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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:BRE-ZNF57

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: BRE-ZNF57
FusionPDB ID: 10245
FusionGDB2.0 ID: 10245
HgeneTgene
Gene symbol

BRE

ZNF57

Gene ID

9577

126295

Gene nameBRISC and BRCA1 A complex member 2zinc finger protein 57
SynonymsBRCC4|BRCC45|BREZNF424
Cytomap

2p23.2

19p13.3

Type of geneprotein-codingprotein-coding
DescriptionBRISC and BRCA1-A complex member 2BRCA1-A complex subunit BREBRCA1/BRCA2-containing complex subunit 45BRCA1/BRCA2-containing complex, subunit 4brain and reproductive organ-expressed (TNFRSF1A modulator)brain and reproductive organ-expressed proteinzinc finger protein 57zinc finger protein 424
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000603461, ENST00000342045, 
ENST00000344773, ENST00000361704, 
ENST00000379624, ENST00000379632, 
ENST00000306908, ENST00000523428, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 9 X 8=9361 X 1 X 1=1
# samples 151
** MAII scorelog2(15/936*10)=-2.64154602908752
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(1/1*10)=3.32192809488736
Fusion gene context

PubMed: BRE [Title/Abstract] AND ZNF57 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: BRE [Title/Abstract] AND ZNF57 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)BRE(28248287)-ZNF57(2915520), # samples:1
Anticipated loss of major functional domain due to fusion event.BRE-ZNF57 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.
BRE-ZNF57 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.
BRE-ZNF57 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.
BRE-ZNF57 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
HgeneBRE

GO:0043066

negative regulation of apoptotic process

15465831



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/chr2:28248287/chr19:2915520)
- 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 BRE (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 ZNF57 (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)
ENST00000344773BREchr228248287+ENST00000306908ZNF57chr192915520+24856331382297719
ENST00000379624BREchr228248287+ENST00000306908ZNF57chr192915520+24646121172276719
ENST00000342045BREchr228248287+ENST00000306908ZNF57chr192915520+24886361412300719
ENST00000379632BREchr228248287+ENST00000306908ZNF57chr192915520+24876351402299719
ENST00000361704BREchr228248287+ENST00000306908ZNF57chr192915520+2421569742233719

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
ENST00000344773ENST00000306908BREchr228248287+ZNF57chr192915520+0.0009500930.99904984
ENST00000379624ENST00000306908BREchr228248287+ZNF57chr192915520+0.000933540.99906653
ENST00000342045ENST00000306908BREchr228248287+ZNF57chr192915520+0.0009360390.999064
ENST00000379632ENST00000306908BREchr228248287+ZNF57chr192915520+0.0009379630.999062
ENST00000361704ENST00000306908BREchr228248287+ZNF57chr192915520+0.0009568130.99904317

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 BRE-ZNF57

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
BREchr228248287ZNF57chr192915520569165ENMEIYAGKKNNWDSVVFEDVAVDFT
BREchr228248287ZNF57chr192915520569299QMPDLTLHKKVSAGEKPYECTKCRTV
BREchr228248287ZNF57chr192915520612165ENMEIYAGKKNNWDSVVFEDVAVDFT
BREchr228248287ZNF57chr192915520612299QMPDLTLHKKVSAGEKPYECTKCRTV
BREchr228248287ZNF57chr192915520633165ENMEIYAGKKNNWDSVVFEDVAVDFT
BREchr228248287ZNF57chr192915520633299QMPDLTLHKKVSAGEKPYECTKCRTV
BREchr228248287ZNF57chr192915520635165ENMEIYAGKKNNWDSVVFEDVAVDFT
BREchr228248287ZNF57chr192915520635299QMPDLTLHKKVSAGEKPYECTKCRTV
BREchr228248287ZNF57chr192915520636165ENMEIYAGKKNNWDSVVFEDVAVDFT
BREchr228248287ZNF57chr192915520636299QMPDLTLHKKVSAGEKPYECTKCRTV

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Potential FusionNeoAntigen Information of BRE-ZNF57 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.
BRE-ZNF57_28248287_2915520.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)
BRE-ZNF57chr228248287chr192915520636HLA-B15:03KKNNWDSVVF0.94770.5671818
BRE-ZNF57chr228248287chr192915520636HLA-B15:68KKNNWDSVVF0.9670.5489818
BRE-ZNF57chr228248287chr192915520636HLA-B15:54KKNNWDSVVF0.96080.6508818

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Potential FusionNeoAntigen Information of BRE-ZNF57 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 BRE-ZNF57

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
230AGKKNNWDSVVFEDBREZNF57chr228248287chr192915520636

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of BRE-ZNF57

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-B14:023BVN230AGKKNNWDSVVFED-7.9962-8.1096
HLA-B14:023BVN230AGKKNNWDSVVFED-5.70842-6.74372
HLA-B52:013W39230AGKKNNWDSVVFED-6.83737-6.95077
HLA-B52:013W39230AGKKNNWDSVVFED-4.4836-5.5189
HLA-A11:014UQ2230AGKKNNWDSVVFED-10.0067-10.1201
HLA-A11:014UQ2230AGKKNNWDSVVFED-9.03915-10.0745
HLA-A24:025HGA230AGKKNNWDSVVFED-6.56204-6.67544
HLA-A24:025HGA230AGKKNNWDSVVFED-5.42271-6.45801
HLA-B44:053DX8230AGKKNNWDSVVFED-7.85648-8.89178
HLA-B44:053DX8230AGKKNNWDSVVFED-5.3978-5.5112
HLA-A02:016TDR230AGKKNNWDSVVFED-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of BRE-ZNF57

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
BRE-ZNF57chr228248287chr192915520818KKNNWDSVVFAAAAAAAACAACTGGGACTCAGTGGTCTTT

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 BRE-ZNF57

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
SKCMBRE-ZNF57chr228248287ENST00000342045chr192915520ENST00000306908TCGA-FS-A1Z4-06A

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Potential target of CAR-T therapy development for BRE-ZNF57

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 BRE-ZNF57

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 BRE-ZNF57

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