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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:VAMP4-MYRFL

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VAMP4-MYRFL
FusionPDB ID: 97863
FusionGDB2.0 ID: 97863
HgeneTgene
Gene symbol

VAMP4

MYRFL

Gene ID

8674

196446

Gene namevesicle associated membrane protein 4myelin regulatory factor like
SynonymsVAMP-4|VAMP24C12orf15|C12orf28|bcm1377
Cytomap

1q24.3

12q15

Type of geneprotein-codingprotein-coding
Descriptionvesicle-associated membrane protein 4VAMP4/TAF3 fusionmyelin regulatory factor-like protein
Modification date2020031320200322
UniProtAcc.

Q96LU7

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000236192, ENST00000367740, 
ENST00000415773, ENST00000482519, 
ENST00000299350, ENST00000535034, 
ENST00000547771, ENST00000552032, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score1 X 1 X 1=129 X 16 X 7=3248
# samples 126
** MAII scorelog2(1/1*10)=3.32192809488736log2(26/3248*10)=-3.64296810415672
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VAMP4 [Title/Abstract] AND MYRFL [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VAMP4 [Title/Abstract] AND MYRFL [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VAMP4(171707489)-MYRFL(70320351), # samples:1
Anticipated loss of major functional domain due to fusion event.VAMP4-MYRFL 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.
VAMP4-MYRFL 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.
VAMP4-MYRFL seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
VAMP4-MYRFL 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
HgeneVAMP4

GO:0035493

SNARE complex assembly

21151919



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/chr1:171707489/chr12:70320351)
- 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 VAMP4 (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 MYRFL (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)
ENST00000415773VAMP4chr1171707489-ENST00000552032MYRFLchr1270320351+15912681871398403
ENST00000415773VAMP4chr1171707489-ENST00000547771MYRFLchr1270320351+19292681871362391

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
ENST00000415773ENST00000552032VAMP4chr1171707489-MYRFLchr1270320351+0.0049840050.99501604
ENST00000415773ENST00000547771VAMP4chr1171707489-MYRFLchr1270320351+0.0016544630.9983455

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 VAMP4-MYRFL

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VAMP4chr1171707489MYRFLchr127032035126827NDDDVTGSVKSERDQIFMENVGAVKQ

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Potential FusionNeoAntigen Information of VAMP4-MYRFL 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.
VAMP4-MYRFL_171707489_70320351.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)
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B18:01SERDQIFM0.98620.6991018
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B18:11SERDQIFM0.9950.56411018
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B18:05SERDQIFM0.98620.6991018
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B18:06SERDQIFM0.98610.70691018
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B18:03SERDQIFM0.97850.68661018
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B48:02VKSERDQIF0.15640.7545817
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B15:54VKSERDQIF0.04240.6029817
VAMP4-MYRFLchr1171707489chr1270320351268HLA-B15:53VKSERDQIF0.0220.665817

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Potential FusionNeoAntigen Information of VAMP4-MYRFL 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 VAMP4-MYRFL

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
3158GSVKSERDQIFMENVAMP4MYRFLchr1171707489chr1270320351268

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VAMP4-MYRFL

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-B14:023BVN3158GSVKSERDQIFMEN-7.15543-7.26883
HLA-B14:023BVN3158GSVKSERDQIFMEN-4.77435-5.80965
HLA-B52:013W393158GSVKSERDQIFMEN-6.80875-6.92215
HLA-B52:013W393158GSVKSERDQIFMEN-4.20386-5.23916
HLA-A11:014UQ23158GSVKSERDQIFMEN-7.5194-8.5547
HLA-A11:014UQ23158GSVKSERDQIFMEN-6.9601-7.0735
HLA-A24:025HGA3158GSVKSERDQIFMEN-7.52403-7.63743
HLA-A24:025HGA3158GSVKSERDQIFMEN-5.82433-6.85963
HLA-B27:056PYJ3158GSVKSERDQIFMEN-3.28285-4.31815
HLA-B44:053DX83158GSVKSERDQIFMEN-5.91172-6.94702
HLA-B44:053DX83158GSVKSERDQIFMEN-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of VAMP4-MYRFL

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
VAMP4-MYRFLchr1171707489chr12703203511018SERDQIFMAGTGAAAGGGACCAGATCTTTATG
VAMP4-MYRFLchr1171707489chr1270320351817VKSERDQIFGTGAAAAGTGAAAGGGACCAGATCTTT

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 VAMP4-MYRFL

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
SARCVAMP4-MYRFLchr1171707489ENST00000415773chr1270320351ENST00000547771TCGA-FX-A2QS-01A

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Potential target of CAR-T therapy development for VAMP4-MYRFL

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
TgeneMYRFLchr1:171707489chr12:70320351ENST000005520321225628_6480911.0TransmembraneHelical

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 VAMP4-MYRFL

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 VAMP4-MYRFL

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