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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:VMP1-KDM2A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: VMP1-KDM2A
FusionPDB ID: 98202
FusionGDB2.0 ID: 98202
HgeneTgene
Gene symbol

VMP1

KDM2A

Gene ID

81671

22992

Gene namevacuole membrane protein 1lysine demethylase 2A
SynonymsEPG3|TANGO5|TMEM49CXXC8|FBL11|FBL7|FBXL11|JHDM1A|LILINA
Cytomap

17q23.1

11q13.2

Type of geneprotein-codingprotein-coding
Descriptionvacuole membrane protein 1ectopic P-granules autophagy protein 3 homologtransmembrane protein 49transport and golgi organization 5 homologlysine-specific demethylase 2ACXXC-type zinc finger protein 8F-box and leucine-rich repeat protein 11F-box/LRR-repeat protein 11[Histone-H3]-lysine-36 demethylase 1AjmjC domain-containing histone demethylation protein 1Ajumonji C domain-containing h
Modification date2020032720200320
UniProtAcc.

Q9Y2K7

Main function of 5'-partner protein: FUNCTION: Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis. Regulates circadian gene expression by repressing the transcriptional activator activity of CLOCK-ARNTL/BMAL1 heterodimer and RORA in a catalytically-independent manner (PubMed:26037310). {ECO:0000269|PubMed:16362057, ECO:0000269|PubMed:19001877, ECO:0000269|PubMed:26037310, ECO:0000269|PubMed:28262558}.
Ensembl transtripts involved in fusion geneENST idsENST00000262291, ENST00000536180, 
ENST00000537567, ENST00000539763, 
ENST00000545362, ENST00000588617, 
ENST00000308783, ENST00000526258, 
ENST00000530342, ENST00000398645, 
ENST00000529006, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score34 X 17 X 12=693628 X 27 X 8=6048
# samples 3832
** MAII scorelog2(38/6936*10)=-4.19003257489089
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(32/6048*10)=-4.24031432933371
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: VMP1 [Title/Abstract] AND KDM2A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: VMP1 [Title/Abstract] AND KDM2A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)VMP1(57851246)-KDM2A(66947550), # samples:2
Anticipated loss of major functional domain due to fusion event.VMP1-KDM2A 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.
VMP1-KDM2A 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.
VMP1-KDM2A 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.
VMP1-KDM2A 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/chr17:57851246/chr11:66947550)
- 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 VMP1 (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 KDM2A (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)
ENST00000262291VMP1chr1757851246+ENST00000398645KDM2Achr1166947550+6629102425333301025
ENST00000262291VMP1chr1757851246+ENST00000529006KDM2Achr1166947550+7503102425344701405
ENST00000537567VMP1chr1757851246+ENST00000398645KDM2Achr1166947550+62446393272945872
ENST00000537567VMP1chr1757851246+ENST00000529006KDM2Achr1166947550+711863932740851252
ENST00000539763VMP1chr1757851246+ENST00000398645KDM2Achr1166947550+63087032383009923
ENST00000539763VMP1chr1757851246+ENST00000529006KDM2Achr1166947550+718270323841491303
ENST00000536180VMP1chr1757851246+ENST00000398645KDM2Achr1166947550+63387333103039909
ENST00000536180VMP1chr1757851246+ENST00000529006KDM2Achr1166947550+721273331041791289
ENST00000545362VMP1chr1757851246+ENST00000398645KDM2Achr1166947550+6204599412905954
ENST00000545362VMP1chr1757851246+ENST00000529006KDM2Achr1166947550+70785994140451334

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
ENST00000262291ENST00000398645VMP1chr1757851246+KDM2Achr1166947550+0.0006494430.9993506
ENST00000262291ENST00000529006VMP1chr1757851246+KDM2Achr1166947550+0.0004236050.9995764
ENST00000537567ENST00000398645VMP1chr1757851246+KDM2Achr1166947550+0.0009148380.9990852
ENST00000537567ENST00000529006VMP1chr1757851246+KDM2Achr1166947550+0.0004323160.9995677
ENST00000539763ENST00000398645VMP1chr1757851246+KDM2Achr1166947550+0.0012625890.9987374
ENST00000539763ENST00000529006VMP1chr1757851246+KDM2Achr1166947550+0.0005617720.9994382
ENST00000536180ENST00000398645VMP1chr1757851246+KDM2Achr1166947550+0.0007779990.99922204
ENST00000536180ENST00000529006VMP1chr1757851246+KDM2Achr1166947550+0.0004400930.99955994
ENST00000545362ENST00000398645VMP1chr1757851246+KDM2Achr1166947550+0.0008127030.9991873
ENST00000545362ENST00000529006VMP1chr1757851246+KDM2Achr1166947550+0.0003114570.9996885

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 VMP1-KDM2A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
VMP1chr1757851246KDM2Achr11669475501024257EFEEMLEHAESAQRGTMRRRYEDDGI
VMP1chr1757851246KDM2Achr1166947550599186EFEEMLEHAESAQRGTMRRRYEDDGI
VMP1chr1757851246KDM2Achr1166947550639104EFEEMLEHAESAQRGTMRRRYEDDGI
VMP1chr1757851246KDM2Achr1166947550703155EFEEMLEHAESAQRGTMRRRYEDDGI
VMP1chr1757851246KDM2Achr1166947550733141EFEEMLEHAESAQRGTMRRRYEDDGI

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Potential FusionNeoAntigen Information of VMP1-KDM2A 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.
VMP1-KDM2A_57851246_66947550.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)
VMP1-KDM2Achr1757851246chr11669475501024HLA-B44:03AESAQRGTM0.99660.7004817
VMP1-KDM2Achr1757851246chr11669475501024HLA-A26:03ESAQRGTMR0.86310.507918
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:13AESAQRGTM0.45540.7467817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:01AQRGTMRRRY0.99970.77261121
VMP1-KDM2Achr1757851246chr11669475501024HLA-A68:24ESAQRGTMRR0.99660.5108919
VMP1-KDM2Achr1757851246chr11669475501024HLA-A66:01ESAQRGTMRR0.99360.5535919
VMP1-KDM2Achr1757851246chr11669475501024HLA-A68:08ESAQRGTMRR0.88680.5126919
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:01EHAESAQRGTM0.99920.7455617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B38:02EHAESAQRGTM0.99870.8417617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B38:01EHAESAQRGTM0.99850.8538617
VMP1-KDM2Achr1757851246chr11669475501024HLA-A33:01EMLEHAESAQR0.9940.5223314
VMP1-KDM2Achr1757851246chr11669475501024HLA-A33:05EMLEHAESAQR0.9940.5223314
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:24EHAESAQRGTM0.99390.5064617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:08AESAQRGTM0.73090.6929817
VMP1-KDM2Achr1757851246chr11669475501024HLA-A68:01ESAQRGTMRR0.99660.5108919
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:04AQRGTMRRRY0.96950.81721121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:09EHAESAQRGTM0.9990.6106617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:05EHAESAQRGTM0.99850.7187617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B14:03EHAESAQRGTM0.99080.7827617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B40:04AESAQRGTM0.99750.5824817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B44:13AESAQRGTM0.99660.7004817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B44:26AESAQRGTM0.99660.7004817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B44:07AESAQRGTM0.99660.7004817
VMP1-KDM2Achr1757851246chr11669475501024HLA-C07:01QRGTMRRRY0.98750.62071221
VMP1-KDM2Achr1757851246chr11669475501024HLA-B41:03AESAQRGTM0.57380.549817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:53AESAQRGTM0.32950.5659817
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:135AQRGTMRRRY0.99970.7911121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:33AQRGTMRRRY0.99970.77261121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:125AQRGTMRRRY0.99970.77261121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:34AQRGTMRRRY0.99970.77261121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:27AQRGTMRRRY0.99970.79921121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:50AQRGTMRRRY0.99940.80121121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:35AQRGTMRRRY0.99710.76821121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:12AQRGTMRRRY0.99390.69051121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B15:54AQRGTMRRRY0.98850.73411121
VMP1-KDM2Achr1757851246chr11669475501024HLA-B39:31EHAESAQRGTM0.99930.7465617
VMP1-KDM2Achr1757851246chr11669475501024HLA-B38:05EHAESAQRGTM0.99850.8538617

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Potential FusionNeoAntigen Information of VMP1-KDM2A 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.
VMP1-KDM2A_57851246_66947550.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)
VMP1-KDM2Achr1757851246chr11669475501024DRB5-0106EEMLEHAESAQRGTM217
VMP1-KDM2Achr1757851246chr11669475501024DRB5-0106FEEMLEHAESAQRGT116
VMP1-KDM2Achr1757851246chr11669475501024DRB5-0205EEMLEHAESAQRGTM217

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Fusion breakpoint peptide structures of VMP1-KDM2A

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
1770EHAESAQRGTMRRRVMP1KDM2Achr1757851246chr11669475501024

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of VMP1-KDM2A

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-B14:023BVN1770EHAESAQRGTMRRR-7.9962-8.1096
HLA-B14:023BVN1770EHAESAQRGTMRRR-5.70842-6.74372
HLA-B52:013W391770EHAESAQRGTMRRR-6.83737-6.95077
HLA-B52:013W391770EHAESAQRGTMRRR-4.4836-5.5189
HLA-A11:014UQ21770EHAESAQRGTMRRR-10.0067-10.1201
HLA-A11:014UQ21770EHAESAQRGTMRRR-9.03915-10.0745
HLA-A24:025HGA1770EHAESAQRGTMRRR-6.56204-6.67544
HLA-A24:025HGA1770EHAESAQRGTMRRR-5.42271-6.45801
HLA-B44:053DX81770EHAESAQRGTMRRR-7.85648-8.89178
HLA-B44:053DX81770EHAESAQRGTMRRR-5.3978-5.5112
HLA-A02:016TDR1770EHAESAQRGTMRRR-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of VMP1-KDM2A

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
VMP1-KDM2Achr1757851246chr11669475501121AQRGTMRRRYGCACAACGTGGTACCATGCGACGACGCTAT
VMP1-KDM2Achr1757851246chr11669475501221QRGTMRRRYCAACGTGGTACCATGCGACGACGCTAT
VMP1-KDM2Achr1757851246chr1166947550314EMLEHAESAQRGAGATGCTGGAACATGCAGAGTCTGCACAACGT
VMP1-KDM2Achr1757851246chr1166947550617EHAESAQRGTMGAACATGCAGAGTCTGCACAACGTGGTACCATG
VMP1-KDM2Achr1757851246chr1166947550817AESAQRGTMGCAGAGTCTGCACAACGTGGTACCATG
VMP1-KDM2Achr1757851246chr1166947550918ESAQRGTMRGAGTCTGCACAACGTGGTACCATGCGA
VMP1-KDM2Achr1757851246chr1166947550919ESAQRGTMRRGAGTCTGCACAACGTGGTACCATGCGACGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
VMP1-KDM2Achr1757851246chr1166947550116FEEMLEHAESAQRGTTTTGAAGAGATGCTGGAACATGCAGAGTCTGCACAACGTGGTACC
VMP1-KDM2Achr1757851246chr1166947550217EEMLEHAESAQRGTMGAAGAGATGCTGGAACATGCAGAGTCTGCACAACGTGGTACCATG

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Information of the samples that have these potential fusion neoantigens of VMP1-KDM2A

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
BRCAVMP1-KDM2Achr1757851246ENST00000262291chr1166947550ENST00000398645TCGA-A1-A0SN-01A

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Potential target of CAR-T therapy development for VMP1-KDM2A

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
HgeneVMP1chr17:57851246chr11:66947550ENST00000262291+712110_130238407.0TransmembraneHelical
HgeneVMP1chr17:57851246chr11:66947550ENST00000262291+71244_64238407.0TransmembraneHelical
HgeneVMP1chr17:57851246chr11:66947550ENST00000262291+71278_98238407.0TransmembraneHelical

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 VMP1-KDM2A

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 VMP1-KDM2A

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