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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:ZNF695-SMYD3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF695-SMYD3
FusionPDB ID: 102729
FusionGDB2.0 ID: 102729
HgeneTgene
Gene symbol

ZNF695

SMYD3

Gene ID

57116

64754

Gene namezinc finger protein 695SET and MYND domain containing 3
SynonymsSBZF3KMT3E|ZMYND1|ZNFN3A1|bA74P14.1
Cytomap

1q44

1q44

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 695zinc finger protein SBZF3histone-lysine N-methyltransferase SMYD3SET and MYND domain-containing protein 3bA74P14.1 (novel protein)zinc finger MYND domain-containing protein 1zinc finger protein, subfamily 3A (MYND domain containing), 1zinc finger, MYND domain containing 1
Modification date2020031320200320
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000339986, ENST00000487338, 
ENST00000498046, 
ENST00000366517, 
ENST00000403792, ENST00000388985, 
ENST00000490107, ENST00000541742, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=129 X 14 X 17=6902
# samples 147
** MAII scorelog2(1/1*10)=3.32192809488736log2(47/6902*10)=-3.87628181187052
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF695 [Title/Abstract] AND SMYD3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF695 [Title/Abstract] AND SMYD3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SMYD3(246670356)-ZNF695(247131094), # samples:3
ZNF695(247171208)-SMYD3(246093239), # samples:1
Anticipated loss of major functional domain due to fusion event.SMYD3-ZNF695 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.
SMYD3-ZNF695 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.
ZNF695-SMYD3 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.
ZNF695-SMYD3 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.
ZNF695-SMYD3 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.
ZNF695-SMYD3 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.
SMYD3-ZNF695 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
SMYD3-ZNF695 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
SMYD3-ZNF695 seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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/chr1:246670356/chr1:247131094)
- 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 ZNF695 (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 SMYD3 (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)
ENST00000487338ZNF695chr1247171208-ENST00000541742SMYD3chr1246093239-116718826943305
ENST00000487338ZNF695chr1247171208-ENST00000490107SMYD3chr1246093239-116518826943305
ENST00000487338ZNF695chr1247171208-ENST00000388985SMYD3chr1246093239-94418826943306
ENST00000339986ZNF695chr1247171208-ENST00000541742SMYD3chr1246093239-11301511906301
ENST00000339986ZNF695chr1247171208-ENST00000490107SMYD3chr1246093239-11281511906301
ENST00000339986ZNF695chr1247171208-ENST00000388985SMYD3chr1246093239-9071511906302

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
ENST00000487338ENST00000541742ZNF695chr1247171208-SMYD3chr1246093239-0.0024390910.99756086
ENST00000487338ENST00000490107ZNF695chr1247171208-SMYD3chr1246093239-0.0025128370.9974872
ENST00000487338ENST00000388985ZNF695chr1247171208-SMYD3chr1246093239-0.002018420.99798155
ENST00000339986ENST00000541742ZNF695chr1247171208-SMYD3chr1246093239-0.0021940580.9978059
ENST00000339986ENST00000490107ZNF695chr1247171208-SMYD3chr1246093239-0.002303770.9976962
ENST00000339986ENST00000388985ZNF695chr1247171208-SMYD3chr1246093239-0.001594740.9984053

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 ZNF695-SMYD3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF695chr1247171208SMYD3chr124609323915150YREDAGTPKSWEMVICNSFTICNAEM
ZNF695chr1247171208SMYD3chr124609323918854YREDAGTPKSWEMVICNSFTICNAEM

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Potential FusionNeoAntigen Information of ZNF695-SMYD3 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.
ZNF695-SMYD3_247171208_246093239.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)
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:01WEMVICNSF0.99690.64951019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B35:03TPKSWEMVI0.73440.852615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B08:09TPKSWEMVI0.72350.574615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B57:01KSWEMVICNSF0.99980.9021819
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B57:03KSWEMVICNSF0.99880.9396819
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B42:02TPKSWEMVI0.85350.5647615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B78:01TPKSWEMVI0.84080.7416615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B51:07TPKSWEMVI0.78720.9087615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B42:01TPKSWEMVI0.78590.5552615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B39:10TPKSWEMVI0.13620.8419615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B51:21TPKSWEMV0.9680.5573614
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:04WEMVICNSF0.99840.69311019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:07WEMVICNSF0.9980.59071019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:06WEMVICNSF0.99730.66241019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:05WEMVICNSF0.99690.64951019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:03WEMVICNSF0.99630.63171019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B18:11WEMVICNSF0.96430.64131019
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B78:02TPKSWEMVI0.82620.7549615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B67:01TPKSWEMVI0.22120.7369615
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B57:10KSWEMVICNSF0.99980.9021819
ZNF695-SMYD3chr1247171208chr1246093239151HLA-A32:01KSWEMVICNSF0.99490.8873819
ZNF695-SMYD3chr1247171208chr1246093239151HLA-B57:02KSWEMVICNSF0.99450.8445819

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Potential FusionNeoAntigen Information of ZNF695-SMYD3 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 ZNF695-SMYD3

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
9545TPKSWEMVICNSFTZNF695SMYD3chr1247171208chr1246093239151

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF695-SMYD3

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-B14:023BVN9545TPKSWEMVICNSFT-7.15543-7.26883
HLA-B14:023BVN9545TPKSWEMVICNSFT-4.77435-5.80965
HLA-B52:013W399545TPKSWEMVICNSFT-6.80875-6.92215
HLA-B52:013W399545TPKSWEMVICNSFT-4.20386-5.23916
HLA-A11:014UQ29545TPKSWEMVICNSFT-7.5194-8.5547
HLA-A11:014UQ29545TPKSWEMVICNSFT-6.9601-7.0735
HLA-A24:025HGA9545TPKSWEMVICNSFT-7.52403-7.63743
HLA-A24:025HGA9545TPKSWEMVICNSFT-5.82433-6.85963
HLA-B27:056PYJ9545TPKSWEMVICNSFT-3.28285-4.31815
HLA-B44:053DX89545TPKSWEMVICNSFT-5.91172-6.94702
HLA-B44:053DX89545TPKSWEMVICNSFT-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZNF695-SMYD3

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
ZNF695-SMYD3chr1247171208chr12460932391019WEMVICNSFTGGGAAATGGTGATCTGCAACTCTTTC
ZNF695-SMYD3chr1247171208chr1246093239614TPKSWEMVACCCCCAAAAGCTGGGAAATGGTG
ZNF695-SMYD3chr1247171208chr1246093239615TPKSWEMVIACCCCCAAAAGCTGGGAAATGGTGATC
ZNF695-SMYD3chr1247171208chr1246093239819KSWEMVICNSFAAAAGCTGGGAAATGGTGATCTGCAACTCTTTC

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 ZNF695-SMYD3

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
STADZNF695-SMYD3chr1247171208ENST00000339986chr1246093239ENST00000388985TCGA-BR-4369-01A

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Potential target of CAR-T therapy development for ZNF695-SMYD3

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 ZNF695-SMYD3

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 ZNF695-SMYD3

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