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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:RPS6KB1-CLTC

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPS6KB1-CLTC
FusionPDB ID: 78031
FusionGDB2.0 ID: 78031
HgeneTgene
Gene symbol

RPS6KB1

CLTC

Gene ID

6198

1213

Gene nameribosomal protein S6 kinase B1clathrin heavy chain
SynonymsPS6K|S6K|S6K-beta-1|S6K1|STK14A|p70 S6KA|p70(S6K)-alpha|p70-S6K|p70-alphaCHC|CHC17|CLH-17|CLTCL2|Hc|MRD56
Cytomap

17q23.1

17q23.1

Type of geneprotein-codingprotein-coding
Descriptionribosomal protein S6 kinase beta-1p70 S6 kinase, alpharibosomal protein S6 kinase Iribosomal protein S6 kinase, 70kDa, polypeptide 1serine/threonine kinase 14 alphaserine/threonine-protein kinase 14Aclathrin heavy chain 1clathrin heavy chain on chromosome 17clathrin, heavy polypeptide (Hc)clathrin, heavy polypeptide-like 2
Modification date2020031320200313
UniProtAcc.

P53675

Main function of 5'-partner protein: FUNCTION: Clathrin is the major protein of the polyhedral coat of coated pits and vesicles. Two different adapter protein complexes link the clathrin lattice either to the plasma membrane or to the trans-Golgi network (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000225577, ENST00000406116, 
ENST00000443572, ENST00000393021, 
ENST00000587061, 
ENST00000579815, 
ENST00000269122, ENST00000393043, 
ENST00000579456, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 17 X 14=333218 X 18 X 8=2592
# samples 4722
** MAII scorelog2(47/3332*10)=-2.82565573880055
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(22/2592*10)=-3.55849028935997
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: RPS6KB1 [Title/Abstract] AND CLTC [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPS6KB1 [Title/Abstract] AND CLTC [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CLTC(57746301)-RPS6KB1(57987923), # samples:1
RPS6KB1(57970686)-CLTC(57762417), # samples:1
Anticipated loss of major functional domain due to fusion event.CLTC-RPS6KB1 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.
CLTC-RPS6KB1 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.
RPS6KB1-CLTC 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.
RPS6KB1-CLTC 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.
RPS6KB1-CLTC 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.
RPS6KB1-CLTC 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
HgeneRPS6KB1

GO:0031667

response to nutrient levels

29750193

HgeneRPS6KB1

GO:0031929

TOR signaling

12150926

HgeneRPS6KB1

GO:0071363

cellular response to growth factor stimulus

17936702

TgeneCLTC

GO:1900126

negative regulation of hyaluronan biosynthetic process

24251095



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/chr17:57746301/chr17:57987923)
- 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 RPS6KB1 (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 CLTC (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)
ENST00000443572RPS6KB1chr1757970686+ENST00000393043CLTCchr1757762417+78019655681208
ENST00000443572RPS6KB1chr1757970686+ENST00000269122CLTCchr1757762417+324819655789244
ENST00000443572RPS6KB1chr1757970686+ENST00000579456CLTCchr1757762417+105219655789244
ENST00000406116RPS6KB1chr1757970686+ENST00000393043CLTCchr1757762417+76518140666208
ENST00000406116RPS6KB1chr1757970686+ENST00000269122CLTCchr1757762417+323318140774244
ENST00000406116RPS6KB1chr1757970686+ENST00000579456CLTCchr1757762417+103718140774244
ENST00000225577RPS6KB1chr1757970686+ENST00000393043CLTCchr1757762417+74616221647208
ENST00000225577RPS6KB1chr1757970686+ENST00000269122CLTCchr1757762417+321416221755244
ENST00000225577RPS6KB1chr1757970686+ENST00000579456CLTCchr1757762417+101816221755244

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
ENST00000443572ENST00000393043RPS6KB1chr1757970686+CLTCchr1757762417+0.0005024920.99949753
ENST00000443572ENST00000269122RPS6KB1chr1757970686+CLTCchr1757762417+0.0002701440.9997298
ENST00000443572ENST00000579456RPS6KB1chr1757970686+CLTCchr1757762417+0.0004784510.9995216
ENST00000406116ENST00000393043RPS6KB1chr1757970686+CLTCchr1757762417+0.0005094830.9994905
ENST00000406116ENST00000269122RPS6KB1chr1757970686+CLTCchr1757762417+0.0002664990.9997335
ENST00000406116ENST00000579456RPS6KB1chr1757970686+CLTCchr1757762417+0.0004352780.9995647
ENST00000225577ENST00000393043RPS6KB1chr1757970686+CLTCchr1757762417+0.0004449970.99955493
ENST00000225577ENST00000269122RPS6KB1chr1757970686+CLTCchr1757762417+0.0002534910.9997465
ENST00000225577ENST00000579456RPS6KB1chr1757970686+CLTCchr1757762417+0.0004298960.9995701

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 RPS6KB1-CLTC

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RPS6KB1chr1757970686CLTCchr175776241716247PEDAGSEDELEEGALRTSIDAYDNFD
RPS6KB1chr1757970686CLTCchr175776241718147PEDAGSEDELEEGALRTSIDAYDNFD
RPS6KB1chr1757970686CLTCchr175776241719647PEDAGSEDELEEGALRTSIDAYDNFD

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Potential FusionNeoAntigen Information of RPS6KB1-CLTC 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.
RPS6KB1-CLTC_57970686_57762417.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)
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B18:01DELEEGAL0.99660.9317715
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B44:03EEGALRTSI0.99390.95081019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B45:01EEGALRTSI0.99090.94611019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:01GALRTSIDAY0.9970.88561222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B39:13SEDELEEGAL0.7950.8791515
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B44:10EEGALRTSI0.99330.65881019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:07GALRTSIDAY0.99490.68331222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B39:08SEDELEEGAL0.9610.6155515
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B18:05DELEEGAL0.99660.9317715
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B18:06DELEEGAL0.99560.9373715
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B18:03DELEEGAL0.99380.9249715
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B44:26EEGALRTSI0.99390.95081019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B44:07EEGALRTSI0.99390.95081019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B44:13EEGALRTSI0.99390.95081019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B18:03EEGALRTSI0.86160.96541019
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:33GALRTSIDAY0.9970.88561222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:125GALRTSIDAY0.9970.88561222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:34GALRTSIDAY0.9970.88561222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B15:35GALRTSIDAY0.99390.89891222
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B40:04SEDELEEGAL0.99380.706515
RPS6KB1-CLTCchr1757970686chr1757762417162HLA-B39:11SEDELEEGAL0.97110.6041515

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Potential FusionNeoAntigen Information of RPS6KB1-CLTC 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.
RPS6KB1-CLTC_57970686_57762417.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)
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0411EGALRTSIDAYDNFD1126
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0411EEGALRTSIDAYDNF1025
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0411LEEGALRTSIDAYDN924
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0417EGALRTSIDAYDNFD1126
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0417EEGALRTSIDAYDNF1025
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0467EGALRTSIDAYDNFD1126
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0467EEGALRTSIDAYDNF1025
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0491EGALRTSIDAYDNFD1126
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0491EEGALRTSIDAYDNF1025
RPS6KB1-CLTCchr1757970686chr1757762417162DRB1-0491LEEGALRTSIDAYDN924

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Fusion breakpoint peptide structures of RPS6KB1-CLTC

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
1580EDELEEGALRTSIDRPS6KB1CLTCchr1757970686chr1757762417162

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPS6KB1-CLTC

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-B14:023BVN1580EDELEEGALRTSID-7.15543-7.26883
HLA-B14:023BVN1580EDELEEGALRTSID-4.77435-5.80965
HLA-B52:013W391580EDELEEGALRTSID-6.80875-6.92215
HLA-B52:013W391580EDELEEGALRTSID-4.20386-5.23916
HLA-A11:014UQ21580EDELEEGALRTSID-7.5194-8.5547
HLA-A11:014UQ21580EDELEEGALRTSID-6.9601-7.0735
HLA-A24:025HGA1580EDELEEGALRTSID-7.52403-7.63743
HLA-A24:025HGA1580EDELEEGALRTSID-5.82433-6.85963
HLA-B27:056PYJ1580EDELEEGALRTSID-3.28285-4.31815
HLA-B44:053DX81580EDELEEGALRTSID-5.91172-6.94702
HLA-B44:053DX81580EDELEEGALRTSID-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of RPS6KB1-CLTC

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
RPS6KB1-CLTCchr1757970686chr17577624171019EEGALRTSIGAGGAGGGGGCTCTGCGAACATCAATA
RPS6KB1-CLTCchr1757970686chr17577624171222GALRTSIDAYGGGGCTCTGCGAACATCAATAGATGCTTAT
RPS6KB1-CLTCchr1757970686chr1757762417515SEDELEEGALTCTGAGGATGAGCTGGAGGAGGGGGCTCTG
RPS6KB1-CLTCchr1757970686chr1757762417715DELEEGALGATGAGCTGGAGGAGGGGGCTCTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
RPS6KB1-CLTCchr1757970686chr17577624171025EEGALRTSIDAYDNFGAGGAGGGGGCTCTGCGAACATCAATAGATGCTTATGACAACTTT
RPS6KB1-CLTCchr1757970686chr17577624171126EGALRTSIDAYDNFDGAGGGGGCTCTGCGAACATCAATAGATGCTTATGACAACTTTGAC
RPS6KB1-CLTCchr1757970686chr1757762417924LEEGALRTSIDAYDNCTGGAGGAGGGGGCTCTGCGAACATCAATAGATGCTTATGACAAC

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Information of the samples that have these potential fusion neoantigens of RPS6KB1-CLTC

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
KIRCRPS6KB1-CLTCchr1757970686ENST00000225577chr1757762417ENST00000269122TCGA-BP-5198-01A

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Potential target of CAR-T therapy development for RPS6KB1-CLTC

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 RPS6KB1-CLTC

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 RPS6KB1-CLTC

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
TgeneCLTCC4518356MiT family translocation renal cell carcinoma2ORPHANET
TgeneCLTCC4693389MENTAL RETARDATION, AUTOSOMAL DOMINANT 562GENOMICS_ENGLAND;UNIPROT
TgeneCLTCC0079744Diffuse Large B-Cell Lymphoma1CTD_human
TgeneCLTCC0334121Inflammatory Myofibroblastic Tumor1ORPHANET