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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-LIFR

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TRIO-LIFR
FusionPDB ID: 94208
FusionGDB2.0 ID: 94208
HgeneTgene
Gene symbol

TRIO

LIFR

Gene ID

7204

3977

Gene nametrio Rho guanine nucleotide exchange factorLIF receptor subunit alpha
SynonymsARHGEF23|MEBAS|MRD44|tgatCD118|LIF-R|SJS2|STWS|SWS
Cytomap

5p15.2

5p13.1

Type of geneprotein-codingprotein-coding
Descriptiontriple functional domain proteinPTPRF-interacting proteintriple functional domain (PTPRF interacting)leukemia inhibitory factor receptorCD118 antigenLIF receptorLIF receptor alphaleukemia inhibitory factor receptor alpha
Modification date2020031320200313
UniProtAcc

TPI1

Main function of 5'-partner protein: 249

P42702

Main function of 5'-partner protein: FUNCTION: Signal-transducing molecule. May have a common pathway with IL6ST. The soluble form inhibits the biological activity of LIF by blocking its binding to receptors on target cells.
Ensembl transtripts involved in fusion geneENST idsENST00000344204, ENST00000537187, 
ENST00000344135, ENST00000509967, 
ENST00000515710, 
ENST00000503088, 
ENST00000263409, ENST00000453190, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 28 X 12=114246 X 5 X 3=90
# samples 356
** MAII scorelog2(35/11424*10)=-5.02856915219677
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/90*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

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

Fusion neoantigen context

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

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TRIO(14143991)-LIFR(38489347), # samples:2
Anticipated loss of major functional domain due to fusion event.TRIO-LIFR 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-LIFR 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-LIFR 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-LIFR 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
TgeneLIFR

GO:0008284

positive regulation of cell proliferation

7957045|8999038

TgeneLIFR

GO:0019221

cytokine-mediated signaling pathway

7957045

TgeneLIFR

GO:0034097

response to cytokine

8999038

TgeneLIFR

GO:0048861

leukemia inhibitory factor signaling pathway

8999038|12643274

TgeneLIFR

GO:0070120

ciliary neurotrophic factor-mediated signaling pathway

12643274



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/chr5:14143991/chr5:38489347)
- 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 LIFR (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)
ENST00000344204TRIOchr514143991+ENST00000263409LIFRchr538489347-7940181241307427
ENST00000344204TRIOchr514143991+ENST00000453190LIFRchr538489347-1935181241307427
ENST00000537187TRIOchr514143991+ENST00000263409LIFRchr538489347-792216361289427
ENST00000537187TRIOchr514143991+ENST00000453190LIFRchr538489347-191716361289427

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
ENST00000344204ENST00000263409TRIOchr514143991+LIFRchr538489347-7.24E-050.99992764
ENST00000344204ENST00000453190TRIOchr514143991+LIFRchr538489347-0.0001481460.9998518
ENST00000537187ENST00000263409TRIOchr514143991+LIFRchr538489347-7.32E-050.9999268
ENST00000537187ENST00000453190TRIOchr514143991+LIFRchr538489347-0.0001537260.9998462

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-LIFR

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TRIOchr514143991LIFRchr53848934716352AKDLADIAAFFRSAPIVAPNFTVEDT
TRIOchr514143991LIFRchr53848934718152AKDLADIAAFFRSAPIVAPNFTVEDT

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Potential FusionNeoAntigen Information of TRIO-LIFR 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-LIFR_14143991_38489347.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-LIFRchr514143991chr538489347181HLA-B39:06FRSAPIVA0.99940.8691018
TRIO-LIFRchr514143991chr538489347181HLA-B39:06FRSAPIVAP0.9930.83651019
TRIO-LIFRchr514143991chr538489347181HLA-B08:09DIAAFFRSA0.94190.6667514
TRIO-LIFRchr514143991chr538489347181HLA-B46:01SAPIVAPNF0.81830.52971221
TRIO-LIFRchr514143991chr538489347181HLA-B57:01RSAPIVAPNF0.99980.99191121
TRIO-LIFRchr514143991chr538489347181HLA-B58:02RSAPIVAPNF0.99960.9731121
TRIO-LIFRchr514143991chr538489347181HLA-B57:03RSAPIVAPNF0.99940.99281121
TRIO-LIFRchr514143991chr538489347181HLA-B15:16RSAPIVAPNF0.99840.86561121
TRIO-LIFRchr514143991chr538489347181HLA-B15:17RSAPIVAPNF0.99820.95781121
TRIO-LIFRchr514143991chr538489347181HLA-B58:01RSAPIVAPNF0.9980.96911121
TRIO-LIFRchr514143991chr538489347181HLA-A32:13RSAPIVAPNF0.98460.96571121
TRIO-LIFRchr514143991chr538489347181HLA-B27:02FRSAPIVAPNF10.58421021
TRIO-LIFRchr514143991chr538489347181HLA-B27:04FRSAPIVAPNF10.80191021
TRIO-LIFRchr514143991chr538489347181HLA-B27:07FRSAPIVAPNF0.99990.51661021
TRIO-LIFRchr514143991chr538489347181HLA-B73:01FRSAPIVA0.99890.951018
TRIO-LIFRchr514143991chr538489347181HLA-B73:01FRSAPIVAP0.9820.93031019
TRIO-LIFRchr514143991chr538489347181HLA-C03:07SAPIVAPNF0.82480.94771221
TRIO-LIFRchr514143991chr538489347181HLA-C12:12SAPIVAPNF0.64780.88941221
TRIO-LIFRchr514143991chr538489347181HLA-B51:07SAPIVAPNF0.62950.90721221
TRIO-LIFRchr514143991chr538489347181HLA-C03:14SAPIVAPNF0.48510.97631221
TRIO-LIFRchr514143991chr538489347181HLA-C06:03SAPIVAPNF0.31370.99091221
TRIO-LIFRchr514143991chr538489347181HLA-C12:04SAPIVAPNF0.30980.99291221
TRIO-LIFRchr514143991chr538489347181HLA-C01:30SAPIVAPNF0.26680.97841221
TRIO-LIFRchr514143991chr538489347181HLA-C01:17SAPIVAPNF0.20880.96921221
TRIO-LIFRchr514143991chr538489347181HLA-B73:01FFRSAPIVAP0.87810.9659919
TRIO-LIFRchr514143991chr538489347181HLA-C07:95FRSAPIVAPNF0.99990.79231021
TRIO-LIFRchr514143991chr538489347181HLA-C07:46FRSAPIVAPNF0.99980.93561021
TRIO-LIFRchr514143991chr538489347181HLA-B27:03FRSAPIVAPNF0.99920.87481021
TRIO-LIFRchr514143991chr538489347181HLA-C03:02SAPIVAPNF0.99070.981221
TRIO-LIFRchr514143991chr538489347181HLA-A68:02DIAAFFRSA0.98960.6487514
TRIO-LIFRchr514143991chr538489347181HLA-C03:17AAFFRSAPI0.98460.9673716
TRIO-LIFRchr514143991chr538489347181HLA-A69:01DIAAFFRSA0.96980.6863514
TRIO-LIFRchr514143991chr538489347181HLA-C03:17SAPIVAPNF0.94660.97691221
TRIO-LIFRchr514143991chr538489347181HLA-C16:04SAPIVAPNF0.75780.97081221
TRIO-LIFRchr514143991chr538489347181HLA-B57:02SAPIVAPNF0.64640.92251221
TRIO-LIFRchr514143991chr538489347181HLA-C16:01SAPIVAPNF0.57750.9841221
TRIO-LIFRchr514143991chr538489347181HLA-C02:10SAPIVAPNF0.25910.97771221
TRIO-LIFRchr514143991chr538489347181HLA-C02:02SAPIVAPNF0.25910.97771221
TRIO-LIFRchr514143991chr538489347181HLA-C16:02SAPIVAPNF0.24410.99541221
TRIO-LIFRchr514143991chr538489347181HLA-C01:02SAPIVAPNF0.20070.96871221
TRIO-LIFRchr514143991chr538489347181HLA-C01:03SAPIVAPNF0.0190.9481221
TRIO-LIFRchr514143991chr538489347181HLA-B57:10RSAPIVAPNF0.99980.99191121
TRIO-LIFRchr514143991chr538489347181HLA-B57:04RSAPIVAPNF0.99960.83131121
TRIO-LIFRchr514143991chr538489347181HLA-B58:06RSAPIVAPNF0.99950.93361121
TRIO-LIFRchr514143991chr538489347181HLA-B57:02RSAPIVAPNF0.99910.94661121
TRIO-LIFRchr514143991chr538489347181HLA-A32:01RSAPIVAPNF0.99640.96881121
TRIO-LIFRchr514143991chr538489347181HLA-B27:06FRSAPIVAPNF10.80151021
TRIO-LIFRchr514143991chr538489347181HLA-B27:08FRSAPIVAPNF10.76671021
TRIO-LIFRchr514143991chr538489347181HLA-B27:09FRSAPIVAPNF0.99990.84851021
TRIO-LIFRchr514143991chr538489347181HLA-C07:22FRSAPIVAPNF0.99940.81381021

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Potential FusionNeoAntigen Information of TRIO-LIFR 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-LIFR_14143991_38489347.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-LIFRchr514143991chr538489347181DRB1-0902DIAAFFRSAPIVAPN520
TRIO-LIFRchr514143991chr538489347181DRB5-0106AKDLADIAAFFRSAP015
TRIO-LIFRchr514143991chr538489347181DRB5-0202AKDLADIAAFFRSAP015
TRIO-LIFRchr514143991chr538489347181DRB5-0205AKDLADIAAFFRSAP015

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Fusion breakpoint peptide structures of TRIO-LIFR

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
3565IAAFFRSAPIVAPNTRIOLIFRchr514143991chr538489347181

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

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-B14:023BVN3565IAAFFRSAPIVAPN-7.15543-7.26883
HLA-B14:023BVN3565IAAFFRSAPIVAPN-4.77435-5.80965
HLA-B52:013W393565IAAFFRSAPIVAPN-6.80875-6.92215
HLA-B52:013W393565IAAFFRSAPIVAPN-4.20386-5.23916
HLA-A11:014UQ23565IAAFFRSAPIVAPN-7.5194-8.5547
HLA-A11:014UQ23565IAAFFRSAPIVAPN-6.9601-7.0735
HLA-A24:025HGA3565IAAFFRSAPIVAPN-7.52403-7.63743
HLA-A24:025HGA3565IAAFFRSAPIVAPN-5.82433-6.85963
HLA-B27:056PYJ3565IAAFFRSAPIVAPN-3.28285-4.31815
HLA-B44:053DX83565IAAFFRSAPIVAPN-5.91172-6.94702
HLA-B44:053DX83565IAAFFRSAPIVAPN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TRIO-LIFR

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-LIFRchr514143991chr5384893471018FRSAPIVATCCGATCCGCTCCCATTGTTGCAC
TRIO-LIFRchr514143991chr5384893471019FRSAPIVAPTCCGATCCGCTCCCATTGTTGCACCAA
TRIO-LIFRchr514143991chr5384893471021FRSAPIVAPNFTCCGATCCGCTCCCATTGTTGCACCAAATTTTA
TRIO-LIFRchr514143991chr5384893471121RSAPIVAPNFGATCCGCTCCCATTGTTGCACCAAATTTTA
TRIO-LIFRchr514143991chr5384893471221SAPIVAPNFCCGCTCCCATTGTTGCACCAAATTTTA
TRIO-LIFRchr514143991chr538489347514DIAAFFRSAACATCGCGGCCTTCTTCCGATCCGCTC
TRIO-LIFRchr514143991chr538489347716AAFFRSAPICGGCCTTCTTCCGATCCGCTCCCATTG
TRIO-LIFRchr514143991chr538489347919FFRSAPIVAPTCTTCCGATCCGCTCCCATTGTTGCACCAA

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-LIFRchr514143991chr538489347015AKDLADIAAFFRSAPCCAAGGACCTGGCCGACATCGCGGCCTTCTTCCGATCCGCTCCCA
TRIO-LIFRchr514143991chr538489347520DIAAFFRSAPIVAPNACATCGCGGCCTTCTTCCGATCCGCTCCCATTGTTGCACCAAATT

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

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
SKCMTRIO-LIFRchr514143991ENST00000344204chr538489347ENST00000263409TCGA-EB-A44Q-06A

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

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
TgeneLIFRchr5:14143991chr5:38489347ENST000002634091420834_85801098.0TransmembraneHelical
TgeneLIFRchr5:14143991chr5:38489347ENST000004531901420834_85801098.0TransmembraneHelical

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-LIFR

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-LIFR

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