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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:LTA4H-LAMA2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LTA4H-LAMA2
FusionPDB ID: 50253
FusionGDB2.0 ID: 50253
HgeneTgene
Gene symbol

LTA4H

LAMA2

Gene ID

4048

3908

Gene nameleukotriene A4 hydrolaselaminin subunit alpha 2
Synonyms-LAMM|MDC1A
Cytomap

12q23.1

6q22.33

Type of geneprotein-codingprotein-coding
Descriptionleukotriene A-4 hydrolaseLTA-4 hydrolasetesticular secretory protein Li 27laminin subunit alpha-2laminin M chainlaminin, alpha 2laminin-12 subunit alphalaminin-2 subunit alphalaminin-4 subunit alphamerosin heavy chainmutant laminin subunit alpha 2
Modification date2020031320200328
UniProtAcc

P09960

Main function of 5'-partner protein: FUNCTION: Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the proinflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:20813919, PubMed:18804029). In addition to its proinflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090). {ECO:0000269|PubMed:11917124, ECO:0000269|PubMed:12207002, ECO:0000269|PubMed:15078870, ECO:0000269|PubMed:18804029, ECO:0000269|PubMed:1897988, ECO:0000269|PubMed:1975494, ECO:0000269|PubMed:20813919, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:2244921, ECO:0000269|PubMed:24591641}.

P24043

Main function of 5'-partner protein: FUNCTION: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
Ensembl transtripts involved in fusion geneENST idsENST00000228740, ENST00000413268, 
ENST00000548375, ENST00000552789, 
ENST00000498257, ENST00000421865, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 11 X 4=39616 X 17 X 7=1904
# samples 1117
** MAII scorelog2(11/396*10)=-1.84799690655495
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(17/1904*10)=-3.48542682717024
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: LTA4H [Title/Abstract] AND LAMA2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LTA4H [Title/Abstract] AND LAMA2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LTA4H(96429139)-LAMA2(129571257), # samples:1
Anticipated loss of major functional domain due to fusion event.LTA4H-LAMA2 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.
LTA4H-LAMA2 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.
LTA4H-LAMA2 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.
LTA4H-LAMA2 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
HgeneLTA4H

GO:0019370

leukotriene biosynthetic process

9774412|15078870

HgeneLTA4H

GO:0043171

peptide catabolic process

9774412|15078870|18804029



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/chr12:96429139/chr6:129571257)
- 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 LTA4H (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 LAMA2 (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)
ENST00000228740LTA4Hchr1296429139-ENST00000421865LAMA2chr6129571257+811030114278872581

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
ENST00000228740ENST00000421865LTA4Hchr1296429139-LAMA2chr6129571257+0.000486210.99951375

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 LTA4H-LAMA2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LTA4Hchr1296429139LAMA2chr612957125730153LTVQSQEDNLRSLLPAVGGQLTFTIS

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Potential FusionNeoAntigen Information of LTA4H-LAMA2 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.
LTA4H-LAMA2_96429139_129571257.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)
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B08:09NLRSLLPAV0.99180.7513817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B44:03QEDNLRSLL0.99170.9639514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B50:02QEDNLRSLL0.98850.5945514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:22NLRSLLPAV0.98760.7286817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B47:01QEDNLRSLL0.98190.5562514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:13NLRSLLPAV0.95930.7841817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:13QEDNLRSLL0.95110.8807514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B45:01QEDNLRSLL0.93150.8674514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:27NLRSLLPAV0.91640.7558817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:38NLRSLLPAV0.88910.7287817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:11NLRSLLPAV0.81590.7291817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:04NLRSLLPAV0.7180.8289817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:19NLRSLLPAV0.65720.6649817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:17NLRSLLPAV0.63430.7619817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B41:01QEDNLRSLL0.5630.9132514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B45:01QEDNLRSLLP0.9930.8632515
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:13SQEDNLRSLL0.92380.8349414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B13:01SQEDNLRSLL0.8180.8074414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:08QEDNLRSLL0.92020.9197514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:07LLPAVGGQL0.85310.52721221
LTA4H-LAMA2chr1296429139chr6129571257301HLA-C01:17LLPAVGGQL0.80840.91361221
LTA4H-LAMA2chr1296429139chr6129571257301HLA-C01:30LLPAVGGQL0.70240.90361221
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:08SQEDNLRSLL0.95610.8556414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B40:04QEDNLRSLL0.99880.6869514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-A02:03NLRSLLPAV0.99650.7735817
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B44:07QEDNLRSLL0.99170.9639514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B44:26QEDNLRSLL0.99170.9639514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B44:13QEDNLRSLL0.99170.9639514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:02QEDNLRSLL0.9510.8824514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B18:11QEDNLRSLL0.94310.8653514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:11QEDNLRSLL0.920.8928514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-C01:02LLPAVGGQL0.79450.90991221
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B41:03QEDNLRSLL0.76660.7528514
LTA4H-LAMA2chr1296429139chr6129571257301HLA-C01:03LLPAVGGQL0.73330.92881221
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B39:02SQEDNLRSLL0.95250.8378414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B15:73SQEDNLRSLL0.93940.6573414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B15:30SQEDNLRSLL0.93860.6452414
LTA4H-LAMA2chr1296429139chr6129571257301HLA-B41:03SQEDNLRSLL0.65760.6245414

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Potential FusionNeoAntigen Information of LTA4H-LAMA2 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.
LTA4H-LAMA2_96429139_129571257.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)
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1001QEDNLRSLLPAVGGQ520
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1001EDNLRSLLPAVGGQL621
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1002QEDNLRSLLPAVGGQ520
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1002EDNLRSLLPAVGGQL621
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1002SQEDNLRSLLPAVGG419
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1003QEDNLRSLLPAVGGQ520
LTA4H-LAMA2chr1296429139chr6129571257301DRB1-1003EDNLRSLLPAVGGQL621

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Fusion breakpoint peptide structures of LTA4H-LAMA2

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
1605EDNLRSLLPAVGGQLTA4HLAMA2chr1296429139chr6129571257301

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LTA4H-LAMA2

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-B14:023BVN1605EDNLRSLLPAVGGQ-7.9962-8.1096
HLA-B14:023BVN1605EDNLRSLLPAVGGQ-5.70842-6.74372
HLA-B52:013W391605EDNLRSLLPAVGGQ-6.83737-6.95077
HLA-B52:013W391605EDNLRSLLPAVGGQ-4.4836-5.5189
HLA-A11:014UQ21605EDNLRSLLPAVGGQ-10.0067-10.1201
HLA-A11:014UQ21605EDNLRSLLPAVGGQ-9.03915-10.0745
HLA-A24:025HGA1605EDNLRSLLPAVGGQ-6.56204-6.67544
HLA-A24:025HGA1605EDNLRSLLPAVGGQ-5.42271-6.45801
HLA-B44:053DX81605EDNLRSLLPAVGGQ-7.85648-8.89178
HLA-B44:053DX81605EDNLRSLLPAVGGQ-5.3978-5.5112
HLA-A02:016TDR1605EDNLRSLLPAVGGQ-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of LTA4H-LAMA2

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
LTA4H-LAMA2chr1296429139chr61295712571221LLPAVGGQLCTGCTCCCAGCAGTAGGAGGACAGTTG
LTA4H-LAMA2chr1296429139chr6129571257414SQEDNLRSLLTCTCAGGAGGACAATCTGCGCAGCCTGCTC
LTA4H-LAMA2chr1296429139chr6129571257514QEDNLRSLLCAGGAGGACAATCTGCGCAGCCTGCTC
LTA4H-LAMA2chr1296429139chr6129571257515QEDNLRSLLPCAGGAGGACAATCTGCGCAGCCTGCTCCCA
LTA4H-LAMA2chr1296429139chr6129571257817NLRSLLPAVAATCTGCGCAGCCTGCTCCCAGCAGTA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
LTA4H-LAMA2chr1296429139chr6129571257419SQEDNLRSLLPAVGGTCTCAGGAGGACAATCTGCGCAGCCTGCTCCCAGCAGTAGGAGGA
LTA4H-LAMA2chr1296429139chr6129571257520QEDNLRSLLPAVGGQCAGGAGGACAATCTGCGCAGCCTGCTCCCAGCAGTAGGAGGACAG
LTA4H-LAMA2chr1296429139chr6129571257621EDNLRSLLPAVGGQLGAGGACAATCTGCGCAGCCTGCTCCCAGCAGTAGGAGGACAGTTG

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Information of the samples that have these potential fusion neoantigens of LTA4H-LAMA2

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
SARCLTA4H-LAMA2chr1296429139ENST00000228740chr6129571257ENST00000421865TCGA-3B-A9HS-01A

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Potential target of CAR-T therapy development for LTA4H-LAMA2

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 LTA4H-LAMA2

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 LTA4H-LAMA2

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