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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:YWHAZ-EIF3A

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: YWHAZ-EIF3A
FusionPDB ID: 100213
FusionGDB2.0 ID: 100213
HgeneTgene
Gene symbol

YWHAZ

EIF3A

Gene ID

7534

8661

Gene nametyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zetaeukaryotic translation initiation factor 3 subunit A
Synonyms14-3-3-zeta|HEL-S-3|HEL-S-93|HEL4|KCIP-1|POPCHAS|YWHADEIF3|EIF3S10|P167|TIF32|eIF3-p170|eIF3-theta|p180|p185
Cytomap

8q22.3

10q26.11

Type of geneprotein-codingprotein-coding
Description14-3-3 protein zeta/delta14-3-3 delta14-3-3 protein/cytosolic phospholipase A214-3-3 zetaepididymis luminal protein 4epididymis secretory protein Li 3epididymis secretory protein Li 93phospholipase A2protein kinase C inhibitor protein-1tyrosine 3eukaryotic translation initiation factor 3 subunit AEIF3, p180 subunitcentrosomin homologcytoplasmic protein p167eIF-3-thetaeIF3 p167eIF3 p180eIF3 p185eukaryotic translation initiation factor 3 subunit 10eukaryotic translation initiation factor 3
Modification date2020032920200313
UniProtAcc.

Q14152

Main function of 5'-partner protein: FUNCTION: RNA-binding 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). 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, PubMed:11169732). 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, PubMed:27462815). {ECO:0000255|HAMAP-Rule:MF_03000, ECO:0000269|PubMed:11169732, ECO:0000269|PubMed:17581632, ECO:0000269|PubMed:25849773, ECO:0000269|PubMed:27462815}.; FUNCTION: (Microbial infection) Essential for the initiation of translation on type-1 viral ribosomal entry sites (IRESs), like for HCV, PV, EV71 or BEV translation (PubMed:23766293, PubMed:24357634). {ECO:0000269|PubMed:23766293, ECO:0000269|PubMed:24357634}.; FUNCTION: (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426). {ECO:0000269|PubMed:18056426}.
Ensembl transtripts involved in fusion geneENST idsENST00000353245, ENST00000395948, 
ENST00000395956, ENST00000395958, 
ENST00000457309, ENST00000521309, 
ENST00000522542, ENST00000395951, 
ENST00000395953, ENST00000395957, 
ENST00000419477, ENST00000522819, 
ENST00000492736, 
ENST00000369144, 
ENST00000541549, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score22 X 20 X 10=44008 X 9 X 3=216
# samples 299
** MAII scorelog2(29/4400*10)=-3.92337871839709
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/216*10)=-1.26303440583379
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: YWHAZ [Title/Abstract] AND EIF3A [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: YWHAZ [Title/Abstract] AND EIF3A [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)YWHAZ(101937143)-EIF3A(120796821), # samples:1
Anticipated loss of major functional domain due to fusion event.YWHAZ-EIF3A 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.
YWHAZ-EIF3A 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.
YWHAZ-EIF3A seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
YWHAZ-EIF3A seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF.
YWHAZ-EIF3A seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
YWHAZ-EIF3A seems lost the major protein functional domain in Tgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
YWHAZ-EIF3A 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
HgeneYWHAZ

GO:0070372

regulation of ERK1 and ERK2 cascade

31024343

HgeneYWHAZ

GO:0090128

regulation of synapse maturation

16959763

TgeneEIF3A

GO:0001732

formation of cytoplasmic translation initiation complex

17581632

TgeneEIF3A

GO:0075522

IRES-dependent viral translational initiation

9573242|23766293|24357634

TgeneEIF3A

GO:0075525

viral translational termination-reinitiation

21347434



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/chr8:101937143/chr10:120796821)
- 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 YWHAZ (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 EIF3A (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)
ENST00000395957YWHAZchr8101937143-ENST00000369144EIF3Achr10120796821-2376760978340212
ENST00000395957YWHAZchr8101937143-ENST00000541549EIF3Achr10120796821-1427760978340212
ENST00000522819YWHAZchr8101937143-ENST00000369144EIF3Achr10120796821-200438859784281
ENST00000522819YWHAZchr8101937143-ENST00000541549EIF3Achr10120796821-1055388606103167
ENST00000395953YWHAZchr8101937143-ENST00000369144EIF3Achr10120796821-2184568786148212
ENST00000395953YWHAZchr8101937143-ENST00000541549EIF3Achr10120796821-1235568786148212
ENST00000395951YWHAZchr8101937143-ENST00000369144EIF3Achr10120796821-219758125702225
ENST00000395951YWHAZchr8101937143-ENST00000541549EIF3Achr10120796821-124858125702225
ENST00000419477YWHAZchr8101937143-ENST00000369144EIF3Achr10120796821-2136520738100212
ENST00000419477YWHAZchr8101937143-ENST00000541549EIF3Achr10120796821-1187520738100212

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
ENST00000395957ENST00000369144YWHAZchr8101937143-EIF3Achr10120796821-0.0016209490.998379
ENST00000395957ENST00000541549YWHAZchr8101937143-EIF3Achr10120796821-0.0034009970.996599
ENST00000522819ENST00000369144YWHAZchr8101937143-EIF3Achr10120796821-0.452177260.5478227
ENST00000522819ENST00000541549YWHAZchr8101937143-EIF3Achr10120796821-0.353739380.6462607
ENST00000395953ENST00000369144YWHAZchr8101937143-EIF3Achr10120796821-0.0007179640.99928206
ENST00000395953ENST00000541549YWHAZchr8101937143-EIF3Achr10120796821-0.0015624060.9984376
ENST00000395951ENST00000369144YWHAZchr8101937143-EIF3Achr10120796821-0.0010340010.998966
ENST00000395951ENST00000541549YWHAZchr8101937143-EIF3Achr10120796821-0.0016971630.9983028
ENST00000419477ENST00000369144YWHAZchr8101937143-EIF3Achr10120796821-0.0006412260.99935883
ENST00000419477ENST00000541549YWHAZchr8101937143-EIF3Achr10120796821-0.0016217430.9983783

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 YWHAZ-EIF3A

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
YWHAZchr8101937143EIF3Achr10120796821581185RYLAEVAAGDDKKGMKVAGEEDQLRN

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Potential FusionNeoAntigen Information of YWHAZ-EIF3A 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 YWHAZ-EIF3A 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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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 YWHAZ-EIF3A

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