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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-NFATC2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NSD1-NFATC2
FusionPDB ID: 60429
FusionGDB2.0 ID: 60429
HgeneTgene
Gene symbol

NSD1

NFATC2

Gene ID

64324

4773

Gene namenuclear receptor binding SET domain protein 1nuclear factor of activated T cells 2
SynonymsARA267|KMT3B|SOTOS|SOTOS1|STONFAT1|NFATP
Cytomap

5q35.3

20q13.2

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-asnuclear factor of activated T-cells, cytoplasmic 2NF-ATc2NFAT pre-existing subunitNFAT transcription complex, preexisting componentT cell transcription factor NFAT1nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2nuclear fact
Modification date2020032120200329
UniProtAcc.

Q8NCF5

Main function of 5'-partner protein: FUNCTION: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000347982, ENST00000354179, 
ENST00000361032, ENST00000439151, 
ENST00000511258, 		ENST00000371564, 
ENST00000396009, ENST00000414705, 
ENST00000609507, ENST00000609943, 
ENST00000610033, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score23 X 14 X 17=547410 X 12 X 6=720
# samples 3712
** MAII scorelog2(37/5474*10)=-3.88699825884864
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(12/720*10)=-2.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NSD1 [Title/Abstract] AND NFATC2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NSD1 [Title/Abstract] AND NFATC2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NSD1(176675325)-NFATC2(50092197), # samples:1
Anticipated loss of major functional domain due to fusion event.NSD1-NFATC2 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-NFATC2 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-NFATC2 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-NFATC2 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

TgeneNFATC2

GO:0016477

cell migration

21871017

TgeneNFATC2

GO:0045893

positive regulation of transcription, DNA-templated

15790681

TgeneNFATC2

GO:1905064

negative regulation of vascular smooth muscle cell differentiation

23853098



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/chr5:176675325/chr20:50092197)
- 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 NFATC2 (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)
ENST00000354179NSD1chr5176675325+ENST00000371564NFATC2chr2050092197-9967399416054271755
ENST00000354179NSD1chr5176675325+ENST00000396009NFATC2chr2050092197-9879399416054391759
ENST00000354179NSD1chr5176675325+ENST00000609943NFATC2chr2050092197-8210399416054391759
ENST00000354179NSD1chr5176675325+ENST00000610033NFATC2chr2050092197-5696399416054271755
ENST00000354179NSD1chr5176675325+ENST00000414705NFATC2chr2050092197-5696399416054271755
ENST00000354179NSD1chr5176675325+ENST00000609507NFATC2chr2050092197-5696399416054271755
ENST00000439151NSD1chr5176675325+ENST00000371564NFATC2chr2050092197-1065946864561192024
ENST00000439151NSD1chr5176675325+ENST00000396009NFATC2chr2050092197-1057146864561312028
ENST00000439151NSD1chr5176675325+ENST00000609943NFATC2chr2050092197-890246864561312028
ENST00000439151NSD1chr5176675325+ENST00000610033NFATC2chr2050092197-638846864561192024
ENST00000439151NSD1chr5176675325+ENST00000414705NFATC2chr2050092197-638846864561192024
ENST00000439151NSD1chr5176675325+ENST00000609507NFATC2chr2050092197-638846864561192024
ENST00000347982NSD1chr5176675325+ENST00000371564NFATC2chr2050092197-9908393510153681755
ENST00000347982NSD1chr5176675325+ENST00000396009NFATC2chr2050092197-9820393510153801759
ENST00000347982NSD1chr5176675325+ENST00000609943NFATC2chr2050092197-8151393510153801759
ENST00000347982NSD1chr5176675325+ENST00000610033NFATC2chr2050092197-5637393510153681755
ENST00000347982NSD1chr5176675325+ENST00000414705NFATC2chr2050092197-5637393510153681755
ENST00000347982NSD1chr5176675325+ENST00000609507NFATC2chr2050092197-5637393510153681755
ENST00000361032NSD1chr5176675325+ENST00000371564NFATC2chr2050092197-103054332057651921
ENST00000361032NSD1chr5176675325+ENST00000396009NFATC2chr2050092197-102174332057771925
ENST00000361032NSD1chr5176675325+ENST00000609943NFATC2chr2050092197-85484332057771925
ENST00000361032NSD1chr5176675325+ENST00000610033NFATC2chr2050092197-60344332057651921
ENST00000361032NSD1chr5176675325+ENST00000414705NFATC2chr2050092197-60344332057651921
ENST00000361032NSD1chr5176675325+ENST00000609507NFATC2chr2050092197-60344332057651921

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
ENST00000354179ENST00000371564NSD1chr5176675325+NFATC2chr2050092197-0.000269840.99973017
ENST00000354179ENST00000396009NSD1chr5176675325+NFATC2chr2050092197-0.0004471550.9995528
ENST00000354179ENST00000609943NSD1chr5176675325+NFATC2chr2050092197-0.0005225490.99947745
ENST00000354179ENST00000610033NSD1chr5176675325+NFATC2chr2050092197-0.000582910.99941707
ENST00000354179ENST00000414705NSD1chr5176675325+NFATC2chr2050092197-0.000582910.99941707
ENST00000354179ENST00000609507NSD1chr5176675325+NFATC2chr2050092197-0.000582910.99941707
ENST00000439151ENST00000371564NSD1chr5176675325+NFATC2chr2050092197-0.0002492650.9997507
ENST00000439151ENST00000396009NSD1chr5176675325+NFATC2chr2050092197-0.0004120460.99958795
ENST00000439151ENST00000609943NSD1chr5176675325+NFATC2chr2050092197-0.0004820740.9995179
ENST00000439151ENST00000610033NSD1chr5176675325+NFATC2chr2050092197-0.0005163450.9994836
ENST00000439151ENST00000414705NSD1chr5176675325+NFATC2chr2050092197-0.0005163450.9994836
ENST00000439151ENST00000609507NSD1chr5176675325+NFATC2chr2050092197-0.0005163450.9994836
ENST00000347982ENST00000371564NSD1chr5176675325+NFATC2chr2050092197-0.0002529940.999747
ENST00000347982ENST00000396009NSD1chr5176675325+NFATC2chr2050092197-0.0004175440.99958247
ENST00000347982ENST00000609943NSD1chr5176675325+NFATC2chr2050092197-0.0004902010.9995098
ENST00000347982ENST00000610033NSD1chr5176675325+NFATC2chr2050092197-0.0005538350.9994462
ENST00000347982ENST00000414705NSD1chr5176675325+NFATC2chr2050092197-0.0005538350.9994462
ENST00000347982ENST00000609507NSD1chr5176675325+NFATC2chr2050092197-0.0005538350.9994462
ENST00000361032ENST00000371564NSD1chr5176675325+NFATC2chr2050092197-0.0002449920.99975497
ENST00000361032ENST00000396009NSD1chr5176675325+NFATC2chr2050092197-0.0004064930.99959356
ENST00000361032ENST00000609943NSD1chr5176675325+NFATC2chr2050092197-0.0004800360.99951994
ENST00000361032ENST00000610033NSD1chr5176675325+NFATC2chr2050092197-0.000531550.9994685
ENST00000361032ENST00000414705NSD1chr5176675325+NFATC2chr2050092197-0.000531550.9994685
ENST00000361032ENST00000609507NSD1chr5176675325+NFATC2chr2050092197-0.000531550.9994685

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-NFATC2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NSD1chr5176675325NFATC2chr205009219739351277ERGGGAALKENVCQLHGYMENKPLGL
NSD1chr5176675325NFATC2chr205009219739941277ERGGGAALKENVCQLHGYMENKPLGL
NSD1chr5176675325NFATC2chr205009219743321443ERGGGAALKENVCQLHGYMENKPLGL
NSD1chr5176675325NFATC2chr205009219746861546ERGGGAALKENVCQLHGYMENKPLGL

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Potential FusionNeoAntigen Information of NSD1-NFATC2 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-NFATC2_176675325_50092197.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-NFATC2chr5176675325chr20500921973935HLA-A02:13ALKENVCQL0.99520.5631615
NSD1-NFATC2chr5176675325chr20500921973935HLA-A02:38ALKENVCQL0.97540.5545615
NSD1-NFATC2chr5176675325chr20500921973935HLA-A02:21ALKENVCQL0.96310.5631615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B08:01ALKENVCQL0.78390.5248615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B08:09ALKENVCQL0.69960.5442615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B13:01ALKENVCQL0.03550.7774615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B44:03KENVCQLHGY0.99880.824818
NSD1-NFATC2chr5176675325chr20500921973935HLA-B15:04ALKENVCQL0.98720.6506615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B15:73ALKENVCQL0.98010.6629615
NSD1-NFATC2chr5176675325chr20500921973935HLA-A02:06ALKENVCQL0.96310.5631615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B15:30ALKENVCQL0.95320.7336615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B08:18ALKENVCQL0.78390.5248615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B08:12ALKENVCQL0.69220.6507615
NSD1-NFATC2chr5176675325chr20500921973935HLA-C01:03ALKENVCQL0.69060.7672615
NSD1-NFATC2chr5176675325chr20500921973935HLA-C07:04ALKENVCQL0.61970.8831615
NSD1-NFATC2chr5176675325chr20500921973935HLA-B44:26KENVCQLHGY0.99880.824818
NSD1-NFATC2chr5176675325chr20500921973935HLA-B44:13KENVCQLHGY0.99880.824818
NSD1-NFATC2chr5176675325chr20500921973935HLA-B44:07KENVCQLHGY0.99880.824818

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Potential FusionNeoAntigen Information of NSD1-NFATC2 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 NSD1-NFATC2

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
379ALKENVCQLHGYMENSD1NFATC2chr5176675325chr20500921973935

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of NSD1-NFATC2

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-B14:023BVN379ALKENVCQLHGYME-6.15818-6.27158
HLA-B14:023BVN379ALKENVCQLHGYME-3.7599-4.7952
HLA-B52:013W39379ALKENVCQLHGYME-8.09045-8.20385
HLA-B52:013W39379ALKENVCQLHGYME-5.48575-6.52105
HLA-A11:014UQ2379ALKENVCQLHGYME-6.05919-6.17259
HLA-A24:025HGA379ALKENVCQLHGYME-6.07167-6.18507
HLA-A24:025HGA379ALKENVCQLHGYME-4.48358-5.51888
HLA-B27:036PZ5379ALKENVCQLHGYME-0.729415-1.76472
HLA-B44:053DX8379ALKENVCQLHGYME-6.41695-6.53035
HLA-B44:053DX8379ALKENVCQLHGYME-3.53647-4.57177

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Vaccine Design for the FusionNeoAntigens of NSD1-NFATC2

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-NFATC2chr5176675325chr2050092197615ALKENVCQLCTCAAGGAGAATGTCTGTCAGCTCCAT
NSD1-NFATC2chr5176675325chr2050092197818KENVCQLHGYGAGAATGTCTGTCAGCTCCATGGCTACATG

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 NSD1-NFATC2

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
GBMNSD1-NFATC2chr5176675325ENST00000347982chr2050092197ENST00000371564TCGA-19-2625-01A

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Potential target of CAR-T therapy development for NSD1-NFATC2

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-NFATC2

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-NFATC2

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
TgeneNFATC2C0011860Diabetes Mellitus, Non-Insulin-Dependent1CTD_human
TgeneNFATC2C0020542Pulmonary Hypertension1CTD_human
TgeneNFATC2C0027765nervous system disorder1CTD_human