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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:VAT1-CTNND1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VAT1-CTNND1
FusionPDB ID: 97918
FusionGDB2.0 ID: 97918
HgeneTgene
Gene symbol

VAT1

CTNND1

Gene ID

10493

100528016

Gene namevesicle amine transport 1TMX2-CTNND1 readthrough (NMD candidate)
SynonymsVATICAS|CTNND1|p120(cas)|p120(ctn)
Cytomap

17q21.31

11q12.1

Type of geneprotein-codingncRNA
Descriptionsynaptic vesicle membrane protein VAT-1 homologmembrane protein of cholinergic synaptic vesiclesvesicle amine transport protein 1 homolog (T. californica)Cadherin-associated Src substrateCatenin delta-1TMX2-CTNND1 readthrough (non-protein coding)p120 catenin
Modification date2020031320200313
UniProtAcc.

O60716

Main function of 5'-partner protein: FUNCTION: Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476). {ECO:0000269|PubMed:10207085, ECO:0000269|PubMed:14610055, ECO:0000269|PubMed:17344476, ECO:0000269|PubMed:20371349}.
Ensembl transtripts involved in fusion geneENST idsENST00000355653, ENST00000420567, 
ENST00000587173, 
ENST00000358694, 
ENST00000360682, ENST00000361332, 
ENST00000361391, ENST00000361796, 
ENST00000399039, ENST00000399050, 
ENST00000415361, ENST00000426142, 
ENST00000428599, ENST00000524630, 
ENST00000525902, ENST00000526357, 
ENST00000526772, ENST00000526938, 
ENST00000527467, ENST00000528232, 
ENST00000528621, ENST00000529526, 
ENST00000529873, ENST00000529919, 
ENST00000529986, ENST00000530094, 
ENST00000530748, ENST00000531014, 
ENST00000532245, ENST00000532463, 
ENST00000532649, ENST00000532787, 
ENST00000532844, ENST00000533667, 
ENST00000534579, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score11 X 7 X 2=15417 X 21 X 10=3570
# samples 1225
** MAII scorelog2(12/154*10)=-0.359895945086383
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(25/3570*10)=-3.83592407425437
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VAT1 [Title/Abstract] AND CTNND1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VAT1 [Title/Abstract] AND CTNND1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VAT1(41166624)-CTNND1(57574387), # samples:1
Anticipated loss of major functional domain due to fusion event.VAT1-CTNND1 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.
VAT1-CTNND1 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/chr17:41166624/chr11:57574387)
- 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 VAT1 (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 CTNND1 (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)
ENST00000355653VAT1chr1741166624-ENST00000524630CTNND1chr1157574387+68982734961277393
ENST00000355653VAT1chr1741166624-ENST00000529919CTNND1chr1157574387+52892734961277393
ENST00000355653VAT1chr1741166624-ENST00000399039CTNND1chr1157574387+56972734961277393
ENST00000355653VAT1chr1741166624-ENST00000360682CTNND1chr1157574387+65552734961277393
ENST00000355653VAT1chr1741166624-ENST00000361796CTNND1chr1157574387+65312734961277393
ENST00000355653VAT1chr1741166624-ENST00000361391CTNND1chr1157574387+65542734961277393
ENST00000355653VAT1chr1741166624-ENST00000530094CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000428599CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000361332CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000527467CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000415361CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000532245CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000532463CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000528232CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000529986CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000531014CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000358694CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000526772CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000532787CTNND1chr1157574387+65542734961277393
ENST00000355653VAT1chr1741166624-ENST00000533667CTNND1chr1157574387+65542734961277393
ENST00000355653VAT1chr1741166624-ENST00000529873CTNND1chr1157574387+65542734961277393
ENST00000355653VAT1chr1741166624-ENST00000525902CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000529526CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000532649CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000426142CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000532844CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000528621CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000399050CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000526357CTNND1chr1157574387+66172734961277393
ENST00000355653VAT1chr1741166624-ENST00000530748CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000534579CTNND1chr1157574387+65302734961277393
ENST00000355653VAT1chr1741166624-ENST00000526938CTNND1chr1157574387+40062734961277393

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
ENST00000355653ENST00000524630VAT1chr1741166624-CTNND1chr1157574387+0.0028584740.99714154
ENST00000355653ENST00000529919VAT1chr1741166624-CTNND1chr1157574387+0.0062609990.993739
ENST00000355653ENST00000399039VAT1chr1741166624-CTNND1chr1157574387+0.0042529670.995747
ENST00000355653ENST00000360682VAT1chr1741166624-CTNND1chr1157574387+0.0029675120.9970325
ENST00000355653ENST00000361796VAT1chr1741166624-CTNND1chr1157574387+0.0030631330.9969369
ENST00000355653ENST00000361391VAT1chr1741166624-CTNND1chr1157574387+0.0029891530.9970108
ENST00000355653ENST00000530094VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000428599VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000361332VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000527467VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000415361VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000532245VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000532463VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000528232VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000529986VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000531014VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000358694VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000526772VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000532787VAT1chr1741166624-CTNND1chr1157574387+0.0029891530.9970108
ENST00000355653ENST00000533667VAT1chr1741166624-CTNND1chr1157574387+0.0029891530.9970108
ENST00000355653ENST00000529873VAT1chr1741166624-CTNND1chr1157574387+0.0029891530.9970108
ENST00000355653ENST00000525902VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000529526VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000532649VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000426142VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000532844VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000528621VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000399050VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000526357VAT1chr1741166624-CTNND1chr1157574387+0.0030495320.99695045
ENST00000355653ENST00000530748VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000534579VAT1chr1741166624-CTNND1chr1157574387+0.0030807210.9969193
ENST00000355653ENST00000526938VAT1chr1741166624-CTNND1chr1157574387+0.0069233920.99307656

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 VAT1-CTNND1

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

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Potential FusionNeoAntigen Information of VAT1-CTNND1 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 VAT1-CTNND1 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 VAT1-CTNND1

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 VAT1-CTNND1

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 VAT1-CTNND1

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 VAT1-CTNND1

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 VAT1-CTNND1

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 VAT1-CTNND1

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 VAT1-CTNND1

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