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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:MSI2-ENPP3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MSI2-ENPP3
FusionPDB ID: 55311
FusionGDB2.0 ID: 55311
HgeneTgene
Gene symbol

MSI2

ENPP3

Gene ID

124540

5169

Gene namemusashi RNA binding protein 2ectonucleotide pyrophosphatase/phosphodiesterase 3
SynonymsMSI2HB10|CD203c|NPP3|PD-IBETA|PDNP3
Cytomap

17q22

6q23.2

Type of geneprotein-codingprotein-coding
DescriptionRNA-binding protein Musashi homolog 2musashi homolog 2musashi-2ectonucleotide pyrophosphatase/phosphodiesterase family member 3dJ1005H11.3 (phosphodiesterase I/nucleotide pyrophosphatase 3)dJ914N13.3 (phosphodiesterase I/nucleotide pyrophosphatase 3)gp130RB13-6phosphodiesterase I/nucleotide pyrophosphatase 3phos
Modification date2020031320200313
UniProtAcc

Q96DH6

Main function of 5'-partner protein: FUNCTION: RNA binding protein that regulates the expression of target mRNAs at the translation level. May play a role in the proliferation and maintenance of stem cells in the central nervous system (By similarity). {ECO:0000250}.

O14638

Main function of 5'-partner protein: FUNCTION: Hydrolase that metabolizes extracellular nucleotides, including ATP, GTP, UTP and CTP (PubMed:29717535). Limits mast cell and basophil responses during inflammation and during the chronic phases of allergic responses by eliminating the extracellular ATP that functions as signaling molecule and activates basophils and mast cells and induces the release of inflammatory cytokines. Metabolizes extracellular ATP in the lumen of the small intestine, and thereby prevents ATP-induced apoptosis of intestinal plasmacytoid dendritic cells (By similarity). Has also alkaline phosphodiesterase activity (PubMed:11342463). {ECO:0000250|UniProtKB:Q6DYE8, ECO:0000269|PubMed:11342463, ECO:0000269|PubMed:29717535}.
Ensembl transtripts involved in fusion geneENST idsENST00000579505, ENST00000284073, 
ENST00000322684, ENST00000416426, 
ENST00000442934, ENST00000579180, 
ENST00000414305, ENST00000357639, 
ENST00000358229, ENST00000427148, 
ENST00000470930, ENST00000543135, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score40 X 16 X 16=102404 X 3 X 3=36
# samples 454
** MAII scorelog2(45/10240*10)=-4.50814690367033
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(4/36*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: MSI2 [Title/Abstract] AND ENPP3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MSI2 [Title/Abstract] AND ENPP3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MSI2(55607085)-ENPP3(132043367), # samples:1
Anticipated loss of major functional domain due to fusion event.MSI2-ENPP3 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.
MSI2-ENPP3 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.
MSI2-ENPP3 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.
MSI2-ENPP3 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
TgeneENPP3

GO:0006796

phosphate-containing compound metabolic process

10513816

TgeneENPP3

GO:0009143

nucleoside triphosphate catabolic process

10513816

TgeneENPP3

GO:0030505

inorganic diphosphate transport

10513816

TgeneENPP3

GO:0046034

ATP metabolic process

29717535



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/chr17:55607085/chr6:132043367)
- 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 MSI2 (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 ENPP3 (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)
ENST00000416426MSI2chr1755607085+ENST00000414305ENPP3chr6132043367+2041523931583496
ENST00000284073MSI2chr1755607085+ENST00000414305ENPP3chr6132043367+21816631791723514
ENST00000322684MSI2chr1755607085+ENST00000414305ENPP3chr6132043367+1995477351537500
ENST00000442934MSI2chr1755607085+ENST00000414305ENPP3chr6132043367+1829311401371443
ENST00000579180MSI2chr1755607085+ENST00000414305ENPP3chr6132043367+17652471051307400

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
ENST00000416426ENST00000414305MSI2chr1755607085+ENPP3chr6132043367+0.0003333740.9996667
ENST00000284073ENST00000414305MSI2chr1755607085+ENPP3chr6132043367+0.0002990910.9997009
ENST00000322684ENST00000414305MSI2chr1755607085+ENPP3chr6132043367+0.0001305850.99986935
ENST00000442934ENST00000414305MSI2chr1755607085+ENPP3chr6132043367+5.58E-050.9999442
ENST00000579180ENST00000414305MSI2chr1755607085+ENPP3chr6132043367+0.000143670.99985635

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 MSI2-ENPP3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MSI2chr1755607085ENPP3chr613204336724747AMLMFDKTTNRHRDLLRIQPAPNNGT
MSI2chr1755607085ENPP3chr613204336731190AMLMFDKTTNRHRDLLRIQPAPNNGT
MSI2chr1755607085ENPP3chr6132043367477147AMLMFDKTTNRHRDLLRIQPAPNNGT
MSI2chr1755607085ENPP3chr6132043367523143AMLMFDKTTNRHRDLLRIQPAPNNGT
MSI2chr1755607085ENPP3chr6132043367663161AMLMFDKTTNRHRDLLRIQPAPNNGT

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Potential FusionNeoAntigen Information of MSI2-ENPP3 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.
MSI2-ENPP3_55607085_132043367.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)
MSI2-ENPP3chr1755607085chr6132043367663HLA-B39:06HRDLLRIQP0.98790.73981120
MSI2-ENPP3chr1755607085chr6132043367663HLA-B73:01HRDLLRIQP0.97020.6721120
MSI2-ENPP3chr1755607085chr6132043367663HLA-B73:01HRDLLRIQPA0.9890.8111121
MSI2-ENPP3chr1755607085chr6132043367663HLA-B73:01NRHRDLLRIQP0.9940.7987920
MSI2-ENPP3chr1755607085chr6132043367663HLA-C06:08NRHRDLLRI0.85240.9492918
MSI2-ENPP3chr1755607085chr6132043367663HLA-C06:02NRHRDLLRI0.11560.9778918
MSI2-ENPP3chr1755607085chr6132043367663HLA-C06:17NRHRDLLRI0.11560.9778918

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Potential FusionNeoAntigen Information of MSI2-ENPP3 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.
MSI2-ENPP3_55607085_132043367.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)
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0301AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0303AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0313AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0318AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0320AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0322AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0326AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0328AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0330AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0332AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0334AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0336AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0342AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0344AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0346AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0348AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0350AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0352AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-0354AMLMFDKTTNRHRDL015
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1001HRDLLRIQPAPNNGT1126
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1001RHRDLLRIQPAPNNG1025
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1002HRDLLRIQPAPNNGT1126
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1002RHRDLLRIQPAPNNG1025
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1003HRDLLRIQPAPNNGT1126
MSI2-ENPP3chr1755607085chr6132043367663DRB1-1003RHRDLLRIQPAPNNG1025

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Fusion breakpoint peptide structures of MSI2-ENPP3

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
4654KTTNRHRDLLRIQPMSI2ENPP3chr1755607085chr6132043367663

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MSI2-ENPP3

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-B14:023BVN4654KTTNRHRDLLRIQP-7.9962-8.1096
HLA-B14:023BVN4654KTTNRHRDLLRIQP-5.70842-6.74372
HLA-B52:013W394654KTTNRHRDLLRIQP-6.83737-6.95077
HLA-B52:013W394654KTTNRHRDLLRIQP-4.4836-5.5189
HLA-A11:014UQ24654KTTNRHRDLLRIQP-10.0067-10.1201
HLA-A11:014UQ24654KTTNRHRDLLRIQP-9.03915-10.0745
HLA-A24:025HGA4654KTTNRHRDLLRIQP-6.56204-6.67544
HLA-A24:025HGA4654KTTNRHRDLLRIQP-5.42271-6.45801
HLA-B44:053DX84654KTTNRHRDLLRIQP-7.85648-8.89178
HLA-B44:053DX84654KTTNRHRDLLRIQP-5.3978-5.5112
HLA-A02:016TDR4654KTTNRHRDLLRIQP-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of MSI2-ENPP3

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
MSI2-ENPP3chr1755607085chr61320433671120HRDLLRIQPACAGAGATCTTCTACGCATTCAACCAG
MSI2-ENPP3chr1755607085chr61320433671121HRDLLRIQPAACAGAGATCTTCTACGCATTCAACCAGCAC
MSI2-ENPP3chr1755607085chr6132043367918NRHRDLLRIACAGGCACAGAGATCTTCTACGCATTC
MSI2-ENPP3chr1755607085chr6132043367920NRHRDLLRIQPACAGGCACAGAGATCTTCTACGCATTCAACCAG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
MSI2-ENPP3chr1755607085chr6132043367015AMLMFDKTTNRHRDLCAATGCTGATGTTTGATAAAACTACCAACAGGCACAGAGATCTTC
MSI2-ENPP3chr1755607085chr61320433671025RHRDLLRIQPAPNNGGGCACAGAGATCTTCTACGCATTCAACCAGCACCAAACAATGGAA
MSI2-ENPP3chr1755607085chr61320433671126HRDLLRIQPAPNNGTACAGAGATCTTCTACGCATTCAACCAGCACCAAACAATGGAACCC

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Information of the samples that have these potential fusion neoantigens of MSI2-ENPP3

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
UCECMSI2-ENPP3chr1755607085ENST00000284073chr6132043367ENST00000414305TCGA-AX-A3FX-01A

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Potential target of CAR-T therapy development for MSI2-ENPP3

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 MSI2-ENPP3

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 MSI2-ENPP3

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