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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:RPS3-UVRAG

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPS3-UVRAG
FusionPDB ID: 77916
FusionGDB2.0 ID: 77916
HgeneTgene
Gene symbol

RPS3

UVRAG

Gene ID

6188

7405

Gene nameribosomal protein S3UV radiation resistance associated
SynonymsS3DHTX|VPS38|p63
Cytomap

11q13.4

11q13.5

Type of geneprotein-codingprotein-coding
Description40S ribosomal protein S3IMR-90 ribosomal protein S3small ribosomal subunit protein uS3UV radiation resistance-associated gene proteinbeclin 1 binding proteindisrupted in heterotaxy
Modification date2020032720200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000529285, ENST00000278572, 
ENST00000524851, ENST00000527446, 
ENST00000530164, ENST00000531188, 
ENST00000534440, ENST00000526608, 
ENST00000356136, ENST00000528420, 
ENST00000525872, ENST00000531818, 
ENST00000532130, ENST00000533454, 
ENST00000538870, ENST00000539288, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score17 X 19 X 5=161528 X 21 X 11=6468
# samples 2236
** MAII scorelog2(22/1615*10)=-2.87595873605663
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(36/6468*10)=-4.16725086714399
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RPS3 [Title/Abstract] AND UVRAG [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPS3 [Title/Abstract] AND UVRAG [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPS3(75112777)-UVRAG(75599872), # samples:1
UVRAG(75572825)-RPS3(75111737), # samples:1
Anticipated loss of major functional domain due to fusion event.RPS3-UVRAG 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.
RPS3-UVRAG 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.
RPS3-UVRAG 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.
RPS3-UVRAG 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.
UVRAG-RPS3 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.
UVRAG-RPS3 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
HgeneRPS3

GO:0006979

response to oxidative stress

23911537

HgeneRPS3

GO:0017148

negative regulation of translation

20217897

HgeneRPS3

GO:0031397

negative regulation of protein ubiquitination

19656744

HgeneRPS3

GO:0032079

positive regulation of endodeoxyribonuclease activity

18973764

HgeneRPS3

GO:0042769

DNA damage response, detection of DNA damage

23911537

HgeneRPS3

GO:0045739

positive regulation of DNA repair

23911537

HgeneRPS3

GO:0061481

response to TNF agonist

20041225

HgeneRPS3

GO:0070301

cellular response to hydrogen peroxide

23911537

HgeneRPS3

GO:1901224

positive regulation of NIK/NF-kappaB signaling

20041225

HgeneRPS3

GO:1902546

positive regulation of DNA N-glycosylase activity

15518571

HgeneRPS3

GO:1905053

positive regulation of base-excision repair

18973764

HgeneRPS3

GO:2001235

positive regulation of apoptotic signaling pathway

14988002

TgeneUVRAG

GO:0071900

regulation of protein serine/threonine kinase activity

22542840

TgeneUVRAG

GO:0097352

autophagosome maturation

28306502

TgeneUVRAG

GO:0097680

double-strand break repair via classical nonhomologous end joining

22542840



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/chr11:75112777/chr11:75599872)
- 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 RPS3 (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 UVRAG (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)
ENST00000531188RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+3767317621984640
ENST00000531188RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+2366317621984640
ENST00000530164RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+3734284291951640
ENST00000530164RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+2333284291951640
ENST00000278572RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+3723273181940640
ENST00000278572RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+2322273181940640
ENST00000534440RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+3722272171939640
ENST00000534440RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+2321272171939640
ENST00000527446RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+3722272171939640
ENST00000527446RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+2321272171939640
ENST00000524851RPS3chr1175112777+ENST00000356136UVRAGchr1175599872+371026051927640
ENST00000524851RPS3chr1175112777+ENST00000528420UVRAGchr1175599872+230926051927640

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
ENST00000531188ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.000822570.9991774
ENST00000531188ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0023289480.99767107
ENST00000530164ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.000868590.9991314
ENST00000530164ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0024608570.99753916
ENST00000278572ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.0008826870.9991173
ENST00000278572ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0024556030.99754435
ENST00000534440ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.0008801350.9991198
ENST00000534440ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0024515570.9975484
ENST00000527446ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.0008801350.9991198
ENST00000527446ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0024515570.9975484
ENST00000524851ENST00000356136RPS3chr1175112777+UVRAGchr1175599872+0.0008672430.9991328
ENST00000524851ENST00000528420RPS3chr1175112777+UVRAGchr1175599872+0.0024779980.99752194

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 RPS3-UVRAG

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

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Potential FusionNeoAntigen Information of RPS3-UVRAG 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.

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)

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Potential FusionNeoAntigen Information of RPS3-UVRAG 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 RPS3-UVRAG

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPS3-UVRAG

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

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Vaccine Design for the FusionNeoAntigens of RPS3-UVRAG

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

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 RPS3-UVRAG

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

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Potential target of CAR-T therapy development for RPS3-UVRAG

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 RPS3-UVRAG

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 RPS3-UVRAG

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