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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:PVR-SIRT2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PVR-SIRT2
FusionPDB ID: 70766
FusionGDB2.0 ID: 70766
HgeneTgene
Gene symbol

PVR

SIRT2

Gene ID

5817

22933

Gene namePVR cell adhesion moleculesirtuin 2
SynonymsCD155|HVED|NECL5|Necl-5|PVS|TAGE4SIR2|SIR2L|SIR2L2
Cytomap

19q13.31

19q13.2

Type of geneprotein-codingprotein-coding
Descriptionpoliovirus receptornectin-like protein 5NAD-dependent protein deacetylase sirtuin-2NAD-dependent deacetylase sirtuin-2SIR2-like protein 2regulatory protein SIR2 homolog 2silent information regulator 2sir2-related protein type 2sirtuin type 2
Modification date2020032920200329
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000344956, ENST00000403059, 
ENST00000406449, ENST00000425690, 
ENST00000481381, ENST00000249396, 
ENST00000358931, ENST00000392081, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 7 X 5=1756 X 6 X 6=216
# samples 67
** MAII scorelog2(6/175*10)=-1.54432051622381
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(7/216*10)=-1.6256044852185
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PVR [Title/Abstract] AND SIRT2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PVR [Title/Abstract] AND SIRT2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PVR(45147475)-SIRT2(39372131), # samples:2
Anticipated loss of major functional domain due to fusion event.PVR-SIRT2 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.
PVR-SIRT2 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.
PVR-SIRT2 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.
PVR-SIRT2 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
HgenePVR

GO:0060370

susceptibility to T cell mediated cytotoxicity

15039383

TgeneSIRT2

GO:0000122

negative regulation of transcription by RNA polymerase II

18722353

TgeneSIRT2

GO:0006471

protein ADP-ribosylation

10381378

TgeneSIRT2

GO:0006476

protein deacetylation

17172643|20543840|21949390

TgeneSIRT2

GO:0034983

peptidyl-lysine deacetylation

23932781

TgeneSIRT2

GO:0035729

cellular response to hepatocyte growth factor stimulus

23908241

TgeneSIRT2

GO:0045843

negative regulation of striated muscle tissue development

12887892

TgeneSIRT2

GO:0045892

negative regulation of transcription, DNA-templated

12887892

TgeneSIRT2

GO:0048012

hepatocyte growth factor receptor signaling pathway

23908241

TgeneSIRT2

GO:0070933

histone H4 deacetylation

16648462|17488717

TgeneSIRT2

GO:0071219

cellular response to molecule of bacterial origin

23908241

TgeneSIRT2

GO:0071456

cellular response to hypoxia

24681946

TgeneSIRT2

GO:0090042

tubulin deacetylation

18722353|23886946



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/chr19:45147475/chr19:39372131)
- 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 PVR (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 SIRT2 (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)
ENST00000425690PVRchr1945147475+ENST00000249396SIRT2chr1939372131-1515378122916264
ENST00000425690PVRchr1945147475+ENST00000392081SIRT2chr1939372131-1515378122916264
ENST00000425690PVRchr1945147475+ENST00000358931SIRT2chr1939372131-1339378122562146
ENST00000344956PVRchr1945147475+ENST00000249396SIRT2chr1939372131-1515378122916264
ENST00000344956PVRchr1945147475+ENST00000392081SIRT2chr1939372131-1515378122916264
ENST00000344956PVRchr1945147475+ENST00000358931SIRT2chr1939372131-1339378122562146
ENST00000403059PVRchr1945147475+ENST00000249396SIRT2chr1939372131-140326610804264
ENST00000403059PVRchr1945147475+ENST00000392081SIRT2chr1939372131-140326610804264
ENST00000403059PVRchr1945147475+ENST00000358931SIRT2chr1939372131-122726610450146
ENST00000406449PVRchr1945147475+ENST00000249396SIRT2chr1939372131-1216790617205
ENST00000406449PVRchr1945147475+ENST00000392081SIRT2chr1939372131-1216790617205
ENST00000406449PVRchr1945147475+ENST00000358931SIRT2chr1939372131-104079547119142

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
ENST00000425690ENST00000249396PVRchr1945147475+SIRT2chr1939372131-0.0410342370.9589658
ENST00000425690ENST00000392081PVRchr1945147475+SIRT2chr1939372131-0.0410342370.9589658
ENST00000425690ENST00000358931PVRchr1945147475+SIRT2chr1939372131-0.95189470.048105367
ENST00000344956ENST00000249396PVRchr1945147475+SIRT2chr1939372131-0.0410342370.9589658
ENST00000344956ENST00000392081PVRchr1945147475+SIRT2chr1939372131-0.0410342370.9589658
ENST00000344956ENST00000358931PVRchr1945147475+SIRT2chr1939372131-0.95189470.048105367
ENST00000403059ENST00000249396PVRchr1945147475+SIRT2chr1939372131-0.0501719680.9498281
ENST00000403059ENST00000392081PVRchr1945147475+SIRT2chr1939372131-0.0501719680.9498281
ENST00000403059ENST00000358931PVRchr1945147475+SIRT2chr1939372131-0.96344270.036557317
ENST00000406449ENST00000249396PVRchr1945147475+SIRT2chr1939372131-0.043729250.95627075
ENST00000406449ENST00000392081PVRchr1945147475+SIRT2chr1939372131-0.043729250.95627075
ENST00000406449ENST00000358931PVRchr1945147475+SIRT2chr1939372131-0.969006060.03099397

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 PVR-SIRT2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PVRchr1945147475SIRT2chr193937213126677AAAWPLLLVALLVLSWPPPGTEKIFS
PVRchr1945147475SIRT2chr193937213137877AAAWPLLLVALLVLSWPPPGTEKIFS
PVRchr1945147475SIRT2chr19393721317918AAAWPLLLVALLVLSWPPPGTEKIFS

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Potential FusionNeoAntigen Information of PVR-SIRT2 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.
PVR-SIRT2_45147475_39372131.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)
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:01VALLVLSW0.99970.9888816
PVR-SIRT2chr1945147475chr1939372131378HLA-B58:01VALLVLSW0.99830.9815816
PVR-SIRT2chr1945147475chr1939372131378HLA-B58:01LVALLVLSW0.99430.9786716
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:01LVALLVLSW0.9870.9873716
PVR-SIRT2chr1945147475chr1939372131378HLA-B15:17LVALLVLSW0.98610.9778716
PVR-SIRT2chr1945147475chr1939372131378HLA-B58:02LVALLVLSW0.96560.9807716
PVR-SIRT2chr1945147475chr1939372131378HLA-A32:13LVALLVLSW0.94470.9949716
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:03LVALLVLSW0.8650.9973716
PVR-SIRT2chr1945147475chr1939372131378HLA-B53:01LVALLVLSW0.84510.8079716
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:10VALLVLSW0.99970.9888816
PVR-SIRT2chr1945147475chr1939372131378HLA-B53:02VALLVLSW0.96330.8036816
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:04LVALLVLSW0.99610.8883716
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:10LVALLVLSW0.9870.9873716
PVR-SIRT2chr1945147475chr1939372131378HLA-B58:06LVALLVLSW0.97710.9691716
PVR-SIRT2chr1945147475chr1939372131378HLA-A32:01LVALLVLSW0.96370.994716
PVR-SIRT2chr1945147475chr1939372131378HLA-B57:02LVALLVLSW0.92850.9817716
PVR-SIRT2chr1945147475chr1939372131378HLA-B15:13LVALLVLSW0.91880.9653716
PVR-SIRT2chr1945147475chr1939372131378HLA-B53:02LVALLVLSW0.73120.8095716
PVR-SIRT2chr1945147475chr1939372131378HLA-A25:01LVALLVLSW0.50490.9613716

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Potential FusionNeoAntigen Information of PVR-SIRT2 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 PVR-SIRT2

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
5281LLVALLVLSWPPPGPVRSIRT2chr1945147475chr1939372131378

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PVR-SIRT2

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-B14:023BVN5281LLVALLVLSWPPPG-6.47228-6.58568
HLA-B14:023BVN5281LLVALLVLSWPPPG-5.17277-6.20807
HLA-B52:013W395281LLVALLVLSWPPPG-5.78127-6.81657
HLA-B52:013W395281LLVALLVLSWPPPG-5.54909-5.66249
HLA-A11:014UQ25281LLVALLVLSWPPPG-6.10996-7.14526
HLA-A24:025HGA5281LLVALLVLSWPPPG-6.56315-6.67655
HLA-A24:025HGA5281LLVALLVLSWPPPG-4.43018-5.46548
HLA-B27:056PYJ5281LLVALLVLSWPPPG-6.44184-7.47714
HLA-B27:056PYJ5281LLVALLVLSWPPPG-5.32442-5.43782
HLA-B44:053DX85281LLVALLVLSWPPPG-6.86074-6.97414
HLA-B44:053DX85281LLVALLVLSWPPPG-6.38877-7.42407

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Vaccine Design for the FusionNeoAntigens of PVR-SIRT2

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
PVR-SIRT2chr1945147475chr1939372131716LVALLVLSWGGCCACCCCCAGGAACCGAGAAGATCT
PVR-SIRT2chr1945147475chr1939372131816VALLVLSWCACCCCCAGGAACCGAGAAGATCT

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 PVR-SIRT2

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
UCSPVR-SIRT2chr1945147475ENST00000344956chr1939372131ENST00000249396TCGA-N7-A4Y8-01A

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Potential target of CAR-T therapy development for PVR-SIRT2

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 PVR-SIRT2

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 PVR-SIRT2

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