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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:TCTA-TBX6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TCTA-TBX6
FusionPDB ID: 89888
FusionGDB2.0 ID: 89888
HgeneTgene
Gene symbol

TCTA

TBX6

Gene ID

6988

6911

Gene nameT cell leukemia translocation alteredT-box transcription factor 6
Synonyms-SCDO5
Cytomap

3p21.31

16p11.2

Type of geneprotein-codingprotein-coding
DescriptionT-cell leukemia translocation-altered gene proteinT-cell leukemia translocation-associated gene proteinT-box transcription factor TBX6T-box 6T-box protein 6
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000493381, ENST00000273590, 
ENST00000279386, ENST00000395224, 
ENST00000553607, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=1442 X 1 X 1=2
# samples 83
** MAII scorelog2(8/144*10)=-0.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/2*10)=3.90689059560852
Fusion gene context

PubMed: TCTA [Title/Abstract] AND TBX6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TCTA [Title/Abstract] AND TBX6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TCTA(49450543)-TBX6(30098172), # samples:1
Anticipated loss of major functional domain due to fusion event.TCTA-TBX6 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.
TCTA-TBX6 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
HgeneTCTA

GO:0045671

negative regulation of osteoclast differentiation

19560569

HgeneTCTA

GO:0072675

osteoclast fusion

19560569



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/chr3:49450543/chr16:30098172)
- 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 TCTA (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 TBX6 (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)
ENST00000273590TCTAchr349450543+ENST00000395224TBX6chr1630098172-1394490119961280
ENST00000273590TCTAchr349450543+ENST00000279386TBX6chr1630098172-1391490119961280

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
ENST00000273590ENST00000395224TCTAchr349450543+TBX6chr1630098172-0.444973860.5550261
ENST00000273590ENST00000279386TCTAchr349450543+TBX6chr1630098172-0.445251580.5547484

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 TCTA-TBX6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TCTAchr349450543TBX6chr1630098172490124GSTPDGSTHFPSWERDARVKRKLRGP

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Potential FusionNeoAntigen Information of TCTA-TBX6 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.
TCTA-TBX6_49450543_30098172.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)
TCTA-TBX6chr349450543chr1630098172490HLA-A11:03STHFPSWER0.99290.5119615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:11STHFPSWER0.98740.826615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:09STHFPSWER0.98740.826615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:03STHFPSWER0.98740.826615
TCTA-TBX6chr349450543chr1630098172490HLA-A31:06STHFPSWER0.97610.588615
TCTA-TBX6chr349450543chr1630098172490HLA-A31:02STHFPSWER0.93490.8426615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:03GSTHFPSWER0.97910.8472515
TCTA-TBX6chr349450543chr1630098172490HLA-A74:11GSTHFPSWER0.97910.8472515
TCTA-TBX6chr349450543chr1630098172490HLA-A74:09GSTHFPSWER0.97910.8472515
TCTA-TBX6chr349450543chr1630098172490HLA-B39:06THFPSWERDA0.97710.9041717
TCTA-TBX6chr349450543chr1630098172490HLA-A31:06GSTHFPSWER0.95520.5773515
TCTA-TBX6chr349450543chr1630098172490HLA-B51:02FPSWERDARV0.930.5452919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:01FPSWERDARV0.86230.5866919
TCTA-TBX6chr349450543chr1630098172490HLA-A31:02SWERDARVKR0.69590.69561121
TCTA-TBX6chr349450543chr1630098172490HLA-A68:24DGSTHFPSWER0.99770.7398415
TCTA-TBX6chr349450543chr1630098172490HLA-A68:03DGSTHFPSWER0.99710.7117415
TCTA-TBX6chr349450543chr1630098172490HLA-A33:01DGSTHFPSWER0.99650.5546415
TCTA-TBX6chr349450543chr1630098172490HLA-A33:05DGSTHFPSWER0.99650.5546415
TCTA-TBX6chr349450543chr1630098172490HLA-A11:01STHFPSWER0.99480.5486615
TCTA-TBX6chr349450543chr1630098172490HLA-A31:01STHFPSWER0.99110.8136615
TCTA-TBX6chr349450543chr1630098172490HLA-B54:01FPSWERDARV0.99420.9093919
TCTA-TBX6chr349450543chr1630098172490HLA-A68:01DGSTHFPSWER0.99770.7398415
TCTA-TBX6chr349450543chr1630098172490HLA-A33:03DGSTHFPSWER0.99430.6251415
TCTA-TBX6chr349450543chr1630098172490HLA-A11:02STHFPSWER0.99480.5486615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:01STHFPSWER0.98740.826615
TCTA-TBX6chr349450543chr1630098172490HLA-A74:01GSTHFPSWER0.97910.8472515
TCTA-TBX6chr349450543chr1630098172490HLA-B59:01FPSWERDARV0.97150.8286919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:09FPSWERDARV0.89650.5655919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:13FPSWERDARV0.85520.6357919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:14FPSWERDARV0.83240.6008919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:05FPSWERDARV0.76650.6149919
TCTA-TBX6chr349450543chr1630098172490HLA-B51:29FPSWERDARV0.74310.6105919

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Potential FusionNeoAntigen Information of TCTA-TBX6 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.
TCTA-TBX6_49450543_30098172.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)
TCTA-TBX6chr349450543chr1630098172490DRB1-0305FPSWERDARVKRKLR924
TCTA-TBX6chr349450543chr1630098172490DRB1-0305HFPSWERDARVKRKL823
TCTA-TBX6chr349450543chr1630098172490DRB1-0305THFPSWERDARVKRK722
TCTA-TBX6chr349450543chr1630098172490DRB1-0305PSWERDARVKRKLRG1025
TCTA-TBX6chr349450543chr1630098172490DRB1-0340FPSWERDARVKRKLR924
TCTA-TBX6chr349450543chr1630098172490DRB1-0340HFPSWERDARVKRKL823
TCTA-TBX6chr349450543chr1630098172490DRB1-0340THFPSWERDARVKRK722
TCTA-TBX6chr349450543chr1630098172490DRB1-0340PSWERDARVKRKLRG1025
TCTA-TBX6chr349450543chr1630098172490DRB1-1179FPSWERDARVKRKLR924
TCTA-TBX6chr349450543chr1630098172490DRB1-1179HFPSWERDARVKRKL823
TCTA-TBX6chr349450543chr1630098172490DRB1-1179THFPSWERDARVKRK722
TCTA-TBX6chr349450543chr1630098172490DRB1-1341FPSWERDARVKRKLR924

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Fusion breakpoint peptide structures of TCTA-TBX6

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
9106STHFPSWERDARVKTCTATBX6chr349450543chr1630098172490

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TCTA-TBX6

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-B14:023BVN9106STHFPSWERDARVK-7.9962-8.1096
HLA-B14:023BVN9106STHFPSWERDARVK-5.70842-6.74372
HLA-B52:013W399106STHFPSWERDARVK-6.83737-6.95077
HLA-B52:013W399106STHFPSWERDARVK-4.4836-5.5189
HLA-A11:014UQ29106STHFPSWERDARVK-10.0067-10.1201
HLA-A11:014UQ29106STHFPSWERDARVK-9.03915-10.0745
HLA-A24:025HGA9106STHFPSWERDARVK-6.56204-6.67544
HLA-A24:025HGA9106STHFPSWERDARVK-5.42271-6.45801
HLA-B44:053DX89106STHFPSWERDARVK-7.85648-8.89178
HLA-B44:053DX89106STHFPSWERDARVK-5.3978-5.5112
HLA-A02:016TDR9106STHFPSWERDARVK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TCTA-TBX6

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
TCTA-TBX6chr349450543chr16300981721121SWERDARVKRTTCGTGGGAGCGAGACGCCCGTGTGAAGAG
TCTA-TBX6chr349450543chr1630098172415DGSTHFPSWERTGATGGCTCCACGCATTTCCCTTCGTGGGAGCG
TCTA-TBX6chr349450543chr1630098172515GSTHFPSWERTGGCTCCACGCATTTCCCTTCGTGGGAGCG
TCTA-TBX6chr349450543chr1630098172615STHFPSWERCTCCACGCATTTCCCTTCGTGGGAGCG
TCTA-TBX6chr349450543chr1630098172717THFPSWERDACACGCATTTCCCTTCGTGGGAGCGAGACGC
TCTA-TBX6chr349450543chr1630098172919FPSWERDARVTTTCCCTTCGTGGGAGCGAGACGCCCGTGT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TCTA-TBX6chr349450543chr16300981721025PSWERDARVKRKLRGCCCTTCGTGGGAGCGAGACGCCCGTGTGAAGAGGAAACTGCGGGG
TCTA-TBX6chr349450543chr1630098172722THFPSWERDARVKRKCACGCATTTCCCTTCGTGGGAGCGAGACGCCCGTGTGAAGAGGAA
TCTA-TBX6chr349450543chr1630098172823HFPSWERDARVKRKLGCATTTCCCTTCGTGGGAGCGAGACGCCCGTGTGAAGAGGAAACT
TCTA-TBX6chr349450543chr1630098172924FPSWERDARVKRKLRTTTCCCTTCGTGGGAGCGAGACGCCCGTGTGAAGAGGAAACTGCG

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Information of the samples that have these potential fusion neoantigens of TCTA-TBX6

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
STADTCTA-TBX6chr349450543ENST00000273590chr1630098172ENST00000279386TCGA-D7-6518

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Potential target of CAR-T therapy development for TCTA-TBX6

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
HgeneTCTAchr3:49450543chr16:30098172ENST00000273590+2341_6189104.0TransmembraneHelical
HgeneTCTAchr3:49450543chr16:30098172ENST00000273590+239_2689104.0TransmembraneHelical

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 TCTA-TBX6

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 TCTA-TBX6

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