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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:RTN4-KIAA0196

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RTN4-KIAA0196
FusionPDB ID: 78575
FusionGDB2.0 ID: 78575
HgeneTgene
Gene symbol

RTN4

KIAA0196

Gene ID

57142

9897

Gene namereticulon 4WASH complex subunit 5
SynonymsASY|NI220/250|NOGO|NSP|NSP-CL|Nbla00271|Nbla10545|RTN-X|RTN4-A|RTN4-B1|RTN4-B2|RTN4-CKIAA0196|RTSC|RTSC1|SPG8
Cytomap

2p16.1

8q24.13

Type of geneprotein-codingprotein-coding
Descriptionreticulon-4Human NogoAMy043 proteinfoocenneurite growth inhibitor 220neurite outgrowth inhibitorneuroendocrine-specific protein C homologreticulon 5WASH complex subunit 5WASH complex subunit strumpellinstrumpellin
Modification date2020032720200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000317610, ENST00000337526, 
ENST00000354474, ENST00000357376, 
ENST00000357732, ENST00000394609, 
ENST00000394611, ENST00000402434, 
ENST00000404909, ENST00000405240, 
ENST00000486085, 
ENST00000521109, 
ENST00000318410, ENST00000517845, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 22 X 7=27724 X 4 X 3=48
# samples 275
** MAII scorelog2(27/2772*10)=-3.35989594508638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/48*10)=0.0588936890535686
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: RTN4 [Title/Abstract] AND KIAA0196 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RTN4 [Title/Abstract] AND KIAA0196 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RTN4(55209650)-KIAA0196(126052140), # samples:1
Anticipated loss of major functional domain due to fusion event.RTN4-KIAA0196 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.
RTN4-KIAA0196 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.
RTN4-KIAA0196 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.
RTN4-KIAA0196 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.
RTN4-KIAA0196 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
RTN4-KIAA0196 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
RTN4-KIAA0196 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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
HgeneRTN4

GO:0030517

negative regulation of axon extension

10667797

HgeneRTN4

GO:0071787

endoplasmic reticulum tubular network formation

24262037|25612671

HgeneRTN4

GO:1905552

positive regulation of protein localization to endoplasmic reticulum

27353365



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/chr2:55209650/chr8:126052140)
- 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 RTN4 (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 KIAA0196 (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)
ENST00000394609RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-16977103291339336
ENST00000394609RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-16907103291339336
ENST00000317610RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-213411472171776519
ENST00000317610RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-212711472171776519
ENST00000357732RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-219112042171833538
ENST00000357732RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-218412042171833538
ENST00000337526RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-4591360421742331338
ENST00000337526RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-4584360421742331338
ENST00000354474RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-36512664032931097
ENST00000354474RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-36442664032931097
ENST00000402434RTN4chr255209650-ENST00000318410KIAA0196chr8126052140-1882895491524491
ENST00000402434RTN4chr255209650-ENST00000517845KIAA0196chr8126052140-1875895491524491

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
ENST00000394609ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0008068080.99919325
ENST00000394609ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.0008064790.9991935
ENST00000317610ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0016847170.99831533
ENST00000317610ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.001690680.9983094
ENST00000357732ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0015979130.99840206
ENST00000357732ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.0015839570.99841607
ENST00000337526ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0007516570.9992483
ENST00000337526ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.0007717280.99922824
ENST00000354474ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0005262510.99947375
ENST00000354474ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.0005398920.99946016
ENST00000402434ENST00000318410RTN4chr255209650-KIAA0196chr8126052140-0.0017181340.99828184
ENST00000402434ENST00000517845RTN4chr255209650-KIAA0196chr8126052140-0.0017491960.9982508

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 RTN4-KIAA0196

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RTN4chr255209650KIAA0196chr81260521401147310RLFLVDDLVDSLKVGQMQILRQQIAN
RTN4chr255209650KIAA0196chr81260521401204329RLFLVDDLVDSLKVGQMQILRQQIAN
RTN4chr255209650KIAA0196chr81260521402664888RLFLVDDLVDSLKVGQMQILRQQIAN
RTN4chr255209650KIAA0196chr812605214036041129RLFLVDDLVDSLKVGQMQILRQQIAN
RTN4chr255209650KIAA0196chr8126052140710127RLFLVDDLVDSLKVGQMQILRQQIAN
RTN4chr255209650KIAA0196chr8126052140895282RLFLVDDLVDSLKVGQMQILRQQIAN

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Potential FusionNeoAntigen Information of RTN4-KIAA0196 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.
RTN4-KIAA0196_55209650_126052140.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)
RTN4-KIAA0196chr255209650chr81260521401147HLA-A74:09KVGQMQILR0.99060.6091221
RTN4-KIAA0196chr255209650chr81260521401147HLA-A74:03KVGQMQILR0.99060.6091221
RTN4-KIAA0196chr255209650chr81260521401147HLA-A74:11KVGQMQILR0.99060.6091221
RTN4-KIAA0196chr255209650chr81260521401147HLA-A31:02KVGQMQILR0.92650.64291221
RTN4-KIAA0196chr255209650chr81260521401147HLA-B13:02SLKVGQMQI0.17170.68541019
RTN4-KIAA0196chr255209650chr81260521401147HLA-A31:01KVGQMQILR0.9890.57961221
RTN4-KIAA0196chr255209650chr81260521401147HLA-A74:01KVGQMQILR0.99060.6091221

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Potential FusionNeoAntigen Information of RTN4-KIAA0196 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 RTN4-KIAA0196

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
1246DLVDSLKVGQMQILRTN4KIAA0196chr255209650chr81260521401147

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RTN4-KIAA0196

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-B14:023BVN1246DLVDSLKVGQMQIL-7.9962-8.1096
HLA-B14:023BVN1246DLVDSLKVGQMQIL-5.70842-6.74372
HLA-B52:013W391246DLVDSLKVGQMQIL-6.83737-6.95077
HLA-B52:013W391246DLVDSLKVGQMQIL-4.4836-5.5189
HLA-A11:014UQ21246DLVDSLKVGQMQIL-10.0067-10.1201
HLA-A11:014UQ21246DLVDSLKVGQMQIL-9.03915-10.0745
HLA-A24:025HGA1246DLVDSLKVGQMQIL-6.56204-6.67544
HLA-A24:025HGA1246DLVDSLKVGQMQIL-5.42271-6.45801
HLA-B44:053DX81246DLVDSLKVGQMQIL-7.85648-8.89178
HLA-B44:053DX81246DLVDSLKVGQMQIL-5.3978-5.5112
HLA-A02:016TDR1246DLVDSLKVGQMQIL-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of RTN4-KIAA0196

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
RTN4-KIAA0196chr255209650chr81260521401019SLKVGQMQITCTCTGAAGGTTGGGCAGATGCAGATT
RTN4-KIAA0196chr255209650chr81260521401221KVGQMQILRAAGGTTGGGCAGATGCAGATTCTGAGA

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 RTN4-KIAA0196

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
OVRTN4-KIAA0196chr255209650ENST00000317610chr8126052140ENST00000318410TCGA-25-1313

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Potential target of CAR-T therapy development for RTN4-KIAA0196

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
HgeneRTN4chr2:55209650chr8:126052140ENST00000337526-591019_103911201193.0TransmembraneHelical

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 RTN4-KIAA0196

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 RTN4-KIAA0196

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