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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:DST-ZNF451

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DST-ZNF451
FusionPDB ID: 24334
FusionGDB2.0 ID: 24334
HgeneTgene
Gene symbol

DST

ZNF451

Gene ID

667

26036

Gene namedystoninzinc finger protein 451
SynonymsBP240|BPA|BPAG1|CATX-15|CATX15|D6S1101|DMH|DT|EBSB2|HSAN6|MACF2COASTER|dJ417I1.1
Cytomap

6p12.1

6p12.1

Type of geneprotein-codingprotein-coding
Descriptiondystoninbullous pemphigoid antigen 1dystonia musculorum proteinhemidesmosomal plaque proteintrabeculin-betaE3 SUMO-protein ligase ZNF451E3 SUMO-protein transferase ZNF451coactivator for steroid receptors
Modification date2020031320200320
UniProtAcc

Q6XUX3

Main function of 5'-partner protein: FUNCTION: Acts as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation (PubMed:23862974, PubMed:28157540). Involved in the regulation of both caspase-dependent apoptosis and caspase-independent cell death (PubMed:15178406). In the skin, it plays a predominant role in suppressing caspase-dependent apoptosis in response to UV stress in a range of dermal cell types (PubMed:28157540). {ECO:0000269|PubMed:15178406, ECO:0000269|PubMed:23862974, ECO:0000269|PubMed:28157540}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000312431, ENST00000361203, 
ENST00000370769, ENST00000370788, 
ENST00000421834, ENST00000244364, 
ENST00000340834, ENST00000370754, 
ENST00000370765, ENST00000446842, 
ENST00000518935, 
ENST00000370702, 
ENST00000370708, ENST00000370710, 
ENST00000510989, ENST00000357489, 
ENST00000370706, ENST00000491832, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score28 X 24 X 12=80647 X 6 X 7=294
# samples 278
** MAII scorelog2(27/8064*10)=-4.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/294*10)=-1.877744249949
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DST [Title/Abstract] AND ZNF451 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DST [Title/Abstract] AND ZNF451 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DST(56707853)-ZNF451(57006100), # samples:1
Anticipated loss of major functional domain due to fusion event.DST-ZNF451 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.
DST-ZNF451 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.
DST-ZNF451 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.
DST-ZNF451 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
HgeneDST

GO:0009611

response to wounding

19403692

TgeneZNF451

GO:0016925

protein sumoylation

26524494



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/chr6:56707853/chr6:57006100)
- 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 DST (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 ZNF451 (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)
ENST00000421834DSTchr656707853-ENST00000370706ZNF451chr657006100+441391192574851
ENST00000421834DSTchr656707853-ENST00000357489ZNF451chr657006100+416391192430803
ENST00000421834DSTchr656707853-ENST00000491832ZNF451chr657006100+295691192514831
ENST00000370769DSTchr656707853-ENST00000370706ZNF451chr657006100+441391192574851
ENST00000370769DSTchr656707853-ENST00000357489ZNF451chr657006100+416391192430803
ENST00000370769DSTchr656707853-ENST00000491832ZNF451chr657006100+295691192514831
ENST00000312431DSTchr656707853-ENST00000370706ZNF451chr657006100+441391192574851
ENST00000312431DSTchr656707853-ENST00000357489ZNF451chr657006100+416391192430803
ENST00000312431DSTchr656707853-ENST00000491832ZNF451chr657006100+295691192514831
ENST00000370788DSTchr656707853-ENST00000370706ZNF451chr657006100+49336115393094851
ENST00000370788DSTchr656707853-ENST00000357489ZNF451chr657006100+46836115392950803
ENST00000370788DSTchr656707853-ENST00000491832ZNF451chr657006100+34766115393034831
ENST00000361203DSTchr656707853-ENST00000370706ZNF451chr657006100+442199272582851
ENST00000361203DSTchr656707853-ENST00000357489ZNF451chr657006100+417199272438803
ENST00000361203DSTchr656707853-ENST00000491832ZNF451chr657006100+296499272522831

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
ENST00000421834ENST00000370706DSTchr656707853-ZNF451chr657006100+0.0004647920.9995352
ENST00000421834ENST00000357489DSTchr656707853-ZNF451chr657006100+0.0005807590.9994192
ENST00000421834ENST00000491832DSTchr656707853-ZNF451chr657006100+0.0012133240.99878675
ENST00000370769ENST00000370706DSTchr656707853-ZNF451chr657006100+0.0004647920.9995352
ENST00000370769ENST00000357489DSTchr656707853-ZNF451chr657006100+0.0005807590.9994192
ENST00000370769ENST00000491832DSTchr656707853-ZNF451chr657006100+0.0012133240.99878675
ENST00000312431ENST00000370706DSTchr656707853-ZNF451chr657006100+0.0004647920.9995352
ENST00000312431ENST00000357489DSTchr656707853-ZNF451chr657006100+0.0005807590.9994192
ENST00000312431ENST00000491832DSTchr656707853-ZNF451chr657006100+0.0012133240.99878675
ENST00000370788ENST00000370706DSTchr656707853-ZNF451chr657006100+0.0004688230.99953115
ENST00000370788ENST00000357489DSTchr656707853-ZNF451chr657006100+0.000606570.99939346
ENST00000370788ENST00000491832DSTchr656707853-ZNF451chr657006100+0.0014848230.9985152
ENST00000361203ENST00000370706DSTchr656707853-ZNF451chr657006100+0.0004658390.99953413
ENST00000361203ENST00000357489DSTchr656707853-ZNF451chr657006100+0.0005808930.9994191
ENST00000361203ENST00000491832DSTchr656707853-ZNF451chr657006100+0.0012227520.9987772

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 DST-ZNF451

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DSTchr656707853ZNF451chr65700610061124ISRPTRMSWRGTKEATDDGHNNNLLP
DSTchr656707853ZNF451chr6570061009124ISRPTRMSWRGTKEATDDGHNNNLLP
DSTchr656707853ZNF451chr6570061009924ISRPTRMSWRGTKEATDDGHNNNLLP

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Potential FusionNeoAntigen Information of DST-ZNF451 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.
DST-ZNF451_56707853_57006100.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)
DST-ZNF451chr656707853chr65700610091HLA-B73:01TRMSWRGTKEA0.99890.8039415

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Potential FusionNeoAntigen Information of DST-ZNF451 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.
DST-ZNF451_56707853_57006100.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)
DST-ZNF451chr656707853chr65700610091DRB1-0903RMSWRGTKEATDDGH520
DST-ZNF451chr656707853chr65700610091DRB1-0903TRMSWRGTKEATDDG419
DST-ZNF451chr656707853chr65700610091DRB1-0908RMSWRGTKEATDDGH520
DST-ZNF451chr656707853chr65700610091DRB1-0908TRMSWRGTKEATDDG419

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Fusion breakpoint peptide structures of DST-ZNF451

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
6025MSWRGTKEATDDGHDSTZNF451chr656707853chr65700610091

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DST-ZNF451

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-B14:023BVN6025MSWRGTKEATDDGH-6.80051-6.89641
HLA-B14:023BVN6025MSWRGTKEATDDGH-6.13874-6.23464
HLA-B14:023BVN6025MSWRGTKEATDDGH-3.29054-4.41694
HLA-B14:023BVN6025MSWRGTKEATDDGH-3.29054-4.41694
HLA-B52:013W396025MSWRGTKEATDDGH-4.74123-4.83713
HLA-B52:013W396025MSWRGTKEATDDGH-3.53968-3.63558
HLA-B52:013W396025MSWRGTKEATDDGH-2.60045-3.72685
HLA-B52:013W396025MSWRGTKEATDDGH-2.60045-3.72685
HLA-B18:014JQV6025MSWRGTKEATDDGH10000.110000
HLA-A24:025HGA6025MSWRGTKEATDDGH-9.38916-9.48506
HLA-A24:025HGA6025MSWRGTKEATDDGH-6.92452-8.05092
HLA-A24:025HGA6025MSWRGTKEATDDGH-6.92452-8.05092
HLA-A24:025HGA6025MSWRGTKEATDDGH-5.79708-5.89298
HLA-B27:056PYJ6025MSWRGTKEATDDGH-4.887-4.9829
HLA-B44:053DX86025MSWRGTKEATDDGH-6.74437-6.84027
HLA-B44:053DX86025MSWRGTKEATDDGH-5.52821-6.65461
HLA-B44:053DX86025MSWRGTKEATDDGH-5.52821-6.65461
HLA-B44:053DX86025MSWRGTKEATDDGH-5.17216-5.26806

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Vaccine Design for the FusionNeoAntigens of DST-ZNF451

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
DST-ZNF451chr656707853chr657006100415TRMSWRGTKEAACGAGGATGTCCTGGAGAGGTACAAAGGAAGCC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
DST-ZNF451chr656707853chr657006100419TRMSWRGTKEATDDGACGAGGATGTCCTGGAGAGGTACAAAGGAAGCCACAGATGATGGA
DST-ZNF451chr656707853chr657006100520RMSWRGTKEATDDGHAGGATGTCCTGGAGAGGTACAAAGGAAGCCACAGATGATGGACAT

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Information of the samples that have these potential fusion neoantigens of DST-ZNF451

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
STADDST-ZNF451chr656707853ENST00000312431chr657006100ENST00000357489TCGA-BR-8364-01A

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Potential target of CAR-T therapy development for DST-ZNF451

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 DST-ZNF451

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 DST-ZNF451

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