9725817
WWP1-ITGB4chr887414432chr1773750657734HLA-B40:04TEHLVNGRM0.99270.77721221
WWP1-ITGB4chr887414432chr1773750657734HLA-B18:05TEHLVNGRM0.9740.83771221
WWP1-ITGB4chr887414432chr1773750657734HLA-B18:06TEHLVNGRM0.95420.85731221
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:23EPADDTEHL0.95280.7891716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:77EPADDTEHL0.94940.8023716
WWP1-ITGB4chr887414432chr1773750657734HLA-B18:03TEHLVNGRM0.84740.81971221
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:24EPADDTEHL0.82350.8093716
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:09EPADDTEHL0.75380.8675716
WWP1-ITGB4chr887414432chr1773750657734HLA-B18:11TEHLVNGRM0.67890.84511221
WWP1-ITGB4chr887414432chr1773750657734HLA-B67:01EPADDTEHL0.51630.6183716
WWP1-ITGB4chr887414432chr1773750657734HLA-B41:03TEHLVNGRM0.38980.66271221
WWP1-ITGB4chr887414432chr1773750657734HLA-B67:01SEPADDTEHL0.74040.5178616
WWP1-ITGB4chr887414432chr1773750657734HLA-B35:09SEPADDTEHL0.63570.8206616
WWP1-ITGB4chr887414432chr1773750657734HLA-C05:01SEPADDTEHLV0.99980.8504617

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Potential FusionNeoAntigen Information of WWP1-ITGB4 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.
WWP1-ITGB4_87414432_73750657.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)
WWP1-ITGB4chr887414432chr1773750657734DRB4-0104PKPLASEPADDTEHL116
WWP1-ITGB4chr887414432chr1773750657734DRB4-0104APKPLASEPADDTEH015

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Fusion breakpoint peptide structures of WWP1-ITGB4

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
8525SEPADDTEHLVNGRWWP1ITGB4chr887414432chr1773750657734

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of WWP1-ITGB4

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-B14:023BVN8525SEPADDTEHLVNGR-7.15543-7.26883
HLA-B14:023BVN8525SEPADDTEHLVNGR-4.77435-5.80965
HLA-B52:013W398525SEPADDTEHLVNGR-6.80875-6.92215
HLA-B52:013W398525SEPADDTEHLVNGR-4.20386-5.23916
HLA-A11:014UQ28525SEPADDTEHLVNGR-7.5194-8.5547
HLA-A11:014UQ28525SEPADDTEHLVNGR-6.9601-7.0735
HLA-A24:025HGA8525SEPADDTEHLVNGR-7.52403-7.63743
HLA-A24:025HGA8525SEPADDTEHLVNGR-5.82433-6.85963
HLA-B27:056PYJ8525SEPADDTEHLVNGR-3.28285-4.31815
HLA-B44:053DX88525SEPADDTEHLVNGR-5.91172-6.94702
HLA-B44:053DX88525SEPADDTEHLVNGR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of WWP1-ITGB4

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
WWP1-ITGB4chr887414432chr17737506571221TEHLVNGRMCTGAGCACCTGGTGAATGGCCGGATGG
WWP1-ITGB4chr887414432chr1773750657616SEPADDTEHLCTGAGCCTGCCGATGACACTGAGCACCTGG
WWP1-ITGB4chr887414432chr1773750657617SEPADDTEHLVCTGAGCCTGCCGATGACACTGAGCACCTGGTGA
WWP1-ITGB4chr887414432chr1773750657716EPADDTEHLAGCCTGCCGATGACACTGAGCACCTGG
WWP1-ITGB4chr887414432chr1773750657817PADDTEHLVCTGCCGATGACACTGAGCACCTGGTGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
WWP1-ITGB4chr887414432chr1773750657015APKPLASEPADDTEHCTCCAAAACCACTCGCATCTGAGCCTGCCGATGACACTGAGCACC
WWP1-ITGB4chr887414432chr1773750657116PKPLASEPADDTEHLCAAAACCACTCGCATCTGAGCCTGCCGATGACACTGAGCACCTGG

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Information of the samples that have these potential fusion neoantigens of WWP1-ITGB4

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
STADWWP1-ITGB4chr887414432ENST00000265428chr1773750657ENST00000200181TCGA-HU-8238-01A

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Potential target of CAR-T therapy development for WWP1-ITGB4

check button Predicted 3D structure. We used RoseTTAFold.
527_WWP1-ITGB4_t000_.e2e.pdb


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
WWP1chr887414432ENST00000265428ITGB4chr1773750657ENST00000200181
WWP1chr887414432ENST00000265428ITGB4chr1773750657ENST00000339591

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Related Drugs to WWP1-ITGB4

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 WWP1-ITGB4

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