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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:ETV6-PRDM16

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ETV6-PRDM16
FusionPDB ID: 27741
FusionGDB2.0 ID: 27741
HgeneTgene
Gene symbol

ETV6

PRDM16

Gene ID

2120

63976

Gene nameETS variant transcription factor 6PR/SET domain 16
SynonymsTEL|TEL/ABL|THC5CMD1LL|KMT8F|LVNC8|MEL1|PFM13
Cytomap

12p13.2

1p36.32

Type of geneprotein-codingprotein-coding
Descriptiontranscription factor ETV6ETS translocation variant 6ETS variant 6ETS-related protein Tel1TEL1 oncogeneets variant gene 6 (TEL oncogene)histone-lysine N-methyltransferase PRDM16MDS1/EVI1-like gene 1PR domain 16PR domain containing 16PR domain zinc finger protein 16transcription factor MEL1
Modification date2020031320200313
UniProtAcc

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 idsENST00000396373, ENST00000544715, 
ENST00000512462, ENST00000270722, 
ENST00000378391, ENST00000378398, 
ENST00000441472, ENST00000442529, 
ENST00000511072, ENST00000514189, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score59 X 37 X 25=545759 X 8 X 7=504
# samples 589
** MAII scorelog2(58/54575*10)=-6.55604351475058
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/504*10)=-2.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ETV6 [Title/Abstract] AND PRDM16 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ETV6 [Title/Abstract] AND PRDM16 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ETV6(12006497)-PRDM16(3102687), # samples:2
Anticipated loss of major functional domain due to fusion event.ETV6-PRDM16 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.
ETV6-PRDM16 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.
ETV6-PRDM16 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.
ETV6-PRDM16 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
HgeneETV6

GO:0000122

negative regulation of transcription by RNA polymerase II

10514502

TgenePRDM16

GO:0000122

negative regulation of transcription by RNA polymerase II

19049980

TgenePRDM16

GO:0030512

negative regulation of transforming growth factor beta receptor signaling pathway

14656887

TgenePRDM16

GO:0045892

negative regulation of transcription, DNA-templated

12816872

TgenePRDM16

GO:0045893

positive regulation of transcription, DNA-templated

25578880



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/chr12:12006497/chr1:3102687)
- 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 ETV6 (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 PRDM16 (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)
ENST00000396373ETV6chr1212006497ENST00000511072PRDM16chr13102687489073727442361320
ENST00000396373ETV6chr1212006497ENST00000442529PRDM16chr13102687927973727444701398
ENST00000396373ETV6chr1212006497ENST00000378398PRDM16chr13102687933973727445301418
ENST00000396373ETV6chr1212006497ENST00000441472PRDM16chr13102687933673727445271417
ENST00000396373ETV6chr1212006497ENST00000378391PRDM16chr13102687608473727444731399
ENST00000396373ETV6chr1212006497ENST00000514189PRDM16chr13102687488773727442331319
ENST00000396373ETV6chr1212006497ENST00000270722PRDM16chr13102687934173727445301418

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
ENST00000396373ENST00000511072ETV6chr1212006497PRDM16chr131026870.0024824270.9975176
ENST00000396373ENST00000442529ETV6chr1212006497PRDM16chr131026870.0007021340.99929786
ENST00000396373ENST00000378398ETV6chr1212006497PRDM16chr131026870.0004928020.9995072
ENST00000396373ENST00000441472ETV6chr1212006497PRDM16chr131026870.0004950940.9995049
ENST00000396373ENST00000378391ETV6chr1212006497PRDM16chr131026870.0010749230.99892503
ENST00000396373ENST00000514189ETV6chr1212006497PRDM16chr131026870.0015323620.9984676
ENST00000396373ENST00000270722ETV6chr1212006497PRDM16chr131026870.0008810490.999119

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 ETV6-PRDM16

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ETV6chr1212006497PRDM16chr13102687737154TQPEVILHQNHEEGDGDVVNNMYEPN

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Potential FusionNeoAntigen Information of ETV6-PRDM16 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.
ETV6-PRDM16_12006497_3102687.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)
ETV6-PRDM16chr1212006497chr13102687737HLA-B39:08HEEGDGDVV0.25040.81251019
ETV6-PRDM16chr1212006497chr13102687737HLA-B39:05NHEEGDGDVV0.93050.7217919
ETV6-PRDM16chr1212006497chr13102687737HLA-B39:11NHEEGDGDV0.37060.56918
ETV6-PRDM16chr1212006497chr13102687737HLA-B39:11NHEEGDGDVV0.8460.6659919

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Potential FusionNeoAntigen Information of ETV6-PRDM16 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.
ETV6-PRDM16_12006497_3102687.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)
ETV6-PRDM16chr1212006497chr13102687737DRB1-0437QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-0437TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-0437PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB1-0473QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-0810QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-0810TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-0812QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-0812TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1304QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1304TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1332QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1332TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1332PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB1-1338QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1343QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1348QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1348TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1348PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB1-1365QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1375QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1393QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1393TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1416QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1416TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1437QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1457QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB1-1457TQPEVILHQNHEEGD015
ETV6-PRDM16chr1212006497chr13102687737DRB1-1457PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB1-1512QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0101PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0101QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0103PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0103QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0104PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0104QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0106PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0106QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0107PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0107QPEVILHQNHEEGDG116
ETV6-PRDM16chr1212006497chr13102687737DRB4-0108PEVILHQNHEEGDGD217
ETV6-PRDM16chr1212006497chr13102687737DRB4-0108QPEVILHQNHEEGDG116

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Fusion breakpoint peptide structures of ETV6-PRDM16

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
5063LHQNHEEGDGDVVNETV6PRDM16chr1212006497chr13102687737

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ETV6-PRDM16

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-B14:023BVN5063LHQNHEEGDGDVVN-7.02924-7.14264
HLA-B14:023BVN5063LHQNHEEGDGDVVN-3.38077-4.41607
HLA-B52:013W395063LHQNHEEGDGDVVN-6.41355-6.52695
HLA-B52:013W395063LHQNHEEGDGDVVN-4.44188-5.47718
HLA-A24:025HGA5063LHQNHEEGDGDVVN-7.76595-8.80125
HLA-A24:025HGA5063LHQNHEEGDGDVVN-7.30892-7.42232
HLA-B44:053DX85063LHQNHEEGDGDVVN-5.65486-5.76826
HLA-B44:053DX85063LHQNHEEGDGDVVN-2.95775-3.99305

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Vaccine Design for the FusionNeoAntigens of ETV6-PRDM16

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
ETV6-PRDM16chr1212006497chr131026871019HEEGDGDVVATGAAGAAGGTGACGGTGACGTTGTAA
ETV6-PRDM16chr1212006497chr13102687918NHEEGDGDVACCATGAAGAAGGTGACGGTGACGTTG
ETV6-PRDM16chr1212006497chr13102687919NHEEGDGDVVACCATGAAGAAGGTGACGGTGACGTTGTAA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ETV6-PRDM16chr1212006497chr13102687015TQPEVILHQNHEEGDCACAGCCGGAGGTCATACTGCATCAGAACCATGAAGAAGGTGACG
ETV6-PRDM16chr1212006497chr13102687116QPEVILHQNHEEGDGAGCCGGAGGTCATACTGCATCAGAACCATGAAGAAGGTGACGGTG
ETV6-PRDM16chr1212006497chr13102687217PEVILHQNHEEGDGDCGGAGGTCATACTGCATCAGAACCATGAAGAAGGTGACGGTGACG

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Information of the samples that have these potential fusion neoantigens of ETV6-PRDM16

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
acute myeloid leukemiaETV6-PRDM16chr1212006497ENST00000396373chr13102687ENST00000270722FR719953
N/AETV6-PRDM16chr1212006497ENST00000396373chr13102687ENST00000270722FR719953

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Potential target of CAR-T therapy development for ETV6-PRDM16

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 ETV6-PRDM16

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 ETV6-PRDM16

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
HgeneETV6C4015537THROMBOCYTOPENIA 54CTD_human;GENOMICS_ENGLAND;UNIPROT
HgeneETV6C0023485Precursor B-Cell Lymphoblastic Leukemia-Lymphoma3CTD_human
HgeneETV6C0040034Thrombocytopenia3CTD_human;GENOMICS_ENGLAND
HgeneETV6C0023480Leukemia, Myelomonocytic, Chronic2ORPHANET
HgeneETV6C1332965Congenital Mesoblastic Nephroma2ORPHANET
HgeneETV6C0006413Burkitt Lymphoma1ORPHANET
HgeneETV6C0013146Drug abuse1CTD_human
HgeneETV6C0013170Drug habituation1CTD_human
HgeneETV6C0013222Drug Use Disorders1CTD_human
HgeneETV6C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
HgeneETV6C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
HgeneETV6C0023467Leukemia, Myelocytic, Acute1CGI;CTD_human;GENOMICS_ENGLAND
HgeneETV6C0029231Organic Mental Disorders, Substance-Induced1CTD_human
HgeneETV6C0038580Substance Dependence1CTD_human
HgeneETV6C0038586Substance Use Disorders1CTD_human
HgeneETV6C0087031Juvenile-Onset Still Disease1CTD_human
HgeneETV6C0236969Substance-Related Disorders1CTD_human
HgeneETV6C0238463Papillary thyroid carcinoma1ORPHANET
HgeneETV6C0376544Hematopoietic Neoplasms1CTD_human
HgeneETV6C0376545Hematologic Neoplasms1CTD_human
HgeneETV6C0740858Substance abuse problem1CTD_human
HgeneETV6C1292769Precursor B-cell lymphoblastic leukemia1ORPHANET
HgeneETV6C1510472Drug Dependence1CTD_human
HgeneETV6C1832388Platelet Disorder, Familial, with Associated Myeloid Malignancy1ORPHANET
HgeneETV6C1838656Macrocytosis, Familial1CTD_human
HgeneETV6C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
HgeneETV6C3495559Juvenile arthritis1CTD_human
HgeneETV6C3714758Juvenile psoriatic arthritis1CTD_human
HgeneETV6C4316881Prescription Drug Abuse1CTD_human
HgeneETV6C4552091Polyarthritis, Juvenile, Rheumatoid Factor Negative1CTD_human
HgeneETV6C4704862Polyarthritis, Juvenile, Rheumatoid Factor Positive1CTD_human