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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:NOP2-TCF3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: NOP2-TCF3
FusionPDB ID: 59634
FusionGDB2.0 ID: 59634
HgeneTgene
Gene symbol

NOP2

TCF3

Gene ID

4839

83439

Gene nameNOP2 nucleolar proteintranscription factor 7 like 1
SynonymsNOL1|NOP120|NSUN1|p120TCF-3|TCF3
Cytomap

12p13.31

2p11.2

Type of geneprotein-codingprotein-coding
Descriptionprobable 28S rRNA (cytosine(4447)-C(5))-methyltransferaseNOL1/NOP2/Sun domain family, member 1NOP2 nucleolar protein homolognucleolar protein 1, 120kDanucleolar protein 2 homologproliferating-cell nucleolar antigen p120proliferation-associated nucletranscription factor 7-like 1HMG box transcription factor 3transcription factor 7-like 1 (T-cell specific, HMG-box)
Modification date2020031320200313
UniProtAcc

P46087

Main function of 5'-partner protein: FUNCTION: Involved in ribosomal large subunit assembly (PubMed:24120868). S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C(5) position of cytosine 4447 in 28S rRNA (Probable). May play a role in the regulation of the cell cycle and the increased nucleolar activity that is associated with the cell proliferation (Probable). {ECO:0000269|PubMed:24120868, ECO:0000305, ECO:0000305|PubMed:23913415}.

TFPT

Main function of 5'-partner protein: 253
Ensembl transtripts involved in fusion geneENST idsENST00000542015, ENST00000322166, 
ENST00000382421, ENST00000541778, 
ENST00000399466, ENST00000537442, 
ENST00000545200, ENST00000540228, 
ENST00000545915, 
ENST00000262965, 
ENST00000344749, ENST00000395423, 
ENST00000453954, ENST00000588136, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 6 X 5=12012 X 15 X 8=1440
# samples 617
** MAII scorelog2(6/120*10)=-1
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/1440*10)=-3.08246216019197
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: NOP2 [Title/Abstract] AND TCF3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: NOP2 [Title/Abstract] AND TCF3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)NOP2(6669283)-TCF3(1621017), # samples:1
NOP2(6669263)-TCF3(1621194), # samples:1
NOP2(6668949)-TCF3(1621522), # samples:1
Anticipated loss of major functional domain due to fusion event.NOP2-TCF3 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.
NOP2-TCF3 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.
NOP2-TCF3 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.
NOP2-TCF3 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.
NOP2-TCF3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
NOP2-TCF3 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
NOP2-TCF3 seems lost the major protein functional domain in Tgene partner, which is a transcription factor due to the frame-shifted ORF.
NOP2-TCF3 seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor due to the frame-shifted 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
HgeneNOP2

GO:0008284

positive regulation of cell proliferation

1394192



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/chr12:6669283/chr19:1621017)
- 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 NOP2 (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 TCF3 (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)
ENST00000537442NOP2chr126669263-ENST00000344749TCF3chr191621194-52471833442833929
ENST00000537442NOP2chr126669263-ENST00000262965TCF3chr191621194-52561833442842932
ENST00000537442NOP2chr126669263-ENST00000453954TCF3chr191621194-37851833442830928
ENST00000537442NOP2chr126669263-ENST00000395423TCF3chr191621194-34661833443007987
ENST00000537442NOP2chr126669263-ENST00000588136TCF3chr191621194-29581833442833929
ENST00000545200NOP2chr126669263-ENST00000344749TCF3chr191621194-52711857802857925
ENST00000545200NOP2chr126669263-ENST00000262965TCF3chr191621194-52801857802866928
ENST00000545200NOP2chr126669263-ENST00000453954TCF3chr191621194-38091857802854924
ENST00000545200NOP2chr126669263-ENST00000395423TCF3chr191621194-34901857803031983
ENST00000545200NOP2chr126669263-ENST00000588136TCF3chr191621194-29821857802857925
ENST00000399466NOP2chr126669263-ENST00000344749TCF3chr191621194-53431929772929950
ENST00000399466NOP2chr126669263-ENST00000262965TCF3chr191621194-53521929772938953
ENST00000399466NOP2chr126669263-ENST00000453954TCF3chr191621194-38811929772926949
ENST00000399466NOP2chr126669263-ENST00000395423TCF3chr191621194-356219297731031008
ENST00000399466NOP2chr126669263-ENST00000588136TCF3chr191621194-30541929772929950

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
ENST00000537442ENST00000344749NOP2chr126669263-TCF3chr191621194-0.0014171780.99858284
ENST00000537442ENST00000262965NOP2chr126669263-TCF3chr191621194-0.0015021650.99849784
ENST00000537442ENST00000453954NOP2chr126669263-TCF3chr191621194-0.002438710.99756134
ENST00000537442ENST00000395423NOP2chr126669263-TCF3chr191621194-0.0024766140.99752337
ENST00000537442ENST00000588136NOP2chr126669263-TCF3chr191621194-0.0041844250.9958156
ENST00000545200ENST00000344749NOP2chr126669263-TCF3chr191621194-0.0021846990.99781525
ENST00000545200ENST00000262965NOP2chr126669263-TCF3chr191621194-0.0022596240.9977404
ENST00000545200ENST00000453954NOP2chr126669263-TCF3chr191621194-0.0038158060.9961842
ENST00000545200ENST00000395423NOP2chr126669263-TCF3chr191621194-0.0035697730.9964302
ENST00000545200ENST00000588136NOP2chr126669263-TCF3chr191621194-0.006068890.9939312
ENST00000399466ENST00000344749NOP2chr126669263-TCF3chr191621194-0.0021538860.9978461
ENST00000399466ENST00000262965NOP2chr126669263-TCF3chr191621194-0.0022263150.9977737
ENST00000399466ENST00000453954NOP2chr126669263-TCF3chr191621194-0.0037240270.996276
ENST00000399466ENST00000395423NOP2chr126669263-TCF3chr191621194-0.003387790.99661225
ENST00000399466ENST00000588136NOP2chr126669263-TCF3chr191621194-0.005700310.99429965

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 NOP2-TCF3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
NOP2chr126669263TCF3chr1916211941833593IAKFKKFSNSIPQSQTGSRGTTAGSS
NOP2chr126669263TCF3chr1916211941857589IAKFKKFSNSIPQSQTGSRGTTAGSS
NOP2chr126669263TCF3chr1916211941929614IAKFKKFSNSIPQSQTGSRGTTAGSS

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Potential FusionNeoAntigen Information of NOP2-TCF3 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 NOP2-TCF3 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.
NOP2-TCF3_6669263_1621194.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)
NOP2-TCF3chr126669263chr1916211941929DRB1-0902FKKFSNSIPQSQTGS318
NOP2-TCF3chr126669263chr1916211941929DRB1-1502IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1508IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1511IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1514IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1519IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1526IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1530IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1531IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1538IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1539IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1544IAKFKKFSNSIPQSQ015
NOP2-TCF3chr126669263chr1916211941929DRB1-1547IAKFKKFSNSIPQSQ015

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Fusion breakpoint peptide structures of NOP2-TCF3

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 NOP2-TCF3

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 NOP2-TCF3

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
NOP2-TCF3chr126669263chr191621194015IAKFKKFSNSIPQSQTCAAGAAATTTTCCAATTCTATCCCTCAGTCCCAGACAGGCTCCC
NOP2-TCF3chr126669263chr191621194318FKKFSNSIPQSQTGSTTTCCAATTCTATCCCTCAGTCCCAGACAGGCTCCCGAGGGACCA

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Information of the samples that have these potential fusion neoantigens of NOP2-TCF3

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 NOP2-TCF3

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 NOP2-TCF3

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 NOP2-TCF3

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
TgeneTCF3C0006413Burkitt Lymphoma2CTD_human;ORPHANET
TgeneTCF3C0343640African Burkitt's lymphoma2CTD_human
TgeneTCF3C4721444Burkitt Leukemia2CTD_human
TgeneTCF3C0001768Agammaglobulinemia1CTD_human;GENOMICS_ENGLAND
TgeneTCF3C0023452Childhood Acute Lymphoblastic Leukemia1CTD_human
TgeneTCF3C0023453L2 Acute Lymphoblastic Leukemia1CTD_human
TgeneTCF3C0023485Precursor B-Cell Lymphoblastic Leukemia-Lymphoma1CTD_human
TgeneTCF3C0398686Primary immune deficiency disorder1GENOMICS_ENGLAND
TgeneTCF3C1832241Agammaglobulinemia, non-Bruton type1ORPHANET
TgeneTCF3C1844383Recurrent bacterial infection1GENOMICS_ENGLAND
TgeneTCF3C1961102Precursor Cell Lymphoblastic Leukemia Lymphoma1CTD_human
TgeneTCF3C4310786AGAMMAGLOBULINEMIA 8, AUTOSOMAL DOMINANT1GENOMICS_ENGLAND