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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:PPP3CC-TNFRSF10A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PPP3CC-TNFRSF10A
FusionPDB ID: 68158
FusionGDB2.0 ID: 68158
HgeneTgene
Gene symbol

PPP3CC

TNFRSF10A

Gene ID

5533

8797

Gene nameprotein phosphatase 3 catalytic subunit gammaTNF receptor superfamily member 10a
SynonymsCALNA3|CNA3|PP2BgammaAPO2|CD261|DR4|TRAILR-1|TRAILR1
Cytomap

8p21.3

8p21.3

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein phosphatase 2B catalytic subunit gamma isoformCAM-PRP catalytic subunitcalcineurin, testis-specific catalytic subunitcalmodulin-dependent calcineurin A subunit gamma isoformprotein phosphatase 2B, catalytic subunit, gamma isoftumor necrosis factor receptor superfamily member 10ATNF-related apoptosis-inducing ligand receptor 1TRAIL receptor 1TRAIL-R1cytotoxic TRAIL receptordeath receptor 4tumor necrosis factor receptor superfamily member 10a variant 2tumor necrosis facto
Modification date2020031320200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000240139, ENST00000289963, 
ENST00000397775, ENST00000518852, 
ENST00000221132, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score12 X 11 X 7=9242 X 2 X 2=8
# samples 202
** MAII scorelog2(20/924*10)=-2.20789285164133
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: PPP3CC [Title/Abstract] AND TNFRSF10A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PPP3CC [Title/Abstract] AND TNFRSF10A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PPP3CC(22333137)-TNFRSF10A(23069725), # samples:1
Anticipated loss of major functional domain due to fusion event.PPP3CC-TNFRSF10A 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.
PPP3CC-TNFRSF10A 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.
PPP3CC-TNFRSF10A 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.
PPP3CC-TNFRSF10A 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
HgenePPP3CC

GO:0006470

protein dephosphorylation

19154138

HgenePPP3CC

GO:0033173

calcineurin-NFAT signaling cascade

19154138

TgeneTNFRSF10A

GO:0036462

TRAIL-activated apoptotic signaling pathway

21785459

TgeneTNFRSF10A

GO:0097191

extrinsic apoptotic signaling pathway

21785459



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/chr8:22333137/chr8:23069725)
- 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 PPP3CC (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 TNFRSF10A (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)
ENST00000518852PPP3CCchr822333137+ENST00000221132TNFRSF10Achr823069725-33069635702063497
ENST00000240139PPP3CCchr822333137+ENST00000221132TNFRSF10Achr823069725-30426993061799497
ENST00000289963PPP3CCchr822333137+ENST00000221132TNFRSF10Achr823069725-30016582651758497
ENST00000397775PPP3CCchr822333137+ENST00000221132TNFRSF10Achr823069725-29896462531746497

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
ENST00000518852ENST00000221132PPP3CCchr822333137+TNFRSF10Achr823069725-0.0006122530.99938774
ENST00000240139ENST00000221132PPP3CCchr822333137+TNFRSF10Achr823069725-0.0004508580.9995491
ENST00000289963ENST00000221132PPP3CCchr822333137+TNFRSF10Achr823069725-0.0004326360.99956733
ENST00000397775ENST00000221132PPP3CCchr822333137+TNFRSF10Achr823069725-0.0004096390.99959034

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 PPP3CC-TNFRSF10A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PPP3CCchr822333137TNFRSF10Achr823069725646131LGDYVDRGYFSIEVVPSSAATIKLHD
PPP3CCchr822333137TNFRSF10Achr823069725646307SGCGGDPKCMDRVCFWRLGLLRGPGA
PPP3CCchr822333137TNFRSF10Achr823069725658131LGDYVDRGYFSIEVVPSSAATIKLHD
PPP3CCchr822333137TNFRSF10Achr823069725658307SGCGGDPKCMDRVCFWRLGLLRGPGA
PPP3CCchr822333137TNFRSF10Achr823069725699131LGDYVDRGYFSIEVVPSSAATIKLHD
PPP3CCchr822333137TNFRSF10Achr823069725699307SGCGGDPKCMDRVCFWRLGLLRGPGA
PPP3CCchr822333137TNFRSF10Achr823069725963131LGDYVDRGYFSIEVVPSSAATIKLHD
PPP3CCchr822333137TNFRSF10Achr823069725963307SGCGGDPKCMDRVCFWRLGLLRGPGA

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Potential FusionNeoAntigen Information of PPP3CC-TNFRSF10A 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.
PPP3CC-TNFRSF10A_22333137_23069725.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)
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B57:01KCMDRVCFW0.99760.8817716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B58:02KCMDRVCFW0.99520.8119716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B58:01KCMDRVCFW0.99390.7825716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B57:03KCMDRVCFW0.98820.855716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A74:03RVCFWRLGLLR0.98650.86811122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A74:11RVCFWRLGLLR0.98650.86811122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A74:09RVCFWRLGLLR0.98650.86811122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A31:06RVCFWRLGLLR0.95040.73141122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A31:02RVCFWRLGLLR0.94740.87491122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A31:01RVCFWRLGLLR0.98840.84391122
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B57:10KCMDRVCFW0.99760.8817716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B58:06KCMDRVCFW0.98490.7627716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B57:04KCMDRVCFW0.96950.7772716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A32:01RVCFWRLGL0.95580.97561120
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-B57:02KCMDRVCFW0.80610.8153716
PPP3CC-TNFRSF10Achr822333137chr823069725699HLA-A74:01RVCFWRLGLLR0.98650.86811122

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Potential FusionNeoAntigen Information of PPP3CC-TNFRSF10A 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 PPP3CC-TNFRSF10A

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
6714PKCMDRVCFWRLGLPPP3CCTNFRSF10Achr822333137chr823069725699

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PPP3CC-TNFRSF10A

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-B14:023BVN6714PKCMDRVCFWRLGL-7.411-7.5244
HLA-B14:023BVN6714PKCMDRVCFWRLGL-7.10244-8.13774
HLA-B52:013W396714PKCMDRVCFWRLGL-6.26037-6.37377
HLA-B52:013W396714PKCMDRVCFWRLGL-4.25074-5.28604
HLA-A11:014UQ26714PKCMDRVCFWRLGL-6.53046-7.56576
HLA-A24:025HGA6714PKCMDRVCFWRLGL-8.81216-8.92556
HLA-A24:025HGA6714PKCMDRVCFWRLGL-6.41278-7.44808
HLA-B44:053DX86714PKCMDRVCFWRLGL-6.00394-6.11734
HLA-B44:053DX86714PKCMDRVCFWRLGL-3.79908-4.83438

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Vaccine Design for the FusionNeoAntigens of PPP3CC-TNFRSF10A

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
PPP3CC-TNFRSF10Achr822333137chr8230697251120RVCFWRLGLATAGAGGTCGTACCTAGCTCAGCTGCA
PPP3CC-TNFRSF10Achr822333137chr8230697251122RVCFWRLGLLRATAGAGGTCGTACCTAGCTCAGCTGCAACCATC
PPP3CC-TNFRSF10Achr822333137chr823069725716KCMDRVCFWGGCTATTTCAGTATAGAGGTCGTACCT

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 PPP3CC-TNFRSF10A

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
ESCAPPP3CC-TNFRSF10Achr822333137ENST00000240139chr823069725ENST00000221132TCGA-LN-A49K

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Potential target of CAR-T therapy development for PPP3CC-TNFRSF10A

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
TgeneTNFRSF10Achr8:22333137chr8:23069725ENST00000221132010240_2620469.0TransmembraneHelical

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 PPP3CC-TNFRSF10A

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 PPP3CC-TNFRSF10A

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