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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:YBX3-RPS6KA3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: YBX3-RPS6KA3
FusionPDB ID: 99940
FusionGDB2.0 ID: 99940
HgeneTgene
Gene symbol

YBX3

RPS6KA3

Gene ID

8531

6197

Gene nameY-box binding protein 3ribosomal protein S6 kinase A3
SynonymsCSDA|CSDA1|DBPA|ZONABCLS|HU-3|ISPK-1|MAPKAPK1B|MRX19|RSK|RSK2|S6K-alpha3|p90-RSK2|pp90RSK2
Cytomap

12p13.2

Xp22.12

Type of geneprotein-codingprotein-coding
DescriptionY-box-binding protein 3DNA-binding protein AZO-1-associated nucleic acid-binding proteincold shock domain-containing protein Acold-shock domain containing A1cold-shock domain protein Asingle-strand DNA-binding protein NF-GMBribosomal protein S6 kinase alpha-3MAP kinase-activated protein kinase 1bMAPK-activated protein kinase 1bMAPKAP kinase 1bMAPKAPK-1bRSK-2S6K-alpha-3epididymis secretory sperm binding proteininsulin-stimulated protein kinase 1p90-RSK 3ribosomal S6
Modification date2020031320200327
UniProtAcc

P16989

Main function of 5'-partner protein: FUNCTION: Binds to the GM-CSF promoter. Seems to act as a repressor. Binds also to full-length mRNA and to short RNA sequences containing the consensus site 5'-UCCAUCA-3'. May have a role in translation repression (By similarity). {ECO:0000250}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000228251, ENST00000279550, 
ENST00000546164, 
ENST00000540702, 
ENST00000544447, ENST00000379548, 
ENST00000479809, ENST00000379565, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 10 X 6=72010 X 8 X 5=400
# samples 1210
** MAII scorelog2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(10/400*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: YBX3 [Title/Abstract] AND RPS6KA3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: YBX3 [Title/Abstract] AND RPS6KA3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)YBX3(10865810)-RPS6KA3(20252932), # samples:1
Anticipated loss of major functional domain due to fusion event.YBX3-RPS6KA3 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.
YBX3-RPS6KA3 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
TgeneRPS6KA3

GO:0043154

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

18402937



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/chr12:10865810/chrX:20252932)
- 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 YBX3 (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 RPS6KA3 (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)
ENST00000279550YBX3chr1210865810-ENST00000379565RPS6KA3chrX20252932-8410769732922949
ENST00000228251YBX3chr1210865810-ENST00000379565RPS6KA3chrX20252932-8415774782927949

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
ENST00000279550ENST00000379565YBX3chr1210865810-RPS6KA3chrX20252932-0.0001053410.9998946
ENST00000228251ENST00000379565YBX3chr1210865810-RPS6KA3chrX20252932-0.0001054120.9998946

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 YBX3-RPS6KA3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
YBX3chr1210865810RPS6KA3chrX20252932769232RGYYGRRRGPPRNNGQQIMDEPMGEE
YBX3chr1210865810RPS6KA3chrX20252932774232RGYYGRRRGPPRNNGQQIMDEPMGEE

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Potential FusionNeoAntigen Information of YBX3-RPS6KA3 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.
YBX3-RPS6KA3_10865810_20252932.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)
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:02GPPRNNGQQI0.88250.7197818
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:05RGPPRNNGQQI0.97530.7664718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:02RGPPRNNGQQI0.96820.794718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:04GPPRNNGQQI0.79040.6552818
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:04RGPPRNNGQQI0.96860.7461718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:12RGPPRNNGQQI0.96340.8676718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:22GPPRNNGQQI0.88250.7197818
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:26GPPRNNGQQI0.63690.5344818
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:09RGPPRNNGQQI0.97080.7886718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:22RGPPRNNGQQI0.96820.794718
YBX3-RPS6KA3chr1210865810chrX20252932774HLA-B07:26RGPPRNNGQQI0.95510.6638718

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Potential FusionNeoAntigen Information of YBX3-RPS6KA3 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 YBX3-RPS6KA3

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
8163RRGPPRNNGQQIMDYBX3RPS6KA3chr1210865810chrX20252932774

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of YBX3-RPS6KA3

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-B14:023BVN8163RRGPPRNNGQQIMD-7.15543-7.26883
HLA-B14:023BVN8163RRGPPRNNGQQIMD-4.77435-5.80965
HLA-B52:013W398163RRGPPRNNGQQIMD-6.80875-6.92215
HLA-B52:013W398163RRGPPRNNGQQIMD-4.20386-5.23916
HLA-A11:014UQ28163RRGPPRNNGQQIMD-7.5194-8.5547
HLA-A11:014UQ28163RRGPPRNNGQQIMD-6.9601-7.0735
HLA-A24:025HGA8163RRGPPRNNGQQIMD-7.52403-7.63743
HLA-A24:025HGA8163RRGPPRNNGQQIMD-5.82433-6.85963
HLA-B27:056PYJ8163RRGPPRNNGQQIMD-3.28285-4.31815
HLA-B44:053DX88163RRGPPRNNGQQIMD-5.91172-6.94702
HLA-B44:053DX88163RRGPPRNNGQQIMD-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of YBX3-RPS6KA3

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
YBX3-RPS6KA3chr1210865810chrX20252932718RGPPRNNGQQICGTGGCCCTCCCCGGAATAATGGACAGCAAATT
YBX3-RPS6KA3chr1210865810chrX20252932818GPPRNNGQQIGGCCCTCCCCGGAATAATGGACAGCAAATT

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 YBX3-RPS6KA3

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
STADYBX3-RPS6KA3chr1210865810ENST00000228251chrX20252932ENST00000379565TCGA-IN-7808-01A

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Potential target of CAR-T therapy development for YBX3-RPS6KA3

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 YBX3-RPS6KA3

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 YBX3-RPS6KA3

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