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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:PPP2R4-PRRX2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP2R4-PRRX2
FusionPDB ID: 68058
FusionGDB2.0 ID: 68058
HgeneTgene
Gene symbol

PPP2R4

PRRX2

Gene ID

5524

51450

Gene nameprotein phosphatase 2 phosphatase activatorpaired related homeobox 2
SynonymsPP2A|PPP2R4|PR53PMX2|PRX2
Cytomap

9q34.11

9q34.11

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 2A activatorPP2A phosphatase activatorPP2A subunit B' isoform PR53phosphotyrosyl phosphatase activatorprotein phosphatase 2 regulatory subunit 4protein phosphatase 2A activator, regulatory subunit 4protein phosphpaired mesoderm homeobox protein 2PRX-2paired-like homeodomain protein PRX2paired-related homeobox protein 2testicular tissue protein Li 148testicular tissue protein Li 160
Modification date2020032920200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000337738, ENST00000348141, 
ENST00000355007, ENST00000357197, 
ENST00000358994, ENST00000393370, 
ENST00000452489, ENST00000347048, 
ENST00000414510, ENST00000419582, 
ENST00000423100, ENST00000432124, 
ENST00000432651, ENST00000434095, 
ENST00000435132, ENST00000435305, 
ENST00000436883, ENST00000524946, 
ENST00000372469, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 9 X 8=7205 X 4 X 6=120
# samples 127
** MAII scorelog2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/120*10)=-0.777607578663552
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PPP2R4 [Title/Abstract] AND PRRX2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP2R4 [Title/Abstract] AND PRRX2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP2R4(131898874)-PRRX2(132481509), # samples:1
PRRX2(132428405)-PPP2R4(131882791), # samples:1
PRRX2(132428405)-PPP2R4(131882792), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP2R4-PRRX2 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.
PPP2R4-PRRX2 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.
PRRX2-PPP2R4 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.
PRRX2-PPP2R4 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
HgenePPP2R4

GO:0032515

negative regulation of phosphoprotein phosphatase activity

16916641

HgenePPP2R4

GO:0032516

positive regulation of phosphoprotein phosphatase activity

16916641

HgenePPP2R4

GO:0035307

positive regulation of protein dephosphorylation

16916641

HgenePPP2R4

GO:0035308

negative regulation of protein dephosphorylation

16916641

HgenePPP2R4

GO:0043065

positive regulation of apoptotic process

17333320

HgenePPP2R4

GO:0043666

regulation of phosphoprotein phosphatase activity

16916641



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/chr9:131898874/chr9:132481509)
- 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 PPP2R4 (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 PRRX2 (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)
ENST00000358994PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+164489781399463
ENST00000393370PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+17159681691470433
ENST00000337738PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+180410571531559468
ENST00000348141PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+17159681511470439
ENST00000452489PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+17501003991505468
ENST00000357197PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+1537790781292404
ENST00000355007PPP2R4chr9131898874+ENST00000372469PRRX2chr9132481509+1493746731248391

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
ENST00000358994ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0169122740.9830877
ENST00000393370ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0133338020.98666614
ENST00000337738ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0086334980.99136645
ENST00000348141ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0138391270.9861609
ENST00000452489ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0094824930.99051756
ENST00000357197ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.021925860.9780741
ENST00000355007ENST00000372469PPP2R4chr9131898874+PRRX2chr9132481509+0.0178049580.9821951

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 PPP2R4-PRRX2

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

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Potential FusionNeoAntigen Information of PPP2R4-PRRX2 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.

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)

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Potential FusionNeoAntigen Information of PPP2R4-PRRX2 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 PPP2R4-PRRX2

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP2R4-PRRX2

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

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Vaccine Design for the FusionNeoAntigens of PPP2R4-PRRX2

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

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 PPP2R4-PRRX2

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

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Potential target of CAR-T therapy development for PPP2R4-PRRX2

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 PPP2R4-PRRX2

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 PPP2R4-PRRX2

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