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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:ZMYM4-SMYD3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZMYM4-SMYD3
FusionPDB ID: 101366
FusionGDB2.0 ID: 101366
HgeneTgene
Gene symbol

ZMYM4

SMYD3

Gene ID

9202

64754

Gene namezinc finger MYM-type containing 4SET and MYND domain containing 3
SynonymsCDIR|MYM|ZNF198L3|ZNF262KMT3E|ZMYND1|ZNFN3A1|bA74P14.1
Cytomap

1p34.3

1q44

Type of geneprotein-codingprotein-coding
Descriptionzinc finger MYM-type protein 4cell death inhibiting RNAzinc finger protein 262zinc finger, MYM-type 4histone-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 idsENST00000482131, ENST00000314607, 
ENST00000373297, 
ENST00000388985, 
ENST00000490107, ENST00000541742, 
ENST00000366517, ENST00000403792, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score14 X 8 X 10=112029 X 14 X 17=6902
# samples 1547
** MAII scorelog2(15/1120*10)=-2.90046432644909
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(47/6902*10)=-3.87628181187052
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZMYM4 [Title/Abstract] AND SMYD3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZMYM4 [Title/Abstract] AND SMYD3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SMYD3(246490503)-ZMYM4(35835630), # samples:3
ZMYM4(35827390)-SMYD3(246093239), # samples:3
Anticipated loss of major functional domain due to fusion event.SMYD3-ZMYM4 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-ZMYM4 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.
ZMYM4-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.
ZMYM4-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.
ZMYM4-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.
ZMYM4-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-ZMYM4 seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
SMYD3-ZMYM4 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
SMYD3-ZMYM4 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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/chr1:246490503/chr1:35835630)
- 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 ZMYM4 (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)
ENST00000373297ZMYM4chr135827390+ENST00000541742SMYD3chr1246093239-1899920801675531
ENST00000373297ZMYM4chr135827390+ENST00000490107SMYD3chr1246093239-1897920801675531
ENST00000373297ZMYM4chr135827390+ENST00000388985SMYD3chr1246093239-1676920801675532
ENST00000314607ZMYM4chr135827390+ENST00000541742SMYD3chr1246093239-1899920801675531
ENST00000314607ZMYM4chr135827390+ENST00000490107SMYD3chr1246093239-1897920801675531
ENST00000314607ZMYM4chr135827390+ENST00000388985SMYD3chr1246093239-1676920801675532

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
ENST00000373297ENST00000541742ZMYM4chr135827390+SMYD3chr1246093239-0.0005712530.9994287
ENST00000373297ENST00000490107ZMYM4chr135827390+SMYD3chr1246093239-0.0005751940.9994248
ENST00000373297ENST00000388985ZMYM4chr135827390+SMYD3chr1246093239-0.0006273420.99937266
ENST00000314607ENST00000541742ZMYM4chr135827390+SMYD3chr1246093239-0.0005712530.9994287
ENST00000314607ENST00000490107ZMYM4chr135827390+SMYD3chr1246093239-0.0005751940.9994248
ENST00000314607ENST00000388985ZMYM4chr135827390+SMYD3chr1246093239-0.0006273420.99937266

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 ZMYM4-SMYD3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZMYM4chr135827390SMYD3chr1246093239920279GLLDKIKDEPDNAQVICNSFTICNAE

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Potential FusionNeoAntigen Information of ZMYM4-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.
ZMYM4-SMYD3_35827390_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)
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B18:01DEPDNAQVI0.5640.8612716
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B39:10EPDNAQVI0.42680.8744816
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B51:07DEPDNAQVI0.49660.7586716
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B35:23NAQVICNSF0.97090.69021120
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B35:24NAQVICNSF0.90320.71951120
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B18:05DEPDNAQVI0.5640.8612716
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B18:08DEPDNAQVI0.54760.9449716
ZMYM4-SMYD3chr135827390chr1246093239920HLA-B18:03DEPDNAQVI0.53990.8517716

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Potential FusionNeoAntigen Information of ZMYM4-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.
ZMYM4-SMYD3_35827390_246093239.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)
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0413LLDKIKDEPDNAQVI116
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0413GLLDKIKDEPDNAQV015
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0413LDKIKDEPDNAQVIC217
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0422LLDKIKDEPDNAQVI116
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0467GLLDKIKDEPDNAQV015
ZMYM4-SMYD3chr135827390chr1246093239920DRB1-0467LLDKIKDEPDNAQVI116

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Fusion breakpoint peptide structures of ZMYM4-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
4142KDEPDNAQVICNSFZMYM4SMYD3chr135827390chr1246093239920

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZMYM4-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-B14:023BVN4142KDEPDNAQVICNSF-7.15543-7.26883
HLA-B14:023BVN4142KDEPDNAQVICNSF-4.77435-5.80965
HLA-B52:013W394142KDEPDNAQVICNSF-6.80875-6.92215
HLA-B52:013W394142KDEPDNAQVICNSF-4.20386-5.23916
HLA-A11:014UQ24142KDEPDNAQVICNSF-7.5194-8.5547
HLA-A11:014UQ24142KDEPDNAQVICNSF-6.9601-7.0735
HLA-A24:025HGA4142KDEPDNAQVICNSF-7.52403-7.63743
HLA-A24:025HGA4142KDEPDNAQVICNSF-5.82433-6.85963
HLA-B27:056PYJ4142KDEPDNAQVICNSF-3.28285-4.31815
HLA-B44:053DX84142KDEPDNAQVICNSF-5.91172-6.94702
HLA-B44:053DX84142KDEPDNAQVICNSF-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZMYM4-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
ZMYM4-SMYD3chr135827390chr12460932391120NAQVICNSFGCTCAAGTGATCTGCAACTCTTTCACC
ZMYM4-SMYD3chr135827390chr1246093239716DEPDNAQVIGAACCTGACAATGCTCAAGTGATCTGC
ZMYM4-SMYD3chr135827390chr1246093239816EPDNAQVICCTGACAATGCTCAAGTGATCTGC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ZMYM4-SMYD3chr135827390chr1246093239015GLLDKIKDEPDNAQVCTACTAGACAAAATAAAAGATGAACCTGACAATGCTCAAGTGATC
ZMYM4-SMYD3chr135827390chr1246093239116LLDKIKDEPDNAQVICTAGACAAAATAAAAGATGAACCTGACAATGCTCAAGTGATCTGC
ZMYM4-SMYD3chr135827390chr1246093239217LDKIKDEPDNAQVICGACAAAATAAAAGATGAACCTGACAATGCTCAAGTGATCTGCAAC

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Information of the samples that have these potential fusion neoantigens of ZMYM4-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
SKCMZMYM4-SMYD3chr135827390ENST00000314607chr1246093239ENST00000388985TCGA-DA-A1I7-06A

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Potential target of CAR-T therapy development for ZMYM4-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 ZMYM4-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 ZMYM4-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