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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:GATA4-TRIB1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: GATA4-TRIB1
FusionPDB ID: 32588
FusionGDB2.0 ID: 32588
HgeneTgene
Gene symbol

GATA4

TRIB1

Gene ID

2626

10221

Gene nameGATA binding protein 4tribbles pseudokinase 1
SynonymsASD2|TACHD|TOF|VSD1C8FW|GIG-2|GIG2|SKIP1|TRB-1|TRB1
Cytomap

8p23.1

8q24.13

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor GATA-4GATA-binding factor 4tribbles homolog 1G-protein-coupled receptor induced proteinG-protein-coupled receptor-induced gene 2 proteinG-protein-coupled receptor-induced protein 2phosphoprotein regulated by mitogenic pathwaystribbles-like protein 1
Modification date2020031320200313
UniProtAcc

P43694

Main function of 5'-partner protein: FUNCTION: Transcriptional activator that binds to the consensus sequence 5'-AGATAG-3' and plays a key role in cardiac development and function (PubMed:24000169, PubMed:27984724). In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it downregulates endocardial and endothelial gene expression (PubMed:27984724). Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). Acts as a transcriptional activator of ANF in cooperation with NKX2-5 (By similarity). Promotes cardiac myocyte enlargement (PubMed:20081228). Required during testicular development (PubMed:21220346). May play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate degrading enzyme, sphingosine-1-phosphate lyase (PubMed:15734735). {ECO:0000250|UniProtKB:P46152, ECO:0000250|UniProtKB:Q08369, ECO:0000269|PubMed:15734735, ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:21220346, ECO:0000269|PubMed:24000169, ECO:0000269|PubMed:27984724}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000335135, ENST00000532059, 
ENST00000528712, 
ENST00000519576, 
ENST00000521778, ENST00000520847, 
ENST00000311922, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=274 X 4 X 3=48
# samples 46
** MAII scorelog2(4/27*10)=0.567040592723894
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(6/48*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: GATA4 [Title/Abstract] AND TRIB1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: GATA4 [Title/Abstract] AND TRIB1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)GATA4(11566437)-TRIB1(126448247), # samples:2
Anticipated loss of major functional domain due to fusion event.GATA4-TRIB1 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.
GATA4-TRIB1 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.
GATA4-TRIB1 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.
GATA4-TRIB1 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.
GATA4-TRIB1 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
GATA4-TRIB1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
GATA4-TRIB1 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
GATA4-TRIB1 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
GATA4-TRIB1 seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted 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
HgeneGATA4

GO:0045893

positive regulation of transcription, DNA-templated

24000169

HgeneGATA4

GO:0045944

positive regulation of transcription by RNA polymerase II

21330551|29325903

HgeneGATA4

GO:0060575

intestinal epithelial cell differentiation

9566909

TgeneTRIB1

GO:0043405

regulation of MAP kinase activity

15299019



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/chr8:11566437/chr8:126448247)
- 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 GATA4 (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 TRIB1 (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)
ENST00000335135GATA4chr811566437+ENST00000311922TRIB1chr8126448248+357411744731639388
ENST00000532059GATA4chr811566437+ENST00000311922TRIB1chr8126448248+3096696341161375
ENST00000335135GATA4chr811566437+ENST00000311922TRIB1chr8126448247+357411744731639388
ENST00000532059GATA4chr811566437+ENST00000311922TRIB1chr8126448247+3096696341161375

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
ENST00000335135ENST00000311922GATA4chr811566437+TRIB1chr8126448248+0.49474690.5052531
ENST00000532059ENST00000311922GATA4chr811566437+TRIB1chr8126448248+0.460042540.5399574
ENST00000335135ENST00000311922GATA4chr811566437+TRIB1chr8126448247+0.49474690.5052531
ENST00000532059ENST00000311922GATA4chr811566437+TRIB1chr8126448247+0.460042540.5399574

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 GATA4-TRIB1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
GATA4chr811566437TRIB1chr81264482471174233ARPGQPGRPTPQSRTQLRLESLEDTH
GATA4chr811566437TRIB1chr8126448247696220ARPGQPGRPTPQSRTQLRLESLEDTH
GATA4chr811566437TRIB1chr81264482481174233ARPGQPGRPTPQSRTQLRLESLEDTH
GATA4chr811566437TRIB1chr8126448248696220ARPGQPGRPTPQSRTQLRLESLEDTH

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Potential FusionNeoAntigen Information of GATA4-TRIB1 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.
GATA4-TRIB1_11566437_126448247.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)
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:02SRTQLRLESL0.99990.57011222
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:04SRTQLRLESL0.99990.76161222
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:07SRTQLRLESL0.99980.56441222
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:10RPTPQSRTQL0.99950.5267717
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:10SRTQLRLESL0.78470.60411222
GATA4-TRIB1chr811566437chr81264482471174HLA-B35:03RPTPQSRTQL0.59360.6165717
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:02RPTPQSRTQLR0.99720.5681718
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:05GRPTPQSRTQL0.99660.5049617
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:02GRPTPQSRTQL0.99650.5252617
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:12TPQSRTQL0.9990.5281917
GATA4-TRIB1chr811566437chr81264482471174HLA-B14:03TPQSRTQL0.99270.6629917
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:17TPQSRTQL0.96430.9416917
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:30TPQSRTQL0.95590.9325917
GATA4-TRIB1chr811566437chr81264482471174HLA-B39:10TPQSRTQL0.67470.7722917
GATA4-TRIB1chr811566437chr81264482471174HLA-B73:01SRTQLRLES0.96110.63131221
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:17PTPQSRTQL0.81390.9211817
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:30PTPQSRTQL0.75690.9289817
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:12RPTPQSRTQL0.99820.5866717
GATA4-TRIB1chr811566437chr81264482471174HLA-B39:12SRTQLRLESL0.9950.88491222
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:17RPTPQSRTQL0.95090.9342717
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:30RPTPQSRTQL0.92940.928717
GATA4-TRIB1chr811566437chr81264482471174HLA-B39:10RPTPQSRTQL0.64660.6587717
GATA4-TRIB1chr811566437chr81264482471174HLA-B39:10TPQSRTQLRL0.37650.7238919
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:04GRPTPQSRTQL0.9960.5423617
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:04RPTPQSRTQLR0.99150.5871718
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:02TPQSRTQL0.95760.9335917
GATA4-TRIB1chr811566437chr81264482471174HLA-B67:01TPQSRTQL0.64730.6268917
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:09RPTPQSRTQ0.9630.5189716
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:02PTPQSRTQL0.80720.9124817
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:03PTPQSRTQL0.60580.9079817
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:10SRTQLRLESL0.99990.85511222
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:08SRTQLRLESL0.99990.73251222
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:06SRTQLRLESL0.99980.78191222
GATA4-TRIB1chr811566437chr81264482471174HLA-B27:09SRTQLRLESL0.99980.77181222
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:02RPTPQSRTQL0.9530.9255717
GATA4-TRIB1chr811566437chr81264482471174HLA-C01:03RPTPQSRTQL0.82530.9188717
GATA4-TRIB1chr811566437chr81264482471174HLA-B67:01RPTPQSRTQL0.57160.5706717
GATA4-TRIB1chr811566437chr81264482471174HLA-B35:13RPTPQSRTQL0.56990.6254717
GATA4-TRIB1chr811566437chr81264482471174HLA-B67:01TPQSRTQLRL0.36520.6623919
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:22RPTPQSRTQLR0.99720.5681718
GATA4-TRIB1chr811566437chr81264482471174HLA-B07:22GRPTPQSRTQL0.99650.5252617

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Potential FusionNeoAntigen Information of GATA4-TRIB1 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 GATA4-TRIB1

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
3089GRPTPQSRTQLRLEGATA4TRIB1chr811566437chr81264482471174

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of GATA4-TRIB1

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-B14:023BVN3089GRPTPQSRTQLRLE-7.9962-8.1096
HLA-B14:023BVN3089GRPTPQSRTQLRLE-5.70842-6.74372
HLA-B52:013W393089GRPTPQSRTQLRLE-6.83737-6.95077
HLA-B52:013W393089GRPTPQSRTQLRLE-4.4836-5.5189
HLA-A11:014UQ23089GRPTPQSRTQLRLE-10.0067-10.1201
HLA-A11:014UQ23089GRPTPQSRTQLRLE-9.03915-10.0745
HLA-A24:025HGA3089GRPTPQSRTQLRLE-6.56204-6.67544
HLA-A24:025HGA3089GRPTPQSRTQLRLE-5.42271-6.45801
HLA-B44:053DX83089GRPTPQSRTQLRLE-7.85648-8.89178
HLA-B44:053DX83089GRPTPQSRTQLRLE-5.3978-5.5112
HLA-A02:016TDR3089GRPTPQSRTQLRLE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of GATA4-TRIB1

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
GATA4-TRIB1chr811566437chr81264482471221SRTQLRLESTCGAACCCAGCTTAGACTAGAAAGTCT
GATA4-TRIB1chr811566437chr81264482471222SRTQLRLESLTCGAACCCAGCTTAGACTAGAAAGTCTAGA
GATA4-TRIB1chr811566437chr8126448247617GRPTPQSRTQLCCGCCCGACACCCCAATCTCGAACCCAGCTTAG
GATA4-TRIB1chr811566437chr8126448247716RPTPQSRTQCCCGACACCCCAATCTCGAACCCAGCT
GATA4-TRIB1chr811566437chr8126448247717RPTPQSRTQLCCCGACACCCCAATCTCGAACCCAGCTTAG
GATA4-TRIB1chr811566437chr8126448247718RPTPQSRTQLRCCCGACACCCCAATCTCGAACCCAGCTTAGACT
GATA4-TRIB1chr811566437chr8126448247817PTPQSRTQLGACACCCCAATCTCGAACCCAGCTTAG
GATA4-TRIB1chr811566437chr8126448247917TPQSRTQLACCCCAATCTCGAACCCAGCTTAG
GATA4-TRIB1chr811566437chr8126448247919TPQSRTQLRLACCCCAATCTCGAACCCAGCTTAGACTAGA

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 GATA4-TRIB1

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
ESCAGATA4-TRIB1chr811566437ENST00000335135chr8126448247ENST00000311922TCGA-L5-A4OJ

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Potential target of CAR-T therapy development for GATA4-TRIB1

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 GATA4-TRIB1

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 GATA4-TRIB1

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