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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:ZNF398-UBE3C

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF398-UBE3C
FusionPDB ID: 101990
FusionGDB2.0 ID: 101990
HgeneTgene
Gene symbol

ZNF398

UBE3C

Gene ID

57541

9690

Gene namezinc finger protein 398ubiquitin protein ligase E3C
SynonymsP51|P71|ZER6HECTH2
Cytomap

7q36.1

7q36.3

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 398zinc finger DNA binding protein ZER6zinc finger DNA binding protein p52/p71zinc finger-estrogen receptor interaction, clone 6ubiquitin-protein ligase E3CHECT-type ubiquitin transferase E3Cubiquitin-protein isopeptide ligase (E3)
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000335901, ENST00000420008, 
ENST00000426851, ENST00000475153, 
ENST00000483892, ENST00000491174, 
ENST00000540950, ENST00000485111, 
ENST00000389103, ENST00000348165, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=14411 X 13 X 7=1001
# samples 613
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(13/1001*10)=-2.94485844580754
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF398 [Title/Abstract] AND UBE3C [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF398 [Title/Abstract] AND UBE3C [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF398(148864022)-UBE3C(157049608), # samples:1
Anticipated loss of major functional domain due to fusion event.ZNF398-UBE3C 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.
ZNF398-UBE3C 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.
ZNF398-UBE3C 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.
ZNF398-UBE3C 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
TgeneUBE3C

GO:0000209

protein polyubiquitination

11278995



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/chr7:148864022/chr7:157049608)
- 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 ZNF398 (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 UBE3C (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)
ENST00000426851ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+29189993501300316
ENST00000420008ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+2855936621237391
ENST00000475153ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+2847928541229391
ENST00000483892ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+26907713951072225
ENST00000491174ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+27468271511128325
ENST00000540950ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+27368171411118325
ENST00000335901ZNF398chr7148864022+ENST00000348165UBE3Cchr7157049608+26797601111061316

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
ENST00000426851ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.438739030.56126094
ENST00000420008ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.0008286980.9991714
ENST00000475153ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.0008266710.99917334
ENST00000483892ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.73808980.26191023
ENST00000491174ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.0007181070.99928194
ENST00000540950ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.0006749930.99932504
ENST00000335901ENST00000348165ZNF398chr7148864022+UBE3Cchr7157049608+0.87301770.12698232

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 ZNF398-UBE3C

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF398chr7148864022UBE3Cchr7157049608760216GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608771125GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608817225GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608827225GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608928291GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608936291GPEESEIPTDPSEGGYSADHPVIKVF
ZNF398chr7148864022UBE3Cchr7157049608999216GPEESEIPTDPSEGGYSADHPVIKVF

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Potential FusionNeoAntigen Information of ZNF398-UBE3C 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.
ZNF398-UBE3C_148864022_157049608.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)
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:01IPTDPSEGGY0.97250.6061616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:08IPTDPSEGGY0.96280.6504616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B56:01TDPSEGGYSA0.73470.5083818
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-A26:15EIPTDPSEGGY0.98290.5527516
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-A26:14EIPTDPSEGGY0.98290.5527516
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B54:01DPSEGGYSA0.91550.5742918
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B78:01DPSEGGYSA0.49780.6873918
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B39:10DPSEGGYSA0.06570.945918
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B54:01TDPSEGGYSA0.78850.7182818
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-A26:01EIPTDPSEGGY0.98290.5527516
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B56:05DPSEGGYSA0.84410.566918
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B78:02DPSEGGYSA0.42890.7691918
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:77IPTDPSEGGY0.97250.6061616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:23IPTDPSEGGY0.96930.6527616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:11IPTDPSEGGY0.90190.662616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:24IPTDPSEGGY0.8670.6835616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B15:08IPTDPSEGGY0.80140.6282616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B15:11IPTDPSEGGY0.79940.649616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B35:43IPTDPSEGGY0.76950.627616
ZNF398-UBE3Cchr7148864022chr7157049608760HLA-B55:02TDPSEGGYSA0.57030.5241818

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Potential FusionNeoAntigen Information of ZNF398-UBE3C 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.
ZNF398-UBE3C_148864022_157049608.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)
ZNF398-UBE3Cchr7148864022chr7157049608760DRB1-0305SEGGYSADHPVIKVF1126

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Fusion breakpoint peptide structures of ZNF398-UBE3C

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
3897IPTDPSEGGYSADHZNF398UBE3Cchr7148864022chr7157049608760

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF398-UBE3C

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-B14:023BVN3897IPTDPSEGGYSADH-7.15543-7.26883
HLA-B14:023BVN3897IPTDPSEGGYSADH-4.77435-5.80965
HLA-B52:013W393897IPTDPSEGGYSADH-6.80875-6.92215
HLA-B52:013W393897IPTDPSEGGYSADH-4.20386-5.23916
HLA-A11:014UQ23897IPTDPSEGGYSADH-7.5194-8.5547
HLA-A11:014UQ23897IPTDPSEGGYSADH-6.9601-7.0735
HLA-A24:025HGA3897IPTDPSEGGYSADH-7.52403-7.63743
HLA-A24:025HGA3897IPTDPSEGGYSADH-5.82433-6.85963
HLA-B27:056PYJ3897IPTDPSEGGYSADH-3.28285-4.31815
HLA-B44:053DX83897IPTDPSEGGYSADH-5.91172-6.94702
HLA-B44:053DX83897IPTDPSEGGYSADH-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZNF398-UBE3C

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
ZNF398-UBE3Cchr7148864022chr7157049608516EIPTDPSEGGYAGATTCCCACAGACCCCAGTGAAGGAGGCTATT
ZNF398-UBE3Cchr7148864022chr7157049608616IPTDPSEGGYTTCCCACAGACCCCAGTGAAGGAGGCTATT
ZNF398-UBE3Cchr7148864022chr7157049608818TDPSEGGYSACAGACCCCAGTGAAGGAGGCTATTCTGCAG
ZNF398-UBE3Cchr7148864022chr7157049608918DPSEGGYSAACCCCAGTGAAGGAGGCTATTCTGCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZNF398-UBE3Cchr7148864022chr71570496081126SEGGYSADHPVIKVFGTGAAGGAGGCTATTCTGCAGACCATCCTGTTATTAAGGTCTTCT

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Information of the samples that have these potential fusion neoantigens of ZNF398-UBE3C

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
STADZNF398-UBE3Cchr7148864022ENST00000335901chr7157049608ENST00000348165TCGA-BR-A4PD-01A

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Potential target of CAR-T therapy development for ZNF398-UBE3C

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 ZNF398-UBE3C

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 ZNF398-UBE3C

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