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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:PPP2CA-PDLIM4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP2CA-PDLIM4
FusionPDB ID: 67959
FusionGDB2.0 ID: 67959
HgeneTgene
Gene symbol

PPP2CA

PDLIM4

Gene ID

5515

8572

Gene nameprotein phosphatase 2 catalytic subunit alphaPDZ and LIM domain 4
SynonymsNEDLBA|PP2Ac|PP2CA|PP2Calpha|RP-CRIL
Cytomap

5q31.1

5q31.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 2A catalytic subunit alpha isoformPP2A-alphaprotein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoformprotein phosphatase 2, catalytic subunit, alpha isozymereplication protein Cserine/threonine proteinPDZ and LIM domain protein 4LIM domain proteinLIM protein RILenigma homologreversion-induced LIM protein
Modification date2020031520200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000481195, ENST00000231504, 
ENST00000484620, ENST00000253754, 
ENST00000379018, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 9 X 8=10084 X 2 X 4=32
# samples 184
** MAII scorelog2(18/1008*10)=-2.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/32*10)=0.321928094887362
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: PPP2CA [Title/Abstract] AND PDLIM4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP2CA [Title/Abstract] AND PDLIM4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP2CA(133561451)-PDLIM4(131598302), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP2CA-PDLIM4 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.
PPP2CA-PDLIM4 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.
PPP2CA-PDLIM4 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.
PPP2CA-PDLIM4 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
HgenePPP2CA

GO:0035970

peptidyl-threonine dephosphorylation

30611118

TgenePDLIM4

GO:0031532

actin cytoskeleton reorganization

21636573



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/chr5:133561451/chr5:131598302)
- 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 PPP2CA (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 PDLIM4 (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)
ENST00000481195PPP2CAchr5133561451-ENST00000253754PDLIM4chr5131598302+25083832811282333
ENST00000481195PPP2CAchr5133561451-ENST00000379018PDLIM4chr5131598302+12683832811030249

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
ENST00000481195ENST00000253754PPP2CAchr5133561451-PDLIM4chr5131598302+0.042121480.95787853
ENST00000481195ENST00000379018PPP2CAchr5133561451-PDLIM4chr5131598302+0.079924670.9200753

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 PPP2CA-PDLIM4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP2CAchr5133561451PDLIM4chr513159830238334QLSESQVKSLCEKVHAGSKAALAALC

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Potential FusionNeoAntigen Information of PPP2CA-PDLIM4 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.
PPP2CA-PDLIM4_133561451_131598302.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)
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-A30:08KVHAGSKAA0.96270.80531221
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B07:10KVHAGSKAAL0.99750.53841222
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B13:02SQVKSLCEKV0.59490.7388414
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:24EKVHAGSKAAL0.99940.79341122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:01EKVHAGSKAAL0.99810.91541122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B38:02EKVHAGSKAAL0.98130.96631122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B38:01EKVHAGSKAAL0.98090.96541122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:05KVHAGSKAAL0.20650.85221222
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:09EKVHAGSKAAL0.99850.88041122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B14:03EKVHAGSKAAL0.99720.87341122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:05EKVHAGSKAAL0.97120.90511122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-A30:01KVHAGSKAA0.96350.90951221
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:11KVHAGSKAAL0.48840.75091222
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B15:09KVHAGSKAAL0.2450.73171222
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:31EKVHAGSKAAL0.9980.91321122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B15:09EKVHAGSKAAL0.98880.60311122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B39:11EKVHAGSKAAL0.98550.81011122
PPP2CA-PDLIM4chr5133561451chr5131598302383HLA-B38:05EKVHAGSKAAL0.98090.96541122

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Potential FusionNeoAntigen Information of PPP2CA-PDLIM4 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 PPP2CA-PDLIM4

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
10054VKSLCEKVHAGSKAPPP2CAPDLIM4chr5133561451chr5131598302383

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP2CA-PDLIM4

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-B14:023BVN10054VKSLCEKVHAGSKA-4.90311-5.01651
HLA-B14:023BVN10054VKSLCEKVHAGSKA-1.98102-3.01632
HLA-B52:013W3910054VKSLCEKVHAGSKA-5.89733-6.01073
HLA-B52:013W3910054VKSLCEKVHAGSKA-4.93657-5.97187
HLA-A24:025HGA10054VKSLCEKVHAGSKA-6.32379-6.43719
HLA-A24:025HGA10054VKSLCEKVHAGSKA-5.44633-6.48163
HLA-B44:053DX810054VKSLCEKVHAGSKA-5.19893-5.31233
HLA-B44:053DX810054VKSLCEKVHAGSKA-4.49659-5.53189
HLA-B35:011A1N10054VKSLCEKVHAGSKA-7.4022-7.5156
HLA-B35:011A1N10054VKSLCEKVHAGSKA-4.6767-5.712

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Vaccine Design for the FusionNeoAntigens of PPP2CA-PDLIM4

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
PPP2CA-PDLIM4chr5133561451chr51315983021122EKVHAGSKAALGAGAAGGTCCATGCTGGCAGCAAGGCTGCATTG
PPP2CA-PDLIM4chr5133561451chr51315983021221KVHAGSKAAAAGGTCCATGCTGGCAGCAAGGCTGCA
PPP2CA-PDLIM4chr5133561451chr51315983021222KVHAGSKAALAAGGTCCATGCTGGCAGCAAGGCTGCATTG
PPP2CA-PDLIM4chr5133561451chr5131598302414SQVKSLCEKVTCCCAGGTCAAGAGCCTCTGCGAGAAGGTC

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 PPP2CA-PDLIM4

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
SARCPPP2CA-PDLIM4chr5133561451ENST00000481195chr5131598302ENST00000253754TCGA-WK-A8XO-01A

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Potential target of CAR-T therapy development for PPP2CA-PDLIM4

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 PPP2CA-PDLIM4

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 PPP2CA-PDLIM4

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