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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-KIFC1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPS6KA2-KIFC1
FusionPDB ID: 77990
FusionGDB2.0 ID: 77990
HgeneTgene
Gene symbol

RPS6KA2

KIFC1

Gene ID

6196

3833

Gene nameribosomal protein S6 kinase A2kinesin family member C1
SynonymsHU-2|MAPKAPK1C|RSK|RSK3|S6K-alpha|S6K-alpha2|p90-RSK3|p90RSK2|pp90RSK3HSET|KNSL2
Cytomap

6q27

6p21.32

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, polypeptidekinesin-like protein KIFC1kinesin-like 2kinesin-like protein 2kinesin-related protein HSET
Modification date2020031320200313
UniProtAcc.

Q9BW19

Main function of 5'-partner protein: FUNCTION: Minus end-directed microtubule-dependent motor required for bipolar spindle formation (PubMed:15843429). May contribute to movement of early endocytic vesicles (By similarity). Regulates cilium formation and structure (By similarity). {ECO:0000250|UniProtKB:Q9QWT9, ECO:0000269|PubMed:15843429}.
Ensembl transtripts involved in fusion geneENST idsENST00000265678, ENST00000366863, 
ENST00000405189, ENST00000481261, 
ENST00000503859, ENST00000509742, 
ENST00000510118, 
ENST00000374523, 
ENST00000417146, ENST00000448818, 
ENST00000467671, ENST00000486695, 
ENST00000492999, ENST00000428849, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 9 X 5=4053 X 3 X 2=18
# samples 103
** MAII scorelog2(10/405*10)=-2.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/18*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: RPS6KA2 [Title/Abstract] AND KIFC1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPS6KA2 [Title/Abstract] AND KIFC1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPS6KA2(167040409)-KIFC1(33365806), # samples:2
Anticipated loss of major functional domain due to fusion event.RPS6KA2-KIFC1 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-KIFC1 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-KIFC1 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.
RPS6KA2-KIFC1 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



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/chr6:167040409/chr6:33365806)
- 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 KIFC1 (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)
ENST00000265678RPS6KA2chr6167040409-ENST00000428849KIFC1chr633365806+25673231942332712

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
ENST00000265678ENST00000428849RPS6KA2chr6167040409-KIFC1chr633365806+0.0129628670.98703706

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-KIFC1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RPS6KA2chr6167040409KIFC1chr63336580632338VYLRRKSRSKSSSLSRLERSPLLEVK

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Potential FusionNeoAntigen Information of RPS6KA2-KIFC1 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-KIFC1_167040409_33365806.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-KIFC1chr6167040409chr633365806323HLA-B14:01SRSKSSSL0.98640.6428614
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B14:02SRSKSSSL0.98640.6428614
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:08RSKSSSLSR0.99690.7925716
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:08KSRSKSSSL0.98950.7821514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B15:17KSRSKSSSL0.95030.8652514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:08RSKSSSLSRL0.99130.8513717
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A02:04SLSRLERSPLL0.72660.51991223
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B39:12SRSKSSSL0.98790.9576614
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B14:03SRSKSSSL0.93690.8815614
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C15:04KSRSKSSSL0.9980.8693514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C03:08KSRSKSSSL0.98370.9301514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C15:06KSRSKSSSL0.98210.9066514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C12:12KSRSKSSSL0.97020.9348514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B15:04KSRSKSSSL0.90660.924514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B14:03KSRSKSSSL0.8110.873514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C15:09KSRSKSSSL0.9980.8693514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:01RSKSSSLSR0.99720.9089716
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:01KSRSKSSSL0.990.9057514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C15:02KSRSKSSSL0.98320.8621514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C15:05KSRSKSSSL0.98130.8992514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C03:05KSRSKSSSL0.96240.9359514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B08:12KSRSKSSSL0.95990.5707514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B07:13KSRSKSSSL0.95690.7704514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C03:17KSRSKSSSL0.93430.9752514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B58:06KSRSKSSSL0.92510.6667514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C16:04KSRSKSSSL0.92270.9812514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C12:03KSRSKSSSL0.92090.9828514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C16:01KSRSKSSSL0.78360.9767514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-C16:02KSRSKSSSL0.78220.9893514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B15:30KSRSKSSSL0.74250.6873514
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B27:10SRSKSSSLSR0.99890.869616
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:01RSKSSSLSRL0.99340.9446717
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B27:06RRKSRSKSSSL0.99960.8314
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-A30:01KSRSKSSSLSR0.99650.8844516
RPS6KA2-KIFC1chr6167040409chr633365806323HLA-B27:06SLSRLERSPLL0.99560.75121223

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Potential FusionNeoAntigen Information of RPS6KA2-KIFC1 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-KIFC1

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
8985SRSKSSSLSRLERSRPS6KA2KIFC1chr6167040409chr633365806323

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPS6KA2-KIFC1

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-B14:023BVN8985SRSKSSSLSRLERS-6.9015-7.0162
HLA-B14:023BVN8985SRSKSSSLSRLERS-6.88733-7.92393
HLA-B52:013W398985SRSKSSSLSRLERS-6.20276-6.31746
HLA-B52:013W398985SRSKSSSLSRLERS-3.23728-4.27388
HLA-A24:025HGA8985SRSKSSSLSRLERS-6.25402-7.29062
HLA-A24:025HGA8985SRSKSSSLSRLERS-5.4385-5.5532
HLA-B44:053DX88985SRSKSSSLSRLERS-6.77944-6.89414
HLA-B44:053DX88985SRSKSSSLSRLERS-5.78397-6.82057
HLA-A02:016TDR8985SRSKSSSLSRLERS-2.00985-3.04645

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Vaccine Design for the FusionNeoAntigens of RPS6KA2-KIFC1

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-KIFC1chr6167040409chr6333658061223SLSRLERSPLLGAGAGGTCCCCCCTATTGGAAGTAAAGGGGAAC
RPS6KA2-KIFC1chr6167040409chr633365806314RRKSRSKSSSLTCCAAGAGCTCCAGCCTGAGCCGGCTCGAGAGG
RPS6KA2-KIFC1chr6167040409chr633365806514KSRSKSSSLAGCTCCAGCCTGAGCCGGCTCGAGAGG
RPS6KA2-KIFC1chr6167040409chr633365806516KSRSKSSSLSRAGCTCCAGCCTGAGCCGGCTCGAGAGGTCCCCC
RPS6KA2-KIFC1chr6167040409chr633365806614SRSKSSSLTCCAGCCTGAGCCGGCTCGAGAGG
RPS6KA2-KIFC1chr6167040409chr633365806616SRSKSSSLSRTCCAGCCTGAGCCGGCTCGAGAGGTCCCCC
RPS6KA2-KIFC1chr6167040409chr633365806716RSKSSSLSRAGCCTGAGCCGGCTCGAGAGGTCCCCC
RPS6KA2-KIFC1chr6167040409chr633365806717RSKSSSLSRLAGCCTGAGCCGGCTCGAGAGGTCCCCCCTA

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-KIFC1

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
SARCRPS6KA2-KIFC1chr6167040409ENST00000265678chr633365806ENST00000428849TCGA-IE-A3OV-01A

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Potential target of CAR-T therapy development for RPS6KA2-KIFC1

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-KIFC1

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-KIFC1

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