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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:ZNF586-EIF4A1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ZNF586-EIF4A1
FusionPDB ID: 102457
FusionGDB2.0 ID: 102457
HgeneTgene
Gene symbol

ZNF586

EIF4A1

Gene ID

54807

1973

Gene namezinc finger protein 586eukaryotic translation initiation factor 4A1
Synonyms-DDX2A|EIF-4A|EIF4A|eIF-4A-I|eIF4A-I
Cytomap

19q13.43

17p13.1

Type of geneprotein-codingprotein-coding
Descriptionzinc finger protein 586eukaryotic initiation factor 4A-IATP-dependent RNA helicase eIF4A-1eukaryotic initiation factor 4AIeukaryotic translation initiation factor 4A
Modification date2020031320200322
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}.
Ensembl transtripts involved in fusion geneENST idsENST00000391702, ENST00000396154, 
ENST00000396150, ENST00000598183, 
ENST00000598885, ENST00000599802, 
ENST00000581808, ENST00000380512, 
ENST00000293831, ENST00000577269, 
ENST00000582746, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score6 X 5 X 5=1508 X 5 X 5=200
# samples 78
** MAII scorelog2(7/150*10)=-1.09953567355091
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/200*10)=-1.32192809488736
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ZNF586 [Title/Abstract] AND EIF4A1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ZNF586 [Title/Abstract] AND EIF4A1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ZNF586(58288037)-EIF4A1(7478436), # samples:1
Anticipated loss of major functional domain due to fusion event.ZNF586-EIF4A1 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.
ZNF586-EIF4A1 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.
ZNF586-EIF4A1 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.
ZNF586-EIF4A1 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.
ZNF586-EIF4A1 seems lost the major protein functional domain in Hgene partner, which is a transcription factor due to the frame-shifted ORF.
ZNF586-EIF4A1 seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
ZNF586-EIF4A1 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted 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


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/chr19:58288037/chr17:7478436)
- 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 ZNF586 (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 EIF4A1 (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)
ENST00000391702ZNF586chr1958288037+ENST00000293831EIF4A1chr177478436+19364013131416367
ENST00000391702ZNF586chr1958288037+ENST00000577269EIF4A1chr177478436+15104013131239308
ENST00000391702ZNF586chr1958288037+ENST00000582746EIF4A1chr177478436+18414013131221302
ENST00000396154ZNF586chr1958288037+ENST00000293831EIF4A1chr177478436+187133681351447
ENST00000396154ZNF586chr1958288037+ENST00000577269EIF4A1chr177478436+144533681174388
ENST00000396154ZNF586chr1958288037+ENST00000582746EIF4A1chr177478436+177633681156382

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
ENST00000391702ENST00000293831ZNF586chr1958288037+EIF4A1chr177478436+0.0016750080.99832493
ENST00000391702ENST00000577269ZNF586chr1958288037+EIF4A1chr177478436+0.0028536560.9971463
ENST00000391702ENST00000582746ZNF586chr1958288037+EIF4A1chr177478436+0.0028326940.9971673
ENST00000396154ENST00000293831ZNF586chr1958288037+EIF4A1chr177478436+0.0008619780.999138
ENST00000396154ENST00000577269ZNF586chr1958288037+EIF4A1chr177478436+0.0013577950.99864227
ENST00000396154ENST00000582746ZNF586chr1958288037+EIF4A1chr177478436+0.0011667460.99883324

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 ZNF586-EIF4A1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ZNF586chr1958288037EIF4A1chr177478436336108RDVMLETLTLISSLGYDVIAQAQSGT
ZNF586chr1958288037EIF4A1chr17747843640128RDVMLETLTLISSLGYDVIAQAQSGT

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Potential FusionNeoAntigen Information of ZNF586-EIF4A1 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.
ZNF586-EIF4A1_58288037_7478436.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)
ZNF586-EIF4A1chr1958288037chr177478436401HLA-B15:17LTLISSLGY0.98820.5666716
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:13SLGYDVIAQA0.93150.6571222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:27SLGYDVIAQA0.93040.54651222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:60SLGYDVIAQA0.92330.52661222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:30SLGYDVIAQA0.92240.53831222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:67SLGYDVIAQA0.92240.53831222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:24SLGYDVIAQA0.92240.53831222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:11SLGYDVIAQA0.91950.56921222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:38SLGYDVIAQA0.91580.6731222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:21SLGYDVIAQA0.91550.66221222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:35SLGYDVIAQA0.88530.58071222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:29SLGYDVIAQA0.84760.54381222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:04SLGYDVIAQA0.84490.75871222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:19SLGYDVIAQA0.84470.52441222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:20SLGYDVIAQA0.83860.54071222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:01SLGYDVIAQA0.92240.53831222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:03SLGYDVIAQA0.96090.64171222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A02:06SLGYDVIAQA0.91550.66221222
ZNF586-EIF4A1chr1958288037chr177478436401HLA-A25:01ETLTLISSLGY0.96250.5815516

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Potential FusionNeoAntigen Information of ZNF586-EIF4A1 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 ZNF586-EIF4A1

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
9497TLTLISSLGYDVIAZNF586EIF4A1chr1958288037chr177478436401

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ZNF586-EIF4A1

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-B14:023BVN9497TLTLISSLGYDVIA-7.15543-7.26883
HLA-B14:023BVN9497TLTLISSLGYDVIA-4.77435-5.80965
HLA-B52:013W399497TLTLISSLGYDVIA-6.80875-6.92215
HLA-B52:013W399497TLTLISSLGYDVIA-4.20386-5.23916
HLA-A11:014UQ29497TLTLISSLGYDVIA-7.5194-8.5547
HLA-A11:014UQ29497TLTLISSLGYDVIA-6.9601-7.0735
HLA-A24:025HGA9497TLTLISSLGYDVIA-7.52403-7.63743
HLA-A24:025HGA9497TLTLISSLGYDVIA-5.82433-6.85963
HLA-B27:056PYJ9497TLTLISSLGYDVIA-3.28285-4.31815
HLA-B44:053DX89497TLTLISSLGYDVIA-5.91172-6.94702
HLA-B44:053DX89497TLTLISSLGYDVIA-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of ZNF586-EIF4A1

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
ZNF586-EIF4A1chr1958288037chr1774784361222SLGYDVIAQATGGGTTATGATGTGATTGCTCAAGCCCAAT
ZNF586-EIF4A1chr1958288037chr177478436516ETLTLISSLGYCCTTGACACTTATATCCTCCCTGGGTTATGATG
ZNF586-EIF4A1chr1958288037chr177478436716LTLISSLGYCACTTATATCCTCCCTGGGTTATGATG

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 ZNF586-EIF4A1

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
OVZNF586-EIF4A1chr1958288037ENST00000391702chr177478436ENST00000293831TCGA-29-1766

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Potential target of CAR-T therapy development for ZNF586-EIF4A1

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 ZNF586-EIF4A1

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 ZNF586-EIF4A1

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