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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:ZEB1-TAOK3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZEB1-TAOK3
FusionPDB ID: 100861
FusionGDB2.0 ID: 100861
HgeneTgene
Gene symbol

ZEB1

TAOK3

Gene ID

6935

51347

Gene namezinc finger E-box binding homeobox 1TAO kinase 3
SynonymsAREB6|BZP|DELTAEF1|FECD6|NIL2A|PPCD3|TCF8|ZFHEP|ZFHX1ADPK|JIK|MAP3K18|hKFC-A
Cytomap

10p11.22

12q24.23

Type of geneprotein-codingprotein-coding
Descriptionzinc finger E-box-binding homeobox 1delta-crystallin enhancer binding factor 1negative regulator of IL2posterior polymorphous corneal dystrophy 3transcription factor 8 (represses interleukin 2 expression)zinc finger homeodomain enhancer-binding proteserine/threonine-protein kinase TAO3CTCL-associated antigen HD-CL-09JNK/SAPK-inhibitory kinaseSTE20-like kinasecutaneous T-cell lymphoma-associated antigen HD-CL-09dendritic cell-derived protein kinasejun kinase-inhibitory kinasekinase from chicken
Modification date2020032920200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000559858, ENST00000320985, 
ENST00000361642, ENST00000542815, 
ENST00000560721, ENST00000446923, 
ENST00000392533, ENST00000419821, 
ENST00000536979, ENST00000537952, 
ENST00000543709, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 5 X 8=44013 X 15 X 5=975
# samples 1316
** MAII scorelog2(13/440*10)=-1.7589919004962
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(16/975*10)=-2.60733031374961
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZEB1 [Title/Abstract] AND TAOK3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZEB1 [Title/Abstract] AND TAOK3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZEB1(31608221)-TAOK3(118651915), # samples:1
Anticipated loss of major functional domain due to fusion event.ZEB1-TAOK3 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.
ZEB1-TAOK3 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.
ZEB1-TAOK3 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.
ZEB1-TAOK3 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
HgeneZEB1

GO:0000122

negative regulation of transcription by RNA polymerase II

23765923|23814079

HgeneZEB1

GO:0045892

negative regulation of transcription, DNA-templated

20418909

TgeneTAOK3

GO:0006468

protein phosphorylation

10559204

TgeneTAOK3

GO:0006974

cellular response to DNA damage stimulus

17396146

TgeneTAOK3

GO:0046329

negative regulation of JNK cascade

10559204

TgeneTAOK3

GO:0046777

protein autophosphorylation

10559204



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/chr10:31608221/chr12:118651915)
- 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 ZEB1 (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 TAOK3 (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)
ENST00000320985ZEB1chr1031608221+ENST00000419821TAOK3chr12118651915-34181681102221703
ENST00000320985ZEB1chr1031608221+ENST00000392533TAOK3chr12118651915-34181681102221703
ENST00000361642ZEB1chr1031608221+ENST00000419821TAOK3chr12118651915-3371121632174703
ENST00000361642ZEB1chr1031608221+ENST00000392533TAOK3chr12118651915-3371121632174703
ENST00000560721ZEB1chr1031608221+ENST00000419821TAOK3chr12118651915-333181232134703
ENST00000560721ZEB1chr1031608221+ENST00000392533TAOK3chr12118651915-333181232134703
ENST00000542815ZEB1chr1031608221+ENST00000419821TAOK3chr12118651915-332171132124703
ENST00000542815ZEB1chr1031608221+ENST00000392533TAOK3chr12118651915-332171132124703

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
ENST00000320985ENST00000419821ZEB1chr1031608221+TAOK3chr12118651915-0.0076965460.9923035
ENST00000320985ENST00000392533ZEB1chr1031608221+TAOK3chr12118651915-0.0076965460.9923035
ENST00000361642ENST00000419821ZEB1chr1031608221+TAOK3chr12118651915-0.0083059730.99169403
ENST00000361642ENST00000392533ZEB1chr1031608221+TAOK3chr12118651915-0.0083059730.99169403
ENST00000560721ENST00000419821ZEB1chr1031608221+TAOK3chr12118651915-0.0085068770.99149317
ENST00000560721ENST00000392533ZEB1chr1031608221+TAOK3chr12118651915-0.0085068770.99149317
ENST00000542815ENST00000419821ZEB1chr1031608221+TAOK3chr12118651915-0.0086107240.99138933
ENST00000542815ENST00000392533ZEB1chr1031608221+TAOK3chr12118651915-0.0086107240.99138933

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 ZEB1-TAOK3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZEB1chr1031608221TAOK3chr1211865191512119CKRRKQANPRRNNAERKPPLFNMNAM
ZEB1chr1031608221TAOK3chr1211865191516819CKRRKQANPRRNNAERKPPLFNMNAM
ZEB1chr1031608221TAOK3chr121186519157119CKRRKQANPRRNNAERKPPLFNMNAM
ZEB1chr1031608221TAOK3chr121186519158119CKRRKQANPRRNNAERKPPLFNMNAM

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Potential FusionNeoAntigen Information of ZEB1-TAOK3 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.
ZEB1-TAOK3_31608221_118651915.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)
ZEB1-TAOK3chr1031608221chr12118651915168HLA-B08:09QANPRRNNA0.9880.6963514
ZEB1-TAOK3chr1031608221chr12118651915168HLA-C05:09NAERKPPLF0.99920.75911221
ZEB1-TAOK3chr1031608221chr12118651915168HLA-B14:03NNAERKPPL0.73050.55021120
ZEB1-TAOK3chr1031608221chr12118651915168HLA-C05:01NAERKPPLF0.99920.75911221
ZEB1-TAOK3chr1031608221chr12118651915168HLA-C04:03NAERKPPLF0.99920.60851221

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Potential FusionNeoAntigen Information of ZEB1-TAOK3 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.

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)

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Fusion breakpoint peptide structures of ZEB1-TAOK3

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
460ANPRRNNAERKPPLZEB1TAOK3chr1031608221chr12118651915168

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZEB1-TAOK3

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-B14:023BVN460ANPRRNNAERKPPL-7.15543-7.26883
HLA-B14:023BVN460ANPRRNNAERKPPL-4.77435-5.80965
HLA-B52:013W39460ANPRRNNAERKPPL-6.80875-6.92215
HLA-B52:013W39460ANPRRNNAERKPPL-4.20386-5.23916
HLA-A11:014UQ2460ANPRRNNAERKPPL-7.5194-8.5547
HLA-A11:014UQ2460ANPRRNNAERKPPL-6.9601-7.0735
HLA-A24:025HGA460ANPRRNNAERKPPL-7.52403-7.63743
HLA-A24:025HGA460ANPRRNNAERKPPL-5.82433-6.85963
HLA-B27:056PYJ460ANPRRNNAERKPPL-3.28285-4.31815
HLA-B44:053DX8460ANPRRNNAERKPPL-5.91172-6.94702
HLA-B44:053DX8460ANPRRNNAERKPPL-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZEB1-TAOK3

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
ZEB1-TAOK3chr1031608221chr121186519151120NNAERKPPLATAACGCGGAACGGAAGCCGCCCCTTT
ZEB1-TAOK3chr1031608221chr121186519151221NAERKPPLFACGCGGAACGGAAGCCGCCCCTTTTCA
ZEB1-TAOK3chr1031608221chr12118651915514QANPRRNNAAGGCGAACCCGCGGCGCAATAACGCGG

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

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Information of the samples that have these potential fusion neoantigens of ZEB1-TAOK3

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
STADZEB1-TAOK3chr1031608221ENST00000320985chr12118651915ENST00000392533TCGA-CD-A4MJ

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Potential target of CAR-T therapy development for ZEB1-TAOK3

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 ZEB1-TAOK3

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 ZEB1-TAOK3

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