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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:PBRM1-NEK4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: PBRM1-NEK4
FusionPDB ID: 63006
FusionGDB2.0 ID: 63006
HgeneTgene
Gene symbol

PBRM1

NEK4

Gene ID

55193

6787

Gene namepolybromo 1NIMA related kinase 4
SynonymsBAF180|PB1NRK2|STK2|pp12301
Cytomap

3p21.1

3p21.1

Type of geneprotein-codingprotein-coding
Descriptionprotein polybromo-1BRG1-associated factor 180polybromo-1Dserine/threonine-protein kinase Nek4NIMA (never in mitosis gene a)-related kinase 4never in mitosis A-related kinase 4nimA-related protein kinase 4serine/threonine kinase 2serine/threonine protein kinase-2serine/threonine-protein kinase NRK2serine/
Modification date2020031320200313
UniProtAcc.

P51957

Main function of 5'-partner protein: FUNCTION: Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage. {ECO:0000250|UniProtKB:Q9Z1J2, ECO:0000269|PubMed:22851694}.
Ensembl transtripts involved in fusion geneENST idsENST00000296302, ENST00000337303, 
ENST00000356770, ENST00000394830, 
ENST00000409057, ENST00000409114, 
ENST00000409767, ENST00000410007, 
ENST00000233027, ENST00000383721, 
ENST00000535191, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score15 X 15 X 10=22505 X 5 X 4=100
# samples 195
** MAII scorelog2(19/2250*10)=-3.56585367777345
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: PBRM1 [Title/Abstract] AND NEK4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: PBRM1 [Title/Abstract] AND NEK4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)PBRM1(52637537)-NEK4(52773650), # samples:3
Anticipated loss of major functional domain due to fusion event.PBRM1-NEK4 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.
PBRM1-NEK4 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.
PBRM1-NEK4 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.
PBRM1-NEK4 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.
PBRM1-NEK4 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
PBRM1-NEK4 seems lost the major protein functional domain in Tgene partner, which is a kinase 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


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/chr3:52637537/chr3:52773650)
- 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 PBRM1 (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 NEK4 (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)
ENST00000356770PBRM1chr352643329-ENST00000233027NEK4chr352773650-3900247432906967
ENST00000356770PBRM1chr352643329-ENST00000535191NEK4chr352773650-3091247432906967
ENST00000356770PBRM1chr352643329-ENST00000383721NEK4chr352773650-2902247432864953
ENST00000296302PBRM1chr352643329-ENST00000233027NEK4chr352773650-3995256923001999
ENST00000296302PBRM1chr352643329-ENST00000535191NEK4chr352773650-3186256923001999
ENST00000296302PBRM1chr352643329-ENST00000383721NEK4chr352773650-2997256922959985
ENST00000337303PBRM1chr352643329-ENST00000233027NEK4chr352773650-3996257033002999
ENST00000337303PBRM1chr352643329-ENST00000535191NEK4chr352773650-3187257033002999
ENST00000337303PBRM1chr352643329-ENST00000383721NEK4chr352773650-2998257032960985
ENST00000410007PBRM1chr352643329-ENST00000233027NEK4chr352773650-3996257033002999
ENST00000410007PBRM1chr352643329-ENST00000535191NEK4chr352773650-3187257033002999
ENST00000410007PBRM1chr352643329-ENST00000383721NEK4chr352773650-2998257032960985
ENST00000409057PBRM1chr352643329-ENST00000233027NEK4chr352773650-3996257033002999
ENST00000409057PBRM1chr352643329-ENST00000535191NEK4chr352773650-3187257033002999
ENST00000409057PBRM1chr352643329-ENST00000383721NEK4chr352773650-2998257032960985
ENST00000409114PBRM1chr352643329-ENST00000233027NEK4chr352773650-40412615330471014
ENST00000409114PBRM1chr352643329-ENST00000535191NEK4chr352773650-32322615330471014
ENST00000409114PBRM1chr352643329-ENST00000383721NEK4chr352773650-30432615330051000
ENST00000409767PBRM1chr352643329-ENST00000233027NEK4chr352773650-40412615330471014
ENST00000409767PBRM1chr352643329-ENST00000535191NEK4chr352773650-32322615330471014
ENST00000409767PBRM1chr352643329-ENST00000383721NEK4chr352773650-30432615330051000

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
ENST00000356770ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.000200050.9998
ENST00000356770ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0008092650.99919075
ENST00000356770ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0009126690.99908733
ENST00000296302ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.0001708510.9998292
ENST00000296302ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0007281570.9992718
ENST00000296302ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0008039690.999196
ENST00000337303ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.00017150.99982846
ENST00000337303ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0007332610.9992667
ENST00000337303ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0008104590.99918956
ENST00000410007ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.00017150.99982846
ENST00000410007ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0007332610.9992667
ENST00000410007ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0008104590.99918956
ENST00000409057ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.00017150.99982846
ENST00000409057ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0007332610.9992667
ENST00000409057ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0008104590.99918956
ENST00000409114ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.0004579840.999542
ENST00000409114ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0019107360.99808925
ENST00000409114ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0010829930.998917
ENST00000409767ENST00000233027PBRM1chr352643329-NEK4chr352773650-0.0004579840.999542
ENST00000409767ENST00000535191PBRM1chr352643329-NEK4chr352773650-0.0019107360.99808925
ENST00000409767ENST00000383721PBRM1chr352643329-NEK4chr352773650-0.0010829930.998917

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 PBRM1-NEK4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
PBRM1chr352643329NEK4chr3527736502474823HMFEVLERARRMNRKGQTNEINALVQ
PBRM1chr352643329NEK4chr3527736502569855HMFEVLERARRMNRKGQTNEINALVQ
PBRM1chr352643329NEK4chr3527736502570855HMFEVLERARRMNRKGQTNEINALVQ
PBRM1chr352643329NEK4chr3527736502615870HMFEVLERARRMNRKGQTNEINALVQ

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Potential FusionNeoAntigen Information of PBRM1-NEK4 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.
PBRM1-NEK4_52643329_52773650.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)
PBRM1-NEK4chr352643329chr3527736502569HLA-B14:02NRKGQTNEI0.9930.62611221
PBRM1-NEK4chr352643329chr3527736502569HLA-B14:01NRKGQTNEI0.9930.62611221
PBRM1-NEK4chr352643329chr3527736502569HLA-B39:12NRKGQTNEI0.97520.70941221
PBRM1-NEK4chr352643329chr3527736502569HLA-C07:05NRKGQTNEI0.96990.87141221
PBRM1-NEK4chr352643329chr3527736502569HLA-B14:03NRKGQTNEI0.51630.61511221
PBRM1-NEK4chr352643329chr3527736502569HLA-C12:16NRKGQTNEI0.11690.89651221
PBRM1-NEK4chr352643329chr3527736502569HLA-B39:31NRKGQTNEI0.98230.70461221
PBRM1-NEK4chr352643329chr3527736502569HLA-C06:08NRKGQTNEI0.92680.96081221
PBRM1-NEK4chr352643329chr3527736502569HLA-C06:17NRKGQTNEI0.13960.97531221
PBRM1-NEK4chr352643329chr3527736502569HLA-C06:02NRKGQTNEI0.13960.97531221

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Potential FusionNeoAntigen Information of PBRM1-NEK4 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.
PBRM1-NEK4_52643329_52773650.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)
PBRM1-NEK4chr352643329chr3527736502569DRB1-1121FEVLERARRMNRKGQ217
PBRM1-NEK4chr352643329chr3527736502569DRB1-1172HMFEVLERARRMNRK015
PBRM1-NEK4chr352643329chr3527736502569DRB1-1361FEVLERARRMNRKGQ217
PBRM1-NEK4chr352643329chr3527736502569DRB1-1371FEVLERARRMNRKGQ217
PBRM1-NEK4chr352643329chr3527736502569DRB1-1386HMFEVLERARRMNRK015

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Fusion breakpoint peptide structures of PBRM1-NEK4

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
2081ERARRMNRKGQTNEPBRM1NEK4chr352643329chr3527736502569

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of PBRM1-NEK4

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-B14:023BVN2081ERARRMNRKGQTNE-6.01316-6.12656
HLA-B14:023BVN2081ERARRMNRKGQTNE-3.92858-4.96388
HLA-B52:013W392081ERARRMNRKGQTNE-5.92102-6.95632
HLA-B52:013W392081ERARRMNRKGQTNE-4.84472-4.95812
HLA-A24:025HGA2081ERARRMNRKGQTNE-8.26357-9.29887
HLA-A24:025HGA2081ERARRMNRKGQTNE-7.03366-7.14706
HLA-B44:053DX82081ERARRMNRKGQTNE-6.13971-6.25311
HLA-B44:053DX82081ERARRMNRKGQTNE-5.20728-6.24258
HLA-A02:016TDR2081ERARRMNRKGQTNE-5.28864-5.40204

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Vaccine Design for the FusionNeoAntigens of PBRM1-NEK4

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
PBRM1-NEK4chr352643329chr3527736501221NRKGQTNEITCGGAAAGGTCAGACAAATGAAATTAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
PBRM1-NEK4chr352643329chr352773650015HMFEVLERARRMNRKTATGTTTGAAGTATTGGAACGAGCAAGAAGGATGAATCGGAAAGG
PBRM1-NEK4chr352643329chr352773650217FEVLERARRMNRKGQTGAAGTATTGGAACGAGCAAGAAGGATGAATCGGAAAGGTCAGAC

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Information of the samples that have these potential fusion neoantigens of PBRM1-NEK4

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
SKCMPBRM1-NEK4chr352643329ENST00000296302chr352773650ENST00000233027TCGA-EB-A5SE-01A

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Potential target of CAR-T therapy development for PBRM1-NEK4

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 PBRM1-NEK4

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 PBRM1-NEK4

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