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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:MBP-PTPN2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MBP-PTPN2
FusionPDB ID: 52079
FusionGDB2.0 ID: 52079
HgeneTgene
Gene symbol

MBP

PTPN2

Gene ID

5553

5771

Gene nameproteoglycan 2, pro eosinophil major basic proteinprotein tyrosine phosphatase non-receptor type 2
SynonymsBMPG|MBP|MBP1|proMBPPTN2|PTPT|TC-PTP|TCELLPTP|TCPTP
Cytomap

11q12.1

18p11.21

Type of geneprotein-codingprotein-coding
Descriptionbone marrow proteoglycaneosinophil granule major basic proteineosinophil major basic proteinnatural killer cell activatorproteoglycan 2 preproproteinproteoglycan 2, bone marrow (natural killer cell activator, eosinophil granule major basic protein)tyrosine-protein phosphatase non-receptor type 2T-cell protein tyrosine phosphatase
Modification date2020031320200329
UniProtAcc

P02686

Main function of 5'-partner protein: FUNCTION: The classic group of MBP isoforms (isoform 4-isoform 14) are with PLP the most abundant protein components of the myelin membrane in the CNS. They have a role in both its formation and stabilization. The smaller isoforms might have an important role in remyelination of denuded axons in multiple sclerosis. The non-classic group of MBP isoforms (isoform 1-isoform 3/Golli-MBPs) may preferentially have a role in the early developing brain long before myelination, maybe as components of transcriptional complexes, and may also be involved in signaling pathways in T-cells and neural cells. Differential splicing events combined with optional post-translational modifications give a wide spectrum of isomers, with each of them potentially having a specialized function. Induces T-cell proliferation. {ECO:0000269|PubMed:8544862}.
.
Ensembl transtripts involved in fusion geneENST idsENST00000355994, ENST00000397860, 
ENST00000397863, ENST00000579129, 
ENST00000580402, ENST00000487778, 
ENST00000354542, ENST00000359645, 
ENST00000382582, ENST00000397865, 
ENST00000397866, ENST00000397869, 
ENST00000397875, ENST00000526111, 
ENST00000527041, ENST00000528160, 
ENST00000578193, 
ENST00000589086, 
ENST00000591497, ENST00000309660, 
ENST00000327283, ENST00000353319, 
ENST00000591115, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score26 X 20 X 7=36408 X 9 X 5=360
# samples 269
** MAII scorelog2(26/3640*10)=-3.8073549220576
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/360*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MBP [Title/Abstract] AND PTPN2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MBP [Title/Abstract] AND PTPN2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MBP(74817167)-PTPN2(12802150), # samples:1
Anticipated loss of major functional domain due to fusion event.MBP-PTPN2 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.
MBP-PTPN2 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.
MBP-PTPN2 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.
MBP-PTPN2 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.
MBP-PTPN2 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


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/chr18:74817167/chr18:12802150)
- 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 MBP (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 PTPN2 (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)
ENST00000580402MBPchr1874817167-ENST00000327283PTPN2chr1812802150-702510356118
ENST00000580402MBPchr1874817167-ENST00000591115PTPN2chr1812802150-699510356118
ENST00000580402MBPchr1874817167-ENST00000353319PTPN2chr1812802150-59551025484
ENST00000580402MBPchr1874817167-ENST00000309660PTPN2chr1812802150-2566510440146

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
ENST00000580402ENST00000327283MBPchr1874817167-PTPN2chr1812802150-0.0274242440.9725758
ENST00000580402ENST00000591115MBPchr1874817167-PTPN2chr1812802150-0.0279640540.97203594
ENST00000580402ENST00000353319MBPchr1874817167-PTPN2chr1812802150-0.0438678080.95613223
ENST00000580402ENST00000309660MBPchr1874817167-PTPN2chr1812802150-0.0104511050.9895489

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 MBP-PTPN2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MBPchr1874817167PTPN2chr18128021505117AGKRELNAEKASTKRWKELSKEDLSP

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Potential FusionNeoAntigen Information of MBP-PTPN2 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.
MBP-PTPN2_74817167_12802150.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)
MBP-PTPN2chr1874817167chr181280215051HLA-B44:03AEKASTKRW0.99940.958716
MBP-PTPN2chr1874817167chr181280215051HLA-A30:08STKRWKELSK0.99560.63291121
MBP-PTPN2chr1874817167chr181280215051HLA-B44:03NAEKASTKRW0.82430.8829616
MBP-PTPN2chr1874817167chr181280215051HLA-B44:09AEKASTKRW0.99710.5287716
MBP-PTPN2chr1874817167chr181280215051HLA-B44:10AEKASTKRW0.76340.6383716
MBP-PTPN2chr1874817167chr181280215051HLA-B44:07AEKASTKRW0.99940.958716
MBP-PTPN2chr1874817167chr181280215051HLA-B44:13AEKASTKRW0.99940.958716
MBP-PTPN2chr1874817167chr181280215051HLA-B44:26AEKASTKRW0.99940.958716
MBP-PTPN2chr1874817167chr181280215051HLA-C16:02ASTKRWKEL0.64430.99631019
MBP-PTPN2chr1874817167chr181280215051HLA-C16:01ASTKRWKEL0.47760.98631019
MBP-PTPN2chr1874817167chr181280215051HLA-B15:24AEKASTKRW0.20180.932716
MBP-PTPN2chr1874817167chr181280215051HLA-B15:53AEKASTKRW0.01860.8608716
MBP-PTPN2chr1874817167chr181280215051HLA-A30:01STKRWKELSK0.99450.7321121
MBP-PTPN2chr1874817167chr181280215051HLA-B44:07NAEKASTKRW0.82430.8829616
MBP-PTPN2chr1874817167chr181280215051HLA-B44:26NAEKASTKRW0.82430.8829616
MBP-PTPN2chr1874817167chr181280215051HLA-B44:13NAEKASTKRW0.82430.8829616

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Potential FusionNeoAntigen Information of MBP-PTPN2 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.
MBP-PTPN2_74817167_12802150.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)
MBP-PTPN2chr1874817167chr181280215051DRB5-0101KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0101GKRELNAEKASTKRW116
MBP-PTPN2chr1874817167chr181280215051DRB5-0104KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0105KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0105GKRELNAEKASTKRW116
MBP-PTPN2chr1874817167chr181280215051DRB5-0111KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0113KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0113GKRELNAEKASTKRW116
MBP-PTPN2chr1874817167chr181280215051DRB5-0114KRELNAEKASTKRWK217
MBP-PTPN2chr1874817167chr181280215051DRB5-0114GKRELNAEKASTKRW116

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Fusion breakpoint peptide structures of MBP-PTPN2

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
6075NAEKASTKRWKELSMBPPTPN2chr1874817167chr181280215051

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MBP-PTPN2

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-B52:013W396075NAEKASTKRWKELS-5.52507-5.52507
HLA-B44:053DX86075NAEKASTKRWKELS-6.78894-6.78894
HLA-A02:016TDR6075NAEKASTKRWKELS-3.48608-3.48608

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Vaccine Design for the FusionNeoAntigens of MBP-PTPN2

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
MBP-PTPN2chr1874817167chr18128021501019ASTKRWKELGCCAGTACGAAACGATGGAAAGAACTT
MBP-PTPN2chr1874817167chr18128021501121STKRWKELSKAGTACGAAACGATGGAAAGAACTTTCTAAG
MBP-PTPN2chr1874817167chr1812802150616NAEKASTKRWAATGCCGAGAAGGCCAGTACGAAACGATGG
MBP-PTPN2chr1874817167chr1812802150716AEKASTKRWGCCGAGAAGGCCAGTACGAAACGATGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MBP-PTPN2chr1874817167chr1812802150116GKRELNAEKASTKRWGGCAAACGAGAATTAAATGCCGAGAAGGCCAGTACGAAACGATGG
MBP-PTPN2chr1874817167chr1812802150217KRELNAEKASTKRWKAAACGAGAATTAAATGCCGAGAAGGCCAGTACGAAACGATGGAAA

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Information of the samples that have these potential fusion neoantigens of MBP-PTPN2

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
STADMBP-PTPN2chr1874817167ENST00000580402chr1812802150ENST00000309660TCGA-BR-8364-01A

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Potential target of CAR-T therapy development for MBP-PTPN2

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 MBP-PTPN2

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 MBP-PTPN2

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