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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:EIF4A1-DDX5

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EIF4A1-DDX5
FusionPDB ID: 25919
FusionGDB2.0 ID: 25919
HgeneTgene
Gene symbol

EIF4A1

DDX5

Gene ID

1973

1655

Gene nameeukaryotic translation initiation factor 4A1DEAD-box helicase 5
SynonymsDDX2A|EIF-4A|EIF4A|eIF-4A-I|eIF4A-IG17P1|HLR1|HUMP68|p68
Cytomap

17p13.1

17q23.3

Type of geneprotein-codingprotein-coding
Descriptioneukaryotic initiation factor 4A-IATP-dependent RNA helicase eIF4A-1eukaryotic initiation factor 4AIeukaryotic translation initiation factor 4Aprobable ATP-dependent RNA helicase DDX5ATP-dependent RNA helicase DDX5DEAD (Asp-Glu-Ala-Asp) box helicase 5DEAD (Asp-Glu-Ala-Asp) box polypeptide 5DEAD box protein 5DEAD box-5DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 5 (RNA helicase, 68kD)RNA h
Modification date2020032220200313
UniProtAcc

P60842

Main function of 5'-partner protein: FUNCTION: ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon. {ECO:0000269|PubMed:19153607, ECO:0000269|PubMed:19204291}.

Q5T1V6

Main function of 5'-partner protein:
Ensembl transtripts involved in fusion geneENST idsENST00000293831, ENST00000577269, 
ENST00000582746, ENST00000380512, 
ENST00000581808, 
ENST00000580026, 
ENST00000225792, ENST00000450599, 
ENST00000578804, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 2 X 2=1220 X 12 X 8=1920
# samples 519
** MAII scorelog2(5/12*10)=2.05889368905357
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(19/1920*10)=-3.33703498727757
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: EIF4A1 [Title/Abstract] AND DDX5 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EIF4A1 [Title/Abstract] AND DDX5 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EIF4A1(7476182)-DDX5(62500960), # samples:1
Anticipated loss of major functional domain due to fusion event.EIF4A1-DDX5 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.
EIF4A1-DDX5 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.
EIF4A1-DDX5 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.
EIF4A1-DDX5 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
TgeneDDX5

GO:0000122

negative regulation of transcription by RNA polymerase II

15298701

TgeneDDX5

GO:0000381

regulation of alternative mRNA splicing, via spliceosome

21343338

TgeneDDX5

GO:0000956

nuclear-transcribed mRNA catabolic process

23788676



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/chr17:7476182/chr17:62500960)
- 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 EIF4A1 (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 DDX5 (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)
ENST00000293831EIF4A1chr177476182+ENST00000225792DDX5chr1762500960-214739161839607
ENST00000293831EIF4A1chr177476182+ENST00000450599DDX5chr1762500960-190439161602528
ENST00000293831EIF4A1chr177476182+ENST00000578804DDX5chr1762500960-184939161839607
ENST00000577269EIF4A1chr177476182+ENST00000225792DDX5chr1762500960-21362851828607
ENST00000577269EIF4A1chr177476182+ENST00000450599DDX5chr1762500960-18932851591528
ENST00000577269EIF4A1chr177476182+ENST00000578804DDX5chr1762500960-18382851828607
ENST00000582746EIF4A1chr177476182+ENST00000225792DDX5chr1762500960-21312301823607
ENST00000582746EIF4A1chr177476182+ENST00000450599DDX5chr1762500960-18882301586528
ENST00000582746EIF4A1chr177476182+ENST00000578804DDX5chr1762500960-18332301823607

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
ENST00000293831ENST00000225792EIF4A1chr177476182+DDX5chr1762500960-0.0007005610.9992994
ENST00000293831ENST00000450599EIF4A1chr177476182+DDX5chr1762500960-0.0005449280.99945503
ENST00000293831ENST00000578804EIF4A1chr177476182+DDX5chr1762500960-0.0008399040.99916005
ENST00000577269ENST00000225792EIF4A1chr177476182+DDX5chr1762500960-0.0006943410.9993056
ENST00000577269ENST00000450599EIF4A1chr177476182+DDX5chr1762500960-0.0005637720.9994362
ENST00000577269ENST00000578804EIF4A1chr177476182+DDX5chr1762500960-0.0008328220.9991672
ENST00000582746ENST00000225792EIF4A1chr177476182+DDX5chr1762500960-0.0006766620.99932337
ENST00000582746ENST00000450599EIF4A1chr177476182+DDX5chr1762500960-0.0005545010.9994455
ENST00000582746ENST00000578804EIF4A1chr177476182+DDX5chr1762500960-0.0008115920.99918836

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 EIF4A1-DDX5

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

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Potential FusionNeoAntigen Information of EIF4A1-DDX5 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.

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)

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Potential FusionNeoAntigen Information of EIF4A1-DDX5 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 EIF4A1-DDX5

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.

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EIF4A1-DDX5

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

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Vaccine Design for the FusionNeoAntigens of EIF4A1-DDX5

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

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 EIF4A1-DDX5

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

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Potential target of CAR-T therapy development for EIF4A1-DDX5

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 EIF4A1-DDX5

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 EIF4A1-DDX5

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
TgeneDDX5C0014175Endometriosis1CTD_human
TgeneDDX5C0269102Endometrioma1CTD_human