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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:RICTOR-ISL1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RICTOR-ISL1
FusionPDB ID: 74069
FusionGDB2.0 ID: 74069
HgeneTgene
Gene symbol

RICTOR

ISL1

Gene ID

253260

3670

Gene nameRPTOR independent companion of MTOR complex 2ISL LIM homeobox 1
SynonymsAVO3|PIA|hAVO3ISLET1|Isl-1
Cytomap

5p13.1

5q11.1

Type of geneprotein-codingprotein-coding
Descriptionrapamycin-insensitive companion of mTORAVO3 homologTORC2-specific protein AVO3pianissimoinsulin gene enhancer protein ISL-1ISL1 transcription factor, LIM/homeodomainislet-1
Modification date2020031320200313
UniProtAcc.

P61371

Main function of 5'-partner protein: FUNCTION: DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1. Binds to insulin gene enhancer sequences. Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity). {ECO:0000250|UniProtKB:P61372, ECO:0000250|UniProtKB:P61374}.
Ensembl transtripts involved in fusion geneENST idsENST00000296782, ENST00000357387, 
ENST00000503698, 
ENST00000505475, 
ENST00000230658, ENST00000511384, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score19 X 9 X 12=20521 X 1 X 1=1
# samples 201
** MAII scorelog2(20/2052*10)=-3.35895882583233
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: RICTOR [Title/Abstract] AND ISL1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RICTOR [Title/Abstract] AND ISL1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RICTOR(39074213)-ISL1(50680375), # samples:3
Anticipated loss of major functional domain due to fusion event.RICTOR-ISL1 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.
RICTOR-ISL1 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.
RICTOR-ISL1 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.
RICTOR-ISL1 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
HgeneRICTOR

GO:0051896

regulation of protein kinase B signaling

15718470

TgeneISL1

GO:0060913

cardiac cell fate determination

19571884



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/chr5:39074213/chr5:50680375)
- 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 RICTOR (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 ISL1 (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)
ENST00000357387RICTORchr539074213-ENST00000230658ISL1chr550680375+2270128161149377
ENST00000357387RICTORchr539074213-ENST00000511384ISL1chr550680375+1081128161080355
ENST00000296782RICTORchr539074213-ENST00000230658ISL1chr550680375+226111971140377
ENST00000296782RICTORchr539074213-ENST00000511384ISL1chr550680375+107211971071355

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
ENST00000357387ENST00000230658RICTORchr539074213-ISL1chr550680375+0.0008998550.9991002
ENST00000357387ENST00000511384RICTORchr539074213-ISL1chr550680375+0.0039986850.9960013
ENST00000296782ENST00000230658RICTORchr539074213-ISL1chr550680375+0.0009632760.9990368
ENST00000296782ENST00000511384RICTORchr539074213-ISL1chr550680375+0.0040243490.9959757

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 RICTOR-ISL1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RICTORchr539074213ISL1chr55068037511937DSGEENVPLDLTREKRLISLCVGCGN
RICTORchr539074213ISL1chr55068037512837DSGEENVPLDLTREKRLISLCVGCGN

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Potential FusionNeoAntigen Information of RICTOR-ISL1 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.
RICTOR-ISL1_39074213_50680375.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)
RICTOR-ISL1chr539074213chr550680375119HLA-B47:01REKRLISL0.99690.5511220
RICTOR-ISL1chr539074213chr550680375119HLA-B39:13REKRLISL0.9680.83421220
RICTOR-ISL1chr539074213chr550680375119HLA-B14:01TREKRLISL0.9970.50131120
RICTOR-ISL1chr539074213chr550680375119HLA-B14:02TREKRLISL0.9970.50131120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:01TREKRLISL0.99620.80891120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:06TREKRLISL0.99520.67211120
RICTOR-ISL1chr539074213chr550680375119HLA-B27:04TREKRLISL0.99460.69331120
RICTOR-ISL1chr539074213chr550680375119HLA-B38:02TREKRLISL0.99210.90731120
RICTOR-ISL1chr539074213chr550680375119HLA-B15:10TREKRLISL0.93590.52331120
RICTOR-ISL1chr539074213chr550680375119HLA-B15:37TREKRLISL0.89710.54381120
RICTOR-ISL1chr539074213chr550680375119HLA-B41:01REKRLISLC0.36950.56641221
RICTOR-ISL1chr539074213chr550680375119HLA-B40:06REKRLISL0.99970.5611220
RICTOR-ISL1chr539074213chr550680375119HLA-B39:08REKRLISL0.96470.68431220
RICTOR-ISL1chr539074213chr550680375119HLA-B39:12TREKRLISL0.99550.81921120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:05TREKRLISL0.99450.95021120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:95TREKRLISL0.99420.67191120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:13TREKRLISL0.99210.91561120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:29TREKRLISL0.99190.91661120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:05TREKRLISL0.99170.7951120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:27TREKRLISL0.99170.92591120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:19TREKRLISL0.9850.64371120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:67TREKRLISL0.98440.89711120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:80TREKRLISL0.98440.89711120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:10TREKRLISL0.97910.93261120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:46TREKRLISL0.97090.82551120
RICTOR-ISL1chr539074213chr550680375119HLA-B14:03TREKRLISL0.86390.56081120
RICTOR-ISL1chr539074213chr550680375119HLA-C12:16TREKRLISL0.23950.91541120
RICTOR-ISL1chr539074213chr550680375119HLA-B42:01VPLDLTREKRL0.96760.8133617
RICTOR-ISL1chr539074213chr550680375119HLA-B40:04REKRLISL0.99940.69841220
RICTOR-ISL1chr539074213chr550680375119HLA-B39:02REKRLISL0.9860.84241220
RICTOR-ISL1chr539074213chr550680375119HLA-B27:06TREKRLISL0.99670.67671120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:31TREKRLISL0.99630.81491120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:02TREKRLISL0.9960.84091120
RICTOR-ISL1chr539074213chr550680375119HLA-B27:09TREKRLISL0.99550.8511120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:01TREKRLISL0.99480.65831120
RICTOR-ISL1chr539074213chr550680375119HLA-B27:10TREKRLISL0.99390.81361120
RICTOR-ISL1chr539074213chr550680375119HLA-B27:08TREKRLISL0.99230.75641120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:17TREKRLISL0.98960.92631120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:02TREKRLISL0.98440.89711120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:04TREKRLISL0.97570.86221120
RICTOR-ISL1chr539074213chr550680375119HLA-C06:08TREKRLISL0.91170.93511120
RICTOR-ISL1chr539074213chr550680375119HLA-C07:22TREKRLISL0.86660.72341120
RICTOR-ISL1chr539074213chr550680375119HLA-B15:09TREKRLISL0.86250.50321120
RICTOR-ISL1chr539074213chr550680375119HLA-B39:11TREKRLISL0.86120.51321120
RICTOR-ISL1chr539074213chr550680375119HLA-C18:01TREKRLISL0.81650.66461120
RICTOR-ISL1chr539074213chr550680375119HLA-C03:67TREKRLISL0.740.95551120
RICTOR-ISL1chr539074213chr550680375119HLA-C06:06TREKRLISL0.68910.97241120
RICTOR-ISL1chr539074213chr550680375119HLA-C06:02TREKRLISL0.38960.9621120
RICTOR-ISL1chr539074213chr550680375119HLA-C06:17TREKRLISL0.38960.9621120
RICTOR-ISL1chr539074213chr550680375119HLA-B67:01VPLDLTREKRL0.79780.8714617

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Potential FusionNeoAntigen Information of RICTOR-ISL1 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 RICTOR-ISL1

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
10174VPLDLTREKRLISLRICTORISL1chr539074213chr550680375119

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RICTOR-ISL1

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-B14:023BVN10174VPLDLTREKRLISL-7.9962-8.1096
HLA-B14:023BVN10174VPLDLTREKRLISL-5.70842-6.74372
HLA-B52:013W3910174VPLDLTREKRLISL-6.83737-6.95077
HLA-B52:013W3910174VPLDLTREKRLISL-4.4836-5.5189
HLA-A11:014UQ210174VPLDLTREKRLISL-10.0067-10.1201
HLA-A11:014UQ210174VPLDLTREKRLISL-9.03915-10.0745
HLA-A24:025HGA10174VPLDLTREKRLISL-6.56204-6.67544
HLA-A24:025HGA10174VPLDLTREKRLISL-5.42271-6.45801
HLA-B44:053DX810174VPLDLTREKRLISL-7.85648-8.89178
HLA-B44:053DX810174VPLDLTREKRLISL-5.3978-5.5112
HLA-B35:011A1N10174VPLDLTREKRLISL-6.27422-6.38762
HLA-B35:011A1N10174VPLDLTREKRLISL-5.27424-6.30954
HLA-A02:016TDR10174VPLDLTREKRLISL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of RICTOR-ISL1

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
RICTOR-ISL1chr539074213chr5506803751120TREKRLISLCCCGAGAAAAACGTCTGATTTCCCTAT
RICTOR-ISL1chr539074213chr5506803751220REKRLISLGAGAAAAACGTCTGATTTCCCTAT
RICTOR-ISL1chr539074213chr5506803751221REKRLISLCGAGAAAAACGTCTGATTTCCCTATGTG
RICTOR-ISL1chr539074213chr550680375617VPLDLTREKRLTCCCGCTGGATCTGACCCGAGAAAAACGTCTGA

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 RICTOR-ISL1

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
COADRICTOR-ISL1chr539074213ENST00000296782chr550680375ENST00000230658TCGA-CA-5254-01A

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Potential target of CAR-T therapy development for RICTOR-ISL1

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 RICTOR-ISL1

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 RICTOR-ISL1

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