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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:SF3B3-CDH15

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: SF3B3-CDH15
FusionPDB ID: 81065
FusionGDB2.0 ID: 81066
HgeneTgene
Gene symbol

SF3B3

CDH15

Gene ID

23450

1013

Gene namesplicing factor 3b subunit 3cadherin 15
SynonymsRSE1|SAP130|SF3b130|STAF130CDH14|CDH3|CDHM|MCAD|MRD3
Cytomap

16q22.1

16q24.3

Type of geneprotein-codingprotein-coding
Descriptionsplicing factor 3B subunit 3SAP 130pre-mRNA splicing factor SF3b, 130 kDa subunitspliceosome-associated protein 130cadherin-15cadherin 15, type 1, M-cadherin (myotubule)cadherin-14cadherin-3muscle-cadherin
Modification date2020031320200313
UniProtAcc.

P55291

Main function of 5'-partner protein: FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. M-cadherin is part of the myogenic program and may provide a trigger for terminal muscle differentiation.
Ensembl transtripts involved in fusion geneENST idsENST00000302516, ENST00000521087, 
ENST00000289746, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score13 X 15 X 9=17552 X 3 X 2=12
# samples 183
** MAII scorelog2(18/1755*10)=-3.28540221886225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(3/12*10)=1.32192809488736
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: SF3B3 [Title/Abstract] AND CDH15 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: SF3B3 [Title/Abstract] AND CDH15 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)SF3B3(70578436)-CDH15(89245824), # samples:3
Anticipated loss of major functional domain due to fusion event.SF3B3-CDH15 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.
SF3B3-CDH15 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.
SF3B3-CDH15 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.
SF3B3-CDH15 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
HgeneSF3B3

GO:0000398

mRNA splicing, via spliceosome

28781166|29360106

HgeneSF3B3

GO:0042177

negative regulation of protein catabolic process

23951410



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/chr16:70578436/chr16:89245824)
- 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 SF3B3 (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 CDH15 (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)
ENST00000302516SF3B3chr1670578436+ENST00000289746CDH15chr1689245824+4280154010939421277
ENST00000302516SF3B3chr1670578436+ENST00000289746CDH15chr1689245823+4280154010939421277

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
ENST00000302516ENST00000289746SF3B3chr1670578436+CDH15chr1689245824+0.0019604050.99803966
ENST00000302516ENST00000289746SF3B3chr1670578436+CDH15chr1689245823+0.0019604050.99803966

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 SF3B3-CDH15

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
SF3B3chr1670578436CDH15chr16892458231540475RGPRSSLRVLRHGLESLCLSLGVPGW
SF3B3chr1670578436CDH15chr16892458241540475RGPRSSLRVLRHGLESLCLSLGVPGW

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Potential FusionNeoAntigen Information of SF3B3-CDH15 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.
SF3B3-CDH15_70578436_89245823.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)
SF3B3-CDH15chr1670578436chr16892458231540HLA-B39:24LRHGLESL0.9990.8225917
SF3B3-CDH15chr1670578436chr16892458231540HLA-B39:01RHGLESLCL0.99160.93461019
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:22VLRHGLESL0.98130.742817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B38:02RHGLESLCL0.97190.97461019
SF3B3-CDH15chr1670578436chr16892458231540HLA-B38:01RHGLESLCL0.97070.97731019
SF3B3-CDH15chr1670578436chr16892458231540HLA-B08:01VLRHGLESL0.94970.8816817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:13VLRHGLESL0.93880.8632817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:27VLRHGLESL0.8750.7833817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:38VLRHGLESL0.84030.8516817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:04VLRHGLESL0.66240.8634817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:17VLRHGLESL0.64370.8372817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A30:08RVLRHGLESL0.96380.9334717
SF3B3-CDH15chr1670578436chr16892458231540HLA-B39:12LRHGLESL0.9980.9838917
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:02VLRHGLESL0.98310.6071817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B15:04VLRHGLESL0.98030.9572817
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:05VLRHGLESL0.97780.7136817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B39:05RHGLESLCL0.94930.9261019
SF3B3-CDH15chr1670578436chr16892458231540HLA-A02:03VLRHGLESL0.99270.8241817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B38:05RHGLESLCL0.97070.97731019
SF3B3-CDH15chr1670578436chr16892458231540HLA-B08:18VLRHGLESL0.94970.8816817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B15:73VLRHGLESL0.9210.9805817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B15:30VLRHGLESL0.850.9499817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B08:12VLRHGLESL0.66560.9597817
SF3B3-CDH15chr1670578436chr16892458231540HLA-B39:11RHGLESLCL0.4130.86361019
SF3B3-CDH15chr1670578436chr16892458231540HLA-B15:09RHGLESLCL0.41070.73531019
SF3B3-CDH15chr1670578436chr16892458231540HLA-B40:21VLRHGLESL0.03070.7039817

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Potential FusionNeoAntigen Information of SF3B3-CDH15 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 SF3B3-CDH15

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
5573LRVLRHGLESLCLSSF3B3CDH15chr1670578436chr16892458231540

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of SF3B3-CDH15

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-B14:023BVN5573LRVLRHGLESLCLS-7.15543-7.26883
HLA-B14:023BVN5573LRVLRHGLESLCLS-4.77435-5.80965
HLA-B52:013W395573LRVLRHGLESLCLS-6.80875-6.92215
HLA-B52:013W395573LRVLRHGLESLCLS-4.20386-5.23916
HLA-A11:014UQ25573LRVLRHGLESLCLS-7.5194-8.5547
HLA-A11:014UQ25573LRVLRHGLESLCLS-6.9601-7.0735
HLA-A24:025HGA5573LRVLRHGLESLCLS-7.52403-7.63743
HLA-A24:025HGA5573LRVLRHGLESLCLS-5.82433-6.85963
HLA-B27:056PYJ5573LRVLRHGLESLCLS-3.28285-4.31815
HLA-B44:053DX85573LRVLRHGLESLCLS-5.91172-6.94702
HLA-B44:053DX85573LRVLRHGLESLCLS-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of SF3B3-CDH15

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
SF3B3-CDH15chr1670578436chr16892458231019RHGLESLCLGGACTTGAGAGCCTCTGCCTGTCTTTG
SF3B3-CDH15chr1670578436chr1689245823717RVLRHGLESLCTAAGACATGGACTTGAGAGCCTCTGCCTG
SF3B3-CDH15chr1670578436chr1689245823817VLRHGLESLAGACATGGACTTGAGAGCCTCTGCCTG
SF3B3-CDH15chr1670578436chr1689245823917LRHGLESLCATGGACTTGAGAGCCTCTGCCTG

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 SF3B3-CDH15

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
LUADSF3B3-CDH15chr1670578436ENST00000302516chr1689245823ENST00000289746TCGA-44-7667

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Potential target of CAR-T therapy development for SF3B3-CDH15

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
TgeneCDH15chr16:70578436chr16:89245823ENST00000289746014607_6260815.0TransmembraneHelical
TgeneCDH15chr16:70578436chr16:89245824ENST00000289746014607_6260815.0TransmembraneHelical

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 SF3B3-CDH15

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 SF3B3-CDH15

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