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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:TLK2-FN3KRP

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TLK2-FN3KRP
FusionPDB ID: 91155
FusionGDB2.0 ID: 91155
HgeneTgene
Gene symbol

TLK2

FN3KRP

Gene ID

11011

79672

Gene nametousled like kinase 2fructosamine 3 kinase related protein
SynonymsHsHPK|MRD57|PKU-ALPHAFN3KL
Cytomap

17q23.2

17q25.3

Type of geneprotein-codingprotein-coding
Descriptionserine/threonine-protein kinase tousled-like 2ketosamine-3-kinaseFN3K-related proteinprotein-psicosamine 3-kinase FN3KRPtestis secretory sperm-binding protein Li 211a
Modification date2020031320200313
UniProtAcc.

Q9HA64

Main function of 5'-partner protein: FUNCTION: Ketosamine-3-kinase involved in protein deglycation by mediating phosphorylation of ribuloselysine and psicoselysine on glycated proteins, to generate ribuloselysine-3 phosphate and psicoselysine-3 phosphate, respectively (PubMed:14633848, PubMed:15137908). Ribuloselysine-3 phosphate and psicoselysine-3 phosphate adducts are unstable and decompose under physiological conditions (PubMed:14633848, PubMed:15137908). Not able to phosphorylate fructoselysine (PubMed:14633848). {ECO:0000269|PubMed:14633848, ECO:0000269|PubMed:15137908}.
Ensembl transtripts involved in fusion geneENST idsENST00000577616, ENST00000326270, 
ENST00000343388, ENST00000346027, 
ENST00000542523, ENST00000582809, 
ENST00000269373, ENST00000535965, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score18 X 11 X 9=17829 X 9 X 6=486
# samples 2412
** MAII scorelog2(24/1782*10)=-2.8923910259134
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(12/486*10)=-2.01792190799726
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TLK2 [Title/Abstract] AND FN3KRP [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TLK2 [Title/Abstract] AND FN3KRP [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TLK2(60558567)-FN3KRP(80676782), # samples:1
Anticipated loss of major functional domain due to fusion event.TLK2-FN3KRP 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.
TLK2-FN3KRP 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
HgeneTLK2

GO:0001672

regulation of chromatin assembly or disassembly

12660173

HgeneTLK2

GO:0006468

protein phosphorylation

12660173

HgeneTLK2

GO:0006974

cellular response to DNA damage stimulus

12660173

HgeneTLK2

GO:0018105

peptidyl-serine phosphorylation

20016786

HgeneTLK2

GO:0035556

intracellular signal transduction

12660173

HgeneTLK2

GO:0071480

cellular response to gamma radiation

12660173



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/chr17:60558567/chr17:80676782)
- 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 TLK2 (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 FN3KRP (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)
ENST00000326270TLK2chr1760558567+ENST00000269373FN3KRPchr1780676782+19843491211137338
ENST00000346027TLK2chr1760558567+ENST00000269373FN3KRPchr1780676782+19873521211140339
ENST00000343388TLK2chr1760558567+ENST00000269373FN3KRPchr1780676782+1862227501015321
ENST00000542523TLK2chr1760558567+ENST00000269373FN3KRPchr1780676782+174110625894289

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
ENST00000326270ENST00000269373TLK2chr1760558567+FN3KRPchr1780676782+0.0034117230.99658823
ENST00000346027ENST00000269373TLK2chr1760558567+FN3KRPchr1780676782+0.0035216530.9964784
ENST00000343388ENST00000269373TLK2chr1760558567+FN3KRPchr1780676782+0.0029886440.9970113
ENST00000542523ENST00000269373TLK2chr1760558567+FN3KRPchr1780676782+0.0029830350.997017

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 TLK2-FN3KRP

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TLK2chr1760558567FN3KRPchr178067678210627LLEARFTGVGVSKARRMFEGEMASLT
TLK2chr1760558567FN3KRPchr178067678222759LLEARFTGVGVSKARRMFEGEMASLT
TLK2chr1760558567FN3KRPchr178067678234976LLEARFTGVGVSKARRMFEGEMASLT
TLK2chr1760558567FN3KRPchr178067678235277LLEARFTGVGVSKARRMFEGEMASLT

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Potential FusionNeoAntigen Information of TLK2-FN3KRP 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.
TLK2-FN3KRP_60558567_80676782.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)
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A66:01FTGVGVSKAR0.96380.5177515
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A66:03FTGVGVSKAR0.8980.549515
TLK2-FN3KRPchr1760558567chr1780676782349HLA-B27:05ARFTGVGVSKA10.5242314
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A31:02RFTGVGVSKAR0.99550.6354415
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A31:06RFTGVGVSKAR0.97640.523415
TLK2-FN3KRPchr1760558567chr1780676782349HLA-B27:14ARFTGVGVSKA10.5716314
TLK2-FN3KRPchr1760558567chr1780676782349HLA-B73:01ARFTGVGVSKA0.99930.8082314
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A31:01RFTGVGVSKAR0.99590.6065415
TLK2-FN3KRPchr1760558567chr1780676782349HLA-A66:02FTGVGVSKAR0.91120.5384515
TLK2-FN3KRPchr1760558567chr1780676782349HLA-B27:10ARFTGVGVSKA10.7172314

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Potential FusionNeoAntigen Information of TLK2-FN3KRP 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.
TLK2-FN3KRP_60558567_80676782.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)
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0401LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0401EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0407LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0407EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0407LLEARFTGVGVSKAR015
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0419LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0419EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0431LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0431EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0433LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0433EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0435LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0435EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0438LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0438EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0443LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0443EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0447LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0447EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0454LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0454EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0461LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0461EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0463LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0463EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0464LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0464EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0474LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0474EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0475LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0475EARFTGVGVSKARRM217
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0476LEARFTGVGVSKARR116
TLK2-FN3KRPchr1760558567chr1780676782349DRB1-0476EARFTGVGVSKARRM217

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Fusion breakpoint peptide structures of TLK2-FN3KRP

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
9380TGVGVSKARRMFEGTLK2FN3KRPchr1760558567chr1780676782349

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TLK2-FN3KRP

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-B14:023BVN9380TGVGVSKARRMFEG-7.15543-7.26883
HLA-B14:023BVN9380TGVGVSKARRMFEG-4.77435-5.80965
HLA-B52:013W399380TGVGVSKARRMFEG-6.80875-6.92215
HLA-B52:013W399380TGVGVSKARRMFEG-4.20386-5.23916
HLA-A11:014UQ29380TGVGVSKARRMFEG-7.5194-8.5547
HLA-A11:014UQ29380TGVGVSKARRMFEG-6.9601-7.0735
HLA-A24:025HGA9380TGVGVSKARRMFEG-7.52403-7.63743
HLA-A24:025HGA9380TGVGVSKARRMFEG-5.82433-6.85963
HLA-B27:056PYJ9380TGVGVSKARRMFEG-3.28285-4.31815
HLA-B44:053DX89380TGVGVSKARRMFEG-5.91172-6.94702
HLA-B44:053DX89380TGVGVSKARRMFEG-4.24346-4.35686

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Vaccine Design for the FusionNeoAntigens of TLK2-FN3KRP

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
TLK2-FN3KRPchr1760558567chr1780676782314ARFTGVGVSKAGCCAGGTTTACTGGAGTAGGTGTTAGTAAGGCC
TLK2-FN3KRPchr1760558567chr1780676782415RFTGVGVSKARAGGTTTACTGGAGTAGGTGTTAGTAAGGCCAGA
TLK2-FN3KRPchr1760558567chr1780676782515FTGVGVSKARTTTACTGGAGTAGGTGTTAGTAAGGCCAGA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TLK2-FN3KRPchr1760558567chr1780676782015LLEARFTGVGVSKARTTATTGGAGGCCAGGTTTACTGGAGTAGGTGTTAGTAAGGCCAGA
TLK2-FN3KRPchr1760558567chr1780676782116LEARFTGVGVSKARRTTGGAGGCCAGGTTTACTGGAGTAGGTGTTAGTAAGGCCAGAAGA
TLK2-FN3KRPchr1760558567chr1780676782217EARFTGVGVSKARRMGAGGCCAGGTTTACTGGAGTAGGTGTTAGTAAGGCCAGAAGAATG

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Information of the samples that have these potential fusion neoantigens of TLK2-FN3KRP

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
UCSTLK2-FN3KRPchr1760558567ENST00000326270chr1780676782ENST00000269373TCGA-N8-A4PQ-01A

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Potential target of CAR-T therapy development for TLK2-FN3KRP

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 TLK2-FN3KRP

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 TLK2-FN3KRP

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