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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:ADAMTS2-OXCT1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADAMTS2-OXCT1
FusionPDB ID: 2088
FusionGDB2.0 ID: 2088
HgeneTgene
Gene symbol

ADAMTS2

OXCT1

Gene ID

9509

5019

Gene nameADAM metallopeptidase with thrombospondin type 1 motif 23-oxoacid CoA-transferase 1
SynonymsADAM-TS2|ADAMTS-2|ADAMTS-3|EDSDERMS|NPI|PC I-NP|PCI-NP|PCINP|PCPNI|PNPIOXCT|SCOT
Cytomap

5q35.3

5p13.1

Type of geneprotein-codingprotein-coding
DescriptionA disintegrin and metalloproteinase with thrombospondin motifs 2a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 2procollagen I N-proteinaseprocollagen I/II amino propeptide-processing enzymeprocollagen N-endosuccinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial3-oxoacid CoA transferaseSCOT-sepididymis secretory sperm binding proteinsomatic-type succinyl-CoA:3-oxoacid CoA-transferasesuccinyl CoA:3-oxoacid CoA transferasesuccinyl-CoA:3-ketoacid-
Modification date2020031320200313
UniProtAcc

P59510

Main function of 5'-partner protein: FUNCTION: May play a role in tissue-remodeling process occurring in both normal and pathological conditions. May have a protease-independent function in the transport from the endoplasmic reticulum to the Golgi apparatus of secretory cargos, mediated by the GON domain.
.
Ensembl transtripts involved in fusion geneENST idsENST00000251582, ENST00000274609, 
ENST00000513081, ENST00000196371, 
ENST00000509987, ENST00000510634, 
ENST00000512084, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 4=1006 X 6 X 6=216
# samples 58
** MAII scorelog2(5/100*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/216*10)=-1.43295940727611
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADAMTS2 [Title/Abstract] AND OXCT1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADAMTS2 [Title/Abstract] AND OXCT1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADAMTS2(178579143)-OXCT1(41739593), # samples:1
Anticipated loss of major functional domain due to fusion event.ADAMTS2-OXCT1 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.
ADAMTS2-OXCT1 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.
ADAMTS2-OXCT1 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.
ADAMTS2-OXCT1 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/chr5:178579143/chr5:41739593)
- 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 ADAMTS2 (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 OXCT1 (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)
ENST00000251582ADAMTS2chr5178579143-ENST00000196371OXCT1chr541739593-35391731181874618
ENST00000251582ADAMTS2chr5178579143-ENST00000509987OXCT1chr541739593-22341731181874618
ENST00000251582ADAMTS2chr5178579143-ENST00000512084OXCT1chr541739593-28631731181874618
ENST00000251582ADAMTS2chr5178579143-ENST00000510634OXCT1chr541739593-27631731181874618
ENST00000274609ADAMTS2chr5178579143-ENST00000196371OXCT1chr541739593-35391731181874618
ENST00000274609ADAMTS2chr5178579143-ENST00000509987OXCT1chr541739593-22341731181874618
ENST00000274609ADAMTS2chr5178579143-ENST00000512084OXCT1chr541739593-28631731181874618
ENST00000274609ADAMTS2chr5178579143-ENST00000510634OXCT1chr541739593-27631731181874618

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
ENST00000251582ENST00000196371ADAMTS2chr5178579143-OXCT1chr541739593-0.005150280.99484974
ENST00000251582ENST00000509987ADAMTS2chr5178579143-OXCT1chr541739593-0.0217534620.97824657
ENST00000251582ENST00000512084ADAMTS2chr5178579143-OXCT1chr541739593-0.0137154240.9862846
ENST00000251582ENST00000510634ADAMTS2chr5178579143-OXCT1chr541739593-0.0141796570.9858204
ENST00000274609ENST00000196371ADAMTS2chr5178579143-OXCT1chr541739593-0.005150280.99484974
ENST00000274609ENST00000509987ADAMTS2chr5178579143-OXCT1chr541739593-0.0217534620.97824657
ENST00000274609ENST00000512084ADAMTS2chr5178579143-OXCT1chr541739593-0.0137154240.9862846
ENST00000274609ENST00000510634ADAMTS2chr5178579143-OXCT1chr541739593-0.0141796570.9858204

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 ADAMTS2-OXCT1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADAMTS2chr5178579143OXCT1chr5417395931731571GPPLDGTMCAPGKAVFDVDKKKGLTL

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Potential FusionNeoAntigen Information of ADAMTS2-OXCT1 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.
ADAMTS2-OXCT1_178579143_41739593.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)
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:01TMCAPGKAVF0.99960.813616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:25TMCAPGKAVF0.99250.9157616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:02TMCAPGKAVF0.99210.9308616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:21MCAPGKAVF0.98280.9306716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:31MCAPGKAVF0.97750.935716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-C03:14MCAPGKAVF0.7530.9818716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-C03:02MCAPGKAVF0.98850.9726716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B35:11MCAPGKAVF0.98720.9282716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B35:23MCAPGKAVF0.97970.9484716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:08MCAPGKAVF0.95010.8735716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:11MCAPGKAVF0.94890.865716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B35:43MCAPGKAVF0.9480.8773716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-C16:01MCAPGKAVF0.71930.9813716
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:24TMCAPGKAVF0.99970.875616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:34TMCAPGKAVF0.99960.813616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:33TMCAPGKAVF0.99960.813616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:27TMCAPGKAVF0.99960.8681616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:125TMCAPGKAVF0.99960.813616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:135TMCAPGKAVF0.99960.817616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:12TMCAPGKAVF0.99580.8112616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:39TMCAPGKAVF0.9920.8487616
ADAMTS2-OXCT1chr5178579143chr5417395931731HLA-B15:30TMCAPGKAVF0.98910.9365616

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Potential FusionNeoAntigen Information of ADAMTS2-OXCT1 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.
ADAMTS2-OXCT1_178579143_41739593.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)
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0305GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0305PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0338GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0338PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0340GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-0340PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1153GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1153PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1173GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1179GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1179PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1331GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1333GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1333PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1341GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1419GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1419PGKAVFDVDKKKGLT1025
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB1-1493GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB3-0114GKAVFDVDKKKGLTL1126
ADAMTS2-OXCT1chr5178579143chr5417395931731DRB3-0114PGKAVFDVDKKKGLT1025

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Fusion breakpoint peptide structures of ADAMTS2-OXCT1

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
9503TMCAPGKAVFDVDKADAMTS2OXCT1chr5178579143chr5417395931731

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADAMTS2-OXCT1

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-B14:023BVN9503TMCAPGKAVFDVDK-7.9962-8.1096
HLA-B14:023BVN9503TMCAPGKAVFDVDK-5.70842-6.74372
HLA-B52:013W399503TMCAPGKAVFDVDK-6.83737-6.95077
HLA-B52:013W399503TMCAPGKAVFDVDK-4.4836-5.5189
HLA-A11:014UQ29503TMCAPGKAVFDVDK-10.0067-10.1201
HLA-A11:014UQ29503TMCAPGKAVFDVDK-9.03915-10.0745
HLA-A24:025HGA9503TMCAPGKAVFDVDK-6.56204-6.67544
HLA-A24:025HGA9503TMCAPGKAVFDVDK-5.42271-6.45801
HLA-B44:053DX89503TMCAPGKAVFDVDK-7.85648-8.89178
HLA-B44:053DX89503TMCAPGKAVFDVDK-5.3978-5.5112
HLA-A02:016TDR9503TMCAPGKAVFDVDK-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ADAMTS2-OXCT1

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
ADAMTS2-OXCT1chr5178579143chr541739593616TMCAPGKAVFACTATGTGTGCACCTGGCAAGGCTGTGTTT
ADAMTS2-OXCT1chr5178579143chr541739593716MCAPGKAVFATGTGTGCACCTGGCAAGGCTGTGTTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ADAMTS2-OXCT1chr5178579143chr5417395931025PGKAVFDVDKKKGLTCCTGGCAAGGCTGTGTTTGATGTGGACAAGAAGAAAGGGTTGACT
ADAMTS2-OXCT1chr5178579143chr5417395931126GKAVFDVDKKKGLTLGGCAAGGCTGTGTTTGATGTGGACAAGAAGAAAGGGTTGACTCTG

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Information of the samples that have these potential fusion neoantigens of ADAMTS2-OXCT1

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
BRCAADAMTS2-OXCT1chr5178579143ENST00000251582chr541739593ENST00000196371TCGA-BH-A1FM-01A

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Potential target of CAR-T therapy development for ADAMTS2-OXCT1

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 ADAMTS2-OXCT1

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 ADAMTS2-OXCT1

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