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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:LCLAT1-EPHA3

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LCLAT1-EPHA3
FusionPDB ID: 44234
FusionGDB2.0 ID: 44234
HgeneTgene
Gene symbol

LCLAT1

EPHA3

Gene ID

253558

2042

Gene namelysocardiolipin acyltransferase 1EPH receptor A3
Synonyms1AGPAT8|AGPAT8|ALCAT1|HSRG1849|LYCAT|UNQ1849EK4|ETK|ETK1|HEK|HEK4|TYRO4
Cytomap

2p23.1

3p11.1

Type of geneprotein-codingprotein-coding
Descriptionlysocardiolipin acyltransferase 11-AGP acyltransferase 81-AGPAT 81-acylglycerol-3-phosphate O-acyltransferase 8acyl-CoA:lysocardiolipin acyltransferase 1ephrin type-A receptor 3EPH-like kinase 4TYRO4 protein tyrosine kinaseeph-like tyrosine kinase 1human embryo kinase 1testicular tissue protein Li 64tyrosine-protein kinase receptor ETK1
Modification date2020031320200313
UniProtAcc

Q6UWP7

Main function of 5'-partner protein: FUNCTION: Exhibits acyl-CoA:lysocardiolipin acyltransferase (ALCAT) activity; catalyzes the reacylation of lyso-cardiolipin to cardiolipin (CL), a key step in CL remodeling (By similarity). Recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors (By similarity). Also exhibits 1-acyl-sn-glycerol-3-phosphate acyltransferase activity (AGPAT) activity; converts 1-acyl-sn-glycerol-3- phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3- phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:16620771). Possesses both lysophosphatidylinositol acyltransferase (LPIAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities (PubMed:19075029). Required for establishment of the hematopoietic and endothelial lineages (By similarity). {ECO:0000250|UniProtKB:Q3UN02, ECO:0000269|PubMed:16620771, ECO:0000269|PubMed:19075029}.

P29320

Main function of 5'-partner protein: FUNCTION: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation and regulates the formation of the atrioventricular canal and septum during development probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development. {ECO:0000269|PubMed:11870224}.
Ensembl transtripts involved in fusion geneENST idsENST00000491680, ENST00000309052, 
ENST00000319406, ENST00000359433, 
ENST00000379509, ENST00000540623, 
ENST00000336596, ENST00000452448, 
ENST00000494014, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score8 X 6 X 5=2408 X 9 X 5=360
# samples 99
** MAII scorelog2(9/240*10)=-1.41503749927884
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(9/360*10)=-2
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LCLAT1 [Title/Abstract] AND EPHA3 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LCLAT1 [Title/Abstract] AND EPHA3 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LCLAT1(30756180)-EPHA3(89390066), # samples:2
Anticipated loss of major functional domain due to fusion event.LCLAT1-EPHA3 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.
LCLAT1-EPHA3 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.
LCLAT1-EPHA3 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.
LCLAT1-EPHA3 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
TgeneEPHA3

GO:0018108

peptidyl-tyrosine phosphorylation

11877430

TgeneEPHA3

GO:0032956

regulation of actin cytoskeleton organization

11870224

TgeneEPHA3

GO:0043087

regulation of GTPase activity

11870224

TgeneEPHA3

GO:0045806

negative regulation of endocytosis

11877430

TgeneEPHA3

GO:0048013

ephrin receptor signaling pathway

11870224

TgeneEPHA3

GO:0051893

regulation of focal adhesion assembly

11870224

TgeneEPHA3

GO:0070507

regulation of microtubule cytoskeleton organization

11870224

TgeneEPHA3

GO:1903078

positive regulation of protein localization to plasma membrane

11877430



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/chr2:30756180/chr3:89390066)
- 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 LCLAT1 (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 EPHA3 (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)
ENST00000379509LCLAT1chr230756180+ENST00000336596EPHA3chr389390066+5286516982653851
ENST00000379509LCLAT1chr230756180+ENST00000452448EPHA3chr389390066+2161516981321407
ENST00000379509LCLAT1chr230756180+ENST00000494014EPHA3chr389390066+2714516982458786
ENST00000319406LCLAT1chr230756180+ENST00000336596EPHA3chr389390066+54506802022817871
ENST00000319406LCLAT1chr230756180+ENST00000452448EPHA3chr389390066+23256802021485427
ENST00000319406LCLAT1chr230756180+ENST00000494014EPHA3chr389390066+28786802022622806
ENST00000359433LCLAT1chr230756180+ENST00000336596EPHA3chr389390066+54576872092824871
ENST00000359433LCLAT1chr230756180+ENST00000452448EPHA3chr389390066+23326872091492427
ENST00000359433LCLAT1chr230756180+ENST00000494014EPHA3chr389390066+28856872092629806
ENST00000309052LCLAT1chr230756180+ENST00000336596EPHA3chr389390066+54576872092824871
ENST00000309052LCLAT1chr230756180+ENST00000452448EPHA3chr389390066+23326872091492427
ENST00000309052LCLAT1chr230756180+ENST00000494014EPHA3chr389390066+28856872092629806
ENST00000540623LCLAT1chr230756180+ENST00000336596EPHA3chr389390066+56548845203021833
ENST00000540623LCLAT1chr230756180+ENST00000452448EPHA3chr389390066+25298845201689389
ENST00000540623LCLAT1chr230756180+ENST00000494014EPHA3chr389390066+30828845202826768

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
ENST00000379509ENST00000336596LCLAT1chr230756180+EPHA3chr389390066+0.0001081920.99989176
ENST00000379509ENST00000452448LCLAT1chr230756180+EPHA3chr389390066+0.0006432740.9993567
ENST00000379509ENST00000494014LCLAT1chr230756180+EPHA3chr389390066+0.0003897810.99961025
ENST00000319406ENST00000336596LCLAT1chr230756180+EPHA3chr389390066+0.0002703360.9997297
ENST00000319406ENST00000452448LCLAT1chr230756180+EPHA3chr389390066+0.0009501590.99904984
ENST00000319406ENST00000494014LCLAT1chr230756180+EPHA3chr389390066+0.0008640240.99913603
ENST00000359433ENST00000336596LCLAT1chr230756180+EPHA3chr389390066+0.0002748570.99972516
ENST00000359433ENST00000452448LCLAT1chr230756180+EPHA3chr389390066+0.0010218210.99897826
ENST00000359433ENST00000494014LCLAT1chr230756180+EPHA3chr389390066+0.0009249830.99907494
ENST00000309052ENST00000336596LCLAT1chr230756180+EPHA3chr389390066+0.0002748570.99972516
ENST00000309052ENST00000452448LCLAT1chr230756180+EPHA3chr389390066+0.0010218210.99897826
ENST00000309052ENST00000494014LCLAT1chr230756180+EPHA3chr389390066+0.0009249830.99907494
ENST00000540623ENST00000336596LCLAT1chr230756180+EPHA3chr389390066+0.0001257210.99987423
ENST00000540623ENST00000452448LCLAT1chr230756180+EPHA3chr389390066+0.0008094820.9991905
ENST00000540623ENST00000494014LCLAT1chr230756180+EPHA3chr389390066+0.0004944510.9995055

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 LCLAT1-EPHA3

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LCLAT1chr230756180EPHA3chr389390066516139ICLKASLKGVPGFACRPGFYKALDGN
LCLAT1chr230756180EPHA3chr389390066680159ICLKASLKGVPGFACRPGFYKALDGN
LCLAT1chr230756180EPHA3chr389390066687159ICLKASLKGVPGFACRPGFYKALDGN
LCLAT1chr230756180EPHA3chr389390066884121ICLKASLKGVPGFACRPGFYKALDGN

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Potential FusionNeoAntigen Information of LCLAT1-EPHA3 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.
LCLAT1-EPHA3_30756180_89390066.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)
LCLAT1-EPHA3chr230756180chr389390066687HLA-A31:02KGVPGFACR0.90520.6204716
LCLAT1-EPHA3chr230756180chr389390066687HLA-A31:02SLKGVPGFACR0.990.6531516
LCLAT1-EPHA3chr230756180chr389390066687HLA-A31:01KGVPGFACR0.96430.5547716
LCLAT1-EPHA3chr230756180chr389390066687HLA-C01:17FACRPGFYKAL0.99180.96541223
LCLAT1-EPHA3chr230756180chr389390066687HLA-A31:01SLKGVPGFACR0.99160.594516
LCLAT1-EPHA3chr230756180chr389390066687HLA-C01:30FACRPGFYKAL0.96410.97461223
LCLAT1-EPHA3chr230756180chr389390066687HLA-A02:03SLKGVPGFA0.9920.5937514
LCLAT1-EPHA3chr230756180chr389390066687HLA-C01:02FACRPGFYKAL0.9880.96381223

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Potential FusionNeoAntigen Information of LCLAT1-EPHA3 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 LCLAT1-EPHA3

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
5155LKGVPGFACRPGFYLCLAT1EPHA3chr230756180chr389390066687

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LCLAT1-EPHA3

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-B14:023BVN5155LKGVPGFACRPGFY-5.01701-5.12881
HLA-B14:023BVN5155LKGVPGFACRPGFY-4.08172-5.12482
HLA-B52:013W395155LKGVPGFACRPGFY-5.96604-6.07784
HLA-B52:013W395155LKGVPGFACRPGFY-3.70595-4.74905
HLA-A11:014UQ25155LKGVPGFACRPGFY-7.16358-7.27538
HLA-A11:014UQ25155LKGVPGFACRPGFY-1.0381-2.0812
HLA-A24:025HGA5155LKGVPGFACRPGFY-5.54382-5.65562
HLA-A24:025HGA5155LKGVPGFACRPGFY-4.26495-5.30805
HLA-B44:053DX85155LKGVPGFACRPGFY-5.85983-5.97163
HLA-B44:053DX85155LKGVPGFACRPGFY-3.88354-4.92664

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Vaccine Design for the FusionNeoAntigens of LCLAT1-EPHA3

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
LCLAT1-EPHA3chr230756180chr3893900661223FACRPGFYKALTTGCTTGTCGACCAGGTTTCTACAAGGCATTGG
LCLAT1-EPHA3chr230756180chr389390066514SLKGVPGFAGTCTCAAAGGTGTTCCTGGATTTGCTT
LCLAT1-EPHA3chr230756180chr389390066516SLKGVPGFACRGTCTCAAAGGTGTTCCTGGATTTGCTTGTCGAC
LCLAT1-EPHA3chr230756180chr389390066716KGVPGFACRAAGGTGTTCCTGGATTTGCTTGTCGAC

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 LCLAT1-EPHA3

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
SKCMLCLAT1-EPHA3chr230756180ENST00000309052chr389390066ENST00000336596TCGA-EB-A550-01A

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Potential target of CAR-T therapy development for LCLAT1-EPHA3

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
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000309052+4747_67159415.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000309052+4786_106159415.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000319406+4747_67159309.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000319406+4786_106159309.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000359433+4747_67159309.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000359433+4786_106159309.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000379509+3647_67121377.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000379509+3686_106121377.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000540623+5847_67121377.0TransmembraneHelical
HgeneLCLAT1chr2:30756180chr3:89390066ENST00000540623+5886_106121377.0TransmembraneHelical
TgeneEPHA3chr2:30756180chr3:89390066ENST00000336596217542_5650984.0TransmembraneHelical
TgeneEPHA3chr2:30756180chr3:89390066ENST0000045244827542_5650540.0TransmembraneHelical

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 LCLAT1-EPHA3

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 LCLAT1-EPHA3

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