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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:RPS6KA2-FGFR1OP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPS6KA2-FGFR1OP
FusionPDB ID: 77989
FusionGDB2.0 ID: 77989
HgeneTgene
Gene symbol

RPS6KA2

FGFR1OP

Gene ID

6196

11116

Gene nameribosomal protein S6 kinase A2centrosomal protein 43
SynonymsHU-2|MAPKAPK1C|RSK|RSK3|S6K-alpha|S6K-alpha2|p90-RSK3|p90RSK2|pp90RSK3FGFR1OP|FOP
Cytomap

6q27

6q27

Type of geneprotein-codingprotein-coding
Descriptionribosomal protein S6 kinase alpha-2MAP kinase-activated protein kinase 1cMAPK-activated protein kinase 1cMAPKAP kinase 1Cmitogen-activated protein kinase-activated protein kinase 1Cribosomal S6 kinase 3ribosomal protein S6 kinase, 90kDa, polypeptideFGFR1 oncogene partnerfibroblast growth factor receptor 1 oncogene partner
Modification date2020031320200313
UniProtAcc.

Q9NVK5

Main function of 5'-partner protein: FUNCTION: May be involved in wound healing pathway. {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000503859, ENST00000510118, 
ENST00000265678, ENST00000366863, 
ENST00000405189, ENST00000481261, 
ENST00000509742, 
ENST00000476078, 
ENST00000349556, ENST00000366847, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 5=4054 X 4 X 4=64
# samples 104
** MAII scorelog2(10/405*10)=-2.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/64*10)=-0.678071905112638
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RPS6KA2 [Title/Abstract] AND FGFR1OP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPS6KA2 [Title/Abstract] AND FGFR1OP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPS6KA2(167271688)-FGFR1OP(167424301), # samples:1
Anticipated loss of major functional domain due to fusion event.RPS6KA2-FGFR1OP 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.
RPS6KA2-FGFR1OP 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
HgeneRPS6KA2

GO:0008285

negative regulation of cell proliferation

16878154

HgeneRPS6KA2

GO:0043065

positive regulation of apoptotic process

16878154

HgeneRPS6KA2

GO:0045786

negative regulation of cell cycle

16878154

TgeneFGFR1OP

GO:0006469

negative regulation of protein kinase activity

17888034

TgeneFGFR1OP

GO:0008284

positive regulation of cell proliferation

17888034

TgeneFGFR1OP

GO:0030307

positive regulation of cell growth

17888034

TgeneFGFR1OP

GO:0030335

positive regulation of cell migration

17888034



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/chr6:167271688/chr6:167424301)
- 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 RPS6KA2 (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 FGFR1OP (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)
ENST00000510118RPS6KA2chr6167271688-ENST00000366847FGFR1OPchr6167424301+139614641941225343
ENST00000510118RPS6KA2chr6167271688-ENST00000349556FGFR1OPchr6167424301+15054641941165323
ENST00000503859RPS6KA2chr6167271688-ENST00000366847FGFR1OPchr6167424301+1400150491265418
ENST00000503859RPS6KA2chr6167271688-ENST00000349556FGFR1OPchr6167424301+154550491205398

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
ENST00000510118ENST00000366847RPS6KA2chr6167271688-FGFR1OPchr6167424301+0.0003302970.9996697
ENST00000510118ENST00000349556RPS6KA2chr6167271688-FGFR1OPchr6167424301+0.001164150.99883586
ENST00000503859ENST00000366847RPS6KA2chr6167271688-FGFR1OPchr6167424301+0.0003304650.99966955
ENST00000503859ENST00000349556RPS6KA2chr6167271688-FGFR1OPchr6167424301+0.0010273220.99897265

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 RPS6KA2-FGFR1OP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RPS6KA2chr6167271688FGFR1OPchr616742430146490LDVEPTTEDTAEEGALDLSDVHSPPK
RPS6KA2chr6167271688FGFR1OPchr6167424301504165LDVEPTTEDTAEEGALDLSDVHSPPK

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Potential FusionNeoAntigen Information of RPS6KA2-FGFR1OP 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.
RPS6KA2-FGFR1OP_167271688_167424301.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)
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B45:01TEDTAEEGA0.7650.9343615
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B35:04TAEEGALDL0.28570.9851918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B35:02TAEEGALDL0.28570.9851918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B39:08AEEGALDL0.95120.87261018
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C05:09TAEEGALDL0.99960.9468918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:15TAEEGALDL0.99940.9751918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:13TAEEGALDL0.61220.9741918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:04TAEEGALDL0.61220.9741918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:03TAEEGALDL0.29780.9884918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B35:12TAEEGALDL0.28570.9851918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B39:08TEDTAEEGAL0.97070.7802616
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C04:03TAEEGALDL0.99960.892918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C05:01TAEEGALDL0.99960.9468918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:02TAEEGALDL0.99940.9751918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C03:06TAEEGALDL0.75120.9955918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B35:13TAEEGALDL0.4380.944918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-C08:01TAEEGALDL0.29780.9884918
RPS6KA2-FGFR1OPchr6167271688chr6167424301504HLA-B35:09TAEEGALDL0.28570.9851918

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Potential FusionNeoAntigen Information of RPS6KA2-FGFR1OP 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 RPS6KA2-FGFR1OP

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
9295TEDTAEEGALDLSDRPS6KA2FGFR1OPchr6167271688chr6167424301504

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPS6KA2-FGFR1OP

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-B14:023BVN9295TEDTAEEGALDLSD-5.49577-5.60917
HLA-B14:023BVN9295TEDTAEEGALDLSD-4.37152-5.40682
HLA-B52:013W399295TEDTAEEGALDLSD-6.90336-7.01676
HLA-B52:013W399295TEDTAEEGALDLSD-4.80833-5.84363
HLA-A11:014UQ29295TEDTAEEGALDLSD-9.82261-9.93601
HLA-A24:025HGA9295TEDTAEEGALDLSD-9.78612-9.89952
HLA-A24:025HGA9295TEDTAEEGALDLSD-4.98992-6.02522
HLA-B27:056PYJ9295TEDTAEEGALDLSD-5.31553-6.35083
HLA-B44:053DX89295TEDTAEEGALDLSD-5.70582-5.81922
HLA-B44:053DX89295TEDTAEEGALDLSD-4.32241-5.35771

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Vaccine Design for the FusionNeoAntigens of RPS6KA2-FGFR1OP

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
RPS6KA2-FGFR1OPchr6167271688chr61674243011018AEEGALDLGCAGAAGAAGGTGCACTTGATCTA
RPS6KA2-FGFR1OPchr6167271688chr6167424301615TEDTAEEGAACAGAAGACACTGCAGAAGAAGGTGCA
RPS6KA2-FGFR1OPchr6167271688chr6167424301616TEDTAEEGALACAGAAGACACTGCAGAAGAAGGTGCACTT
RPS6KA2-FGFR1OPchr6167271688chr6167424301918TAEEGALDLACTGCAGAAGAAGGTGCACTTGATCTA

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 RPS6KA2-FGFR1OP

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
BRCARPS6KA2-FGFR1OPchr6167271688ENST00000503859chr6167424301ENST00000349556TCGA-A8-A06R-01A

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Potential target of CAR-T therapy development for RPS6KA2-FGFR1OP

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 RPS6KA2-FGFR1OP

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 RPS6KA2-FGFR1OP

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