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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:PRRX2-PPP2R4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PRRX2-PPP2R4
FusionPDB ID: 69285
FusionGDB2.0 ID: 69285
HgeneTgene
Gene symbol

PRRX2

PPP2R4

Gene ID

51450

5524

Gene namepaired related homeobox 2protein phosphatase 2 phosphatase activator
SynonymsPMX2|PRX2PP2A|PPP2R4|PR53
Cytomap

9q34.11

9q34.11

Type of geneprotein-codingprotein-coding
Descriptionpaired mesoderm homeobox protein 2PRX-2paired-like homeodomain protein PRX2paired-related homeobox protein 2testicular tissue protein Li 148testicular tissue protein Li 160serine/threonine-protein phosphatase 2A activatorPP2A phosphatase activatorPP2A subunit B' isoform PR53phosphotyrosyl phosphatase activatorprotein phosphatase 2 regulatory subunit 4protein phosphatase 2A activator, regulatory subunit 4protein phosph
Modification date2020031320200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000372469, ENST00000414510, 
ENST00000419582, ENST00000423100, 
ENST00000432124, ENST00000432651, 
ENST00000434095, ENST00000435132, 
ENST00000435305, ENST00000436883, 
ENST00000524946, ENST00000337738, 
ENST00000347048, ENST00000348141, 
ENST00000355007, ENST00000357197, 
ENST00000358994, ENST00000393370, 
ENST00000452489, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 1 X 2=63 X 4 X 2=24
# samples 44
** MAII scorelog2(4/6*10)=2.73696559416621log2(4/24*10)=0.736965594166206
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

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

Fusion neoantigen context

PubMed: PRRX2 [Title/Abstract] AND PPP2R4 [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.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
TgenePPP2R4

GO:0032515

negative regulation of phosphoprotein phosphatase activity

16916641

TgenePPP2R4

GO:0032516

positive regulation of phosphoprotein phosphatase activity

16916641

TgenePPP2R4

GO:0035307

positive regulation of protein dephosphorylation

16916641

TgenePPP2R4

GO:0035308

negative regulation of protein dephosphorylation

16916641

TgenePPP2R4

GO:0043065

positive regulation of apoptotic process

17333320

TgenePPP2R4

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 PRRX2 (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 PPP2R4 (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)
ENST00000372469PRRX2chr9132428405+ENST00000358994PPP2R4chr9131882791+2907486411426461
ENST00000372469PRRX2chr9132428405+ENST00000393370PPP2R4chr9131882791+2909486411426461
ENST00000372469PRRX2chr9132428405+ENST00000337738PPP2R4chr9131882791+3012486411531496
ENST00000372469PRRX2chr9132428405+ENST00000348141PPP2R4chr9131882791+2927486411444467
ENST00000372469PRRX2chr9132428405+ENST00000452489PPP2R4chr9131882791+2079486411579512
ENST00000372469PRRX2chr9132428405+ENST00000357197PPP2R4chr9131882791+2821486411339432
ENST00000372469PRRX2chr9132428405+ENST00000347048PPP2R4chr9131882791+225248641769242
ENST00000372469PRRX2chr9132428405+ENST00000355007PPP2R4chr9131882791+2783486411300419
ENST00000372469PRRX2chr9132428405+ENST00000358994PPP2R4chr9131882792+2907486411426461
ENST00000372469PRRX2chr9132428405+ENST00000393370PPP2R4chr9131882792+2909486411426461
ENST00000372469PRRX2chr9132428405+ENST00000337738PPP2R4chr9131882792+3012486411531496
ENST00000372469PRRX2chr9132428405+ENST00000348141PPP2R4chr9131882792+2927486411444467
ENST00000372469PRRX2chr9132428405+ENST00000452489PPP2R4chr9131882792+2079486411579512
ENST00000372469PRRX2chr9132428405+ENST00000357197PPP2R4chr9131882792+2821486411339432
ENST00000372469PRRX2chr9132428405+ENST00000347048PPP2R4chr9131882792+225248641769242
ENST00000372469PRRX2chr9132428405+ENST00000355007PPP2R4chr9131882792+2783486411300419

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
ENST00000372469ENST00000358994PRRX2chr9132428405+PPP2R4chr9131882791+0.0024431190.9975568
ENST00000372469ENST00000393370PRRX2chr9132428405+PPP2R4chr9131882791+0.0024250320.997575
ENST00000372469ENST00000337738PRRX2chr9132428405+PPP2R4chr9131882791+0.0033810970.99661887
ENST00000372469ENST00000348141PRRX2chr9132428405+PPP2R4chr9131882791+0.0033748430.9966252
ENST00000372469ENST00000452489PRRX2chr9132428405+PPP2R4chr9131882791+0.0084252460.9915747
ENST00000372469ENST00000357197PRRX2chr9132428405+PPP2R4chr9131882791+0.0038002980.99619967
ENST00000372469ENST00000347048PRRX2chr9132428405+PPP2R4chr9131882791+0.0611645470.9388354
ENST00000372469ENST00000355007PRRX2chr9132428405+PPP2R4chr9131882791+0.0029218840.9970782
ENST00000372469ENST00000358994PRRX2chr9132428405+PPP2R4chr9131882792+0.0024431190.9975568
ENST00000372469ENST00000393370PRRX2chr9132428405+PPP2R4chr9131882792+0.0024250320.997575
ENST00000372469ENST00000337738PRRX2chr9132428405+PPP2R4chr9131882792+0.0033810970.99661887
ENST00000372469ENST00000348141PRRX2chr9132428405+PPP2R4chr9131882792+0.0033748430.9966252
ENST00000372469ENST00000452489PRRX2chr9132428405+PPP2R4chr9131882792+0.0084252460.9915747
ENST00000372469ENST00000357197PRRX2chr9132428405+PPP2R4chr9131882792+0.0038002980.99619967
ENST00000372469ENST00000347048PRRX2chr9132428405+PPP2R4chr9131882792+0.0611645470.9388354
ENST00000372469ENST00000355007PRRX2chr9132428405+PPP2R4chr9131882792+0.0029218840.9970782

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 PRRX2-PPP2R4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PRRX2chr9132428405PPP2R4chr913188279148632RLGGGGSWAERGAAGALAPTRARDPS
PRRX2chr9132428405PPP2R4chr913188279248632RLGGGGSWAERGAAGALAPTRARDPS

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Potential FusionNeoAntigen Information of PRRX2-PPP2R4 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.
PRRX2-PPP2R4_132428405_131882791.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)
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:02AERGAAGA0.99910.9572816
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:01AERGAAGA0.68910.9859816
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:01AERGAAGAL0.99190.6839817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B48:01AERGAAGAL0.97910.7241817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:02AERGAAGAL0.92080.8326817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:05AERGAAGAL0.46440.6641817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B39:13AERGAAGAL0.40020.984817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B41:01AERGAAGAL0.29590.9626817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:01AERGAAGAL0.09210.9767817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B45:01AERGAAGALA0.98780.985818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:02AERGAAGALA0.97370.8464818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B41:01AERGAAGALA0.83390.9603818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:01AERGAAGALA0.75970.9278818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B45:01AERGAAGALAP0.99860.9953819
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:01AERGAAGALAP0.99540.9489819
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:02AERGAAGALAP0.99530.911819
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B41:01AERGAAGALAP0.94740.9772819
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:06AERGAAGAL0.99820.9105817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B48:03AERGAAGAL0.99220.7388817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B73:01ERGAAGALA0.89320.9552918
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B44:09AERGAAGAL0.78640.7272817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:03AERGAAGAL0.78290.5969817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B39:08AERGAAGAL0.52110.9688817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:06AERGAAGALA0.98340.9381818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B73:01ERGAAGALAP0.97130.9704919
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:04AERGAAGA0.68910.9859816
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:05AERGAAGA0.68910.9859816
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:04AERGAAGAL0.99540.9675817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:36AERGAAGAL0.99240.6748817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:12AERGAAGAL0.99220.7388817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B40:49AERGAAGAL0.98660.6904817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B41:03AERGAAGAL0.4050.8559817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B39:02AERGAAGAL0.3860.9822817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B48:05AERGAAGAL0.13060.5438817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B15:53AERGAAGAL0.09310.8978817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:05AERGAAGAL0.09210.9767817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:04AERGAAGAL0.09210.9767817
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:05AERGAAGALA0.75970.9278818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:04AERGAAGALA0.75970.9278818
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:05AERGAAGALAP0.99540.9489819
PRRX2-PPP2R4chr9132428405chr9131882791486HLA-B50:04AERGAAGALAP0.99540.9489819

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Potential FusionNeoAntigen Information of PRRX2-PPP2R4 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 PRRX2-PPP2R4

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
9178SWAERGAAGALAPTPRRX2PPP2R4chr9132428405chr9131882791486

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

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-B14:023BVN9178SWAERGAAGALAPT-7.9962-8.1096
HLA-B14:023BVN9178SWAERGAAGALAPT-5.70842-6.74372
HLA-B52:013W399178SWAERGAAGALAPT-6.83737-6.95077
HLA-B52:013W399178SWAERGAAGALAPT-4.4836-5.5189
HLA-A11:014UQ29178SWAERGAAGALAPT-10.0067-10.1201
HLA-A11:014UQ29178SWAERGAAGALAPT-9.03915-10.0745
HLA-A24:025HGA9178SWAERGAAGALAPT-6.56204-6.67544
HLA-A24:025HGA9178SWAERGAAGALAPT-5.42271-6.45801
HLA-B44:053DX89178SWAERGAAGALAPT-7.85648-8.89178
HLA-B44:053DX89178SWAERGAAGALAPT-5.3978-5.5112
HLA-A02:016TDR9178SWAERGAAGALAPT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PRRX2-PPP2R4

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
PRRX2-PPP2R4chr9132428405chr9131882791816AERGAAGACGGCGCCGCAGGATGATTCTTCAG
PRRX2-PPP2R4chr9132428405chr9131882791817AERGAAGALCGGCGCCGCAGGATGATTCTTCAGAGG
PRRX2-PPP2R4chr9132428405chr9131882791818AERGAAGALACGGCGCCGCAGGATGATTCTTCAGAGGAGG
PRRX2-PPP2R4chr9132428405chr9131882791819AERGAAGALAPCGGCGCCGCAGGATGATTCTTCAGAGGAGGCCC
PRRX2-PPP2R4chr9132428405chr9131882791918ERGAAGALACGCCGCAGGATGATTCTTCAGAGGAGG
PRRX2-PPP2R4chr9132428405chr9131882791919ERGAAGALAPCGCCGCAGGATGATTCTTCAGAGGAGGCCC

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 PRRX2-PPP2R4

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
OVPRRX2-PPP2R4chr9132428405ENST00000372469chr9131882791ENST00000337738TCGA-24-1553

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

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 PRRX2-PPP2R4

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 PRRX2-PPP2R4

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