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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:ADAMTS12-RAI14

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADAMTS12-RAI14
FusionPDB ID: 2045
FusionGDB2.0 ID: 2045
HgeneTgene
Gene symbol

ADAMTS12

RAI14

Gene ID

81792

26064

Gene nameADAM metallopeptidase with thrombospondin type 1 motif 12retinoic acid induced 14
SynonymsPRO4389NORPEG|RAI13
Cytomap

5p13.3-p13.2

5p13.2

Type of geneprotein-codingprotein-coding
DescriptionA disintegrin and metalloproteinase with thrombospondin motifs 12ADAM-TS 12ADAM-TS12ADAMTS-12a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 12ankycorbinankyrin repeat and coiled-coil structure-containing proteinnovel retinal pigment epithelial cell proteinretinoic acid-induced protein 14
Modification date2020031320200313
UniProtAcc

P58397

Main function of 5'-partner protein: FUNCTION: Metalloprotease that may play a role in the degradation of COMP. Cleaves also alpha-2 macroglobulin and aggregan. Has anti-tumorigenic properties. {ECO:0000269|PubMed:16611630, ECO:0000269|PubMed:17895370, ECO:0000269|PubMed:18485748}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000352040, ENST00000504830, 
ENST00000515401, ENST00000504582, 
ENST00000397449, ENST00000507276, 
ENST00000265109, ENST00000428746, 
ENST00000503673, ENST00000506376, 
ENST00000512629, ENST00000515799, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 6 X 4=14410 X 8 X 7=560
# samples 612
** MAII scorelog2(6/144*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/560*10)=-2.22239242133645
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADAMTS12 [Title/Abstract] AND RAI14 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADAMTS12 [Title/Abstract] AND RAI14 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADAMTS12(33881224)-RAI14(34757573), # samples:3
Anticipated loss of major functional domain due to fusion event.ADAMTS12-RAI14 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.
ADAMTS12-RAI14 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.
ADAMTS12-RAI14 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.
ADAMTS12-RAI14 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
HgeneADAMTS12

GO:0030167

proteoglycan catabolic process

17895370

HgeneADAMTS12

GO:0032331

negative regulation of chondrocyte differentiation

22247065

HgeneADAMTS12

GO:0050727

regulation of inflammatory response

23019333

HgeneADAMTS12

GO:0051603

proteolysis involved in cellular protein catabolic process

16611630

HgeneADAMTS12

GO:0071773

cellular response to BMP stimulus

22247065

HgeneADAMTS12

GO:1901509

regulation of endothelial tube morphogenesis

17895370

HgeneADAMTS12

GO:1902203

negative regulation of hepatocyte growth factor receptor signaling pathway

17895370

HgeneADAMTS12

GO:1902548

negative regulation of cellular response to vascular endothelial growth factor stimulus

17895370

HgeneADAMTS12

GO:2001113

negative regulation of cellular response to hepatocyte growth factor stimulus

17895370



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/chr5:33881224/chr5:34757573)
- 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 ADAMTS12 (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 RAI14 (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)
ENST00000504830ADAMTS12chr533881224-ENST00000265109RAI14chr534757573+559482533637311131
ENST00000504830ADAMTS12chr533881224-ENST00000512629RAI14chr534757573+364582533636441102
ENST00000504830ADAMTS12chr533881224-ENST00000428746RAI14chr534757573+557882533637311131
ENST00000504830ADAMTS12chr533881224-ENST00000503673RAI14chr534757573+377282533637311131
ENST00000504830ADAMTS12chr533881224-ENST00000515799RAI14chr534757573+377482533637311131
ENST00000504830ADAMTS12chr533881224-ENST00000506376RAI14chr534757573+375282533637311131
ENST00000352040ADAMTS12chr533881224-ENST00000265109RAI14chr534757573+53435748534801131
ENST00000352040ADAMTS12chr533881224-ENST00000512629RAI14chr534757573+33945748533931103
ENST00000352040ADAMTS12chr533881224-ENST00000428746RAI14chr534757573+53275748534801131
ENST00000352040ADAMTS12chr533881224-ENST00000503673RAI14chr534757573+35215748534801131
ENST00000352040ADAMTS12chr533881224-ENST00000515799RAI14chr534757573+35235748534801131
ENST00000352040ADAMTS12chr533881224-ENST00000506376RAI14chr534757573+35015748534801131
ENST00000515401ADAMTS12chr533881224-ENST00000265109RAI14chr534757573+542165216335581131
ENST00000515401ADAMTS12chr533881224-ENST00000512629RAI14chr534757573+347265216334711103
ENST00000515401ADAMTS12chr533881224-ENST00000428746RAI14chr534757573+540565216335581131
ENST00000515401ADAMTS12chr533881224-ENST00000503673RAI14chr534757573+359965216335581131
ENST00000515401ADAMTS12chr533881224-ENST00000515799RAI14chr534757573+360165216335581131
ENST00000515401ADAMTS12chr533881224-ENST00000506376RAI14chr534757573+357965216335581131

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
ENST00000504830ENST00000265109ADAMTS12chr533881224-RAI14chr534757573+0.0007109030.99928904
ENST00000504830ENST00000512629ADAMTS12chr533881224-RAI14chr534757573+0.0010228670.9989772
ENST00000504830ENST00000428746ADAMTS12chr533881224-RAI14chr534757573+0.0007154460.99928457
ENST00000504830ENST00000503673ADAMTS12chr533881224-RAI14chr534757573+0.0017862050.99821377
ENST00000504830ENST00000515799ADAMTS12chr533881224-RAI14chr534757573+0.0017735210.99822646
ENST00000504830ENST00000506376ADAMTS12chr533881224-RAI14chr534757573+0.0018402960.9981597
ENST00000352040ENST00000265109ADAMTS12chr533881224-RAI14chr534757573+0.0005451710.9994548
ENST00000352040ENST00000512629ADAMTS12chr533881224-RAI14chr534757573+0.0008137070.99918634
ENST00000352040ENST00000428746ADAMTS12chr533881224-RAI14chr534757573+0.0005498180.99945015
ENST00000352040ENST00000503673ADAMTS12chr533881224-RAI14chr534757573+0.0014035570.9985965
ENST00000352040ENST00000515799ADAMTS12chr533881224-RAI14chr534757573+0.0013919450.99860805
ENST00000352040ENST00000506376ADAMTS12chr533881224-RAI14chr534757573+0.0014520410.998548
ENST00000515401ENST00000265109ADAMTS12chr533881224-RAI14chr534757573+0.0006078990.99939203
ENST00000515401ENST00000512629ADAMTS12chr533881224-RAI14chr534757573+0.00088230.9991177
ENST00000515401ENST00000428746ADAMTS12chr533881224-RAI14chr534757573+0.0006130580.9993869
ENST00000515401ENST00000503673ADAMTS12chr533881224-RAI14chr534757573+0.0015371560.9984629
ENST00000515401ENST00000515799ADAMTS12chr533881224-RAI14chr534757573+0.0015246090.9984754
ENST00000515401ENST00000506376ADAMTS12chr533881224-RAI14chr534757573+0.0015916240.9984084

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 ADAMTS12-RAI14

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADAMTS12chr533881224RAI14chr534757573574163RVGTAALSACHGLTNEWNKNDDRLLQ
ADAMTS12chr533881224RAI14chr534757573652163RVGTAALSACHGLTNEWNKNDDRLLQ
ADAMTS12chr533881224RAI14chr534757573825163RVGTAALSACHGLTNEWNKNDDRLLQ

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Potential FusionNeoAntigen Information of ADAMTS12-RAI14 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.
ADAMTS12-RAI14_33881224_34757573.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)
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:01ACHGLTNEW0.98790.9832817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:01ACHGLTNEW0.98710.9891817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:02ACHGLTNEW0.98370.9794817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:01SACHGLTNEW0.99950.9916717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:02SACHGLTNEW0.99850.9748717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:01SACHGLTNEW0.99850.9863717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:03SACHGLTNEW0.9920.9969717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B53:01SACHGLTNEW0.95870.7488717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:01LSACHGLTNEW10.9931617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:02LSACHGLTNEW0.99980.9792617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:01LSACHGLTNEW0.99970.9897617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:03LSACHGLTNEW0.99960.9973617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B44:08ACHGLTNEW0.10930.82817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:04ACHGLTNEW0.98760.8941817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:10ACHGLTNEW0.98710.9891817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:02ACHGLTNEW0.86210.9876817
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:10SACHGLTNEW0.99950.9916717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:04SACHGLTNEW0.99930.9222717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:06SACHGLTNEW0.99860.9705717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:02SACHGLTNEW0.98060.9893717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B53:02SACHGLTNEW0.82030.6782717
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:10LSACHGLTNEW10.9931617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:04LSACHGLTNEW0.99990.9584617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B57:02LSACHGLTNEW0.99960.9926617
ADAMTS12-RAI14chr533881224chr534757573574HLA-B58:06LSACHGLTNEW0.99960.9769617

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Potential FusionNeoAntigen Information of ADAMTS12-RAI14 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 ADAMTS12-RAI14

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
5581LSACHGLTNEWNKNADAMTS12RAI14chr533881224chr534757573574

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADAMTS12-RAI14

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-B14:023BVN5581LSACHGLTNEWNKN-6.9888-7.1022
HLA-B14:023BVN5581LSACHGLTNEWNKN-3.71338-4.74868
HLA-B52:013W395581LSACHGLTNEWNKN-5.59342-6.62872
HLA-B52:013W395581LSACHGLTNEWNKN-5.47943-5.59283
HLA-A24:025HGA5581LSACHGLTNEWNKN-6.88714-7.00054
HLA-A24:025HGA5581LSACHGLTNEWNKN-6.46973-7.50503
HLA-B44:053DX85581LSACHGLTNEWNKN-6.00524-6.11864
HLA-B44:053DX85581LSACHGLTNEWNKN-5.7663-6.8016

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Vaccine Design for the FusionNeoAntigens of ADAMTS12-RAI14

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
ADAMTS12-RAI14chr533881224chr534757573617LSACHGLTNEWCTCAGTGCCTGCCATGGACTGACCAATGAGTGG
ADAMTS12-RAI14chr533881224chr534757573717SACHGLTNEWAGTGCCTGCCATGGACTGACCAATGAGTGG
ADAMTS12-RAI14chr533881224chr534757573817ACHGLTNEWGCCTGCCATGGACTGACCAATGAGTGG

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 ADAMTS12-RAI14

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
SKCMADAMTS12-RAI14chr533881224ENST00000352040chr534757573ENST00000265109TCGA-EB-A44Q-06A

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Potential target of CAR-T therapy development for ADAMTS12-RAI14

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 ADAMTS12-RAI14

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 ADAMTS12-RAI14

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