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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:LMTK3-DBP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: LMTK3-DBP
FusionPDB ID: 45852
FusionGDB2.0 ID: 45852
HgeneTgene
Gene symbol

LMTK3

DBP

Gene ID

114783

3295

Gene namelemur tyrosine kinase 3hydroxysteroid 17-beta dehydrogenase 4
SynonymsLMR3|PPP1R101|TYKLM3DBP|MFE-2|MPF-2|PRLTS1|SDR8C1
Cytomap

19q13.33

5q23.1

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase LMTK3protein phosphatase 1, regulatory subunit 101peroxisomal multifunctional enzyme type 217-beta-HSD 417-beta-HSD IV17-beta-hydroxysteroid dehydrogenase 417beta-estradiol dehydrogenase type IV3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholest-24-enoyl-CoA hydrataseD-3-hydroxyacyl-CoA dehydratase
Modification date2020031320200327
UniProtAcc

Q96Q04

Main function of 5'-partner protein: FUNCTION: Protein kinase which phosphorylates ESR1 (in vitro) and protects it against proteasomal degradation. May also regulate ESR1 levels indirectly via a PKC-AKT-FOXO3 pathway where it decreases the activity of PKC and the phosphorylation of AKT, thereby increasing binding of transcriptional activator FOXO3 to the ESR1 promoter and increasing ESR1 transcription (PubMed:21602804). Involved in endocytic trafficking of N-methyl-D-aspartate receptors (NMDAR) in neurons (By similarity). {ECO:0000250|UniProtKB:Q5XJV6, ECO:0000269|PubMed:21602804}.

Q10586

Main function of 5'-partner protein: FUNCTION: This transcriptional activator recognizes and binds to the sequence 5'-RTTAYGTAAY-3' found in the promoter of genes such as albumin, CYP2A4 and CYP2A5. It is not essential for circadian rhythm generation, but modulates important clock output genes. May be a direct target for regulation by the circadian pacemaker component clock. May affect circadian period and sleep regulation.
Ensembl transtripts involved in fusion geneENST idsENST00000270238, ENST00000600059, 
ENST00000601104, ENST00000593500, 
ENST00000222122, ENST00000599385, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score3 X 3 X 3=273 X 1 X 3=9
# samples 33
** MAII scorelog2(3/27*10)=0.15200309344505
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
log2(3/9*10)=1.73696559416621
effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs).
DoF>8 and MAII>0
Fusion gene context

PubMed: LMTK3 [Title/Abstract] AND DBP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: LMTK3 [Title/Abstract] AND DBP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)LMTK3(48994365)-DBP(49134309), # samples:3
Anticipated loss of major functional domain due to fusion event.LMTK3-DBP 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.
LMTK3-DBP 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.
LMTK3-DBP 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.
LMTK3-DBP 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.
LMTK3-DBP seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
LMTK3-DBP seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF.
LMTK3-DBP seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF.
LMTK3-DBP seems lost the major protein functional domain in Tgene partner, which is a transcription factor 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
HgeneLMTK3

GO:0010923

negative regulation of phosphatase activity

19389623

TgeneDBP

GO:0006635

fatty acid beta-oxidation

10400999

TgeneDBP

GO:0008209

androgen metabolic process

7487879

TgeneDBP

GO:0008210

estrogen metabolic process

7487879

TgeneDBP

GO:0036111

very long-chain fatty-acyl-CoA metabolic process

9482850

TgeneDBP

GO:0036112

medium-chain fatty-acyl-CoA metabolic process

9089413



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/chr19:48994365/chr19:49134309)
- 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 LMTK3 (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 DBP (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)
ENST00000600059LMTK3chr1948994365-ENST00000222122DBPchr1949134309-56174594345981531
ENST00000600059LMTK3chr1948994365-ENST00000599385DBPchr1949134309-49624594345981531
ENST00000270238LMTK3chr1948994365-ENST00000222122DBPchr1949134309-54764453044571485
ENST00000270238LMTK3chr1948994365-ENST00000599385DBPchr1949134309-48214453044571485

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
ENST00000600059ENST00000222122LMTK3chr1948994365-DBPchr1949134309-0.0041404830.99585956
ENST00000600059ENST00000599385LMTK3chr1948994365-DBPchr1949134309-0.0045825420.9954175
ENST00000270238ENST00000222122LMTK3chr1948994365-DBPchr1949134309-0.0033433330.99665666
ENST00000270238ENST00000599385LMTK3chr1948994365-DBPchr1949134309-0.0036740810.9963259

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 LMTK3-DBP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
LMTK3chr1948994365DBPchr19491343094453625WASPLFPAPRPFPAQSSASGSFLLSG
LMTK3chr1948994365DBPchr19491343094453773FLDPLMGAAAPQYPGRGPPPAPPPPP
LMTK3chr1948994365DBPchr19491343094594671WASPLFPAPRPFPAQSSASGSFLLSG

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Potential FusionNeoAntigen Information of LMTK3-DBP 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.
LMTK3-DBP_48994365_49134309.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)
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:05YPGRGPPPA0.99850.58431221
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:01YPGRGPPPA0.98850.71061221
LMTK3-DBPchr1948994365chr19491343094453HLA-A68:08AAAPQYPGR0.98340.5867716
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:01YPGRGPPPA0.96460.63321221
LMTK3-DBPchr1948994365chr19491343094453HLA-A31:06AAAPQYPGR0.96130.7146716
LMTK3-DBPchr1948994365chr19491343094453HLA-A74:09AAAPQYPGR0.95820.839716
LMTK3-DBPchr1948994365chr19491343094453HLA-A74:03AAAPQYPGR0.95820.839716
LMTK3-DBPchr1948994365chr19491343094453HLA-A74:11AAAPQYPGR0.95820.839716
LMTK3-DBPchr1948994365chr19491343094453HLA-A34:01AAAPQYPGR0.9390.5681716
LMTK3-DBPchr1948994365chr19491343094453HLA-A34:05AAAPQYPGR0.9390.5681716
LMTK3-DBPchr1948994365chr19491343094453HLA-A66:01AAAPQYPGR0.93440.5066716
LMTK3-DBPchr1948994365chr19491343094453HLA-A66:03AAAPQYPGR0.90680.6041716
LMTK3-DBPchr1948994365chr19491343094453HLA-A31:02AAAPQYPGR0.90180.7735716
LMTK3-DBPchr1948994365chr19491343094453HLA-B08:09YPGRGPPPA0.89050.90061221
LMTK3-DBPchr1948994365chr19491343094453HLA-A34:02AAAPQYPGR0.87750.6008716
LMTK3-DBPchr1948994365chr19491343094453HLA-B35:04YPGRGPPPA0.78790.95511221
LMTK3-DBPchr1948994365chr19491343094453HLA-B35:02YPGRGPPPA0.78790.95511221
LMTK3-DBPchr1948994365chr19491343094453HLA-B82:01YPGRGPPPA0.28830.72621221
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:05YPGRGPPPAP0.99090.63921222
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:02YPGRGPPPAP0.99050.56721222
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:01YPGRGPPPAP0.9730.68711222
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:01YPGRGPPPAP0.9410.59531222
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:01APQYPGRGPP0.81250.5057919
LMTK3-DBPchr1948994365chr19491343094453HLA-B54:01YPGRGPPPA0.99740.89541221
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:12YPGRGPPPA0.9810.64271221
LMTK3-DBPchr1948994365chr19491343094453HLA-A31:01AAAPQYPGR0.96410.7504716
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:04YPGRGPPPA0.95050.84511221
LMTK3-DBPchr1948994365chr19491343094453HLA-B35:12YPGRGPPPA0.78790.95511221
LMTK3-DBPchr1948994365chr19491343094453HLA-B78:01YPGRGPPPA0.68360.85941221
LMTK3-DBPchr1948994365chr19491343094453HLA-B39:10YPGRGPPPA0.63230.97111221
LMTK3-DBPchr1948994365chr19491343094453HLA-B54:01YPGRGPPPAP0.99630.90031222
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:04YPGRGPPPAP0.96070.61971222
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:02YPGRGPPPA0.98560.78811221
LMTK3-DBPchr1948994365chr19491343094453HLA-B59:01YPGRGPPPA0.96190.8281221
LMTK3-DBPchr1948994365chr19491343094453HLA-A74:01AAAPQYPGR0.95820.839716
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:04YPGRGPPPA0.95720.80191221
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:05YPGRGPPPA0.95080.77531221
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:02YPGRGPPPA0.95050.84511221
LMTK3-DBPchr1948994365chr19491343094453HLA-A66:02AAAPQYPGR0.94430.6223716
LMTK3-DBPchr1948994365chr19491343094453HLA-B35:09YPGRGPPPA0.78790.95511221
LMTK3-DBPchr1948994365chr19491343094453HLA-B67:01YPGRGPPPA0.7280.96981221
LMTK3-DBPchr1948994365chr19491343094453HLA-B78:02YPGRGPPPA0.52860.89731221
LMTK3-DBPchr1948994365chr19491343094453HLA-B82:02YPGRGPPPA0.28830.72621221
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:22YPGRGPPPAP0.99050.56721222
LMTK3-DBPchr1948994365chr19491343094453HLA-B55:02YPGRGPPPAP0.97880.80711222
LMTK3-DBPchr1948994365chr19491343094453HLA-B07:26YPGRGPPPAP0.94310.53941222
LMTK3-DBPchr1948994365chr19491343094453HLA-B56:05YPGRGPPPAP0.80440.71671222
LMTK3-DBPchr1948994365chr19491343094453HLA-B78:02YPGRGPPPAP0.47670.87341222

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Potential FusionNeoAntigen Information of LMTK3-DBP 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 LMTK3-DBP

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
2631GAAAPQYPGRGPPPLMTK3DBPchr1948994365chr19491343094453

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of LMTK3-DBP

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-B14:023BVN2631GAAAPQYPGRGPPP-7.15543-7.26883
HLA-B14:023BVN2631GAAAPQYPGRGPPP-4.77435-5.80965
HLA-B52:013W392631GAAAPQYPGRGPPP-6.80875-6.92215
HLA-B52:013W392631GAAAPQYPGRGPPP-4.20386-5.23916
HLA-A11:014UQ22631GAAAPQYPGRGPPP-7.5194-8.5547
HLA-A11:014UQ22631GAAAPQYPGRGPPP-6.9601-7.0735
HLA-A24:025HGA2631GAAAPQYPGRGPPP-7.52403-7.63743
HLA-A24:025HGA2631GAAAPQYPGRGPPP-5.82433-6.85963
HLA-B27:056PYJ2631GAAAPQYPGRGPPP-3.28285-4.31815
HLA-B44:053DX82631GAAAPQYPGRGPPP-5.91172-6.94702
HLA-B44:053DX82631GAAAPQYPGRGPPP-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of LMTK3-DBP

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
LMTK3-DBPchr1948994365chr19491343091221YPGRGPPPACAGGATGAGAAATACTGGAGCCGGCGG
LMTK3-DBPchr1948994365chr19491343091222YPGRGPPPAPCAGGATGAGAAATACTGGAGCCGGCGGTAC
LMTK3-DBPchr1948994365chr1949134309716AAAPQYPGRCCGACGCCCGGCCCGCAGGATGAGAAA
LMTK3-DBPchr1948994365chr1949134309919APQYPGRGPPCCCGGCCCGCAGGATGAGAAATACTGGAGC

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 LMTK3-DBP

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
STADLMTK3-DBPchr1948994365ENST00000270238chr1949134309ENST00000222122TCGA-CD-8527-01A

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Potential target of CAR-T therapy development for LMTK3-DBP

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
HgeneLMTK3chr19:48994365chr19:49134309ENST00000600059-141540_6014551461.0TransmembraneHelical

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 LMTK3-DBP

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 LMTK3-DBP

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