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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:PPP2R1A-CENPP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP2R1A-CENPP
FusionPDB ID: 67973
FusionGDB2.0 ID: 67973
HgeneTgene
Gene symbol

PPP2R1A

CENPP

Gene ID

5518

401541

Gene nameprotein phosphatase 2 scaffold subunit Aalphacentromere protein P
SynonymsMRD36|PP2A-Aalpha|PP2AA|PP2AAALPHA|PR65ACENP-P
Cytomap

19q13.41

9q22.31

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoformPP2A subunit A isoform PR65-alphaPP2A subunit A isoform R1-alphamedium tumor antigen-associated 61 KDA proteinprotein phosphatase 2 (formerly 2A), regulatory subunit A (Pcentromere protein P
Modification date2020031320200313
UniProtAcc.

Q6IPU0

Main function of 5'-partner protein: FUNCTION: Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex. {ECO:0000269|PubMed:16622420}.
Ensembl transtripts involved in fusion geneENST idsENST00000322088, ENST00000444322, 
ENST00000477989, ENST00000462990, 
ENST00000473455, 
ENST00000375576, 
ENST00000375579, ENST00000375587, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score10 X 8 X 7=56012 X 10 X 6=720
# samples 1115
** MAII scorelog2(11/560*10)=-2.34792330342031
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/720*10)=-2.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PPP2R1A [Title/Abstract] AND CENPP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP2R1A [Title/Abstract] AND CENPP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP2R1A(52693427)-CENPP(95373596), # samples:3
Anticipated loss of major functional domain due to fusion event.PPP2R1A-CENPP 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.
PPP2R1A-CENPP 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.
PPP2R1A-CENPP seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
PPP2R1A-CENPP seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
PPP2R1A-CENPP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PPP2R1A-CENPP seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted 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
HgenePPP2R1A

GO:0007059

chromosome segregation

16580887



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/chr19:52693427/chr9:95373596)
- 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 PPP2R1A (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 CENPP (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)
ENST00000322088PPP2R1Achr1952693427+ENST00000375587CENPPchr995373596+782313671247771215
ENST00000322088PPP2R1Achr1952693427+ENST00000375579CENPPchr995373596+245413658438126
ENST00000477989PPP2R1Achr1952693427+ENST00000375587CENPPchr995373596+77718470727719215
ENST00000477989PPP2R1Achr1952693427+ENST00000375579CENPPchr995373596+2402846386126

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
ENST00000322088ENST00000375587PPP2R1Achr1952693427+CENPPchr995373596+0.45557840.5444216
ENST00000322088ENST00000375579PPP2R1Achr1952693427+CENPPchr995373596+0.0153846870.98461527
ENST00000477989ENST00000375587PPP2R1Achr1952693427+CENPPchr995373596+0.447523650.5524763
ENST00000477989ENST00000375579PPP2R1Achr1952693427+CENPPchr995373596+0.0133279570.98667204

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 PPP2R1A-CENPP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP2R1Achr1952693427CENPPchr99537359613616ADGDDSLYPIAVLIDELRNEDVQEKY
PPP2R1Achr1952693427CENPPchr9953735968416ADGDDSLYPIAVLIDELRNEDVQEKY

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Potential FusionNeoAntigen Information of PPP2R1A-CENPP 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.
PPP2R1A-CENPP_52693427_95373596.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)
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:22SLYPIAVLI0.99370.6572514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:11SLYPIAVLI0.99190.712514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:21SLYPIAVLI0.99170.7962514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:30SLYPIAVLI0.99150.6807514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:24SLYPIAVLI0.99150.6807514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:67SLYPIAVLI0.99150.6807514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:60SLYPIAVLI0.99130.6659514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:27SLYPIAVLI0.98840.5741514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:04SLYPIAVLI0.98820.6818514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:13SLYPIAVLI0.98770.6356514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:16SLYPIAVLI0.98310.5669514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:38SLYPIAVLI0.98070.5414514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:35SLYPIAVLI0.9680.6905514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A32:13SLYPIAVLI0.95850.9469514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:29SLYPIAVLI0.93480.6803514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:20SLYPIAVLI0.92910.681514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B13:01SLYPIAVLI0.30160.9569514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B52:01SLYPIAVLI0.25730.8023514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:03YPIAVLIDEL0.99450.8201717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:04YPIAVLIDEL0.9880.8753717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:02YPIAVLIDEL0.9880.8753717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:07SLYPIAVLI0.99240.6686514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:01SLYPIAVLI0.99150.6807514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C04:06SLYPIAVLI0.92720.9162514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C06:03SLYPIAVLI0.90940.991514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C12:04SLYPIAVLI0.90940.9929514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B15:04SLYPIAVLI0.69110.9458514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C02:06SLYPIAVLI0.42090.9561514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B51:07SLYPIAVLI0.20250.6878514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:12YPIAVLIDEL0.9880.8753717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B39:10YPIAVLIDEL0.95420.9101717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:03SLYPIAVLI0.9930.6889514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:14SLYPIAVLI0.99230.7255514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A02:06SLYPIAVLI0.99170.7962514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A32:01SLYPIAVLI0.97520.9493514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C15:05SLYPIAVLI0.92720.8871514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C15:02SLYPIAVLI0.91450.8522514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C06:17SLYPIAVLI0.86940.9922514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C06:02SLYPIAVLI0.86940.9922514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-A69:01SLYPIAVLI0.76880.7847514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C06:08SLYPIAVLI0.47660.9861514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-C17:01SLYPIAVLI0.41120.7647514
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:13YPIAVLIDEL0.99370.831717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:09YPIAVLIDEL0.9880.8753717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:17YPIAVLIDEL0.98770.6194717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B35:30YPIAVLIDEL0.98770.6194717
PPP2R1A-CENPPchr1952693427chr995373596136HLA-B67:01YPIAVLIDEL0.96210.6942717

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Potential FusionNeoAntigen Information of PPP2R1A-CENPP 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.
PPP2R1A-CENPP_52693427_95373596.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)
PPP2R1A-CENPPchr1952693427chr995373596136DRB1-0411DDSLYPIAVLIDELR318
PPP2R1A-CENPPchr1952693427chr995373596136DRB1-0411GDDSLYPIAVLIDEL217
PPP2R1A-CENPPchr1952693427chr995373596136DRB1-0467DDSLYPIAVLIDELR318
PPP2R1A-CENPPchr1952693427chr995373596136DRB1-0491DDSLYPIAVLIDELR318
PPP2R1A-CENPPchr1952693427chr995373596136DRB1-0491GDDSLYPIAVLIDEL217
PPP2R1A-CENPPchr1952693427chr995373596136DRB5-0205LYPIAVLIDELRNED621

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Fusion breakpoint peptide structures of PPP2R1A-CENPP

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
5838LYPIAVLIDELRNEPPP2R1ACENPPchr1952693427chr995373596136

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP2R1A-CENPP

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-B14:023BVN5838LYPIAVLIDELRNE-7.9962-8.1096
HLA-B14:023BVN5838LYPIAVLIDELRNE-5.70842-6.74372
HLA-B52:013W395838LYPIAVLIDELRNE-6.83737-6.95077
HLA-B52:013W395838LYPIAVLIDELRNE-4.4836-5.5189
HLA-A11:014UQ25838LYPIAVLIDELRNE-10.0067-10.1201
HLA-A11:014UQ25838LYPIAVLIDELRNE-9.03915-10.0745
HLA-A24:025HGA5838LYPIAVLIDELRNE-6.56204-6.67544
HLA-A24:025HGA5838LYPIAVLIDELRNE-5.42271-6.45801
HLA-B44:053DX85838LYPIAVLIDELRNE-7.85648-8.89178
HLA-B44:053DX85838LYPIAVLIDELRNE-5.3978-5.5112
HLA-A02:016TDR5838LYPIAVLIDELRNE-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of PPP2R1A-CENPP

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
PPP2R1A-CENPPchr1952693427chr995373596514SLYPIAVLIGAACTCCGCAATGAGGACGTTCAGGAA
PPP2R1A-CENPPchr1952693427chr995373596717YPIAVLIDELCGCAATGAGGACGTTCAGGAAAAGTACCCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PPP2R1A-CENPPchr1952693427chr995373596217GDDSLYPIAVLIDELCTCATAGACGAACTCCGCAATGAGGACGTTCAGGAAAAGTACCCA
PPP2R1A-CENPPchr1952693427chr995373596318DDSLYPIAVLIDELRATAGACGAACTCCGCAATGAGGACGTTCAGGAAAAGTACCCAGAT
PPP2R1A-CENPPchr1952693427chr995373596621LYPIAVLIDELRNEDCTCCGCAATGAGGACGTTCAGGAAAAGTACCCAGATGCCGTGTAC

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Information of the samples that have these potential fusion neoantigens of PPP2R1A-CENPP

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
KIRCPPP2R1A-CENPPchr1952693427ENST00000322088chr995373596ENST00000375579TCGA-A3-3328-01A

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Potential target of CAR-T therapy development for PPP2R1A-CENPP

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 PPP2R1A-CENPP

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 PPP2R1A-CENPP

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