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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:NSD1-FGF18

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NSD1-FGF18
FusionPDB ID: 60419
FusionGDB2.0 ID: 60419
HgeneTgene
Gene symbol

NSD1

FGF18

Gene ID

64324

8817

Gene namenuclear receptor binding SET domain protein 1fibroblast growth factor 18
SynonymsARA267|KMT3B|SOTOS|SOTOS1|STOFGF-18|ZFGF5
Cytomap

5q35.3

5q35.1

Type of geneprotein-codingprotein-coding
Descriptionhistone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specificH3-K36-HMTaseH4-K20-HMTaseNR-binding SET domain-containing proteinandrogen receptor coactivator 267 kDa proteinandrogen receptor-associated coregulator 267androgen receptor-asfibroblast growth factor 18
Modification date2020032120200315
UniProtAcc..
Ensembl transtripts involved in fusion geneENST idsENST00000347982, ENST00000354179, 
ENST00000361032, ENST00000439151, 
ENST00000511258, 
ENST00000274625, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 14 X 17=54746 X 5 X 4=120
# samples 375
** MAII scorelog2(37/5474*10)=-3.88699825884864
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(5/120*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NSD1 [Title/Abstract] AND FGF18 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NSD1 [Title/Abstract] AND FGF18 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NSD1(176684152)-FGF18(170876151), # samples:2
Anticipated loss of major functional domain due to fusion event.NSD1-FGF18 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.
NSD1-FGF18 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.
NSD1-FGF18 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.
NSD1-FGF18 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
HgeneNSD1

GO:0045893

positive regulation of transcription, DNA-templated

11509567

TgeneFGF18

GO:0001936

regulation of endothelial cell proliferation

16756958

TgeneFGF18

GO:0043406

positive regulation of MAP kinase activity

16756958

TgeneFGF18

GO:1903670

regulation of sprouting angiogenesis

16756958

TgeneFGF18

GO:2000546

positive regulation of endothelial cell chemotaxis to fibroblast growth factor

16756958



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/chr5:176684152/chr5:170876151)
- 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 NSD1 (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 FGF18 (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)
ENST00000354179NSD1chr5176684152+ENST00000274625FGF18chr5170876151+5511431916046921510
ENST00000439151NSD1chr5176684152+ENST00000274625FGF18chr5170876151+620350114553841779
ENST00000347982NSD1chr5176684152+ENST00000274625FGF18chr5170876151+5452426010146331510
ENST00000361032NSD1chr5176684152+ENST00000274625FGF18chr5170876151+58494657050301676

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
ENST00000354179ENST00000274625NSD1chr5176684152+FGF18chr5170876151+0.0003116340.9996884
ENST00000439151ENST00000274625NSD1chr5176684152+FGF18chr5170876151+0.0002894590.9997105
ENST00000347982ENST00000274625NSD1chr5176684152+FGF18chr5170876151+0.0002929840.99970704
ENST00000361032ENST00000274625NSD1chr5176684152+FGF18chr5170876151+0.0002815030.9997185

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 NSD1-FGF18

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NSD1chr5176684152FGF18chr517087615142601381HICITCHAANPANVSASKAQLLVETD
NSD1chr5176684152FGF18chr517087615143191381HICITCHAANPANVSASKAQLLVETD
NSD1chr5176684152FGF18chr517087615146571547HICITCHAANPANVSASKAQLLVETD
NSD1chr5176684152FGF18chr517087615150111650HICITCHAANPANVSASKAQLLVETD

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Potential FusionNeoAntigen Information of NSD1-FGF18 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.
NSD1-FGF18_176684152_170876151.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)
NSD1-FGF18chr5176684152chr51708761514260HLA-A30:08AANPANVSA0.48770.7125716

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Potential FusionNeoAntigen Information of NSD1-FGF18 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.
NSD1-FGF18_176684152_170876151.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)
NSD1-FGF18chr5176684152chr51708761514260DRB1-0102PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0701PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0701NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0701ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0703PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0703NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0703ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0704PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0704NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0704ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0705PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0705NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0705ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0706PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0706NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0706ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0707PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0707NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0707ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0708PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0708NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0708ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0709PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0709NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0711PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0711NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0712PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0712NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0712ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0713PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0713NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0713ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0714PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0714NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0714ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0715PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0715NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0715ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0716PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0716NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0716ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0717PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0717NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0717ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0719PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0719NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0719ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0901PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0901NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0904PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0904NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0904ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0905PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0905NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0906PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0906NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0906ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0907PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0907NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-0907ANPANVSASKAQLLV823
NSD1-FGF18chr5176684152chr51708761514260DRB1-0909PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-0909NPANVSASKAQLLVE924
NSD1-FGF18chr5176684152chr51708761514260DRB1-1439PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB1-1525PANVSASKAQLLVET1025
NSD1-FGF18chr5176684152chr51708761514260DRB3-0301PANVSASKAQLLVET1025

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Fusion breakpoint peptide structures of NSD1-FGF18

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
3262HAANPANVSASKAQNSD1FGF18chr5176684152chr51708761514260

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NSD1-FGF18

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-B14:023BVN3262HAANPANVSASKAQ-7.9962-8.1096
HLA-B14:023BVN3262HAANPANVSASKAQ-5.70842-6.74372
HLA-B52:013W393262HAANPANVSASKAQ-6.83737-6.95077
HLA-B52:013W393262HAANPANVSASKAQ-4.4836-5.5189
HLA-A11:014UQ23262HAANPANVSASKAQ-10.0067-10.1201
HLA-A11:014UQ23262HAANPANVSASKAQ-9.03915-10.0745
HLA-A24:025HGA3262HAANPANVSASKAQ-6.56204-6.67544
HLA-A24:025HGA3262HAANPANVSASKAQ-5.42271-6.45801
HLA-B44:053DX83262HAANPANVSASKAQ-7.85648-8.89178
HLA-B44:053DX83262HAANPANVSASKAQ-5.3978-5.5112
HLA-A02:016TDR3262HAANPANVSASKAQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of NSD1-FGF18

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
NSD1-FGF18chr5176684152chr5170876151716AANPANVSAATGTTTCTGCATCTAAAGCCCAGCTCC

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
NSD1-FGF18chr5176684152chr51708761511025PANVSASKAQLLVETCATCTAAAGCCCAGCTCCTAGTGGAGACAGACACCTTCGGTAGTC
NSD1-FGF18chr5176684152chr5170876151823ANPANVSASKAQLLVTTTCTGCATCTAAAGCCCAGCTCCTAGTGGAGACAGACACCTTCG
NSD1-FGF18chr5176684152chr5170876151924NPANVSASKAQLLVECTGCATCTAAAGCCCAGCTCCTAGTGGAGACAGACACCTTCGGTA

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Information of the samples that have these potential fusion neoantigens of NSD1-FGF18

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
SARCNSD1-FGF18chr5176684152ENST00000347982chr5170876151ENST00000274625TCGA-DX-AB3A-01A

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Potential target of CAR-T therapy development for NSD1-FGF18

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 NSD1-FGF18

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 NSD1-FGF18

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