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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:CSMD1-EIF3E

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: CSMD1-EIF3E
FusionPDB ID: 19739
FusionGDB2.0 ID: 19739
HgeneTgene
Gene symbol

CSMD1

EIF3E

Gene ID

64478

3646

Gene nameCUB and Sushi multiple domains 1eukaryotic translation initiation factor 3 subunit E
SynonymsPPP1R24EIF3-P48|EIF3S6|INT6|eIF3-p46
Cytomap

8p23.2

8q23.1

Type of geneprotein-codingprotein-coding
DescriptionCUB and sushi domain-containing protein 1protein phosphatase 1, regulatory subunit 24eukaryotic translation initiation factor 3 subunit EeIF-3 p48eukaryotic translation initiation factor 3 subunit 6eukaryotic translation initiation factor 3 subunit E isoform 2 transcripteukaryotic translation initiation factor 3, subunit 6 (48kD)euka
Modification date2020031320200313
UniProtAcc

Q96PZ7

Main function of 5'-partner protein: FUNCTION: Potential suppressor of squamous cell carcinomas.

P60228

Main function of 5'-partner protein: FUNCTION: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis (PubMed:17581632, PubMed:25849773, PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:17581632). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). Required for nonsense-mediated mRNA decay (NMD); may act in conjunction with UPF2 to divert mRNAs from translation to the NMD pathway (PubMed:17468741). May interact with MCM7 and EPAS1 and regulate the proteasome-mediated degradation of these proteins (PubMed:17310990, PubMed:17324924). {ECO:0000255|HAMAP-Rule:MF_03004, ECO:0000269|PubMed:17310990, ECO:0000269|PubMed:17324924, ECO:0000269|PubMed:17468741, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.
Ensembl transtripts involved in fusion geneENST idsENST00000400186, ENST00000520002, 
ENST00000537824, ENST00000539096, 
ENST00000542608, ENST00000602557, 
ENST00000602723, ENST00000523387, 
ENST00000519517, ENST00000220849, 
ENST00000519030, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score31 X 30 X 4=372021 X 12 X 10=2520
# samples 3221
** MAII scorelog2(32/3720*10)=-3.53915881110803
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/2520*10)=-3.58496250072116
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: CSMD1 [Title/Abstract] AND EIF3E [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: CSMD1 [Title/Abstract] AND EIF3E [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)CSMD1(4494863)-EIF3E(109215732), # samples:1
Anticipated loss of major functional domain due to fusion event.CSMD1-EIF3E 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.
CSMD1-EIF3E 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.
CSMD1-EIF3E 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.
CSMD1-EIF3E 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
TgeneEIF3E

GO:0006413

translational initiation

17581632



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/chr8:4494863/chr8:109215732)
- 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 CSMD1 (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 EIF3E (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)
ENST00000602723CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-100658781863260
ENST00000602723CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-96958781863260
ENST00000400186CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-100658781863260
ENST00000400186CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-96958781863260
ENST00000520002CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-12778581901134314
ENST00000520002CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-12408581901134314
ENST00000602557CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-12778581901134314
ENST00000602557CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-12408581901134314
ENST00000537824CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-7213020578192
ENST00000537824CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-6843020578192
ENST00000542608CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-7213020578192
ENST00000542608CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-6843020578192
ENST00000539096CSMD1chr84494863-ENST00000220849EIF3Echr8109215732-7213020578192
ENST00000539096CSMD1chr84494863-ENST00000519030EIF3Echr8109215732-6843020578192

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
ENST00000602723ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0017994090.99820054
ENST00000602723ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.001614640.9983854
ENST00000400186ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0017994090.99820054
ENST00000400186ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.001614640.9983854
ENST00000520002ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0021464690.99785346
ENST00000520002ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.001639020.99836093
ENST00000602557ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0021464690.99785346
ENST00000602557ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.001639020.99836093
ENST00000537824ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0014349660.998565
ENST00000537824ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.0016946680.9983053
ENST00000542608ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0014349660.998565
ENST00000542608ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.0016946680.9983053
ENST00000539096ENST00000220849CSMD1chr84494863-EIF3Echr8109215732-0.0014349660.998565
ENST00000539096ENST00000519030CSMD1chr84494863-EIF3Echr8109215732-0.0016946680.9983053

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 CSMD1-EIF3E

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
CSMD1chr84494863EIF3Echr8109215732302100VYDGQPQQGNLKVSMLADKLNMTPEE
CSMD1chr84494863EIF3Echr8109215732587168VYDGQPQQGNLKVSMLADKLNMTPEE
CSMD1chr84494863EIF3Echr8109215732858222VYDGQPQQGNLKVSMLADKLNMTPEE

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Potential FusionNeoAntigen Information of CSMD1-EIF3E 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.
CSMD1-EIF3E_4494863_109215732.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)
CSMD1-EIF3Echr84494863chr8109215732587HLA-B08:01QGNLKVSM0.99760.7554715
CSMD1-EIF3Echr84494863chr8109215732587HLA-B08:01QGNLKVSML0.99340.8211716
CSMD1-EIF3Echr84494863chr8109215732587HLA-B48:01QQGNLKVSM0.97670.5371615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:03QQGNLKVSM0.86820.7299615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B39:13QQGNLKVSM0.85220.9141615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B47:01QQGNLKVSM0.68270.595615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B13:01QQGNLKVSM0.55790.9543615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:03QPQQGNLKVSM0.86490.9162415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B81:01QPQQGNLKVSM0.73820.7395415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B82:01QPQQGNLKVSM0.65980.8844415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:04QPQQGNLKVSM0.63510.973415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:02QPQQGNLKVSM0.63510.973415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B39:08QQGNLKVSM0.77270.9339615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:05QQGNLKVSM0.62910.8571615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B07:12QPQQGNLKVSM0.98020.5699415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B42:02QPQQGNLKVSM0.91880.8511415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B42:01QPQQGNLKVSM0.90440.8438415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B39:10QPQQGNLKVSM0.71490.9579415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:12QPQQGNLKVSM0.63510.973415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B08:18QGNLKVSM0.99760.7554715
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:50QQGNLKVSM0.9940.8321615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B08:18QGNLKVSML0.99340.8211716
CSMD1-EIF3Echr84494863chr8109215732587HLA-B08:12QGNLKVSML0.96580.8758716
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:12QQGNLKVSM0.94590.7499615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B39:02QQGNLKVSM0.94540.9173615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:54QQGNLKVSM0.89140.7217615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:53QQGNLKVSM0.88250.7464615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:73QQGNLKVSM0.87890.8897615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:30QQGNLKVSM0.7840.8539615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B48:02QQGNLKVSM0.71320.9225615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B15:20QQGNLKVSM0.60030.9171615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:28QQGNLKVSM0.60020.9346615
CSMD1-EIF3Echr84494863chr8109215732587HLA-B55:04QPQQGNLKVSM0.84290.582415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:22QPQQGNLKVSM0.8090.6528415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B67:01QPQQGNLKVSM0.75950.9441415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B82:02QPQQGNLKVSM0.65980.8844415
CSMD1-EIF3Echr84494863chr8109215732587HLA-B35:09QPQQGNLKVSM0.63510.973415

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Potential FusionNeoAntigen Information of CSMD1-EIF3E 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 CSMD1-EIF3E

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
7498QQGNLKVSMLADKLCSMD1EIF3Echr84494863chr8109215732587

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of CSMD1-EIF3E

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-B14:023BVN7498QQGNLKVSMLADKL-7.5588-7.6706
HLA-B14:023BVN7498QQGNLKVSMLADKL-4.42712-5.47022
HLA-B52:013W397498QQGNLKVSMLADKL-5.79336-5.90516
HLA-B52:013W397498QQGNLKVSMLADKL-4.82735-5.87045
HLA-A11:014UQ27498QQGNLKVSMLADKL-10.3742-10.486
HLA-A24:025HGA7498QQGNLKVSMLADKL-7.36249-8.40559
HLA-A24:025HGA7498QQGNLKVSMLADKL-7.07591-7.18771
HLA-B27:056PYJ7498QQGNLKVSMLADKL-8.75018-8.86198
HLA-B44:053DX87498QQGNLKVSMLADKL-5.28726-5.39906
HLA-B44:053DX87498QQGNLKVSMLADKL-4.30205-5.34515
HLA-A02:016TDR7498QQGNLKVSMLADKL-4.2167-4.3285

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Vaccine Design for the FusionNeoAntigens of CSMD1-EIF3E

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
CSMD1-EIF3Echr84494863chr8109215732415QPQQGNLKVSMGCCTCAACAAGGGAATTTAAAAGTGAGCATGTT
CSMD1-EIF3Echr84494863chr8109215732615QQGNLKVSMACAAGGGAATTTAAAAGTGAGCATGTT
CSMD1-EIF3Echr84494863chr8109215732715QGNLKVSMAGGGAATTTAAAAGTGAGCATGTT
CSMD1-EIF3Echr84494863chr8109215732716QGNLKVSMLAGGGAATTTAAAAGTGAGCATGTTGGC

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 CSMD1-EIF3E

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
ESCACSMD1-EIF3Echr84494863ENST00000400186chr8109215732ENST00000220849TCGA-IG-A3YA

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Potential target of CAR-T therapy development for CSMD1-EIF3E

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 CSMD1-EIF3E

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 CSMD1-EIF3E

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