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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:CP-WWTR1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CP-WWTR1
FusionPDB ID: 19244
FusionGDB2.0 ID: 19244
HgeneTgene
Gene symbol

CP

WWTR1

Gene ID

1356

25937

Gene nameceruloplasminWW domain containing transcription regulator 1
SynonymsCP-2TAZ
Cytomap

3q24-q25.1

3q25.1

Type of geneprotein-codingprotein-coding
Descriptionceruloplasminceruloplasmin (ferroxidase)WW domain-containing transcription regulator protein 1transcriptional co-activator with PDZ-binding motif
Modification date2020032020200313
UniProtAcc

Q8N436

Main function of 5'-partner protein: FUNCTION: May be involved in cell-cell interactions.
.
Ensembl transtripts involved in fusion geneENST idsENST00000264613, ENST00000462336, 
ENST00000465804, ENST00000360632, 
ENST00000467467, ENST00000474080, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 5=15010 X 8 X 9=720
# samples 713
** MAII scorelog2(7/150*10)=-1.09953567355091
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: CP [Title/Abstract] AND WWTR1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CP [Title/Abstract] AND WWTR1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CP(148905839)-WWTR1(149387678), # samples:3
Anticipated loss of major functional domain due to fusion event.CP-WWTR1 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.
CP-WWTR1 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.
CP-WWTR1 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.
CP-WWTR1 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
TgeneWWTR1

GO:0008284

positive regulation of cell proliferation

18227151

TgeneWWTR1

GO:0010718

positive regulation of epithelial to mesenchymal transition

18227151

TgeneWWTR1

GO:0017145

stem cell division

18568018

TgeneWWTR1

GO:0035329

hippo signaling

18227151|20412773

TgeneWWTR1

GO:0060390

regulation of SMAD protein signal transduction

18568018



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/chr3:148905839/chr3:149387678)
- 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 CP (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 WWTR1 (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)
ENST00000264613CPchr3148905839-ENST00000465804WWTR1chr3149260324-633221272122761849
ENST00000264613CPchr3148905839-ENST00000360632WWTR1chr3149260324-332221272122761849
ENST00000264613CPchr3148905839-ENST00000467467WWTR1chr3149260324-295721272122761849

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
ENST00000264613ENST00000465804CPchr3148905839-WWTR1chr3149260324-0.0002398050.9997602
ENST00000264613ENST00000360632CPchr3148905839-WWTR1chr3149260324-0.0005975170.9994025
ENST00000264613ENST00000467467CPchr3148905839-WWTR1chr3149260324-0.0008629480.9991371

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 CP-WWTR1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CPchr3148905839WWTR1chr31492603242127639EDEDFQESNKMHLMNHQHQQQMAPST

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Potential FusionNeoAntigen Information of CP-WWTR1 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.
CP-WWTR1_148905839_149260324.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)
CP-WWTR1chr3148905839chr31492603242127HLA-B44:03QESNKMHLM0.9980.9579514
CP-WWTR1chr3148905839chr31492603242127HLA-B47:01QESNKMHLM0.99080.5505514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:01QESNKMHLM0.9810.8278514
CP-WWTR1chr3148905839chr31492603242127HLA-B39:13QESNKMHLM0.66570.925514
CP-WWTR1chr3148905839chr31492603242127HLA-B39:08QESNKMHLM0.64390.8452514
CP-WWTR1chr3148905839chr31492603242127HLA-B15:04KMHLMNHQH0.55910.7627918
CP-WWTR1chr3148905839chr31492603242127HLA-B44:07QESNKMHLM0.9980.9579514
CP-WWTR1chr3148905839chr31492603242127HLA-B44:26QESNKMHLM0.9980.9579514
CP-WWTR1chr3148905839chr31492603242127HLA-B44:13QESNKMHLM0.9980.9579514
CP-WWTR1chr3148905839chr31492603242127HLA-B40:04QESNKMHLM0.9940.6614514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:08QESNKMHLM0.98190.7273514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:05QESNKMHLM0.9810.8278514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:06QESNKMHLM0.98090.8301514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:11QESNKMHLM0.98070.8856514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:04QESNKMHLM0.97610.8354514
CP-WWTR1chr3148905839chr31492603242127HLA-B18:03QESNKMHLM0.96340.8123514
CP-WWTR1chr3148905839chr31492603242127HLA-B41:03QESNKMHLM0.69330.5698514
CP-WWTR1chr3148905839chr31492603242127HLA-B15:53QESNKMHLM0.12020.8048514

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Potential FusionNeoAntigen Information of CP-WWTR1 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.
CP-WWTR1_148905839_149260324.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)
CP-WWTR1chr3148905839chr31492603242127DRB1-0804ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-0804SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-0820ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-0820SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-0831ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-0831SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1104ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1135ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1138ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1143ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1144ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1146ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1150ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1150SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1156ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1156SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1158ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1160ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1177ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1178ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1183ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1183SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1184ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1188ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1188SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1192SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1192ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1311ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1342ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1407DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1407EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1414DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1414EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1415ESNKMHLMNHQHQQQ621
CP-WWTR1chr3148905839chr31492603242127DRB1-1415SNKMHLMNHQHQQQM722
CP-WWTR1chr3148905839chr31492603242127DRB1-1436DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1436EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1442DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1442EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1444DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1444EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1468DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1468EDEDFQESNKMHLMN015
CP-WWTR1chr3148905839chr31492603242127DRB1-1493DEDFQESNKMHLMNH116
CP-WWTR1chr3148905839chr31492603242127DRB1-1493EDEDFQESNKMHLMN015

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Fusion breakpoint peptide structures of CP-WWTR1

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
2135ESNKMHLMNHQHQQCPWWTR1chr3148905839chr31492603242127

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CP-WWTR1

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-B14:023BVN2135ESNKMHLMNHQHQQ-7.15543-7.26883
HLA-B14:023BVN2135ESNKMHLMNHQHQQ-4.77435-5.80965
HLA-B52:013W392135ESNKMHLMNHQHQQ-6.80875-6.92215
HLA-B52:013W392135ESNKMHLMNHQHQQ-4.20386-5.23916
HLA-A11:014UQ22135ESNKMHLMNHQHQQ-7.5194-8.5547
HLA-A11:014UQ22135ESNKMHLMNHQHQQ-6.9601-7.0735
HLA-A24:025HGA2135ESNKMHLMNHQHQQ-7.52403-7.63743
HLA-A24:025HGA2135ESNKMHLMNHQHQQ-5.82433-6.85963
HLA-B27:056PYJ2135ESNKMHLMNHQHQQ-3.28285-4.31815
HLA-B44:053DX82135ESNKMHLMNHQHQQ-5.91172-6.94702
HLA-B44:053DX82135ESNKMHLMNHQHQQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of CP-WWTR1

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
CP-WWTR1chr3148905839chr3149260324514QESNKMHLMTTCAGGAATCTAATAAAATGCACTTGA
CP-WWTR1chr3148905839chr3149260324918KMHLMNHQHATAAAATGCACTTGATGAATCACCAAC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
CP-WWTR1chr3148905839chr3149260324015EDEDFQESNKMHLMNAGGAAGATGAAGACTTTCAGGAATCTAATAAAATGCACTTGATGA
CP-WWTR1chr3148905839chr3149260324116DEDFQESNKMHLMNHAAGATGAAGACTTTCAGGAATCTAATAAAATGCACTTGATGAATC
CP-WWTR1chr3148905839chr3149260324621ESNKMHLMNHQHQQQAGGAATCTAATAAAATGCACTTGATGAATCACCAACACCAGCAGC
CP-WWTR1chr3148905839chr3149260324722SNKMHLMNHQHQQQMAATCTAATAAAATGCACTTGATGAATCACCAACACCAGCAGCAGA

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Information of the samples that have these potential fusion neoantigens of CP-WWTR1

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
STADCP-WWTR1chr3148905839ENST00000264613chr3149260324ENST00000360632TCGA-R5-A7ZI-01A

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Potential target of CAR-T therapy development for CP-WWTR1

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 CP-WWTR1

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 CP-WWTR1

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