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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:ADAMTS16-ETV6

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ADAMTS16-ETV6
FusionPDB ID: 2051
FusionGDB2.0 ID: 2051
HgeneTgene
Gene symbol

ADAMTS16

ETV6

Gene ID

170690

2120

Gene nameADAM metallopeptidase with thrombospondin type 1 motif 16ETS variant transcription factor 6
SynonymsADAMTS16sTEL|TEL/ABL|THC5
Cytomap

5p15.32

12p13.2

Type of geneprotein-codingprotein-coding
DescriptionA disintegrin and metalloproteinase with thrombospondin motifs 16ADAM-TS 16ADAM-TS16ADAMTS-16a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 16transcription factor ETV6ETS translocation variant 6ETS variant 6ETS-related protein Tel1TEL1 oncogeneets variant gene 6 (TEL oncogene)
Modification date2020031320200313
UniProtAcc

Q8TE57

Main function of 5'-partner protein:

P41212

Main function of 5'-partner protein: FUNCTION: Transcriptional repressor; binds to the DNA sequence 5'-CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. {ECO:0000269|PubMed:25581430}.
Ensembl transtripts involved in fusion geneENST idsENST00000274181, ENST00000511368, 
ENST00000513709, 
ENST00000544715, 
ENST00000396373, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=2721 X 24 X 6=3024
# samples 319
** MAII scorelog2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(19/3024*10)=-3.99238681589013
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ADAMTS16 [Title/Abstract] AND ETV6 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ADAMTS16 [Title/Abstract] AND ETV6 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ADAMTS16(5209359)-ETV6(11905384), # samples:3
Anticipated loss of major functional domain due to fusion event.ADAMTS16-ETV6 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.
ADAMTS16-ETV6 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.
ADAMTS16-ETV6 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.
ADAMTS16-ETV6 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
TgeneETV6

GO:0000122

negative regulation of transcription by RNA polymerase II

10514502



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/chr5:5209359/chr12:11905384)
- 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 ADAMTS16 (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 ETV6 (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)
ENST00000274181ADAMTS16chr55209359+ENST00000396373ETV6chr1211905384+742517433030681012
ENST00000511368ADAMTS16chr55209359+ENST00000396373ETV6chr1211905384+742517433030681012

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
ENST00000274181ENST00000396373ADAMTS16chr55209359+ETV6chr1211905384+0.0004676650.99953234
ENST00000511368ENST00000396373ADAMTS16chr55209359+ETV6chr1211905384+0.0004676650.99953234

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 ADAMTS16-ETV6

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ADAMTS16chr55209359ETV6chr12119053841743571GEKAKLCMLDFKKQERISYTPPESPV

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Potential FusionNeoAntigen Information of ADAMTS16-ETV6 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.
ADAMTS16-ETV6_5209359_11905384.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)
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:03KKQERISY0.91090.60351119
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:03FKKQERISY0.68720.67571019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:18FKKQERISY0.57450.62091019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:27FKKQERISY0.95260.88241019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:05FKKQERISY0.89090.86971019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:67FKKQERISY0.86860.83261019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:80FKKQERISY0.86860.83261019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:46FKKQERISY0.86710.70831019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:10FKKQERISY0.83980.85591019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:07FKKQERISY0.80310.61841019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:21FKKQERISY0.64940.80221019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:04FKKQERISY0.51970.89361019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C12:16FKKQERISY0.33820.91231019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:02FKKQERISY0.86860.83261019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:17FKKQERISY0.84670.90091019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C07:22FKKQERISY0.82590.5261019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:50FKKQERISY0.76790.80871019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:35FKKQERISY0.76490.83691019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:12FKKQERISY0.70960.79951019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:53FKKQERISY0.52740.83761019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:54FKKQERISY0.45020.82651019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B15:68FKKQERISY0.30680.52841019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-B48:02FKKQERISY0.27590.79731019
ADAMTS16-ETV6chr55209359chr12119053841743HLA-C12:02FKKQERISY0.08710.92391019

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Potential FusionNeoAntigen Information of ADAMTS16-ETV6 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.
ADAMTS16-ETV6_5209359_11905384.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)
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1168MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1172MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1179MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1182MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1329MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1331MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1341MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1385MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1386MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1396MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1419MLDFKKQERISYTPP722
ADAMTS16-ETV6chr55209359chr12119053841743DRB1-1449MLDFKKQERISYTPP722

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Fusion breakpoint peptide structures of ADAMTS16-ETV6

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
881CMLDFKKQERISYTADAMTS16ETV6chr55209359chr12119053841743

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ADAMTS16-ETV6

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-B14:023BVN881CMLDFKKQERISYT-7.9962-8.1096
HLA-B14:023BVN881CMLDFKKQERISYT-5.70842-6.74372
HLA-B52:013W39881CMLDFKKQERISYT-6.83737-6.95077
HLA-B52:013W39881CMLDFKKQERISYT-4.4836-5.5189
HLA-A11:014UQ2881CMLDFKKQERISYT-10.0067-10.1201
HLA-A11:014UQ2881CMLDFKKQERISYT-9.03915-10.0745
HLA-A24:025HGA881CMLDFKKQERISYT-6.56204-6.67544
HLA-A24:025HGA881CMLDFKKQERISYT-5.42271-6.45801
HLA-B44:053DX8881CMLDFKKQERISYT-7.85648-8.89178
HLA-B44:053DX8881CMLDFKKQERISYT-5.3978-5.5112
HLA-A02:016TDR881CMLDFKKQERISYT-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of ADAMTS16-ETV6

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
ADAMTS16-ETV6chr55209359chr12119053841019FKKQERISYTTTAAAAAGCAGGAACGAATTTCATAT
ADAMTS16-ETV6chr55209359chr12119053841119KKQERISYAAAAAGCAGGAACGAATTTCATAT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ADAMTS16-ETV6chr55209359chr1211905384722MLDFKKQERISYTPPATGCTGGACTTTAAAAAGCAGGAACGAATTTCATATACACCTCCA

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Information of the samples that have these potential fusion neoantigens of ADAMTS16-ETV6

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
BRCAADAMTS16-ETV6chr55209359ENST00000274181chr1211905384ENST00000396373TCGA-A7-A4SD-01A

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Potential target of CAR-T therapy development for ADAMTS16-ETV6

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 ADAMTS16-ETV6

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 ADAMTS16-ETV6

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
TgeneETV6C4015537THROMBOCYTOPENIA 54CTD_human;GENOMICS_ENGLAND;UNIPROT
TgeneETV6C0023485Precursor B-Cell Lymphoblastic Leukemia-Lymphoma3CTD_human
TgeneETV6C0040034Thrombocytopenia3CTD_human;GENOMICS_ENGLAND
TgeneETV6C0023480Leukemia, Myelomonocytic, Chronic2ORPHANET
TgeneETV6C1332965Congenital Mesoblastic Nephroma2ORPHANET
TgeneETV6C0006413Burkitt Lymphoma1ORPHANET
TgeneETV6C0013146Drug abuse1CTD_human
TgeneETV6C0013170Drug habituation1CTD_human
TgeneETV6C0013222Drug Use Disorders1CTD_human
TgeneETV6C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
TgeneETV6C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
TgeneETV6C0023467Leukemia, Myelocytic, Acute1CGI;CTD_human;GENOMICS_ENGLAND
TgeneETV6C0029231Organic Mental Disorders, Substance-Induced1CTD_human
TgeneETV6C0038580Substance Dependence1CTD_human
TgeneETV6C0038586Substance Use Disorders1CTD_human
TgeneETV6C0087031Juvenile-Onset Still Disease1CTD_human
TgeneETV6C0236969Substance-Related Disorders1CTD_human
TgeneETV6C0238463Papillary thyroid carcinoma1ORPHANET
TgeneETV6C0376544Hematopoietic Neoplasms1CTD_human
TgeneETV6C0376545Hematologic Neoplasms1CTD_human
TgeneETV6C0740858Substance abuse problem1CTD_human
TgeneETV6C1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
TgeneETV6C1510472Drug Dependence1CTD_human
TgeneETV6C1832388Platelet Disorder, Familial, with Associated Myeloid Malignancy1ORPHANET
TgeneETV6C1838656Macrocytosis, Familial1CTD_human
TgeneETV6C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
TgeneETV6C3495559Juvenile arthritis1CTD_human
TgeneETV6C3714758Juvenile psoriatic arthritis1CTD_human
TgeneETV6C4316881Prescription Drug Abuse1CTD_human
TgeneETV6C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
TgeneETV6C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human