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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-KDSR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIO-KDSR
FusionPDB ID: 94207
FusionGDB2.0 ID: 94207
HgeneTgene
Gene symbol

TRIO

KDSR

Gene ID

7204

2531

Gene nametrio Rho guanine nucleotide exchange factor3-ketodihydrosphingosine reductase
SynonymsARHGEF23|MEBAS|MRD44|tgatDHSR|EKVP4|FVT1|SDR35C1
Cytomap

5p15.2

18q21.33

Type of geneprotein-codingprotein-coding
Descriptiontriple functional domain proteinPTPRF-interacting proteintriple functional domain (PTPRF interacting)3-ketodihydrosphingosine reductase3-dehydrosphinganine reductaseFVT-1KDS reductasefollicular lymphoma variant translocation 1follicular variant translocation protein 1short chain dehydrogenase/reductase family 35C member 1
Modification date2020031320200313
UniProtAcc

TPI1

Main function of 5'-partner protein: 249

Q06136

Main function of 5'-partner protein: FUNCTION: Catalyzes the reduction of 3-ketodihydrosphingosine (KDS) to dihydrosphingosine (DHS). {ECO:0000269|PubMed:28575652}.
Ensembl transtripts involved in fusion geneENST idsENST00000344204, ENST00000509967, 
ENST00000537187, ENST00000344135, 
ENST00000515710, 
ENST00000326575, 
ENST00000589592, ENST00000406396, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 28 X 12=114244 X 4 X 3=48
# samples 354
** MAII scorelog2(35/11424*10)=-5.02856915219677
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/48*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIO(14297372)-KDSR(61006116), # samples:1
Anticipated loss of major functional domain due to fusion event.TRIO-KDSR 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-KDSR 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-KDSR 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-KDSR 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
TgeneKDSR

GO:0006666

3-keto-sphinganine metabolic process

15364918



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/chr5:14297372/chr18:61006116)
- 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 KDSR (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)
ENST00000344204TRIOchr514297372-ENST00000406396KDSRchr1861006116-57541392241697557
ENST00000537187TRIOchr514297372-ENST00000406396KDSRchr1861006116-5736137461679557
ENST00000509967TRIOchr514297372-ENST00000406396KDSRchr1861006116-573513731521678508

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
ENST00000344204ENST00000406396TRIOchr514297372-KDSRchr1861006116-0.0004665230.99953353
ENST00000537187ENST00000406396TRIOchr514297372-KDSRchr1861006116-0.000469310.9995307
ENST00000509967ENST00000406396TRIOchr514297372-KDSRchr1861006116-0.0005179760.9994821

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-KDSR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIOchr514297372KDSRchr18610061161373407LDMSSIFHQKAEKPLETRLISETTSV
TRIOchr514297372KDSRchr18610061161374456LDMSSIFHQKAEKPLETRLISETTSV
TRIOchr514297372KDSRchr18610061161392456LDMSSIFHQKAEKPLETRLISETTSV

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Potential FusionNeoAntigen Information of TRIO-KDSR 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-KDSR_14297372_61006116.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-KDSRchr514297372chr18610061161392HLA-B39:01FHQKAEKPL0.99620.7761615
TRIO-KDSRchr514297372chr18610061161392HLA-B13:01AEKPLETRL0.99430.89511019
TRIO-KDSRchr514297372chr18610061161392HLA-B39:06FHQKAEKPL0.99340.6203615
TRIO-KDSRchr514297372chr18610061161392HLA-B44:03AEKPLETRL0.99320.96271019
TRIO-KDSRchr514297372chr18610061161392HLA-B50:02AEKPLETRL0.99040.54181019
TRIO-KDSRchr514297372chr18610061161392HLA-B38:01FHQKAEKPL0.98910.8654615
TRIO-KDSRchr514297372chr18610061161392HLA-B38:02FHQKAEKPL0.98850.8632615
TRIO-KDSRchr514297372chr18610061161392HLA-B45:01AEKPLETRL0.94230.85641019
TRIO-KDSRchr514297372chr18610061161392HLA-B14:01FHQKAEKPL0.90980.6926615
TRIO-KDSRchr514297372chr18610061161392HLA-B14:02FHQKAEKPL0.90980.6926615
TRIO-KDSRchr514297372chr18610061161392HLA-A31:02KAEKPLETR0.86730.5553918
TRIO-KDSRchr514297372chr18610061161392HLA-B15:18FHQKAEKPL0.64330.61615
TRIO-KDSRchr514297372chr18610061161392HLA-B18:01AEKPLETRL0.6010.92241019
TRIO-KDSRchr514297372chr18610061161392HLA-B41:01AEKPLETRL0.4790.84061019
TRIO-KDSRchr514297372chr18610061161392HLA-B50:01AEKPLETRL0.26560.64721019
TRIO-KDSRchr514297372chr18610061161392HLA-B39:13AEKPLETRL0.06790.94851019
TRIO-KDSRchr514297372chr18610061161392HLA-B40:06AEKPLETRL0.99780.56511019
TRIO-KDSRchr514297372chr18610061161392HLA-B39:09FHQKAEKPL0.99730.5505615
TRIO-KDSRchr514297372chr18610061161392HLA-B39:12FHQKAEKPL0.99340.7812615
TRIO-KDSRchr514297372chr18610061161392HLA-B39:05FHQKAEKPL0.9930.7732615
TRIO-KDSRchr514297372chr18610061161392HLA-A31:01KAEKPLETR0.89740.5183918
TRIO-KDSRchr514297372chr18610061161392HLA-B39:08AEKPLETRL0.46340.7781019
TRIO-KDSRchr514297372chr18610061161392HLA-B14:03FHQKAEKPL0.3540.6491615
TRIO-KDSRchr514297372chr18610061161392HLA-B40:04AEKPLETRL0.99820.681019
TRIO-KDSRchr514297372chr18610061161392HLA-B39:31FHQKAEKPL0.99640.777615
TRIO-KDSRchr514297372chr18610061161392HLA-B44:07AEKPLETRL0.99320.96271019
TRIO-KDSRchr514297372chr18610061161392HLA-B44:13AEKPLETRL0.99320.96271019
TRIO-KDSRchr514297372chr18610061161392HLA-B44:26AEKPLETRL0.99320.96271019
TRIO-KDSRchr514297372chr18610061161392HLA-B38:05FHQKAEKPL0.98910.8654615
TRIO-KDSRchr514297372chr18610061161392HLA-B15:09FHQKAEKPL0.9260.6831615
TRIO-KDSRchr514297372chr18610061161392HLA-B39:11FHQKAEKPL0.76620.5707615
TRIO-KDSRchr514297372chr18610061161392HLA-B41:03AEKPLETRL0.64850.52691019
TRIO-KDSRchr514297372chr18610061161392HLA-B18:06AEKPLETRL0.60490.93111019
TRIO-KDSRchr514297372chr18610061161392HLA-B18:05AEKPLETRL0.6010.92241019
TRIO-KDSRchr514297372chr18610061161392HLA-B18:11AEKPLETRL0.59760.89851019
TRIO-KDSRchr514297372chr18610061161392HLA-B18:03AEKPLETRL0.53280.91771019
TRIO-KDSRchr514297372chr18610061161392HLA-B50:05AEKPLETRL0.26560.64721019
TRIO-KDSRchr514297372chr18610061161392HLA-B50:04AEKPLETRL0.26560.64721019
TRIO-KDSRchr514297372chr18610061161392HLA-B15:68AEKPLETRL0.23630.59011019
TRIO-KDSRchr514297372chr18610061161392HLA-B15:54AEKPLETRL0.19770.80041019
TRIO-KDSRchr514297372chr18610061161392HLA-B15:53AEKPLETRL0.15040.82631019
TRIO-KDSRchr514297372chr18610061161392HLA-B39:02AEKPLETRL0.10270.94971019
TRIO-KDSRchr514297372chr18610061161392HLA-B48:02AEKPLETRL0.08670.89131019

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Potential FusionNeoAntigen Information of TRIO-KDSR 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 TRIO-KDSR

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
2404FHQKAEKPLETRLITRIOKDSRchr514297372chr18610061161392

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

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-B14:023BVN2404FHQKAEKPLETRLI-5.68465-5.87665
HLA-B14:023BVN2404FHQKAEKPLETRLI-5.14767-5.90867
HLA-B52:013W392404FHQKAEKPLETRLI-7.48951-7.68151
HLA-B52:013W392404FHQKAEKPLETRLI-3.17913-3.94013
HLA-A11:014UQ22404FHQKAEKPLETRLI-7.71963-7.91163
HLA-A11:014UQ22404FHQKAEKPLETRLI-3.00852-3.76952
HLA-A24:025HGA2404FHQKAEKPLETRLI-8.10546-8.29746
HLA-A24:025HGA2404FHQKAEKPLETRLI-6.56641-7.32741
HLA-B44:053DX82404FHQKAEKPLETRLI-4.42032-4.61232
HLA-B44:053DX82404FHQKAEKPLETRLI-3.33841-4.09941

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Vaccine Design for the FusionNeoAntigens of TRIO-KDSR

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-KDSRchr514297372chr18610061161019AEKPLETRLGCCGAAAAGCCTTTGGAGACTCGACTT
TRIO-KDSRchr514297372chr1861006116615FHQKAEKPLTTCCACCAGAAGGCCGAAAAGCCTTTG
TRIO-KDSRchr514297372chr1861006116918KAEKPLETRAAGGCCGAAAAGCCTTTGGAGACTCGA

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 TRIO-KDSR

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
COADTRIO-KDSRchr514297372ENST00000344204chr1861006116ENST00000406396TCGA-AY-6196-01A

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

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
TgeneKDSRchr5:14297372chr18:61006116ENST00000406396610271_2910333.0TransmembraneHelical
TgeneKDSRchr5:14297372chr18:61006116ENST00000406396610294_3140333.0TransmembraneHelical

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 TRIO-KDSR

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-KDSR

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