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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:TNRC18-PRDM16

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TNRC18-PRDM16
FusionPDB ID: 92836
FusionGDB2.0 ID: 92836
HgeneTgene
Gene symbol

TNRC18

PRDM16

Gene ID

84629

63976

Gene nametrinucleotide repeat containing 18PR/SET domain 16
SynonymsCAGL79|TNRC18ACMD1LL|KMT8F|LVNC8|MEL1|PFM13
Cytomap

7p22.1

1p36.32

Type of geneprotein-codingprotein-coding
Descriptiontrinucleotide repeat-containing gene 18 proteinlong CAG trinucleotide repeat-containing gene 79 proteinhistone-lysine N-methyltransferase PRDM16MDS1/EVI1-like gene 1PR domain 16PR domain containing 16PR domain zinc finger protein 16transcription factor MEL1
Modification date2020031320200313
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000399537, ENST00000430969, 
ENST00000399434, 
ENST00000512462, 
ENST00000270722, ENST00000378391, 
ENST00000378398, ENST00000441472, 
ENST00000442529, ENST00000511072, 
ENST00000514189, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 26 X 11=62929 X 8 X 7=504
# samples 399
** MAII scorelog2(39/6292*10)=-4.01197264166608
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: TNRC18 [Title/Abstract] AND PRDM16 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TNRC18 [Title/Abstract] AND PRDM16 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TNRC18(5460691)-PRDM16(3301716), # samples:1
Anticipated loss of major functional domain due to fusion event.TNRC18-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.
TNRC18-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.
TNRC18-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.
TNRC18-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
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/chr7:5460691/chr1:3301716)
- 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 TNRC18 (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)
ENST00000399537TNRC18chr75460691-ENST00000511072PRDM16chr13301716+428853655136341027
ENST00000399537TNRC18chr75460691-ENST00000442529PRDM16chr13301716+867753654838681106
ENST00000399537TNRC18chr75460691-ENST00000378398PRDM16chr13301716+873753654839281126
ENST00000399537TNRC18chr75460691-ENST00000441472PRDM16chr13301716+873453654839251125
ENST00000399537TNRC18chr75460691-ENST00000378391PRDM16chr13301716+548253654838711107
ENST00000399537TNRC18chr75460691-ENST00000514189PRDM16chr13301716+428553655136311026
ENST00000399537TNRC18chr75460691-ENST00000270722PRDM16chr13301716+873953654839281126
ENST00000430969TNRC18chr75460691-ENST00000511072PRDM16chr13301716+428853655136341027
ENST00000430969TNRC18chr75460691-ENST00000442529PRDM16chr13301716+867753654838681106
ENST00000430969TNRC18chr75460691-ENST00000378398PRDM16chr13301716+873753654839281126
ENST00000430969TNRC18chr75460691-ENST00000441472PRDM16chr13301716+873453654839251125
ENST00000430969TNRC18chr75460691-ENST00000378391PRDM16chr13301716+548253654838711107
ENST00000430969TNRC18chr75460691-ENST00000514189PRDM16chr13301716+428553655136311026
ENST00000430969TNRC18chr75460691-ENST00000270722PRDM16chr13301716+873953654839281126

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
ENST00000399537ENST00000511072TNRC18chr75460691-PRDM16chr13301716+0.0048974030.9951025
ENST00000399537ENST00000442529TNRC18chr75460691-PRDM16chr13301716+0.0010820470.99891794
ENST00000399537ENST00000378398TNRC18chr75460691-PRDM16chr13301716+0.000774860.99922514
ENST00000399537ENST00000441472TNRC18chr75460691-PRDM16chr13301716+0.0007791840.99922085
ENST00000399537ENST00000378391TNRC18chr75460691-PRDM16chr13301716+0.0018654220.9981345
ENST00000399537ENST00000514189TNRC18chr75460691-PRDM16chr13301716+0.004610190.9953898
ENST00000399537ENST00000270722TNRC18chr75460691-PRDM16chr13301716+0.0013708170.9986292
ENST00000430969ENST00000511072TNRC18chr75460691-PRDM16chr13301716+0.0048974030.9951025
ENST00000430969ENST00000442529TNRC18chr75460691-PRDM16chr13301716+0.0010820470.99891794
ENST00000430969ENST00000378398TNRC18chr75460691-PRDM16chr13301716+0.000774860.99922514
ENST00000430969ENST00000441472TNRC18chr75460691-PRDM16chr13301716+0.0007791840.99922085
ENST00000430969ENST00000378391TNRC18chr75460691-PRDM16chr13301716+0.0018654220.9981345
ENST00000430969ENST00000514189TNRC18chr75460691-PRDM16chr13301716+0.004610190.9953898
ENST00000430969ENST00000270722TNRC18chr75460691-PRDM16chr13301716+0.0013708170.9986292

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 TNRC18-PRDM16

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

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Potential FusionNeoAntigen Information of TNRC18-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.

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)

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Potential FusionNeoAntigen Information of TNRC18-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.

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 TNRC18-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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TNRC18-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

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Vaccine Design for the FusionNeoAntigens of TNRC18-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

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 TNRC18-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

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Potential target of CAR-T therapy development for TNRC18-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 TNRC18-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 TNRC18-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