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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:DTNA-ZNF521

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: DTNA-ZNF521
FusionPDB ID: 24366
FusionGDB2.0 ID: 24366
HgeneTgene
Gene symbol

DTNA

ZNF521

Gene ID

1837

25925

Gene namedystrobrevin alphazinc finger protein 521
SynonymsD18S892E|DRP3|DTN|DTN-A|LVNC1EHZF|Evi3
Cytomap

18q12.1

18q11.2

Type of geneprotein-codingprotein-coding
Descriptiondystrobrevin alphadystrophin-related protein 3zinc finger protein 521LYST-interacting protein 3early hematopoietic zinc finger protein
Modification date2020031320200313
UniProtAcc

Q9Y4J8

Main function of 5'-partner protein: FUNCTION: May be involved in the formation and stability of synapses as well as being involved in the clustering of nicotinic acetylcholine receptors.
.
Ensembl transtripts involved in fusion geneENST idsENST00000269190, ENST00000269191, 
ENST00000283365, ENST00000315456, 
ENST00000348997, ENST00000399113, 
ENST00000399121, ENST00000444659, 
ENST00000554864, ENST00000595022, 
ENST00000596745, ENST00000597599, 
ENST00000598142, ENST00000598334, 
ENST00000598774, ENST00000399097, 
ENST00000269192, ENST00000556414, 
ENST00000590831, ENST00000591182, 
ENST00000592449, ENST00000597674, 
ENST00000599844, ENST00000601125, 
ENST00000538137, ENST00000579111, 
ENST00000584787, ENST00000361524, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 5 X 5=17513 X 10 X 9=1170
# samples 715
** MAII scorelog2(7/175*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(15/1170*10)=-2.96347412397489
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: DTNA [Title/Abstract] AND ZNF521 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: DTNA [Title/Abstract] AND ZNF521 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)DTNA(32346005)-ZNF521(22902151), # samples:1
Anticipated loss of major functional domain due to fusion event.DTNA-ZNF521 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.
DTNA-ZNF521 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.
DTNA-ZNF521 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.
DTNA-ZNF521 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


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/chr18:32346005/chr18:22902151)
- 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 DTNA (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 ZNF521 (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)
ENST00000283365DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-518149933943941351
ENST00000596745DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-516748532543801351
ENST00000315456DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-515447231243671351
ENST00000598334DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-515647431443691351
ENST00000554864DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-513745529543501351
ENST00000399121DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-513745529543501351
ENST00000595022DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-513044828843431351
ENST00000269190DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-513044828843431351
ENST00000598774DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-48872054541001351
ENST00000598142DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-48872054541001351
ENST00000348997DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-499331116342061347
ENST00000597599DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-498029815041931347
ENST00000269191DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-4831149140441347
ENST00000444659DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-4831149140441347
ENST00000399113DTNAchr1832346005-ENST00000361524ZNF521chr1822902151-4830148040431347

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
ENST00000283365ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0014974750.9985025
ENST00000596745ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0014589470.9985411
ENST00000315456ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0014179040.9985821
ENST00000598334ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011998790.99880016
ENST00000554864ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011849720.99881506
ENST00000399121ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011849720.99881506
ENST00000595022ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011664970.9988335
ENST00000269190ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011664970.9988335
ENST00000598774ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011095780.99889046
ENST00000598142ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011095780.99889046
ENST00000348997ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.001177320.9988226
ENST00000597599ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0011447990.99885523
ENST00000269191ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0010941480.9989059
ENST00000444659ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0010941480.9989059
ENST00000399113ENST00000361524DTNAchr1832346005-ZNF521chr1822902151-0.0010960120.998904

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 DTNA-ZNF521

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
DTNAchr1832346005ZNF521chr182290215114850ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215114950ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215120554ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215129850ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215131150ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215144854ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215145554ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215147254ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215147454ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215148554ACKLRFVQKKCNYPNCKLEDKTEDGE
DTNAchr1832346005ZNF521chr182290215149954ACKLRFVQKKCNYPNCKLEDKTEDGE

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Potential FusionNeoAntigen Information of DTNA-ZNF521 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.

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)

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Potential FusionNeoAntigen Information of DTNA-ZNF521 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 DTNA-ZNF521

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of DTNA-ZNF521

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

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Vaccine Design for the FusionNeoAntigens of DTNA-ZNF521

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

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 DTNA-ZNF521

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

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Potential target of CAR-T therapy development for DTNA-ZNF521

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 DTNA-ZNF521

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 DTNA-ZNF521

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