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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:PNKP-FZR1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PNKP-FZR1
FusionPDB ID: 66727
FusionGDB2.0 ID: 66727
HgeneTgene
Gene symbol

PNKP

FZR1

Gene ID

11284

51343

Gene namepolynucleotide kinase 3'-phosphatasefizzy and cell division cycle 20 related 1
SynonymsAOA4|EIEE10|MCSZ|PNKCDC20C|CDH1|FZR|FZR2|HCDH|HCDH1
Cytomap

19q13.33

19p13.3

Type of geneprotein-codingprotein-coding
Descriptionbifunctional polynucleotide phosphatase/kinaseDNA 5'-kinase/3'-phosphataseHomo sapiens polynucleotide kinase 3'-phosphatase (PNKP)fizzy-related protein homologCDC20 homolog 1CDC20-like 1bCDC20-like protein 1cdh1/Hct1 homologfizzy/cell division cycle 20 related 1
Modification date2020031320200313
UniProtAcc.

Q9UM11

Main function of 5'-partner protein: FUNCTION: Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR) (PubMed:25349192). {ECO:0000269|PubMed:18662541, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:25349192, ECO:0000269|PubMed:9734353}.
Ensembl transtripts involved in fusion geneENST idsENST00000322344, ENST00000600573, 
ENST00000600910, ENST00000596014, 
ENST00000595792, 
ENST00000313639, 
ENST00000395095, ENST00000441788, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 3 X 4=726 X 5 X 4=120
# samples 66
** MAII scorelog2(6/72*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PNKP [Title/Abstract] AND FZR1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PNKP [Title/Abstract] AND FZR1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PNKP(50369656)-FZR1(3525866), # samples:1
Anticipated loss of major functional domain due to fusion event.PNKP-FZR1 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.
PNKP-FZR1 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.
PNKP-FZR1 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.
PNKP-FZR1 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.
PNKP-FZR1 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PNKP-FZR1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
PNKP-FZR1 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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
HgenePNKP

GO:0006979

response to oxidative stress

10446192

HgenePNKP

GO:0016311

dephosphorylation

10446193

HgenePNKP

GO:0042769

DNA damage response, detection of DNA damage

10446192

HgenePNKP

GO:0046939

nucleotide phosphorylation

10446193

TgeneFZR1

GO:0031145

anaphase-promoting complex-dependent catabolic process

18662541|21596315

TgeneFZR1

GO:0072425

signal transduction involved in G2 DNA damage checkpoint

18662541

TgeneFZR1

GO:1904668

positive regulation of ubiquitin protein ligase activity

11459826



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/chr19:50369656/chr19:3525866)
- 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 PNKP (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 FZR1 (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)
ENST00000596014PNKPchr1950369656-ENST00000441788FZR1chr193525866+5187280581692544
ENST00000596014PNKPchr1950369656-ENST00000313639FZR1chr193525866+1426280581425456
ENST00000596014PNKPchr1950369656-ENST00000395095FZR1chr193525866+1702280581701548

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
ENST00000596014ENST00000441788PNKPchr1950369656-FZR1chr193525866+0.034417170.96558285
ENST00000596014ENST00000313639PNKPchr1950369656-FZR1chr193525866+0.129599120.87040085
ENST00000596014ENST00000395095PNKPchr1950369656-FZR1chr193525866+0.069254610.93074536

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 PNKP-FZR1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PNKPchr1950369656FZR1chr19352586628073LVADPETRTVAVKQVTEMRRTLTPAS

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Potential FusionNeoAntigen Information of PNKP-FZR1 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.
PNKP-FZR1_50369656_3525866.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)
PNKP-FZR1chr1950369656chr193525866280HLA-B15:17VAVKQVTEM0.9970.8052918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:16VAVKQVTEM0.99440.7758918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:01VAVKQVTEM0.98780.7693918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:03VAVKQVTEM0.97690.7068918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:02VAVKQVTEM0.7380.9343918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:04VAVKQVTEM0.7380.9343918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:08VAVKQVTEM0.99970.7803918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:19VAVKQVTEM0.99970.9798918
PNKP-FZR1chr1950369656chr193525866280HLA-C15:04VAVKQVTEM0.99970.7841918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:07VAVKQVTEM0.99960.9497918
PNKP-FZR1chr1950369656chr193525866280HLA-C15:06VAVKQVTEM0.99910.6915918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:21VAVKQVTEM0.99850.8609918
PNKP-FZR1chr1950369656chr193525866280HLA-C06:03VAVKQVTEM0.99740.9763918
PNKP-FZR1chr1950369656chr193525866280HLA-C04:06VAVKQVTEM0.99730.8608918
PNKP-FZR1chr1950369656chr193525866280HLA-C12:04VAVKQVTEM0.99720.9828918
PNKP-FZR1chr1950369656chr193525866280HLA-C12:12VAVKQVTEM0.99680.8475918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:14VAVKQVTEM0.99450.9313918
PNKP-FZR1chr1950369656chr193525866280HLA-C08:04VAVKQVTEM0.99330.9677918
PNKP-FZR1chr1950369656chr193525866280HLA-C08:13VAVKQVTEM0.99330.9677918
PNKP-FZR1chr1950369656chr193525866280HLA-C01:30VAVKQVTEM0.96280.9332918
PNKP-FZR1chr1950369656chr193525866280HLA-C02:06VAVKQVTEM0.95480.9127918
PNKP-FZR1chr1950369656chr193525866280HLA-C08:03VAVKQVTEM0.88790.9737918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:12VAVKQVTEM0.7380.9343918
PNKP-FZR1chr1950369656chr193525866280HLA-C12:16TRTVAVKQV0.00620.8885615
PNKP-FZR1chr1950369656chr193525866280HLA-C03:03VAVKQVTEM0.99980.9803918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:04VAVKQVTEM0.99980.9803918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:02VAVKQVTEM0.99980.9639918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:67VAVKQVTEM0.99970.9696918
PNKP-FZR1chr1950369656chr193525866280HLA-C15:09VAVKQVTEM0.99970.7841918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:05VAVKQVTEM0.99960.8577918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:17VAVKQVTEM0.99950.9581918
PNKP-FZR1chr1950369656chr193525866280HLA-C12:02VAVKQVTEM0.99920.9219918
PNKP-FZR1chr1950369656chr193525866280HLA-C15:05VAVKQVTEM0.9990.746918
PNKP-FZR1chr1950369656chr193525866280HLA-C15:02VAVKQVTEM0.99890.6603918
PNKP-FZR1chr1950369656chr193525866280HLA-C16:04VAVKQVTEM0.99840.9546918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:11VAVKQVTEM0.99820.8266918
PNKP-FZR1chr1950369656chr193525866280HLA-C12:03VAVKQVTEM0.99750.964918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:11VAVKQVTEM0.99730.7598918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:08VAVKQVTEM0.99710.7368918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:43VAVKQVTEM0.99620.7389918
PNKP-FZR1chr1950369656chr193525866280HLA-C03:06VAVKQVTEM0.99290.984918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:30VAVKQVTEM0.99240.6593918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:17VAVKQVTEM0.99240.6593918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:77VAVKQVTEM0.98780.7693918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:23VAVKQVTEM0.98750.7738918
PNKP-FZR1chr1950369656chr193525866280HLA-C02:02VAVKQVTEM0.98320.9524918
PNKP-FZR1chr1950369656chr193525866280HLA-C02:10VAVKQVTEM0.98320.9524918
PNKP-FZR1chr1950369656chr193525866280HLA-C16:01VAVKQVTEM0.97730.9666918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:13VAVKQVTEM0.97260.7138918
PNKP-FZR1chr1950369656chr193525866280HLA-C06:08TRTVAVKQV0.94890.9812615
PNKP-FZR1chr1950369656chr193525866280HLA-B35:24VAVKQVTEM0.9460.7227918
PNKP-FZR1chr1950369656chr193525866280HLA-B78:02VAVKQVTEM0.9170.7101918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:73VAVKQVTEM0.90110.9014918
PNKP-FZR1chr1950369656chr193525866280HLA-B15:30VAVKQVTEM0.8990.8237918
PNKP-FZR1chr1950369656chr193525866280HLA-C17:01VAVKQVTEM0.88890.9498918
PNKP-FZR1chr1950369656chr193525866280HLA-C08:01VAVKQVTEM0.88790.9737918
PNKP-FZR1chr1950369656chr193525866280HLA-B07:13VAVKQVTEM0.87480.7137918
PNKP-FZR1chr1950369656chr193525866280HLA-C16:02VAVKQVTEM0.85530.9835918
PNKP-FZR1chr1950369656chr193525866280HLA-B35:09VAVKQVTEM0.7380.9343918
PNKP-FZR1chr1950369656chr193525866280HLA-C06:02TRTVAVKQV0.09290.9796615
PNKP-FZR1chr1950369656chr193525866280HLA-C06:17TRTVAVKQV0.09290.9796615

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Potential FusionNeoAntigen Information of PNKP-FZR1 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.
PNKP-FZR1_50369656_3525866.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)
PNKP-FZR1chr1950369656chr193525866280DRB1-1192VKQVTEMRRTLTPAS1126

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Fusion breakpoint peptide structures of PNKP-FZR1

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
9616TRTVAVKQVTEMRRPNKPFZR1chr1950369656chr193525866280

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PNKP-FZR1

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-B14:023BVN9616TRTVAVKQVTEMRR-7.15543-7.26883
HLA-B14:023BVN9616TRTVAVKQVTEMRR-4.77435-5.80965
HLA-B52:013W399616TRTVAVKQVTEMRR-6.80875-6.92215
HLA-B52:013W399616TRTVAVKQVTEMRR-4.20386-5.23916
HLA-A11:014UQ29616TRTVAVKQVTEMRR-7.5194-8.5547
HLA-A11:014UQ29616TRTVAVKQVTEMRR-6.9601-7.0735
HLA-A24:025HGA9616TRTVAVKQVTEMRR-7.52403-7.63743
HLA-A24:025HGA9616TRTVAVKQVTEMRR-5.82433-6.85963
HLA-B27:056PYJ9616TRTVAVKQVTEMRR-3.28285-4.31815
HLA-B44:053DX89616TRTVAVKQVTEMRR-5.91172-6.94702
HLA-B44:053DX89616TRTVAVKQVTEMRR-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of PNKP-FZR1

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
PNKP-FZR1chr1950369656chr193525866615TRTVAVKQVCGGACAGTGGCAGTGAAACAGGTCACA
PNKP-FZR1chr1950369656chr193525866918VAVKQVTEMGCAGTGAAACAGGTCACAGAGATGCGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PNKP-FZR1chr1950369656chr1935258661126VKQVTEMRRTLTPASAAACAGGTCACAGAGATGCGGCGGACCCTGACGCCTGCCAGCTCC

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Information of the samples that have these potential fusion neoantigens of PNKP-FZR1

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
STADPNKP-FZR1chr1950369656ENST00000596014chr193525866ENST00000313639TCGA-BR-A4PD-01A

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Potential target of CAR-T therapy development for PNKP-FZR1

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 PNKP-FZR1

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 PNKP-FZR1

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