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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:SH3KBP1-RPS6KA3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SH3KBP1-RPS6KA3
FusionPDB ID: 81498
FusionGDB2.0 ID: 81498
HgeneTgene
Gene symbol

SH3KBP1

RPS6KA3

Gene ID

30011

6197

Gene nameSH3 domain containing kinase binding protein 1ribosomal protein S6 kinase A3
SynonymsAGMX2|CD2BP3|CIN85|GIG10|HSB-1|HSB1|IMD61|MIG18CLS|HU-3|ISPK-1|MAPKAPK1B|MRX19|RSK|RSK2|S6K-alpha3|p90-RSK2|pp90RSK2
Cytomap

Xp22.12

Xp22.12

Type of geneprotein-codingprotein-coding
DescriptionSH3 domain-containing kinase-binding protein 1CD2-binding protein 3SH3-domain kinase binding protein 1Src family kinase-binding protein 1c-Cbl-interacting proteincbl-interacting protein of 85 kDahuman Src family kinase-binding protein 1migration-inribosomal 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 date2020032720200327
UniProtAcc

SHKBP1

Main function of 5'-partner protein: 707
.
Ensembl transtripts involved in fusion geneENST idsENST00000379697, ENST00000397821, 
ENST00000379698, ENST00000379716, 
ENST00000477102, ENST00000541422, 
ENST00000479809, ENST00000379548, 
ENST00000379565, ENST00000540702, 
ENST00000544447, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 14 X 5=98010 X 8 X 5=400
# samples 1510
** MAII scorelog2(15/980*10)=-2.70781924850669
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: SH3KBP1 [Title/Abstract] AND RPS6KA3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SH3KBP1 [Title/Abstract] AND RPS6KA3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPS6KA3(20252876)-SH3KBP1(19663593), # samples:1
SH3KBP1(19854243)-RPS6KA3(20227522), # samples:1
Anticipated loss of major functional domain due to fusion event.RPS6KA3-SH3KBP1 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.
RPS6KA3-SH3KBP1 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.
SH3KBP1-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.
SH3KBP1-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.
SH3KBP1-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.
SH3KBP1-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.
RPS6KA3-SH3KBP1 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
RPS6KA3-SH3KBP1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
RPS6KA3-SH3KBP1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
RPS6KA3-SH3KBP1 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
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/chrX:20252876/chrX:19663593)
- 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 SH3KBP1 (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)
ENST00000397821SH3KBP1chrX19854243-ENST00000379565RPS6KA3chrX20227522-80374532912549752
ENST00000397821SH3KBP1chrX19854243-ENST00000544447RPS6KA3chrX20227522-29824532912549752
ENST00000397821SH3KBP1chrX19854243-ENST00000379548RPS6KA3chrX20227522-28014532912546751
ENST00000397821SH3KBP1chrX19854243-ENST00000540702RPS6KA3chrX20227522-26884532912546751
ENST00000379697SH3KBP1chrX19854243-ENST00000379565RPS6KA3chrX20227522-78953111492407752
ENST00000379697SH3KBP1chrX19854243-ENST00000544447RPS6KA3chrX20227522-28403111492407752
ENST00000379697SH3KBP1chrX19854243-ENST00000379548RPS6KA3chrX20227522-26593111492404751
ENST00000379697SH3KBP1chrX19854243-ENST00000540702RPS6KA3chrX20227522-25463111492404751

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
ENST00000397821ENST00000379565SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0001286520.9998714
ENST00000397821ENST00000544447SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0007157330.9992843
ENST00000397821ENST00000379548SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0011056630.9988944
ENST00000397821ENST00000540702SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0010815120.99891853
ENST00000379697ENST00000379565SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0001122150.9998878
ENST00000379697ENST00000544447SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0004189850.99958104
ENST00000379697ENST00000379548SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0006402580.9993598
ENST00000379697ENST00000540702SH3KBP1chrX19854243-RPS6KA3chrX20227522-0.0006297440.9993703

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 SH3KBP1-RPS6KA3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SH3KBP1chrX19854243RPS6KA3chrX2022752231154NGRRGLFPDNFVREEVSIKEIAITHH
SH3KBP1chrX19854243RPS6KA3chrX2022752245354NGRRGLFPDNFVREEVSIKEIAITHH

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Potential FusionNeoAntigen Information of SH3KBP1-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.
SH3KBP1-RPS6KA3_19854243_20227522.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)
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:02REEVSIKEI0.99580.60541221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B45:01REEVSIKEI0.97980.76061221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B44:03REEVSIKEI0.97950.94931221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B41:01REEVSIKEI0.59830.77311221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B39:13REEVSIKEI0.50250.78331221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:01REEVSIKEI0.37550.72151221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B35:02FPDNFVREEV0.98150.9748616
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B35:04FPDNFVREEV0.98150.9748616
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B45:01REEVSIKEIA0.9740.75371222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:02REEVSIKEIA0.96560.67231222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B41:01REEVSIKEIA0.78910.79121222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:01REEVSIKEIA0.77290.76241222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B51:07DNFVREEV0.99980.779816
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B40:06REEVSIKEI0.99960.62491221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B39:08REEVSIKEI0.65910.66611221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B40:06REEVSIKEIA0.99220.6591222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B35:12FPDNFVREEV0.98150.9748616
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B40:04REEVSIKEI0.9990.75271221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B44:07REEVSIKEI0.97950.94931221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B44:26REEVSIKEI0.97950.94931221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B44:13REEVSIKEI0.97950.94931221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B39:02REEVSIKEI0.54810.78451221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:04REEVSIKEI0.37550.72151221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:05REEVSIKEI0.37550.72151221
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B35:09FPDNFVREEV0.98150.9748616
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:04REEVSIKEIA0.77290.76241222
SH3KBP1-RPS6KA3chrX19854243chrX20227522311HLA-B50:05REEVSIKEIA0.77290.76241222

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Potential FusionNeoAntigen Information of SH3KBP1-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.
SH3KBP1-RPS6KA3_19854243_20227522.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)
SH3KBP1-RPS6KA3chrX19854243chrX20227522311DRB5-0101PDNFVREEVSIKEIA722
SH3KBP1-RPS6KA3chrX19854243chrX20227522311DRB5-0105PDNFVREEVSIKEIA722
SH3KBP1-RPS6KA3chrX19854243chrX20227522311DRB5-0113PDNFVREEVSIKEIA722
SH3KBP1-RPS6KA3chrX19854243chrX20227522311DRB5-0114PDNFVREEVSIKEIA722

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Fusion breakpoint peptide structures of SH3KBP1-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
2495FPDNFVREEVSIKESH3KBP1RPS6KA3chrX19854243chrX20227522311

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SH3KBP1-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-B14:023BVN2495FPDNFVREEVSIKE-7.9962-8.1096
HLA-B14:023BVN2495FPDNFVREEVSIKE-5.70842-6.74372
HLA-B52:013W392495FPDNFVREEVSIKE-6.83737-6.95077
HLA-B52:013W392495FPDNFVREEVSIKE-4.4836-5.5189
HLA-A11:014UQ22495FPDNFVREEVSIKE-10.0067-10.1201
HLA-A11:014UQ22495FPDNFVREEVSIKE-9.03915-10.0745
HLA-A24:025HGA2495FPDNFVREEVSIKE-6.56204-6.67544
HLA-A24:025HGA2495FPDNFVREEVSIKE-5.42271-6.45801
HLA-B44:053DX82495FPDNFVREEVSIKE-7.85648-8.89178
HLA-B44:053DX82495FPDNFVREEVSIKE-5.3978-5.5112
HLA-A02:016TDR2495FPDNFVREEVSIKE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of SH3KBP1-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
SH3KBP1-RPS6KA3chrX19854243chrX202275221221REEVSIKEIAGAGAAGAAGTCAGTATCAAAGAAATT
SH3KBP1-RPS6KA3chrX19854243chrX202275221222REEVSIKEIAAGAGAAGAAGTCAGTATCAAAGAAATTGCA
SH3KBP1-RPS6KA3chrX19854243chrX20227522616FPDNFVREEVTTCCCTGACAACTTTGTAAGAGAAGAAGTC
SH3KBP1-RPS6KA3chrX19854243chrX20227522816DNFVREEVGACAACTTTGTAAGAGAAGAAGTC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
SH3KBP1-RPS6KA3chrX19854243chrX20227522722PDNFVREEVSIKEIACCTGACAACTTTGTAAGAGAAGAAGTCAGTATCAAAGAAATTGCA

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Information of the samples that have these potential fusion neoantigens of SH3KBP1-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
UCECSH3KBP1-RPS6KA3chrX19854243ENST00000379697chrX20227522ENST00000379548TCGA-AJ-A3QS-01A

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Potential target of CAR-T therapy development for SH3KBP1-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 SH3KBP1-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 SH3KBP1-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