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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:TRIO-DAP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIO-DAP
FusionPDB ID: 94198
FusionGDB2.0 ID: 94198
HgeneTgene
Gene symbol

TRIO

DAP

Gene ID

7204

23549

Gene nametrio Rho guanine nucleotide exchange factoraspartyl aminopeptidase
SynonymsARHGEF23|MEBAS|MRD44|tgatASPEP|DAP
Cytomap

5p15.2

2q35

Type of geneprotein-codingprotein-coding
Descriptiontriple functional domain proteinPTPRF-interacting proteintriple functional domain (PTPRF interacting)aspartyl aminopeptidase
Modification date2020031320200327
UniProtAcc

TPI1

Main function of 5'-partner protein: 249

Q9UN19

Main function of 5'-partner protein: FUNCTION: May act as a B-cell-associated adapter that regulates B-cell antigen receptor (BCR)-signaling downstream of PI3K. {ECO:0000269|PubMed:10770799}.
Ensembl transtripts involved in fusion geneENST idsENST00000344204, ENST00000537187, 
ENST00000344135, ENST00000509967, 
ENST00000515710, 
ENST00000510546, 
ENST00000230895, ENST00000432074, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 28 X 12=1142412 X 7 X 7=588
# samples 3512
** MAII scorelog2(35/11424*10)=-5.02856915219677
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/588*10)=-2.29278174922785
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TRIO [Title/Abstract] AND DAP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TRIO [Title/Abstract] AND DAP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIO(14420130)-DAP(10748383), # samples:1
Anticipated loss of major functional domain due to fusion event.TRIO-DAP 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.
TRIO-DAP 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.
TRIO-DAP 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.
TRIO-DAP 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


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/chr5:14420130/chr5:10748383)
- 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 TRIO (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 DAP (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)
ENST00000344204TRIOchr514420130-ENST00000230895DAPchr510748383-730752272454801818
ENST00000344204TRIOchr514420130-ENST00000432074DAPchr510748383-606052272457861920
ENST00000537187TRIOchr514420130-ENST00000230895DAPchr510748383-72895209654621818
ENST00000537187TRIOchr514420130-ENST00000432074DAPchr510748383-60425209657681920

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
ENST00000344204ENST00000230895TRIOchr514420130-DAPchr510748383-0.0053480680.9946519
ENST00000344204ENST00000432074TRIOchr514420130-DAPchr510748383-0.0075990380.992401
ENST00000537187ENST00000230895TRIOchr514420130-DAPchr510748383-0.0052717780.99472827
ENST00000537187ENST00000432074TRIOchr514420130-DAPchr510748383-0.0075335210.9924665

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 TRIO-DAP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIOchr514420130DAPchr51074838352091734RSSMEMEGIFNHKVKAGGMRIVQKHP
TRIOchr514420130DAPchr51074838352271734RSSMEMEGIFNHKVKAGGMRIVQKHP

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Potential FusionNeoAntigen Information of TRIO-DAP 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.
TRIO-DAP_14420130_10748383.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)
TRIO-DAPchr514420130chr5107483835227HLA-B45:01MEGIFNHKV0.99880.7488514
TRIO-DAPchr514420130chr5107483835227HLA-A30:08KVKAGGMRI0.99250.791221
TRIO-DAPchr514420130chr5107483835227HLA-B14:01NHKVKAGGM0.82560.79671019
TRIO-DAPchr514420130chr5107483835227HLA-B14:02NHKVKAGGM0.82560.79671019
TRIO-DAPchr514420130chr5107483835227HLA-B41:01MEGIFNHKV0.70880.9612514
TRIO-DAPchr514420130chr5107483835227HLA-A30:08KVKAGGMRIV0.99090.80021222
TRIO-DAPchr514420130chr5107483835227HLA-B45:01MEMEGIFNHKV0.99960.8575314
TRIO-DAPchr514420130chr5107483835227HLA-B50:02MEGIFNHKVKA0.99810.5351516
TRIO-DAPchr514420130chr5107483835227HLA-B50:01MEGIFNHKVKA0.91910.5866516
TRIO-DAPchr514420130chr5107483835227HLA-B14:03NHKVKAGGM0.20710.85471019
TRIO-DAPchr514420130chr5107483835227HLA-B40:04MEGIFNHKV0.99490.5776514
TRIO-DAPchr514420130chr5107483835227HLA-A30:01KVKAGGMRI0.99220.86431221
TRIO-DAPchr514420130chr5107483835227HLA-B41:03MEGIFNHKV0.69110.7324514
TRIO-DAPchr514420130chr5107483835227HLA-B50:05MEGIFNHKVKA0.91910.5866516
TRIO-DAPchr514420130chr5107483835227HLA-B50:04MEGIFNHKVKA0.91910.5866516

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Potential FusionNeoAntigen Information of TRIO-DAP 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.
TRIO-DAP_14420130_10748383.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)
TRIO-DAPchr514420130chr5107483835227DRB1-0437MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-0437EMEGIFNHKVKAGGM419
TRIO-DAPchr514420130chr5107483835227DRB1-0437EGIFNHKVKAGGMRI621
TRIO-DAPchr514420130chr5107483835227DRB1-0437MEMEGIFNHKVKAGG318
TRIO-DAPchr514420130chr5107483835227DRB1-1111MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1111EGIFNHKVKAGGMRI621
TRIO-DAPchr514420130chr5107483835227DRB1-1111EMEGIFNHKVKAGGM419
TRIO-DAPchr514420130chr5107483835227DRB1-1132MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1132EGIFNHKVKAGGMRI621
TRIO-DAPchr514420130chr5107483835227DRB1-1145MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1164MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1347MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1363MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1363EGIFNHKVKAGGMRI621
TRIO-DAPchr514420130chr5107483835227DRB1-1363EMEGIFNHKVKAGGM419
TRIO-DAPchr514420130chr5107483835227DRB1-1367MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1427MEGIFNHKVKAGGMR520
TRIO-DAPchr514420130chr5107483835227DRB1-1427EGIFNHKVKAGGMRI621
TRIO-DAPchr514420130chr5107483835227DRB1-1457MEGIFNHKVKAGGMR520

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Fusion breakpoint peptide structures of TRIO-DAP

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
1735EGIFNHKVKAGGMRTRIODAPchr514420130chr5107483835227

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TRIO-DAP

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-B14:023BVN1735EGIFNHKVKAGGMR-7.9962-8.1096
HLA-B14:023BVN1735EGIFNHKVKAGGMR-5.70842-6.74372
HLA-B52:013W391735EGIFNHKVKAGGMR-6.83737-6.95077
HLA-B52:013W391735EGIFNHKVKAGGMR-4.4836-5.5189
HLA-A11:014UQ21735EGIFNHKVKAGGMR-10.0067-10.1201
HLA-A11:014UQ21735EGIFNHKVKAGGMR-9.03915-10.0745
HLA-A24:025HGA1735EGIFNHKVKAGGMR-6.56204-6.67544
HLA-A24:025HGA1735EGIFNHKVKAGGMR-5.42271-6.45801
HLA-B44:053DX81735EGIFNHKVKAGGMR-7.85648-8.89178
HLA-B44:053DX81735EGIFNHKVKAGGMR-5.3978-5.5112
HLA-A02:016TDR1735EGIFNHKVKAGGMR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TRIO-DAP

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
TRIO-DAPchr514420130chr5107483831019NHKVKAGGMACCACAAAGTGAAAGCTGGTGGAATGC
TRIO-DAPchr514420130chr5107483831221KVKAGGMRIAAGTGAAAGCTGGTGGAATGCGAATTG
TRIO-DAPchr514420130chr5107483831222KVKAGGMRIVAAGTGAAAGCTGGTGGAATGCGAATTGTGC
TRIO-DAPchr514420130chr510748383314MEMEGIFNHKVTGGAAATGGAGGGCATCTTCAACCACAAAGTGA
TRIO-DAPchr514420130chr510748383514MEGIFNHKVTGGAGGGCATCTTCAACCACAAAGTGA
TRIO-DAPchr514420130chr510748383516MEGIFNHKVKATGGAGGGCATCTTCAACCACAAAGTGAAAGCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TRIO-DAPchr514420130chr510748383318MEMEGIFNHKVKAGGTGGAAATGGAGGGCATCTTCAACCACAAAGTGAAAGCTGGTGGAA
TRIO-DAPchr514420130chr510748383419EMEGIFNHKVKAGGMAAATGGAGGGCATCTTCAACCACAAAGTGAAAGCTGGTGGAATGC
TRIO-DAPchr514420130chr510748383520MEGIFNHKVKAGGMRTGGAGGGCATCTTCAACCACAAAGTGAAAGCTGGTGGAATGCGAA
TRIO-DAPchr514420130chr510748383621EGIFNHKVKAGGMRIAGGGCATCTTCAACCACAAAGTGAAAGCTGGTGGAATGCGAATTG

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Information of the samples that have these potential fusion neoantigens of TRIO-DAP

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
SARCTRIO-DAPchr514420130ENST00000344204chr510748383ENST00000230895TCGA-DX-AB2X-01A

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Potential target of CAR-T therapy development for TRIO-DAP

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 TRIO-DAP

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 TRIO-DAP

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