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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:LAP3-DDX1

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LAP3-DDX1
FusionPDB ID: 44034
FusionGDB2.0 ID: 44034
HgeneTgene
Gene symbol

LAP3

DDX1

Gene ID

51056

1653

Gene nameleucine aminopeptidase 3DEAD-box helicase 1
SynonymsHEL-S-106|LAP|LAPEP|PEPSDBP-RB|UKVH5d
Cytomap

4p15.32

2p24.3

Type of geneprotein-codingprotein-coding
Descriptioncytosol aminopeptidaseLAP-3epididymis secretory protein Li 106leucyl aminopeptidasepeptidase Sproline aminopeptidaseprolyl aminopeptidaseATP-dependent RNA helicase DDX1DEAD (Asp-Glu-Ala-Asp) box helicase 1DEAD (Asp-Glu-Ala-Asp) box polypeptide 1DEAD box polypeptide 1DEAD box protein 1DEAD box protein retinoblastomaDEAD box-1DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 1DEAD/H-box h
Modification date2020031320200313
UniProtAcc

P28838

Main function of 5'-partner protein: FUNCTION: Cytolosic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status. {ECO:0000250|UniProtKB:P00727}.

Q9UMR2

Main function of 5'-partner protein: FUNCTION: ATP-dependent RNA helicase involved in mRNA export from the nucleus (PubMed:10428971). Rather than unwinding RNA duplexes, DDX19B functions as a remodeler of ribonucleoprotein particles, whereby proteins bound to nuclear mRNA are dissociated and replaced by cytoplasmic mRNA binding proteins (PubMed:10428971). {ECO:0000269|PubMed:10428971}.
Ensembl transtripts involved in fusion geneENST idsENST00000226299, ENST00000606142, 
ENST00000503467, 
ENST00000233084, 
ENST00000381341, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score4 X 4 X 3=484 X 5 X 3=60
# samples 55
** MAII scorelog2(5/48*10)=0.0588936890535686
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(5/60*10)=-0.263034405833794
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LAP3 [Title/Abstract] AND DDX1 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LAP3 [Title/Abstract] AND DDX1 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LAP3(17583437)-DDX1(15746274), # samples:3
Anticipated loss of major functional domain due to fusion event.LAP3-DDX1 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.
LAP3-DDX1 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.
LAP3-DDX1 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.
LAP3-DDX1 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
TgeneDDX1

GO:0006302

double-strand break repair

18710941

TgeneDDX1

GO:0032508

DNA duplex unwinding

18710941

TgeneDDX1

GO:0090305

nucleic acid phosphodiester bond hydrolysis

18710941



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/chr4:17583437/chr2:15746274)
- 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 LAP3 (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 DDX1 (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)
ENST00000226299LAP3chr417583437+ENST00000381341DDX1chr215746274+22735471842067627
ENST00000226299LAP3chr417583437+ENST00000233084DDX1chr215746274+22635471842067627
ENST00000606142LAP3chr417583437+ENST00000381341DDX1chr215746274+1970244191764581
ENST00000606142LAP3chr417583437+ENST00000233084DDX1chr215746274+1960244191764581
ENST00000226299LAP3chr417583437+ENST00000381341DDX1chr215746273+22735471842067627
ENST00000226299LAP3chr417583437+ENST00000233084DDX1chr215746273+22635471842067627
ENST00000606142LAP3chr417583437+ENST00000381341DDX1chr215746273+1970244191764581
ENST00000606142LAP3chr417583437+ENST00000233084DDX1chr215746273+1960244191764581

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
ENST00000226299ENST00000381341LAP3chr417583437+DDX1chr215746274+0.0006296760.9993704
ENST00000226299ENST00000233084LAP3chr417583437+DDX1chr215746274+0.0006107110.9993893
ENST00000606142ENST00000381341LAP3chr417583437+DDX1chr215746274+0.0006362920.9993637
ENST00000606142ENST00000233084LAP3chr417583437+DDX1chr215746274+0.0006209710.99937904
ENST00000226299ENST00000381341LAP3chr417583437+DDX1chr215746273+0.0006296760.9993704
ENST00000226299ENST00000233084LAP3chr417583437+DDX1chr215746273+0.0006107110.9993893
ENST00000606142ENST00000381341LAP3chr417583437+DDX1chr215746273+0.0006362920.9993637
ENST00000606142ENST00000233084LAP3chr417583437+DDX1chr215746273+0.0006209710.99937904

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 LAP3-DDX1

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LAP3chr417583437DDX1chr21574627324475KAGKTRTFYGLHQNAELKFNFGEEEF
LAP3chr417583437DDX1chr215746273547121KAGKTRTFYGLHQNAELKFNFGEEEF
LAP3chr417583437DDX1chr21574627424475KAGKTRTFYGLHQNAELKFNFGEEEF
LAP3chr417583437DDX1chr215746274547121KAGKTRTFYGLHQNAELKFNFGEEEF

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Potential FusionNeoAntigen Information of LAP3-DDX1 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.
LAP3-DDX1_17583437_15746273.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)
LAP3-DDX1chr417583437chr215746273547HLA-B15:03HQNAELKF0.98040.6151119
LAP3-DDX1chr417583437chr215746273547HLA-B38:01LHQNAELKF0.94670.89581019
LAP3-DDX1chr417583437chr215746273547HLA-B38:02LHQNAELKF0.9430.90121019
LAP3-DDX1chr417583437chr215746273547HLA-B15:18LHQNAELKF0.89880.541019
LAP3-DDX1chr417583437chr215746273547HLA-B13:01HQNAELKFNF0.96310.83441121
LAP3-DDX1chr417583437chr215746273547HLA-A30:08RTFYGLHQNA0.94620.8982515
LAP3-DDX1chr417583437chr215746273547HLA-B38:01GLHQNAELKF0.46380.9296919
LAP3-DDX1chr417583437chr215746273547HLA-B38:02GLHQNAELKF0.41430.9337919
LAP3-DDX1chr417583437chr215746273547HLA-B38:01LHQNAELKFNF0.99860.89851021
LAP3-DDX1chr417583437chr215746273547HLA-B38:01YGLHQNAELKF0.8140.9305819
LAP3-DDX1chr417583437chr215746273547HLA-B38:02YGLHQNAELKF0.76730.9389819
LAP3-DDX1chr417583437chr215746273547HLA-C03:19YGLHQNAEL0.99920.9853817
LAP3-DDX1chr417583437chr215746273547HLA-C08:13YGLHQNAEL0.97870.9694817
LAP3-DDX1chr417583437chr215746273547HLA-C08:04YGLHQNAEL0.97870.9694817
LAP3-DDX1chr417583437chr215746273547HLA-C08:03YGLHQNAEL0.95560.9842817
LAP3-DDX1chr417583437chr215746273547HLA-B39:05LHQNAELKF0.92070.8011019
LAP3-DDX1chr417583437chr215746273547HLA-B73:01TRTFYGLHQNA0.99760.9451415
LAP3-DDX1chr417583437chr215746273547HLA-B15:53HQNAELKF0.99760.63751119
LAP3-DDX1chr417583437chr215746273547HLA-B15:54HQNAELKF0.99470.59941119
LAP3-DDX1chr417583437chr215746273547HLA-B48:02HQNAELKF0.92280.7761119
LAP3-DDX1chr417583437chr215746273547HLA-B35:28HQNAELKF0.91790.80041119
LAP3-DDX1chr417583437chr215746273547HLA-C03:04YGLHQNAEL0.99910.981817
LAP3-DDX1chr417583437chr215746273547HLA-C03:03YGLHQNAEL0.99910.981817
LAP3-DDX1chr417583437chr215746273547HLA-C03:05YGLHQNAEL0.99880.9047817
LAP3-DDX1chr417583437chr215746273547HLA-C08:01YGLHQNAEL0.95560.9842817
LAP3-DDX1chr417583437chr215746273547HLA-C03:06YGLHQNAEL0.95430.9842817
LAP3-DDX1chr417583437chr215746273547HLA-B38:05LHQNAELKF0.94670.89581019
LAP3-DDX1chr417583437chr215746273547HLA-B15:09LHQNAELKF0.69980.57951019
LAP3-DDX1chr417583437chr215746273547HLA-B39:11LHQNAELKF0.41660.78291019
LAP3-DDX1chr417583437chr215746273547HLA-B07:13YGLHQNAEL0.30920.8165817
LAP3-DDX1chr417583437chr215746273547HLA-B15:24HQNAELKFNF0.99980.79461121
LAP3-DDX1chr417583437chr215746273547HLA-B15:53HQNAELKFNF0.99910.66991121
LAP3-DDX1chr417583437chr215746273547HLA-B15:12HQNAELKFNF0.99770.66281121
LAP3-DDX1chr417583437chr215746273547HLA-A30:01RTFYGLHQNA0.94590.9632515
LAP3-DDX1chr417583437chr215746273547HLA-B38:05GLHQNAELKF0.46380.9296919
LAP3-DDX1chr417583437chr215746273547HLA-B38:05LHQNAELKFNF0.99860.89851021
LAP3-DDX1chr417583437chr215746273547HLA-B38:05YGLHQNAELKF0.8140.9305819

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Potential FusionNeoAntigen Information of LAP3-DDX1 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.
LAP3-DDX1_17583437_15746273.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)
LAP3-DDX1chr417583437chr215746273547DRB1-0832KTRTFYGLHQNAELK318
LAP3-DDX1chr417583437chr215746273547DRB1-0832TRTFYGLHQNAELKF419

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Fusion breakpoint peptide structures of LAP3-DDX1

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
9350TFYGLHQNAELKFNLAP3DDX1chr417583437chr215746273547

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LAP3-DDX1

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-B14:023BVN9350TFYGLHQNAELKFN-7.9962-8.1096
HLA-B14:023BVN9350TFYGLHQNAELKFN-5.70842-6.74372
HLA-B52:013W399350TFYGLHQNAELKFN-6.83737-6.95077
HLA-B52:013W399350TFYGLHQNAELKFN-4.4836-5.5189
HLA-A11:014UQ29350TFYGLHQNAELKFN-10.0067-10.1201
HLA-A11:014UQ29350TFYGLHQNAELKFN-9.03915-10.0745
HLA-A24:025HGA9350TFYGLHQNAELKFN-6.56204-6.67544
HLA-A24:025HGA9350TFYGLHQNAELKFN-5.42271-6.45801
HLA-B44:053DX89350TFYGLHQNAELKFN-7.85648-8.89178
HLA-B44:053DX89350TFYGLHQNAELKFN-5.3978-5.5112
HLA-A02:016TDR9350TFYGLHQNAELKFN-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LAP3-DDX1

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
LAP3-DDX1chr417583437chr2157462731019LHQNAELKFCTGCATCAGAATGCTGAACTGAAATTT
LAP3-DDX1chr417583437chr2157462731021LHQNAELKFNFCTGCATCAGAATGCTGAACTGAAATTTAACTTC
LAP3-DDX1chr417583437chr2157462731119HQNAELKFCATCAGAATGCTGAACTGAAATTT
LAP3-DDX1chr417583437chr2157462731121HQNAELKFNFCATCAGAATGCTGAACTGAAATTTAACTTC
LAP3-DDX1chr417583437chr215746273415TRTFYGLHQNAACTCGAACCTTTTATGGTCTGCATCAGAATGCT
LAP3-DDX1chr417583437chr215746273515RTFYGLHQNACGAACCTTTTATGGTCTGCATCAGAATGCT
LAP3-DDX1chr417583437chr215746273817YGLHQNAELTATGGTCTGCATCAGAATGCTGAACTG
LAP3-DDX1chr417583437chr215746273819YGLHQNAELKFTATGGTCTGCATCAGAATGCTGAACTGAAATTT
LAP3-DDX1chr417583437chr215746273919GLHQNAELKFGGTCTGCATCAGAATGCTGAACTGAAATTT

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LAP3-DDX1chr417583437chr215746273318KTRTFYGLHQNAELKAAGACTCGAACCTTTTATGGTCTGCATCAGAATGCTGAACTGAAA
LAP3-DDX1chr417583437chr215746273419TRTFYGLHQNAELKFACTCGAACCTTTTATGGTCTGCATCAGAATGCTGAACTGAAATTT

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Information of the samples that have these potential fusion neoantigens of LAP3-DDX1

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
BLCALAP3-DDX1chr417583437ENST00000226299chr215746273ENST00000233084TCGA-G2-A2EF

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Potential target of CAR-T therapy development for LAP3-DDX1

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 LAP3-DDX1

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 LAP3-DDX1

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