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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-CDK17

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LTA4H-CDK17
FusionPDB ID: 50250
FusionGDB2.0 ID: 50250
HgeneTgene
Gene symbol

LTA4H

CDK17

Gene ID

4048

5128

Gene nameleukotriene A4 hydrolasecyclin dependent kinase 17
Synonyms-PCTAIRE2|PCTK2
Cytomap

12q23.1

12q23.1

Type of geneprotein-codingprotein-coding
Descriptionleukotriene A-4 hydrolaseLTA-4 hydrolasetesticular secretory protein Li 27cyclin-dependent kinase 17PCTAIRE-motif protein kinase 2cell division protein kinase 17protein kinase cdc2-related PCTAIRE-2serine/threonine-protein kinase PCTAIRE-2
Modification date2020031320200313
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}.

Q00537

Main function of 5'-partner protein: FUNCTION: May play a role in terminally differentiated neurons. Has a Ser/Thr-phosphorylating activity for histone H1 (By similarity). {ECO:0000250}.
Ensembl transtripts involved in fusion geneENST idsENST00000228740, ENST00000413268, 
ENST00000548375, ENST00000552789, 
ENST00000553042, ENST00000261211, 
ENST00000542666, ENST00000543119, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 11 X 4=3969 X 6 X 4=216
# samples 119
** MAII scorelog2(11/396*10)=-1.84799690655495
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: LTA4H [Title/Abstract] AND CDK17 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LTA4H [Title/Abstract] AND CDK17 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LTA4H(96400091)-CDK17(96694138), # samples:2
Anticipated loss of major functional domain due to fusion event.LTA4H-CDK17 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-CDK17 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-CDK17 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-CDK17 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-CDK17 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF.
LTA4H-CDK17 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
LTA4H-CDK17 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF.
LTA4H-CDK17 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF.
LTA4H-CDK17 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
LTA4H-CDK17 seems lost the major protein functional domain in Tgene partner, which is a kinase 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
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/chr12:96400091/chr12:96694138)
- 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 CDK17 (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)
ENST00000228740LTA4Hchr1296400091-ENST00000261211CDK17chr1296694138-468216721422700852
ENST00000228740LTA4Hchr1296400091-ENST00000543119CDK17chr1296694138-304716721422700852
ENST00000228740LTA4Hchr1296400091-ENST00000542666CDK17chr1296694138-292716721422700852
ENST00000552789LTA4Hchr1296400091-ENST00000261211CDK17chr1296694138-45701560932588831
ENST00000552789LTA4Hchr1296400091-ENST00000543119CDK17chr1296694138-29351560932588831
ENST00000552789LTA4Hchr1296400091-ENST00000542666CDK17chr1296694138-28151560932588831
ENST00000413268LTA4Hchr1296400091-ENST00000261211CDK17chr1296694138-461316031362631831
ENST00000413268LTA4Hchr1296400091-ENST00000543119CDK17chr1296694138-297816031362631831
ENST00000413268LTA4Hchr1296400091-ENST00000542666CDK17chr1296694138-285816031362631831
ENST00000228740LTA4Hchr1296400092-ENST00000261211CDK17chr1296694138-468216721422700852
ENST00000228740LTA4Hchr1296400092-ENST00000543119CDK17chr1296694138-304716721422700852
ENST00000228740LTA4Hchr1296400092-ENST00000542666CDK17chr1296694138-292716721422700852
ENST00000552789LTA4Hchr1296400092-ENST00000261211CDK17chr1296694138-45701560932588831
ENST00000552789LTA4Hchr1296400092-ENST00000543119CDK17chr1296694138-29351560932588831
ENST00000552789LTA4Hchr1296400092-ENST00000542666CDK17chr1296694138-28151560932588831
ENST00000413268LTA4Hchr1296400092-ENST00000261211CDK17chr1296694138-461316031362631831
ENST00000413268LTA4Hchr1296400092-ENST00000543119CDK17chr1296694138-297816031362631831
ENST00000413268LTA4Hchr1296400092-ENST00000542666CDK17chr1296694138-285816031362631831

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
ENST00000228740ENST00000261211LTA4Hchr1296400091-CDK17chr1296694138-0.0001480250.99985194
ENST00000228740ENST00000543119LTA4Hchr1296400091-CDK17chr1296694138-0.0004716560.9995284
ENST00000228740ENST00000542666LTA4Hchr1296400091-CDK17chr1296694138-0.0004166930.9995833
ENST00000552789ENST00000261211LTA4Hchr1296400091-CDK17chr1296694138-0.000219620.99978036
ENST00000552789ENST00000543119LTA4Hchr1296400091-CDK17chr1296694138-0.0006098680.9993901
ENST00000552789ENST00000542666LTA4Hchr1296400091-CDK17chr1296694138-0.0005469260.9994531
ENST00000413268ENST00000261211LTA4Hchr1296400091-CDK17chr1296694138-0.0002244230.9997756
ENST00000413268ENST00000543119LTA4Hchr1296400091-CDK17chr1296694138-0.0006508710.9993492
ENST00000413268ENST00000542666LTA4Hchr1296400091-CDK17chr1296694138-0.0005855250.99941444
ENST00000228740ENST00000261211LTA4Hchr1296400092-CDK17chr1296694138-0.0001480250.99985194
ENST00000228740ENST00000543119LTA4Hchr1296400092-CDK17chr1296694138-0.0004716560.9995284
ENST00000228740ENST00000542666LTA4Hchr1296400092-CDK17chr1296694138-0.0004166930.9995833
ENST00000552789ENST00000261211LTA4Hchr1296400092-CDK17chr1296694138-0.000219620.99978036
ENST00000552789ENST00000543119LTA4Hchr1296400092-CDK17chr1296694138-0.0006098680.9993901
ENST00000552789ENST00000542666LTA4Hchr1296400092-CDK17chr1296694138-0.0005469260.9994531
ENST00000413268ENST00000261211LTA4Hchr1296400092-CDK17chr1296694138-0.0002244230.9997756
ENST00000413268ENST00000543119LTA4Hchr1296400092-CDK17chr1296694138-0.0006508710.9993492
ENST00000413268ENST00000542666LTA4Hchr1296400092-CDK17chr1296694138-0.0005855250.99941444

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-CDK17

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LTA4Hchr1296400091CDK17chr12966941381560489HQLNEFLAQTLQRSEIGFGKMETYIK
LTA4Hchr1296400091CDK17chr12966941381603489HQLNEFLAQTLQRSEIGFGKMETYIK
LTA4Hchr1296400091CDK17chr12966941381672510HQLNEFLAQTLQRSEIGFGKMETYIK
LTA4Hchr1296400092CDK17chr12966941381560489HQLNEFLAQTLQRSEIGFGKMETYIK
LTA4Hchr1296400092CDK17chr12966941381603489HQLNEFLAQTLQRSEIGFGKMETYIK
LTA4Hchr1296400092CDK17chr12966941381672510HQLNEFLAQTLQRSEIGFGKMETYIK

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Potential FusionNeoAntigen Information of LTA4H-CDK17 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-CDK17_96400091_96694138.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-CDK17chr1296400091chr12966941381672HLA-B27:05QRSEIGFGK0.99870.74171120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:04QRSEIGFGK0.99410.59221120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B48:01AQTLQRSEI0.98120.5728716
LTA4H-CDK17chr1296400091chr12966941381672HLA-B13:02AQTLQRSEI0.8820.8566716
LTA4H-CDK17chr1296400091chr12966941381672HLA-B13:01AQTLQRSEI0.70930.9832716
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:05QRSEIGFGKM0.99980.56061121
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:04QRSEIGFGKM0.99970.6321121
LTA4H-CDK17chr1296400091chr12966941381672HLA-B57:03QTLQRSEIGF0.90030.9877818
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:14QRSEIGFGK0.99360.64321120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:03QRSEIGFGK0.97690.77431120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:03QRSEIGFGKM0.99370.58061121
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:14LQRSEIGFGK0.98560.73451020
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:14TLQRSEIGFGK0.98480.5332920
LTA4H-CDK17chr1296400091chr12966941381672HLA-B15:68LQRSEIGF0.99690.58971018
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:08QRSEIGFGK0.99820.62111120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:10QRSEIGFGK0.99810.75891120
LTA4H-CDK17chr1296400091chr12966941381672HLA-B15:73AQTLQRSEI0.80470.923716
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:10QRSEIGFGKM0.99980.72851121
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:06QRSEIGFGKM0.99960.65071121
LTA4H-CDK17chr1296400091chr12966941381672HLA-B27:09QRSEIGFGKM0.99890.57331121

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Potential FusionNeoAntigen Information of LTA4H-CDK17 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 LTA4H-CDK17

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
4779LAQTLQRSEIGFGKLTA4HCDK17chr1296400091chr12966941381672

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LTA4H-CDK17

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-B14:023BVN4779LAQTLQRSEIGFGK-7.15543-7.26883
HLA-B14:023BVN4779LAQTLQRSEIGFGK-4.77435-5.80965
HLA-B52:013W394779LAQTLQRSEIGFGK-6.80875-6.92215
HLA-B52:013W394779LAQTLQRSEIGFGK-4.20386-5.23916
HLA-A11:014UQ24779LAQTLQRSEIGFGK-7.5194-8.5547
HLA-A11:014UQ24779LAQTLQRSEIGFGK-6.9601-7.0735
HLA-A24:025HGA4779LAQTLQRSEIGFGK-7.52403-7.63743
HLA-A24:025HGA4779LAQTLQRSEIGFGK-5.82433-6.85963
HLA-B27:056PYJ4779LAQTLQRSEIGFGK-3.28285-4.31815
HLA-B44:053DX84779LAQTLQRSEIGFGK-5.91172-6.94702
HLA-B44:053DX84779LAQTLQRSEIGFGK-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LTA4H-CDK17

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-CDK17chr1296400091chr12966941381018LQRSEIGFCTCCAGAGGTCAGAAATTGGCTTT
LTA4H-CDK17chr1296400091chr12966941381020LQRSEIGFGKCTCCAGAGGTCAGAAATTGGCTTTGGAAAA
LTA4H-CDK17chr1296400091chr12966941381120QRSEIGFGKCAGAGGTCAGAAATTGGCTTTGGAAAA
LTA4H-CDK17chr1296400091chr12966941381121QRSEIGFGKMCAGAGGTCAGAAATTGGCTTTGGAAAAATG
LTA4H-CDK17chr1296400091chr1296694138716AQTLQRSEIGCACAGACGCTCCAGAGGTCAGAAATT
LTA4H-CDK17chr1296400091chr1296694138818QTLQRSEIGFCAGACGCTCCAGAGGTCAGAAATTGGCTTT
LTA4H-CDK17chr1296400091chr1296694138920TLQRSEIGFGKACGCTCCAGAGGTCAGAAATTGGCTTTGGAAAA

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 LTA4H-CDK17

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
ESCALTA4H-CDK17chr1296400091ENST00000228740chr1296694138ENST00000261211TCGA-2H-A9GN

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Potential target of CAR-T therapy development for LTA4H-CDK17

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-CDK17

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-CDK17

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