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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:LNPEP-FLT4

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LNPEP-FLT4
FusionPDB ID: 45864
FusionGDB2.0 ID: 45864
HgeneTgene
Gene symbol

LNPEP

FLT4

Gene ID

4012

2324

Gene nameleucyl and cystinyl aminopeptidasefms related receptor tyrosine kinase 4
SynonymsCAP|IRAP|P-LAP|PLAPCHTD7|FLT-4|FLT41|LMPH1A|LMPHM1|PCL|VEGFR-3|VEGFR3
Cytomap

5q15

5q35.3

Type of geneprotein-codingprotein-coding
Descriptionleucyl-cystinyl aminopeptidaseAT (4) receptorangiotensin IV receptorcystinyl aminopeptidaseinsulin-regulated aminopeptidaseinsulin-regulated membrane aminopeptidaseinsulin-responsive aminopeptidaseotaseoxytocinaseplacental leucine aminopeptidasevascular endothelial growth factor receptor 3Feline McDonough Sarcoma (FMS)-like tyrosine kinase 4VEGF receptor-3fms related tyrosine kinase 4fms-like tyrosine kinase 4primary congenital lymphedematyrosine-protein kinase receptor FLT4
Modification date2020031320200313
UniProtAcc

Q9UIQ6

Main function of 5'-partner protein: FUNCTION: Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. {ECO:0000269|PubMed:11389728, ECO:0000269|PubMed:11707427, ECO:0000269|PubMed:1731608}.

P35916

Main function of 5'-partner protein: FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardiovascular system during embryonic development. Promotes proliferation, survival and migration of endothelial cells, and regulates angiogenic sprouting. Signaling by activated FLT4 leads to enhanced production of VEGFC, and to a lesser degree VEGFA, thereby creating a positive feedback loop that enhances FLT4 signaling. Modulates KDR signaling by forming heterodimers. The secreted isoform 3 may function as a decoy receptor for VEGFC and/or VEGFD and play an important role as a negative regulator of VEGFC-mediated lymphangiogenesis and angiogenesis. Binding of vascular growth factors to isoform 1 or isoform 2 leads to the activation of several signaling cascades; isoform 2 seems to be less efficient in signal transduction, because it has a truncated C-terminus and therefore lacks several phosphorylation sites. Mediates activation of the MAPK1/ERK2, MAPK3/ERK1 signaling pathway, of MAPK8 and the JUN signaling pathway, and of the AKT1 signaling pathway. Phosphorylates SHC1. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Promotes phosphorylation of MAPK8 at 'Thr-183' and 'Tyr-185', and of AKT1 at 'Ser-473'. {ECO:0000269|PubMed:11532940, ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15474514, ECO:0000269|PubMed:16076871, ECO:0000269|PubMed:16452200, ECO:0000269|PubMed:17210781, ECO:0000269|PubMed:19610651, ECO:0000269|PubMed:19779139, ECO:0000269|PubMed:20224550, ECO:0000269|PubMed:20431062, ECO:0000269|PubMed:20445537, ECO:0000269|PubMed:21273538, ECO:0000269|PubMed:7675451, ECO:0000269|PubMed:8700872, ECO:0000269|PubMed:9435229}.
Ensembl transtripts involved in fusion geneENST idsENST00000395784, ENST00000231368, 
ENST00000395770, 
ENST00000261937, 
ENST00000393347, ENST00000502649, 
ENST00000424276, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score9 X 8 X 6=4325 X 4 X 3=60
# samples 105
** MAII scorelog2(10/432*10)=-2.11103131238874
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
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: LNPEP [Title/Abstract] AND FLT4 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LNPEP [Title/Abstract] AND FLT4 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LNPEP(96271878)-FLT4(180048904), # samples:3
Anticipated loss of major functional domain due to fusion event.LNPEP-FLT4 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.
LNPEP-FLT4 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.
LNPEP-FLT4 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.
LNPEP-FLT4 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
TgeneFLT4

GO:0018108

peptidyl-tyrosine phosphorylation

7898938

TgeneFLT4

GO:0035924

cellular response to vascular endothelial growth factor stimulus

9435229

TgeneFLT4

GO:0038084

vascular endothelial growth factor signaling pathway

23878260

TgeneFLT4

GO:0046777

protein autophosphorylation

7675451|9435229|23878260

TgeneFLT4

GO:0048010

vascular endothelial growth factor receptor signaling pathway

9012504



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/chr5:96271878/chr5:180048904)
- 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 LNPEP (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 FLT4 (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)
ENST00000231368LNPEPchr596271878+ENST00000261937FLT4chr5180048904-48327114913145884
ENST00000231368LNPEPchr596271878+ENST00000393347FLT4chr5180048904-32677114912950819
ENST00000231368LNPEPchr596271878+ENST00000502649FLT4chr5180048904-31397114912974827

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
ENST00000231368ENST00000261937LNPEPchr596271878+FLT4chr5180048904-0.0080076970.9919923
ENST00000231368ENST00000393347LNPEPchr596271878+FLT4chr5180048904-0.0157196820.98428035
ENST00000231368ENST00000502649LNPEPchr596271878+FLT4chr5180048904-0.0149452470.98505473

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 LNPEP-FLT4

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LNPEPchr596271878FLT4chr518004890471173RSRGGGKMEPFTNAIPDGFTIESKPS

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Potential FusionNeoAntigen Information of LNPEP-FLT4 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.
LNPEP-FLT4_96271878_180048904.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)
LNPEP-FLT4chr596271878chr5180048904711HLA-B39:06GKMEPFTNA0.98160.8073514
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:03NAIPDGFTI0.97960.80111221
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:02NAIPDGFTI0.97870.89411221
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:04NAIPDGFTI0.97870.89411221
LNPEP-FLT4chr596271878chr5180048904711HLA-B52:01NAIPDGFTI0.97840.88111221
LNPEP-FLT4chr596271878chr5180048904711HLA-A02:13KMEPFTNAI0.96920.5621615
LNPEP-FLT4chr596271878chr5180048904711HLA-B15:17FTNAIPDGF0.95290.80211019
LNPEP-FLT4chr596271878chr5180048904711HLA-B15:16FTNAIPDGF0.93260.58791019
LNPEP-FLT4chr596271878chr5180048904711HLA-B13:01KMEPFTNAI0.23690.9408615
LNPEP-FLT4chr596271878chr5180048904711HLA-C05:09KMEPFTNAI0.99960.9427615
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:07NAIPDGFTI0.99940.97361221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:19NAIPDGFTI0.99840.98521221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:08NAIPDGFTI0.99540.73441221
LNPEP-FLT4chr596271878chr5180048904711HLA-C04:06NAIPDGFTI0.99280.59481221
LNPEP-FLT4chr596271878chr5180048904711HLA-B51:07NAIPDGFTI0.98030.80951221
LNPEP-FLT4chr596271878chr5180048904711HLA-C08:13NAIPDGFTI0.97970.91821221
LNPEP-FLT4chr596271878chr5180048904711HLA-C08:04NAIPDGFTI0.97970.91821221
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:12NAIPDGFTI0.97870.89411221
LNPEP-FLT4chr596271878chr5180048904711HLA-C15:04FTNAIPDGF0.88680.83641019
LNPEP-FLT4chr596271878chr5180048904711HLA-B73:01GKMEPFTNA0.87250.5918514
LNPEP-FLT4chr596271878chr5180048904711HLA-C08:03NAIPDGFTI0.86930.95681221
LNPEP-FLT4chr596271878chr5180048904711HLA-C06:03NAIPDGFTI0.86710.98851221
LNPEP-FLT4chr596271878chr5180048904711HLA-C12:12NAIPDGFTI0.79010.9161221
LNPEP-FLT4chr596271878chr5180048904711HLA-C02:06NAIPDGFTI0.59170.94331221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:14FTNAIPDGF0.55360.97271019
LNPEP-FLT4chr596271878chr5180048904711HLA-C04:03KMEPFTNAI0.99960.8026615
LNPEP-FLT4chr596271878chr5180048904711HLA-C05:01KMEPFTNAI0.99960.9427615
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:04NAIPDGFTI0.99850.98291221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:03NAIPDGFTI0.99850.98291221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:17NAIPDGFTI0.99830.95211221
LNPEP-FLT4chr596271878chr5180048904711HLA-C01:03KMEPFTNAI0.99780.9512615
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:13NAIPDGFTI0.97970.80261221
LNPEP-FLT4chr596271878chr5180048904711HLA-B35:09NAIPDGFTI0.97870.89411221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:06NAIPDGFTI0.95850.98281221
LNPEP-FLT4chr596271878chr5180048904711HLA-C16:04NAIPDGFTI0.94380.97681221
LNPEP-FLT4chr596271878chr5180048904711HLA-C03:02FTNAIPDGF0.94130.96871019
LNPEP-FLT4chr596271878chr5180048904711HLA-A32:01KMEPFTNAI0.92740.9746615
LNPEP-FLT4chr596271878chr5180048904711HLA-A25:01FTNAIPDGF0.92340.92761019
LNPEP-FLT4chr596271878chr5180048904711HLA-B57:02FTNAIPDGF0.90910.83881019
LNPEP-FLT4chr596271878chr5180048904711HLA-A69:01NAIPDGFTI0.89670.51281221
LNPEP-FLT4chr596271878chr5180048904711HLA-C15:09FTNAIPDGF0.88680.83641019
LNPEP-FLT4chr596271878chr5180048904711HLA-C08:01NAIPDGFTI0.86930.95681221
LNPEP-FLT4chr596271878chr5180048904711HLA-C12:03NAIPDGFTI0.81410.97411221
LNPEP-FLT4chr596271878chr5180048904711HLA-B15:73KMEPFTNAI0.79920.8776615
LNPEP-FLT4chr596271878chr5180048904711HLA-C12:02FTNAIPDGF0.38610.98261019
LNPEP-FLT4chr596271878chr5180048904711HLA-C02:02FTNAIPDGF0.01450.98411019
LNPEP-FLT4chr596271878chr5180048904711HLA-C02:10FTNAIPDGF0.01450.98411019

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Potential FusionNeoAntigen Information of LNPEP-FLT4 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 LNPEP-FLT4

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
4430KMEPFTNAIPDGFTLNPEPFLT4chr596271878chr5180048904711

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LNPEP-FLT4

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-B14:023BVN4430KMEPFTNAIPDGFT-5.50071-6.53601
HLA-B14:023BVN4430KMEPFTNAIPDGFT-5.44997-5.56337
HLA-B52:013W394430KMEPFTNAIPDGFT-6.87928-6.99268
HLA-B52:013W394430KMEPFTNAIPDGFT-3.95744-4.99274
HLA-A24:025HGA4430KMEPFTNAIPDGFT-7.30598-7.41938
HLA-A24:025HGA4430KMEPFTNAIPDGFT-5.09366-6.12896
HLA-B44:053DX84430KMEPFTNAIPDGFT-5.64505-5.75845
HLA-B44:053DX84430KMEPFTNAIPDGFT-4.1878-5.2231
HLA-A02:016TDR4430KMEPFTNAIPDGFT-0.0912853-1.12659

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Vaccine Design for the FusionNeoAntigens of LNPEP-FLT4

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
LNPEP-FLT4chr596271878chr51800489041019FTNAIPDGFTCACCAATGCCATCCCCGACGGCTTCA
LNPEP-FLT4chr596271878chr51800489041221NAIPDGFTIATGCCATCCCCGACGGCTTCACCATCG
LNPEP-FLT4chr596271878chr5180048904514GKMEPFTNAGGAAAATGGAGCCCTTCACCAATGCCA
LNPEP-FLT4chr596271878chr5180048904615KMEPFTNAIAAATGGAGCCCTTCACCAATGCCATCC

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 LNPEP-FLT4

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
SKCMLNPEP-FLT4chr596271878ENST00000231368chr5180048904ENST00000261937TCGA-D3-A8GN-06A

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Potential target of CAR-T therapy development for LNPEP-FLT4

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
TgeneFLT4chr5:96271878chr5:180048904ENST000002619371130776_79601364.0TransmembraneHelical
TgeneFLT4chr5:96271878chr5:180048904ENST000003933471130776_79601299.0TransmembraneHelical

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 LNPEP-FLT4

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 LNPEP-FLT4

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