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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:RPA1-NPIPA5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: RPA1-NPIPA5
FusionPDB ID: 75672
FusionGDB2.0 ID: 75672
HgeneTgene
Gene symbol

RPA1

NPIPA5

Gene ID

25885

100288332

Gene nameRNA polymerase I subunit Anuclear pore complex interacting protein family member A5
SynonymsA190|AFDCIN|RPA1|RPA194|RPO1-4|RPO14NPIP
Cytomap

2p11.2

16p13.11

Type of geneprotein-codingprotein-coding
DescriptionDNA-directed RNA polymerase I subunit RPA1DNA-directed RNA polymerase I largest subunitDNA-directed RNA polymerase I subunit ADNA-directed RNA polymerase I subunit A1RNA polymerase I 194 kDa subunitpolymerase (RNA) I polypeptide A, 194kDapolymerase nuclear pore complex-interacting protein family member A5
Modification date2020031320200313
UniProtAcc.

E9PKD4

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000254719, ENST00000573924, 
ENST00000432570, ENST00000360151, 
ENST00000534094, ENST00000543801, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=1441 X 1 X 1=1
# samples 61
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: RPA1 [Title/Abstract] AND NPIPA5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: RPA1 [Title/Abstract] AND NPIPA5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)RPA1(1787238)-NPIPA5(15463976), # samples:1
Anticipated loss of major functional domain due to fusion event.RPA1-NPIPA5 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.
RPA1-NPIPA5 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.
RPA1-NPIPA5 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.
RPA1-NPIPA5 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


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/chr17:1787238/chr16:15463976)
- 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 RPA1 (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 NPIPA5 (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)
ENST00000254719RPA1chr171787238+ENST00000360151NPIPA5chr1615463976-23451484652344760
ENST00000254719RPA1chr171787238+ENST00000543801NPIPA5chr1615463976-21161484651990641
ENST00000254719RPA1chr171787238+ENST00000534094NPIPA5chr1615463976-21891484652188708

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
ENST00000254719ENST00000360151RPA1chr171787238+NPIPA5chr1615463976-0.0069426870.99305725
ENST00000254719ENST00000543801RPA1chr171787238+NPIPA5chr1615463976-0.004860830.9951391
ENST00000254719ENST00000534094RPA1chr171787238+NPIPA5chr1615463976-0.0032203330.99677974

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 RPA1-NPIPA5

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
RPA1chr171787238NPIPA5chr16154639761484473YEVKSENLGQGDKVSFLKTIFPSQNG

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Potential FusionNeoAntigen Information of RPA1-NPIPA5 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.
RPA1-NPIPA5_1787238_15463976.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)
RPA1-NPIPA5chr171787238chr16154639761484HLA-B15:17KVSFLKTIF0.99130.71521221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B58:02KVSFLKTIF0.98950.73711221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B57:03KVSFLKTIF0.98920.85981221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B48:01GQGDKVSFL0.98340.8552817
RPA1-NPIPA5chr171787238chr16154639761484HLA-A32:13KVSFLKTIF0.95890.88561221
RPA1-NPIPA5chr171787238chr16154639761484HLA-A02:21GQGDKVSFL0.7960.6561817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B39:13GQGDKVSFL0.64110.9517817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B13:02GQGDKVSFL0.64070.7294817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B13:01GQGDKVSFL0.54450.9803817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B52:01DKVSFLKTI0.42240.56371120
RPA1-NPIPA5chr171787238chr16154639761484HLA-C05:09QGDKVSFL10.976917
RPA1-NPIPA5chr171787238chr16154639761484HLA-C08:15QGDKVSFL10.9777917
RPA1-NPIPA5chr171787238chr16154639761484HLA-B48:03GQGDKVSFL0.83380.6431817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B39:08GQGDKVSFL0.60840.9635817
RPA1-NPIPA5chr171787238chr16154639761484HLA-C05:01QGDKVSFL10.976917
RPA1-NPIPA5chr171787238chr16154639761484HLA-C08:02QGDKVSFL10.9777917
RPA1-NPIPA5chr171787238chr16154639761484HLA-A32:01KVSFLKTIF0.99270.89781221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B15:35KVSFLKTIF0.98930.72811221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B57:02KVSFLKTIF0.93240.59561221
RPA1-NPIPA5chr171787238chr16154639761484HLA-B40:12GQGDKVSFL0.83380.6431817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B15:73GQGDKVSFL0.80750.9747817
RPA1-NPIPA5chr171787238chr16154639761484HLA-A02:14GQGDKVSFL0.80090.5552817
RPA1-NPIPA5chr171787238chr16154639761484HLA-A02:06GQGDKVSFL0.7960.6561817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B39:02GQGDKVSFL0.76460.9523817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B40:49GQGDKVSFL0.75740.6078817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B15:30GQGDKVSFL0.67850.9659817
RPA1-NPIPA5chr171787238chr16154639761484HLA-B40:21GQGDKVSFL0.61980.79817

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Potential FusionNeoAntigen Information of RPA1-NPIPA5 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 RPA1-NPIPA5

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
6251NLGQGDKVSFLKTIRPA1NPIPA5chr171787238chr16154639761484

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of RPA1-NPIPA5

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-B14:023BVN6251NLGQGDKVSFLKTI-7.9962-8.1096
HLA-B14:023BVN6251NLGQGDKVSFLKTI-5.70842-6.74372
HLA-B52:013W396251NLGQGDKVSFLKTI-6.83737-6.95077
HLA-B52:013W396251NLGQGDKVSFLKTI-4.4836-5.5189
HLA-A11:014UQ26251NLGQGDKVSFLKTI-10.0067-10.1201
HLA-A11:014UQ26251NLGQGDKVSFLKTI-9.03915-10.0745
HLA-A24:025HGA6251NLGQGDKVSFLKTI-6.56204-6.67544
HLA-A24:025HGA6251NLGQGDKVSFLKTI-5.42271-6.45801
HLA-B44:053DX86251NLGQGDKVSFLKTI-7.85648-8.89178
HLA-B44:053DX86251NLGQGDKVSFLKTI-5.3978-5.5112
HLA-A02:016TDR6251NLGQGDKVSFLKTI-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of RPA1-NPIPA5

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
RPA1-NPIPA5chr171787238chr16154639761120DKVSFLKTIGACAAGGTGTCTTTCCTGAAGACTATC
RPA1-NPIPA5chr171787238chr16154639761221KVSFLKTIFAAGGTGTCTTTCCTGAAGACTATCTTC
RPA1-NPIPA5chr171787238chr1615463976817GQGDKVSFLGGCCAAGGCGACAAGGTGTCTTTCCTG
RPA1-NPIPA5chr171787238chr1615463976917QGDKVSFLCAAGGCGACAAGGTGTCTTTCCTG

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 RPA1-NPIPA5

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
STADRPA1-NPIPA5chr171787238ENST00000254719chr1615463976ENST00000360151TCGA-CD-5803-01A

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Potential target of CAR-T therapy development for RPA1-NPIPA5

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 RPA1-NPIPA5

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 RPA1-NPIPA5

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