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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:ABCC6-LTA4H

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: ABCC6-LTA4H
FusionPDB ID: 312
FusionGDB2.0 ID: 312
HgeneTgene
Gene symbol

ABCC6

LTA4H

Gene ID

368

4048

Gene nameATP binding cassette subfamily C member 6leukotriene A4 hydrolase
SynonymsABC34|ARA|EST349056|GACI2|MLP1|MOAT-E|MOATE|MRP6|PXE|PXE1|URG7-
Cytomap

16p13.11

12q23.1

Type of geneprotein-codingprotein-coding
Descriptionmultidrug resistance-associated protein 6URG7 proteinATP-binding cassette, sub-family C (CFTR/MRP), member 6anthracycline resistance-associated proteinmulti-specific organic anion transporter Eleukotriene A-4 hydrolaseLTA-4 hydrolasetesticular secretory protein Li 27
Modification date2020031320200313
UniProtAcc

O95255

Main function of 5'-partner protein: FUNCTION: [Isoform 1]: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of glutathione conjugates such as leukotriene-c4 (LTC4) and N-ethylmaleimide S-glutathione (NEM-GS) (in vitro), and an anionic cyclopentapeptide endothelin antagonist, BQ-123 (PubMed:11880368, PubMed:12414644). Does not appear to actively transport drugs outside the cell. Confers low levels of cellular resistance to etoposide, teniposide, anthracyclines and cisplatin (PubMed:12414644). {ECO:0000269|PubMed:11880368, ECO:0000269|PubMed:12414644}.; FUNCTION: [Isoform 1]: Mediates the release of nucleoside triphosphates, predominantly ATP, into the circulation, where it is rapidly converted into AMP and the mineralization inhibitor inorganic pyrophosphate (PPi) by the ecto-enzyme ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), therefore playing a role in PPi homeostasis. {ECO:0000269|PubMed:24277820, ECO:0000269|PubMed:24969777}.; FUNCTION: [Isoform 2]: Inhibits TNF-alpha-mediated apoptosis through blocking one or more caspases. {ECO:0000269|PubMed:23912081}.

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}.
Ensembl transtripts involved in fusion geneENST idsENST00000205557, ENST00000574094, 
ENST00000575728, 
ENST00000413268, 
ENST00000548375, ENST00000228740, 
ENST00000552789, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score5 X 5 X 3=759 X 9 X 6=486
# samples 58
** MAII scorelog2(5/75*10)=-0.584962500721156
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(8/486*10)=-2.60288440871842
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: ABCC6 [Title/Abstract] AND LTA4H [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: ABCC6 [Title/Abstract] AND LTA4H [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)ABCC6(16276269)-LTA4H(96397698), # samples:2
Anticipated loss of major functional domain due to fusion event.ABCC6-LTA4H 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.
ABCC6-LTA4H 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.
ABCC6-LTA4H 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.
ABCC6-LTA4H 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
TgeneLTA4H

GO:0019370

leukotriene biosynthetic process

9774412|15078870

TgeneLTA4H

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/chr16:16276269/chr12:96397698)
- 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 ABCC6 (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 LTA4H (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)
ENST00000205557ABCC6chr1616276269-ENST00000228740LTA4Hchr1296397698-27442277302582850
ENST00000205557ABCC6chr1616276269-ENST00000552789LTA4Hchr1296397698-27422277302582850

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
ENST00000205557ENST00000228740ABCC6chr1616276269-LTA4Hchr1296397698-0.0033696750.9966304
ENST00000205557ENST00000552789ABCC6chr1616276269-LTA4Hchr1296397698-0.0033680730.9966319

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 ABCC6-LTA4H

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
ABCC6chr1616276269LTA4Hchr12963976982277749SFPEGIHTSIGEQAPLPLGHIKRMQE

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Potential FusionNeoAntigen Information of ABCC6-LTA4H 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.
ABCC6-LTA4H_16276269_96397698.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)
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B40:01GEQAPLPL0.99960.54021018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:13GEQAPLPL0.96920.97251018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:06IHTSIGEQA0.99410.7454514
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B38:01IHTSIGEQAPL0.99760.9541516
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B38:02IHTSIGEQAPL0.99760.9488516
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:08GEQAPLPL0.98730.95331018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C08:15IGEQAPLPL0.99970.9769918
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:19TSIGEQAPL0.99950.9848716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:08TSIGEQAPL0.99920.9188716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:05IHTSIGEQA0.98630.794514
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C01:30QAPLPLGHI0.64210.94851221
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C01:17QAPLPLGHI0.4520.95641221
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:05IHTSIGEQAPL0.9980.8574516
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B40:36GEQAPLPL0.99960.52241018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B40:04GEQAPLPL0.99950.83871018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B41:03GEQAPLPL0.96110.79571018
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C08:02IGEQAPLPL0.99970.9769918
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:04TSIGEQAPL0.99960.9852716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:03TSIGEQAPL0.99960.9852716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:17TSIGEQAPL0.9990.9475716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C03:06TSIGEQAPL0.99490.9825716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B35:13TSIGEQAPL0.92930.8429716
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B15:09IHTSIGEQA0.89110.8514
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B18:04EQAPLPLGH0.72810.7291120
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B39:11IHTSIGEQA0.55310.739514
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C01:02QAPLPLGHI0.45260.95691221
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-C01:03QAPLPLGHI0.36860.91881221
ABCC6-LTA4Hchr1616276269chr12963976982277HLA-B38:05IHTSIGEQAPL0.99760.9541516

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Potential FusionNeoAntigen Information of ABCC6-LTA4H 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.
ABCC6-LTA4H_16276269_96397698.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)
ABCC6-LTA4Hchr1616276269chr12963976982277DRB1-0906PEGIHTSIGEQAPLP217

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Fusion breakpoint peptide structures of ABCC6-LTA4H

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
3525HTSIGEQAPLPLGHABCC6LTA4Hchr1616276269chr12963976982277

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of ABCC6-LTA4H

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-B14:023BVN3525HTSIGEQAPLPLGH-7.40191-7.51531
HLA-B14:023BVN3525HTSIGEQAPLPLGH-4.51196-5.54726
HLA-B52:013W393525HTSIGEQAPLPLGH-6.11546-6.22886
HLA-B52:013W393525HTSIGEQAPLPLGH-4.26916-5.30446
HLA-A11:014UQ23525HTSIGEQAPLPLGH-6.4796-6.593
HLA-A24:025HGA3525HTSIGEQAPLPLGH-10.1747-10.2881
HLA-A24:025HGA3525HTSIGEQAPLPLGH-3.37098-4.40628
HLA-B27:056PYJ3525HTSIGEQAPLPLGH-7.13632-7.24972
HLA-B44:053DX83525HTSIGEQAPLPLGH-4.68988-4.80328
HLA-B44:053DX83525HTSIGEQAPLPLGH-3.4669-4.5022
HLA-A02:016TDR3525HTSIGEQAPLPLGH-4.29889-5.33419

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Vaccine Design for the FusionNeoAntigens of ABCC6-LTA4H

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
ABCC6-LTA4Hchr1616276269chr12963976981018GEQAPLPLGGGGAGCAGGCACCTCTTCCATTG
ABCC6-LTA4Hchr1616276269chr12963976981120EQAPLPLGHGAGCAGGCACCTCTTCCATTGGGGCAC
ABCC6-LTA4Hchr1616276269chr12963976981221QAPLPLGHICAGGCACCTCTTCCATTGGGGCACATA
ABCC6-LTA4Hchr1616276269chr1296397698514IHTSIGEQAATCCACACTTCAATTGGGGAGCAGGCA
ABCC6-LTA4Hchr1616276269chr1296397698516IHTSIGEQAPLATCCACACTTCAATTGGGGAGCAGGCACCTCTT
ABCC6-LTA4Hchr1616276269chr1296397698716TSIGEQAPLACTTCAATTGGGGAGCAGGCACCTCTT
ABCC6-LTA4Hchr1616276269chr1296397698918IGEQAPLPLATTGGGGAGCAGGCACCTCTTCCATTG

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
ABCC6-LTA4Hchr1616276269chr1296397698217PEGIHTSIGEQAPLPCCTGAGGGAATCCACACTTCAATTGGGGAGCAGGCACCTCTTCCA

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Information of the samples that have these potential fusion neoantigens of ABCC6-LTA4H

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
LUADABCC6-LTA4Hchr1616276269ENST00000205557chr1296397698ENST00000228740TCGA-44-7672-01A

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Potential target of CAR-T therapy development for ABCC6-LTA4H

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
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731132_1497491504.0TransmembraneHelical%3B Name%3D4
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731168_1887491504.0TransmembraneHelical%3B Name%3D5
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731303_3237491504.0TransmembraneHelical%3B Name%3D6
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-173132_527491504.0TransmembraneHelical%3B Name%3D1
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731350_3707491504.0TransmembraneHelical%3B Name%3D7
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731427_4477491504.0TransmembraneHelical%3B Name%3D8
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731451_4717491504.0TransmembraneHelical%3B Name%3D9
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731534_5547491504.0TransmembraneHelical%3B Name%3D10
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-1731576_5967491504.0TransmembraneHelical%3B Name%3D11
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-173173_937491504.0TransmembraneHelical%3B Name%3D2
HgeneABCC6chr16:16276269chr12:96397698ENST00000205557-173199_1197491504.0TransmembraneHelical%3B Name%3D3

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 ABCC6-LTA4H

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 ABCC6-LTA4H

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