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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-BCAS3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: MSI2-BCAS3
FusionPDB ID: 55303
FusionGDB2.0 ID: 55303
HgeneTgene
Gene symbol

MSI2

BCAS3

Gene ID

124540

54828

Gene namemusashi RNA binding protein 2BCAS3 microtubule associated cell migration factor
SynonymsMSI2HGAOB1|MAAB
Cytomap

17q22

17q23.2

Type of geneprotein-codingprotein-coding
DescriptionRNA-binding protein Musashi homolog 2musashi homolog 2musashi-2breast carcinoma-amplified sequence 3BCAS4/BCAS3 fusionRudhirabreast carcinoma amplified sequence 4/3 fusion proteinmetastasis associated antigen of breast cancerprotein Maab1
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}.

Q9H6U6

Main function of 5'-partner protein: FUNCTION: Plays a role in angiogenesis. Participates in the regulation of cell polarity and directional endothelial cell migration by mediating both the activation and recruitment of CDC42 and the reorganization of the actin cytoskeleton at the cell leading edge. Promotes filipodia formation (By similarity). Functions synergistically with PELP1 as a transcriptional coactivator of estrogen receptor-responsive genes. Stimulates histone acetyltransferase activity. Binds to chromatin. {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058}.
Ensembl transtripts involved in fusion geneENST idsENST00000579505, ENST00000284073, 
ENST00000416426, ENST00000442934, 
ENST00000322684, ENST00000579180, 
ENST00000390652, ENST00000407086, 
ENST00000408905, ENST00000588462, 
ENST00000589222, ENST00000585744, 
ENST00000585812, ENST00000588874, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score40 X 16 X 16=1024045 X 32 X 19=27360
# samples 4553
** MAII scorelog2(45/10240*10)=-4.50814690367033
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0		log2(53/27360*10)=-5.6899320603227
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: MSI2 [Title/Abstract] AND BCAS3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: MSI2 [Title/Abstract] AND BCAS3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)MSI2(55729522)-BCAS3(58885365), # samples:3
Anticipated loss of major functional domain due to fusion event.MSI2-BCAS3 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-BCAS3 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-BCAS3 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-BCAS3 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
TgeneBCAS3

GO:0043085

positive regulation of catalytic activity

17505058

TgeneBCAS3

GO:0045944

positive regulation of transcription by RNA polymerase II

17505058

TgeneBCAS3

GO:0071391

cellular response to estrogen stimulus

17505058



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/chr17:55729522/chr17:58885365)
- 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 BCAS3 (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)
ENST00000416426MSI2chr1755729522+ENST00000589222BCAS3chr1758885365+40618599332421049
ENST00000416426MSI2chr1755729522+ENST00000407086BCAS3chr1758885365+39048599331971034
ENST00000416426MSI2chr1755729522+ENST00000390652BCAS3chr1758885365+39568599332421049
ENST00000416426MSI2chr1755729522+ENST00000408905BCAS3chr1758885365+39708599332631056
ENST00000416426MSI2chr1755729522+ENST00000588462BCAS3chr1758885365+40158599333081071
ENST00000284073MSI2chr1755729522+ENST00000589222BCAS3chr1758885365+420199917933821067
ENST00000284073MSI2chr1755729522+ENST00000407086BCAS3chr1758885365+404499917933371052
ENST00000284073MSI2chr1755729522+ENST00000390652BCAS3chr1758885365+409699917933821067
ENST00000284073MSI2chr1755729522+ENST00000408905BCAS3chr1758885365+411099917934031074
ENST00000284073MSI2chr1755729522+ENST00000588462BCAS3chr1758885365+415599917934481089
ENST00000442934MSI2chr1755729522+ENST00000589222BCAS3chr1758885365+3849647403030996
ENST00000442934MSI2chr1755729522+ENST00000407086BCAS3chr1758885365+3692647402985981
ENST00000442934MSI2chr1755729522+ENST00000390652BCAS3chr1758885365+3744647403030996
ENST00000442934MSI2chr1755729522+ENST00000408905BCAS3chr1758885365+37586474030511003
ENST00000442934MSI2chr1755729522+ENST00000588462BCAS3chr1758885365+38036474030961018

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
ENST00000416426ENST00000589222MSI2chr1755729522+BCAS3chr1758885365+0.0002797840.99972016
ENST00000416426ENST00000407086MSI2chr1755729522+BCAS3chr1758885365+0.000399790.99960023
ENST00000416426ENST00000390652MSI2chr1755729522+BCAS3chr1758885365+0.0002982110.9997018
ENST00000416426ENST00000408905MSI2chr1755729522+BCAS3chr1758885365+0.0004014140.99959856
ENST00000416426ENST00000588462MSI2chr1755729522+BCAS3chr1758885365+0.0003740420.9996259
ENST00000284073ENST00000589222MSI2chr1755729522+BCAS3chr1758885365+0.0003703640.9996296
ENST00000284073ENST00000407086MSI2chr1755729522+BCAS3chr1758885365+0.0005220380.99947804
ENST00000284073ENST00000390652MSI2chr1755729522+BCAS3chr1758885365+0.000382010.99961793
ENST00000284073ENST00000408905MSI2chr1755729522+BCAS3chr1758885365+0.0005225560.99947745
ENST00000284073ENST00000588462MSI2chr1755729522+BCAS3chr1758885365+0.0004807360.9995192
ENST00000442934ENST00000589222MSI2chr1755729522+BCAS3chr1758885365+0.0005016370.99949837
ENST00000442934ENST00000407086MSI2chr1755729522+BCAS3chr1758885365+0.0006662720.9993337
ENST00000442934ENST00000390652MSI2chr1755729522+BCAS3chr1758885365+0.0005819030.99941814
ENST00000442934ENST00000408905MSI2chr1755729522+BCAS3chr1758885365+0.0003913860.9996087
ENST00000442934ENST00000588462MSI2chr1755729522+BCAS3chr1758885365+0.0002993060.99970067

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-BCAS3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
MSI2chr1755729522BCAS3chr1758885365647201GPVAAAAVAAARGSGAQKCDNFAEKR
MSI2chr1755729522BCAS3chr1758885365859254GPVAAAAVAAARGSGAQKCDNFAEKR
MSI2chr1755729522BCAS3chr1758885365999272GPVAAAAVAAARGSGAQKCDNFAEKR

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Potential FusionNeoAntigen Information of MSI2-BCAS3 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-BCAS3_55729522_58885365.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-BCAS3chr1755729522chr1758885365999HLA-A30:08AARGSGAQK0.99720.723918
MSI2-BCAS3chr1755729522chr1758885365999HLA-A30:08AAARGSGAQK0.98690.7341818
MSI2-BCAS3chr1755729522chr1758885365999HLA-A30:01AARGSGAQK0.99690.8136918
MSI2-BCAS3chr1755729522chr1758885365999HLA-A30:01AAARGSGAQK0.98460.8212818

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Potential FusionNeoAntigen Information of MSI2-BCAS3 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 MSI2-BCAS3

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
673AVAAARGSGAQKCDMSI2BCAS3chr1755729522chr1758885365999

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of MSI2-BCAS3

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-B14:023BVN673AVAAARGSGAQKCD-8.55667-8.74867
HLA-B14:023BVN673AVAAARGSGAQKCD-3.49457-4.25557
HLA-B52:013W39673AVAAARGSGAQKCD-7.26725-7.45925
HLA-B52:013W39673AVAAARGSGAQKCD-4.01461-4.77561
HLA-A24:025HGA673AVAAARGSGAQKCD-7.65911-8.42011
HLA-A24:025HGA673AVAAARGSGAQKCD-7.10204-7.29404
HLA-B44:053DX8673AVAAARGSGAQKCD-7.5556-8.3166
HLA-B44:053DX8673AVAAARGSGAQKCD-2.76159-2.95359

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Vaccine Design for the FusionNeoAntigens of MSI2-BCAS3

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-BCAS3chr1755729522chr1758885365818AAARGSGAQKCAGCAAGAGGATCAGGTGCTCAAAAATGTG
MSI2-BCAS3chr1755729522chr1758885365918AARGSGAQKCAAGAGGATCAGGTGCTCAAAAATGTG

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 MSI2-BCAS3

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
BLCAMSI2-BCAS3chr1755729522ENST00000284073chr1758885365ENST00000390652TCGA-2F-A9KR-01A

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Potential target of CAR-T therapy development for MSI2-BCAS3

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-BCAS3

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-BCAS3

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