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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:VRK3-PPP6R1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VRK3-PPP6R1
FusionPDB ID: 98547
FusionGDB2.0 ID: 98547
HgeneTgene
Gene symbol

VRK3

PPP6R1

Gene ID

51231

22870

Gene nameVRK serine/threonine kinase 3protein phosphatase 6 regulatory subunit 1
Synonyms-KIAA1115|PP6R1|SAP190|SAPS1
Cytomap

19q13.33

19q13.42

Type of geneprotein-codingprotein-coding
Descriptioninactive serine/threonine-protein kinase VRK3serine/threonine-protein kinase VRK3serine/threonine-protein pseudokinase VRK3vaccinia related kinase 3serine/threonine-protein phosphatase 6 regulatory subunit 1SAPS domain family, member 1
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000424804, ENST00000443401, 
ENST00000593919, ENST00000594092, 
ENST00000594948, ENST00000599538, 
ENST00000601341, ENST00000601912, 
ENST00000316763, ENST00000377011, 
ENST00000412770, ENST00000587283, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 6 X 4=1687 X 6 X 4=168
# samples 98
** MAII scorelog2(9/168*10)=-0.900464326449086
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/168*10)=-1.0703893278914
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VRK3 [Title/Abstract] AND PPP6R1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VRK3 [Title/Abstract] AND PPP6R1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VRK3(50504047)-PPP6R1(55753856), # samples:3
Anticipated loss of major functional domain due to fusion event.VRK3-PPP6R1 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.
VRK3-PPP6R1 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.
VRK3-PPP6R1 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.
VRK3-PPP6R1 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.
VRK3-PPP6R1 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
VRK3-PPP6R1 seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
VRK3-PPP6R1 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
TgenePPP6R1

GO:0043666

regulation of phosphoprotein phosphatase activity

16716191



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/chr19:50504047/chr19:55753856)
- 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 VRK3 (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 PPP6R1 (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)
ENST00000316763VRK3chr1950504047-ENST00000412770PPP6R1chr1955753856-35727961842823879
ENST00000316763VRK3chr1950504047-ENST00000587283PPP6R1chr1955753856-28627961842823879
ENST00000377011VRK3chr1950504047-ENST00000412770PPP6R1chr1955753856-34086321702659829
ENST00000377011VRK3chr1950504047-ENST00000587283PPP6R1chr1955753856-26986321702659829

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
ENST00000316763ENST00000412770VRK3chr1950504047-PPP6R1chr1955753856-0.0066864380.9933136
ENST00000316763ENST00000587283VRK3chr1950504047-PPP6R1chr1955753856-0.0145985810.98540145
ENST00000377011ENST00000412770VRK3chr1950504047-PPP6R1chr1955753856-0.0092070830.99079293
ENST00000377011ENST00000587283VRK3chr1950504047-PPP6R1chr1955753856-0.0213938410.97860616

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 VRK3-PPP6R1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VRK3chr1950504047PPP6R1chr1955753856632154DSGPQKQKFSLKLQHSNASQSLCDII
VRK3chr1950504047PPP6R1chr1955753856796204DSGPQKQKFSLKLQHSNASQSLCDII

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Potential FusionNeoAntigen Information of VRK3-PPP6R1 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.
VRK3-PPP6R1_50504047_55753856.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)
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B08:09SLKLQHSNA0.96770.5407918
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B48:01LQHSNASQSL0.9910.59521222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:01LQHSNASQSL0.910.9241222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:02LQHSNASQSL0.78320.94721222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:01LQHSNASQSL0.76190.92511222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:10KLQHSNASQSL0.71030.56971122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:01KLQHSNASQSL0.55330.96971122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:02KLQHSNASQSL0.53440.97581122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:04LQHSNASQSL0.99780.79891222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:04KQKFSLKLQH0.93910.7013515
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:09LQHSNASQSL0.92370.73721222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:05LQHSNASQSL0.73310.91251222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:05KLQHSNASQSL0.54220.92591122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:73LQHSNASQSL0.99750.89861222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:30LQHSNASQSL0.99580.82131222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:02LQHSNASQSL0.91980.93381222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:11LQHSNASQSL0.84850.87891222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:05LQHSNASQSL0.76190.92511222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:09LQHSNASQSL0.6860.79721222
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B39:11KLQHSNASQSL0.75520.8831122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B15:09KLQHSNASQSL0.57130.80441122
VRK3-PPP6R1chr1950504047chr1955753856796HLA-B38:05KLQHSNASQSL0.55330.96971122

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Potential FusionNeoAntigen Information of VRK3-PPP6R1 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.
VRK3-PPP6R1_50504047_55753856.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)
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0413QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0413KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0437QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0437KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0440QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0444QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0444KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0456QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0468QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0470QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0470KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0473QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0473KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0479QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB1-0479KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0101QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0101KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0101KQKFSLKLQHSNASQ520
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0103QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0103KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0103KQKFSLKLQHSNASQ520
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0104QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0104KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0106QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0106KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0106KQKFSLKLQHSNASQ520
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0107QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0107KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0107KQKFSLKLQHSNASQ520
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0108QKFSLKLQHSNASQS621
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0108KFSLKLQHSNASQSL722
VRK3-PPP6R1chr1950504047chr1955753856796DRB4-0108KQKFSLKLQHSNASQ520

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Fusion breakpoint peptide structures of VRK3-PPP6R1

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
7343QKFSLKLQHSNASQVRK3PPP6R1chr1950504047chr1955753856796

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VRK3-PPP6R1

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-B14:023BVN7343QKFSLKLQHSNASQ-7.15543-7.26883
HLA-B14:023BVN7343QKFSLKLQHSNASQ-4.77435-5.80965
HLA-B52:013W397343QKFSLKLQHSNASQ-6.80875-6.92215
HLA-B52:013W397343QKFSLKLQHSNASQ-4.20386-5.23916
HLA-A11:014UQ27343QKFSLKLQHSNASQ-7.5194-8.5547
HLA-A11:014UQ27343QKFSLKLQHSNASQ-6.9601-7.0735
HLA-A24:025HGA7343QKFSLKLQHSNASQ-7.52403-7.63743
HLA-A24:025HGA7343QKFSLKLQHSNASQ-5.82433-6.85963
HLA-B27:056PYJ7343QKFSLKLQHSNASQ-3.28285-4.31815
HLA-B44:053DX87343QKFSLKLQHSNASQ-5.91172-6.94702
HLA-B44:053DX87343QKFSLKLQHSNASQ-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of VRK3-PPP6R1

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
VRK3-PPP6R1chr1950504047chr19557538561122KLQHSNASQSLAAACTGCAACATTCCAACGCATCCCAGTCCCTG
VRK3-PPP6R1chr1950504047chr19557538561222LQHSNASQSLCTGCAACATTCCAACGCATCCCAGTCCCTG
VRK3-PPP6R1chr1950504047chr1955753856515KQKFSLKLQHAAGCAAAAGTTCTCACTCAAACTGCAACAT
VRK3-PPP6R1chr1950504047chr1955753856918SLKLQHSNATCACTCAAACTGCAACATTCCAACGCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
VRK3-PPP6R1chr1950504047chr1955753856520KQKFSLKLQHSNASQAAGCAAAAGTTCTCACTCAAACTGCAACATTCCAACGCATCCCAG
VRK3-PPP6R1chr1950504047chr1955753856621QKFSLKLQHSNASQSCAAAAGTTCTCACTCAAACTGCAACATTCCAACGCATCCCAGTCC
VRK3-PPP6R1chr1950504047chr1955753856722KFSLKLQHSNASQSLAAGTTCTCACTCAAACTGCAACATTCCAACGCATCCCAGTCCCTG

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Information of the samples that have these potential fusion neoantigens of VRK3-PPP6R1

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
CESCVRK3-PPP6R1chr1950504047ENST00000316763chr1955753856ENST00000412770TCGA-C5-A907-01A

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Potential target of CAR-T therapy development for VRK3-PPP6R1

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 VRK3-PPP6R1

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 VRK3-PPP6R1

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