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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:RB1-RP2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RB1-RP2
FusionPDB ID: 72571
FusionGDB2.0 ID: 72571
HgeneTgene
Gene symbol

RB1

RP2

Gene ID

5925

390916

Gene nameRB transcriptional corepressor 1nudix hydrolase 19
SynonymsOSRC|PPP1R130|RB|p105-Rb|p110-RB1|pRb|pp110RP2
Cytomap

13q14.2

19q13.11

Type of geneprotein-codingprotein-coding
Descriptionretinoblastoma-associated proteinGOS563 exon 17 substitution mutation causes premature stopexon 17 tumor GOS561 substitution mutation causes premature stopprepro-retinoblastoma-associated proteinprotein phosphatase 1, regulatory subunit 130retinoblasnucleoside diphosphate-linked moiety X motif 19CTC-379B2.4nucleoside diphosphate-linked moiety X motif 19, mitochondrialnudix (nucleoside diphosphate linked moiety X)-type motif 19nudix motif 19
Modification date2020032920200313
UniProtAcc

RB1CC1

Main function of 5'-partner protein: 1594
.
Ensembl transtripts involved in fusion geneENST idsENST00000267163, ENST00000484879, 
ENST00000218340, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 9 X 13=26912 X 2 X 2=8
# samples 272
** MAII scorelog2(27/2691*10)=-3.31711107858959
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: RB1 [Title/Abstract] AND RP2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RB1 [Title/Abstract] AND RP2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RB1(48955579)-RP2(46712910), # samples:1
Anticipated loss of major functional domain due to fusion event.RB1-RP2 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.
RB1-RP2 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.
RB1-RP2 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.
RB1-RP2 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
HgeneRB1

GO:0043550

regulation of lipid kinase activity

16286473

HgeneRB1

GO:0045892

negative regulation of transcription, DNA-templated

10783144|12065415|19223331

HgeneRB1

GO:2000679

positive regulation of transcription regulatory region DNA binding

25100735



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/chr13:48955579/chrX:46712910)
- 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 RB1 (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 RP2 (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)
ENST00000267163RB1chr1348955579+ENST00000218340RP2chrX46712910+537318331382783881

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
ENST00000267163ENST00000218340RB1chr1348955579+RP2chrX46712910+9.61E-050.9999039

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 RB1-RP2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RB1chr1348955579RP2chrX467129101833563ERCEHRIMESLAWLSVDPKDYMFSGL

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Potential FusionNeoAntigen Information of RB1-RP2 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.
RB1-RP2_48955579_46712910.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)
RB1-RP2chr1348955579chrX467129101833HLA-B45:01MESLAWLSV0.99770.9825716
RB1-RP2chr1348955579chrX467129101833HLA-A02:22RIMESLAWL0.99410.6514
RB1-RP2chr1348955579chrX467129101833HLA-A02:30RIMESLAWL0.99310.6448514
RB1-RP2chr1348955579chrX467129101833HLA-A02:67RIMESLAWL0.99310.6448514
RB1-RP2chr1348955579chrX467129101833HLA-A02:24RIMESLAWL0.99310.6448514
RB1-RP2chr1348955579chrX467129101833HLA-A02:60RIMESLAWL0.99290.639514
RB1-RP2chr1348955579chrX467129101833HLA-A02:21RIMESLAWL0.99270.7313514
RB1-RP2chr1348955579chrX467129101833HLA-A02:04RIMESLAWL0.99250.6928514
RB1-RP2chr1348955579chrX467129101833HLA-A02:11RIMESLAWL0.99240.6824514
RB1-RP2chr1348955579chrX467129101833HLA-A02:17RIMESLAWL0.99120.7212514
RB1-RP2chr1348955579chrX467129101833HLA-A02:27RIMESLAWL0.98860.7205514
RB1-RP2chr1348955579chrX467129101833HLA-A02:16RIMESLAWL0.98820.519514
RB1-RP2chr1348955579chrX467129101833HLA-A02:13RIMESLAWL0.98720.8337514
RB1-RP2chr1348955579chrX467129101833HLA-A02:38RIMESLAWL0.98380.8209514
RB1-RP2chr1348955579chrX467129101833HLA-A02:35RIMESLAWL0.97970.6632514
RB1-RP2chr1348955579chrX467129101833HLA-A02:29RIMESLAWL0.95030.6462514
RB1-RP2chr1348955579chrX467129101833HLA-A02:19RIMESLAWL0.94310.5193514
RB1-RP2chr1348955579chrX467129101833HLA-A02:20RIMESLAWL0.93480.6466514
RB1-RP2chr1348955579chrX467129101833HLA-B50:01MESLAWLSV0.82630.9763716
RB1-RP2chr1348955579chrX467129101833HLA-B27:04HRIMESLAWL0.99990.7353414
RB1-RP2chr1348955579chrX467129101833HLA-B27:07HRIMESLAWL0.99980.5008414
RB1-RP2chr1348955579chrX467129101833HLA-B39:24HRIMESLAWL0.99720.7304414
RB1-RP2chr1348955579chrX467129101833HLA-B39:01HRIMESLAWL0.99540.9005414
RB1-RP2chr1348955579chrX467129101833HLA-B07:10HRIMESLAWL0.36020.5752414
RB1-RP2chr1348955579chrX467129101833HLA-A02:13RIMESLAWLSV0.99910.841516
RB1-RP2chr1348955579chrX467129101833HLA-A02:27RIMESLAWLSV0.9990.7652516
RB1-RP2chr1348955579chrX467129101833HLA-A02:11RIMESLAWLSV0.99850.7591516
RB1-RP2chr1348955579chrX467129101833HLA-A02:60RIMESLAWLSV0.99840.7323516
RB1-RP2chr1348955579chrX467129101833HLA-A02:38RIMESLAWLSV0.99840.83516
RB1-RP2chr1348955579chrX467129101833HLA-A02:21RIMESLAWLSV0.99830.809516
RB1-RP2chr1348955579chrX467129101833HLA-A02:67RIMESLAWLSV0.99830.7367516
RB1-RP2chr1348955579chrX467129101833HLA-A02:24RIMESLAWLSV0.99830.7367516
RB1-RP2chr1348955579chrX467129101833HLA-A02:30RIMESLAWLSV0.99830.7367516
RB1-RP2chr1348955579chrX467129101833HLA-A02:04RIMESLAWLSV0.99790.7764516
RB1-RP2chr1348955579chrX467129101833HLA-A02:16RIMESLAWLSV0.99740.5271516
RB1-RP2chr1348955579chrX467129101833HLA-A02:35RIMESLAWLSV0.99360.7464516
RB1-RP2chr1348955579chrX467129101833HLA-A02:29RIMESLAWLSV0.98450.7392516
RB1-RP2chr1348955579chrX467129101833HLA-A02:20RIMESLAWLSV0.97180.7416516
RB1-RP2chr1348955579chrX467129101833HLA-B40:06MESLAWLSV0.99910.818716
RB1-RP2chr1348955579chrX467129101833HLA-A02:02RIMESLAWL0.99430.5014514
RB1-RP2chr1348955579chrX467129101833HLA-A02:05RIMESLAWL0.99360.5909514
RB1-RP2chr1348955579chrX467129101833HLA-A02:07RIMESLAWL0.99340.6674514
RB1-RP2chr1348955579chrX467129101833HLA-A02:01RIMESLAWL0.99310.6448514
RB1-RP2chr1348955579chrX467129101833HLA-B39:12HRIMESLAWL0.9950.9061414
RB1-RP2chr1348955579chrX467129101833HLA-A02:01RIMESLAWLSV0.99830.7367516
RB1-RP2chr1348955579chrX467129101833HLA-A02:14RIMESLAWL0.99290.6996514
RB1-RP2chr1348955579chrX467129101833HLA-A02:06RIMESLAWL0.99270.7313514
RB1-RP2chr1348955579chrX467129101833HLA-B40:04MESLAWLSV0.99160.9528716
RB1-RP2chr1348955579chrX467129101833HLA-A02:03RIMESLAWL0.98780.7284514
RB1-RP2chr1348955579chrX467129101833HLA-A32:01RIMESLAWL0.9820.9814514
RB1-RP2chr1348955579chrX467129101833HLA-B50:04MESLAWLSV0.82630.9763716
RB1-RP2chr1348955579chrX467129101833HLA-B50:05MESLAWLSV0.82630.9763716
RB1-RP2chr1348955579chrX467129101833HLA-C17:01RIMESLAWL0.60930.9819514
RB1-RP2chr1348955579chrX467129101833HLA-B40:21RIMESLAWL0.09050.5583514
RB1-RP2chr1348955579chrX467129101833HLA-B27:08HRIMESLAWL0.99990.6337414
RB1-RP2chr1348955579chrX467129101833HLA-B27:09HRIMESLAWL0.99980.6729414
RB1-RP2chr1348955579chrX467129101833HLA-B27:06HRIMESLAWL0.99980.739414
RB1-RP2chr1348955579chrX467129101833HLA-B39:31HRIMESLAWL0.99570.9043414
RB1-RP2chr1348955579chrX467129101833HLA-A02:03RIMESLAWLSV0.99940.8021516
RB1-RP2chr1348955579chrX467129101833HLA-A02:14RIMESLAWLSV0.99840.7781516
RB1-RP2chr1348955579chrX467129101833HLA-A02:06RIMESLAWLSV0.99830.809516

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Potential FusionNeoAntigen Information of RB1-RP2 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.
RB1-RP2_48955579_46712910.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)
RB1-RP2chr1348955579chrX467129101833DRB1-0310LAWLSVDPKDYMFSG1025
RB1-RP2chr1348955579chrX467129101833DRB1-0320LAWLSVDPKDYMFSG1025
RB1-RP2chr1348955579chrX467129101833DRB1-0326LAWLSVDPKDYMFSG1025

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Fusion breakpoint peptide structures of RB1-RP2

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
3831IMESLAWLSVDPKDRB1RP2chr1348955579chrX467129101833

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RB1-RP2

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-B14:023BVN3831IMESLAWLSVDPKD-7.74923-7.86263
HLA-B14:023BVN3831IMESLAWLSVDPKD-5.89384-6.92914
HLA-B52:013W393831IMESLAWLSVDPKD-4.71605-5.75135
HLA-B52:013W393831IMESLAWLSVDPKD-4.60517-4.71857
HLA-A11:014UQ23831IMESLAWLSVDPKD-3.55615-4.59145
HLA-A24:025HGA3831IMESLAWLSVDPKD-6.20641-6.31981
HLA-A24:025HGA3831IMESLAWLSVDPKD-4.60823-5.64353
HLA-B44:053DX83831IMESLAWLSVDPKD-5.79986-5.91326
HLA-B44:053DX83831IMESLAWLSVDPKD-4.0772-5.1125

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Vaccine Design for the FusionNeoAntigens of RB1-RP2

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
RB1-RP2chr1348955579chrX46712910414HRIMESLAWLATCATGGAATCCCTTGCATGGCTCTCAGTT
RB1-RP2chr1348955579chrX46712910514RIMESLAWLATGGAATCCCTTGCATGGCTCTCAGTT
RB1-RP2chr1348955579chrX46712910516RIMESLAWLSVATGGAATCCCTTGCATGGCTCTCAGTTGATCCA
RB1-RP2chr1348955579chrX46712910716MESLAWLSVTCCCTTGCATGGCTCTCAGTTGATCCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
RB1-RP2chr1348955579chrX467129101025LAWLSVDPKDYMFSGTGGCTCTCAGTTGATCCAAAAGACTACATGTTCAGTGGACTGAAG

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Information of the samples that have these potential fusion neoantigens of RB1-RP2

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
Non-CancerRB1-RP2chr1348955579ENST00000267163chrX46712910ENST00000218340149N

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Potential target of CAR-T therapy development for RB1-RP2

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 RB1-RP2

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 RB1-RP2

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