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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:EIF4G3-LIN28A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: EIF4G3-LIN28A
FusionPDB ID: 26056
FusionGDB2.0 ID: 26056
HgeneTgene
Gene symbol

EIF4G3

LIN28A

Gene ID

8672

79727

Gene nameeukaryotic translation initiation factor 4 gamma 3lin-28 homolog A
SynonymseIF-4G 3|eIF4G 3|eIF4GIICSDD1|LIN-28|LIN28|ZCCHC1|lin-28A
Cytomap

1p36.12

1p36.11

Type of geneprotein-codingprotein-coding
Descriptioneukaryotic translation initiation factor 4 gamma 3eIF-4-gamma 3eIF-4-gamma IIprotein lin-28 homolog ARNA-binding protein LIN-28zinc finger CCHC domain-containing protein 1zinc finger, CCHC domain containing 1
Modification date2020031320200322
UniProtAcc

O43432

Main function of 5'-partner protein: FUNCTION: Probable component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome. Thought to be a functional homolog of EIF4G1. {ECO:0000269|PubMed:9418880}.

Q9H9Z2

Main function of 5'-partner protein: FUNCTION: RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:21247876). Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (Probable). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression. Suppressor of microRNA (miRNA) biogenesis, including that of let-7, miR107, miR-143 and miR-200c. Specifically binds the miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in pre-miRNA terminal loop, and recruits TUT4 AND tut7 uridylyltransferaseS. This results in the terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state by preventing let-7-mediated differentiation of embryonic stem cells (PubMed:18951094, PubMed:19703396, PubMed:22118463, PubMed:22898984). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Binds to and enhances the translation of mRNAs for several metabolic enzymes, such as PFKP, PDHA1 or SDHA, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (By similarity). {ECO:0000250|UniProtKB:Q8K3Y3, ECO:0000269|PubMed:18951094, ECO:0000269|PubMed:19703396, ECO:0000269|PubMed:21247876, ECO:0000269|PubMed:22118463, ECO:0000269|PubMed:22898984, ECO:0000305}.
Ensembl transtripts involved in fusion geneENST idsENST00000544689, ENST00000374927, 
ENST00000400422, ENST00000536266, 
ENST00000602326, ENST00000264211, 
ENST00000356916, ENST00000374937, 
ENST00000374933, ENST00000374935, 
ENST00000537738, 
ENST00000254231, 
ENST00000326279, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 20 X 11=48402 X 2 X 2=8
# samples 322
** MAII scorelog2(32/4840*10)=-3.91886323727459
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(2/8*10)=1.32192809488736
Fusion gene context

PubMed: EIF4G3 [Title/Abstract] AND LIN28A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: EIF4G3 [Title/Abstract] AND LIN28A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)EIF4G3(21267984)-LIN28A(26737877), # samples:1
Anticipated loss of major functional domain due to fusion event.EIF4G3-LIN28A 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.
EIF4G3-LIN28A 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.
EIF4G3-LIN28A 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.
EIF4G3-LIN28A 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.
EIF4G3-LIN28A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
EIF4G3-LIN28A seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
EIF4G3-LIN28A seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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/chr1:21267984/chr1:26737877)
- 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 EIF4G3 (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 LIN28A (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)
ENST00000264211EIF4G3chr121267984-ENST00000326279LIN28Achr126737877+555316901682288706
ENST00000264211EIF4G3chr121267984-ENST00000254231LIN28Achr126737877+504216901682288706
ENST00000374937EIF4G3chr121267984-ENST00000326279LIN28Achr126737877+553716741342272712
ENST00000374937EIF4G3chr121267984-ENST00000254231LIN28Achr126737877+502616741342272712
ENST00000356916EIF4G3chr121267984-ENST00000326279LIN28Achr126737877+588820251282623831
ENST00000356916EIF4G3chr121267984-ENST00000254231LIN28Achr126737877+537720251282623831

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
ENST00000264211ENST00000326279EIF4G3chr121267984-LIN28Achr126737877+0.001008940.9989911
ENST00000264211ENST00000254231EIF4G3chr121267984-LIN28Achr126737877+0.0008238150.9991762
ENST00000374937ENST00000326279EIF4G3chr121267984-LIN28Achr126737877+0.0010453250.99895465
ENST00000374937ENST00000254231EIF4G3chr121267984-LIN28Achr126737877+0.0008786060.99912137
ENST00000356916ENST00000326279EIF4G3chr121267984-LIN28Achr126737877+0.0004573960.9995426
ENST00000356916ENST00000254231EIF4G3chr121267984-LIN28Achr126737877+0.0003635320.9996364

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 EIF4G3-LIN28A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
EIF4G3chr121267984LIN28Achr1267378771674507QTEEILDSQNLNSRRSPVPGGCAKAA
EIF4G3chr121267984LIN28Achr1267378771690501QTEEILDSQNLNSRRSPVPGGCAKAA
EIF4G3chr121267984LIN28Achr1267378772025626QTEEILDSQNLNSRRSPVPGGCAKAA

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Potential FusionNeoAntigen Information of EIF4G3-LIN28A 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.
EIF4G3-LIN28A_21267984_26737877.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)
EIF4G3-LIN28Achr121267984chr1267378771690HLA-B08:09NLNSRRSPV0.9970.5894918
EIF4G3-LIN28Achr121267984chr1267378771690HLA-B08:01NLNSRRSPV0.99680.5906918
EIF4G3-LIN28Achr121267984chr1267378771690HLA-B08:18NLNSRRSPV0.99680.5906918

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Potential FusionNeoAntigen Information of EIF4G3-LIN28A 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.
EIF4G3-LIN28A_21267984_26737877.msa

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)
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0403TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0413TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0413QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0422TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0422QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0427TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0427QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0437TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0437QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0439TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0440TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0441TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0444TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0444QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0446TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0449TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0449QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0450TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0451TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0451QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0452TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0455TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0456TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0460TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0465TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0468TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0470TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0470QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0471TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0473TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0478TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0478QTEEILDSQNLNSRR015
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0479TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0485TEEILDSQNLNSRRS116
EIF4G3-LIN28Achr121267984chr1267378771690DRB1-0488TEEILDSQNLNSRRS116

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Fusion breakpoint peptide structures of EIF4G3-LIN28A

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
1421DSQNLNSRRSPVPGEIF4G3LIN28Achr121267984chr1267378771690

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of EIF4G3-LIN28A

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-B14:023BVN1421DSQNLNSRRSPVPG-7.9962-8.1096
HLA-B14:023BVN1421DSQNLNSRRSPVPG-5.70842-6.74372
HLA-B52:013W391421DSQNLNSRRSPVPG-6.83737-6.95077
HLA-B52:013W391421DSQNLNSRRSPVPG-4.4836-5.5189
HLA-A11:014UQ21421DSQNLNSRRSPVPG-10.0067-10.1201
HLA-A11:014UQ21421DSQNLNSRRSPVPG-9.03915-10.0745
HLA-A24:025HGA1421DSQNLNSRRSPVPG-6.56204-6.67544
HLA-A24:025HGA1421DSQNLNSRRSPVPG-5.42271-6.45801
HLA-B44:053DX81421DSQNLNSRRSPVPG-7.85648-8.89178
HLA-B44:053DX81421DSQNLNSRRSPVPG-5.3978-5.5112
HLA-A02:016TDR1421DSQNLNSRRSPVPG-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of EIF4G3-LIN28A

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
EIF4G3-LIN28Achr121267984chr126737877918NLNSRRSPVGCCCTGTCCCAGGTGGCTGCGCCAAGG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
EIF4G3-LIN28Achr121267984chr126737877015QTEEILDSQNLNSRRATTCTCAAAACTTAAATTCAAGAAGGAGCCCTGTCCCAGGTGGCT
EIF4G3-LIN28Achr121267984chr126737877116TEEILDSQNLNSRRSCTCAAAACTTAAATTCAAGAAGGAGCCCTGTCCCAGGTGGCTGCG

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Information of the samples that have these potential fusion neoantigens of EIF4G3-LIN28A

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
HNSCEIF4G3-LIN28Achr121267984ENST00000264211chr126737877ENST00000254231TCGA-DQ-7591-01A

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Potential target of CAR-T therapy development for EIF4G3-LIN28A

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 EIF4G3-LIN28A

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 EIF4G3-LIN28A

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