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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:TSEN2-KLK2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: TSEN2-KLK2
FusionPDB ID: 94532
FusionGDB2.0 ID: 94532
HgeneTgene
Gene symbol

TSEN2

KLK2

Gene ID

80746

3817

Gene nametRNA splicing endonuclease subunit 2kallikrein related peptidase 2
SynonymsPCH2B|SEN2|SEN2LKLK2A2|hGK-1|hK2
Cytomap

3p25.2

19q13.33

Type of geneprotein-codingprotein-coding
DescriptiontRNA-splicing endonuclease subunit Sen2TSEN2 tRNA splicing endonuclease subunithsSen2tRNA-intron endonuclease Sen2kallikrein-2glandular kallikrein 2glandular kallikrein-1kallikrein 2, prostatictissue kallikrein-2
Modification date2020031320200313
UniProtAcc.

P20151

Main function of 5'-partner protein: FUNCTION: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
Ensembl transtripts involved in fusion geneENST idsENST00000284995, ENST00000314571, 
ENST00000383797, ENST00000402228, 
ENST00000415684, ENST00000444864, 
ENST00000454502, ENST00000475595, 
ENST00000597509, ENST00000358049, 
ENST00000391810, ENST00000325321, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score7 X 12 X 4=33615 X 20 X 2=600
# samples 1321
** MAII scorelog2(13/336*10)=-1.36994960975031
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(21/600*10)=-1.51457317282976
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: TSEN2 [Title/Abstract] AND KLK2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: TSEN2 [Title/Abstract] AND KLK2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TSEN2(12533716)-KLK2(51379728), # samples:1
TSEN2(12533716)-KLK2(51377977), # samples:1
TSEN2(12533590)-KLK2(51377976), # samples:1
TSEN2(12533590)-KLK2(51379727), # samples:1
TSEN2(12533715)-KLK2(51379727), # samples:1
Anticipated loss of major functional domain due to fusion event.TSEN2-KLK2 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.
TSEN2-KLK2 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.
TSEN2-KLK2 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF.
TSEN2-KLK2 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF.
TSEN2-KLK2 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target 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
HgeneTSEN2

GO:0006388

tRNA splicing, via endonucleolytic cleavage and ligation

17495927



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/chr3:12533716/chr19:51379728)
- 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 TSEN2 (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 KLK2 (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)
ENST00000314571TSEN2chr312533716+ENST00000325321KLK2chr1951377977+31223741031113336
ENST00000383797TSEN2chr312533716+ENST00000325321KLK2chr1951377977+3111363921102336
ENST00000454502TSEN2chr312533716+ENST00000325321KLK2chr1951377977+3111363921102336
ENST00000402228TSEN2chr312533716+ENST00000325321KLK2chr1951377977+31744261551165336
ENST00000444864TSEN2chr312533716+ENST00000325321KLK2chr1951377977+34066583871397336
ENST00000284995TSEN2chr312533716+ENST00000325321KLK2chr1951377977+34066583871397336
ENST00000415684TSEN2chr312533716+ENST00000325321KLK2chr1951377977+3040292211031336

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
ENST00000314571ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.0290440730.97095597
ENST00000383797ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.0281912090.9718088
ENST00000454502ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.0281912090.9718088
ENST00000402228ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.0267640650.97323596
ENST00000444864ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.028240870.97175914
ENST00000284995ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.028240870.97175914
ENST00000415684ENST00000325321TSEN2chr312533716+KLK2chr1951377977+0.0268614390.9731386

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 TSEN2-KLK2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
TSEN2chr312533716KLK2chr195137797729290FTISDPKLVAKWKGAVPLIQSRIVGG
TSEN2chr312533716KLK2chr195137797729291TISDPKLVAKWKGAVPLIQSRIVGGW
TSEN2chr312533716KLK2chr195137797736390FTISDPKLVAKWKGAVPLIQSRIVGG
TSEN2chr312533716KLK2chr195137797736391TISDPKLVAKWKGAVPLIQSRIVGGW
TSEN2chr312533716KLK2chr195137797737490FTISDPKLVAKWKGAVPLIQSRIVGG
TSEN2chr312533716KLK2chr195137797737491TISDPKLVAKWKGAVPLIQSRIVGGW
TSEN2chr312533716KLK2chr195137797742690FTISDPKLVAKWKGAVPLIQSRIVGG
TSEN2chr312533716KLK2chr195137797742691TISDPKLVAKWKGAVPLIQSRIVGGW
TSEN2chr312533716KLK2chr195137797765890FTISDPKLVAKWKGAVPLIQSRIVGG
TSEN2chr312533716KLK2chr195137797765891TISDPKLVAKWKGAVPLIQSRIVGGW

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Potential FusionNeoAntigen Information of TSEN2-KLK2 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.
TSEN2-KLK2_12533716_51377977.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)
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:24AKWKGAVPL0.9810.7014817
TSEN2-KLK2chr312533716chr1951377977658HLA-B27:07AKWKGAVPL0.95110.7138817
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:01AKWKGAVPL0.94690.9632817
TSEN2-KLK2chr312533716chr1951377977658HLA-A31:02GAVPLIQSR0.92240.69071221
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:13AKWKGAVPL0.77860.9825817
TSEN2-KLK2chr312533716chr1951377977658HLA-B15:10AKWKGAVPL0.57310.7807817
TSEN2-KLK2chr312533716chr1951377977658HLA-B48:01AKWKGAVPL0.36350.8057817
TSEN2-KLK2chr312533716chr1951377977658HLA-B15:03AKWKGAVPL0.35560.9324817
TSEN2-KLK2chr312533716chr1951377977658HLA-B07:10AKWKGAVPL0.03230.5433817
TSEN2-KLK2chr312533716chr1951377977658HLA-A31:02KGAVPLIQSR0.94590.75451121
TSEN2-KLK2chr312533716chr1951377977658HLA-A31:06KGAVPLIQSR0.85010.62641121
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:09AKWKGAVPL0.9560.8278817
TSEN2-KLK2chr312533716chr1951377977658HLA-A31:01GAVPLIQSR0.94950.65841221
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:05AKWKGAVPL0.76590.9557817
TSEN2-KLK2chr312533716chr1951377977658HLA-B48:03AKWKGAVPL0.17210.8088817
TSEN2-KLK2chr312533716chr1951377977658HLA-A31:01KGAVPLIQSR0.95770.71741121
TSEN2-KLK2chr312533716chr1951377977658HLA-B27:06AKWKGAVPL0.99140.8938817
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:02AKWKGAVPL0.9540.9819817
TSEN2-KLK2chr312533716chr1951377977658HLA-B39:31AKWKGAVPL0.9410.9633817
TSEN2-KLK2chr312533716chr1951377977658HLA-A30:01KWKGAVPLI0.77690.8746918
TSEN2-KLK2chr312533716chr1951377977658HLA-B15:09AKWKGAVPL0.40260.932817
TSEN2-KLK2chr312533716chr1951377977658HLA-B48:02AKWKGAVPL0.21340.9651817
TSEN2-KLK2chr312533716chr1951377977658HLA-B15:68AKWKGAVPL0.190.8515817
TSEN2-KLK2chr312533716chr1951377977658HLA-B40:12AKWKGAVPL0.17210.8088817
TSEN2-KLK2chr312533716chr1951377977658HLA-B48:05AKWKGAVPL0.07960.5086817

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Potential FusionNeoAntigen Information of TSEN2-KLK2 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.
TSEN2-KLK2_12533716_51377977.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)
TSEN2-KLK2chr312533716chr1951377977658DRB1-0902LVAKWKGAVPLIQSR621
TSEN2-KLK2chr312533716chr1951377977658DRB1-0902VAKWKGAVPLIQSRI722
TSEN2-KLK2chr312533716chr1951377977658DRB1-1103SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1103DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1155DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1155SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1163SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1163DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1176SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1176DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1185SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1185DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1324SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1324DPKLVAKWKGAVPLI318
TSEN2-KLK2chr312533716chr1951377977658DRB1-1354SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB1-1375SDPKLVAKWKGAVPL217
TSEN2-KLK2chr312533716chr1951377977658DRB5-0112LVAKWKGAVPLIQSR621

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Fusion breakpoint peptide structures of TSEN2-KLK2

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
5759LVAKWKGAVPLIQSTSEN2KLK2chr312533716chr1951377977658

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TSEN2-KLK2

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-B14:023BVN5759LVAKWKGAVPLIQS-7.9962-8.1096
HLA-B14:023BVN5759LVAKWKGAVPLIQS-5.70842-6.74372
HLA-B52:013W395759LVAKWKGAVPLIQS-6.83737-6.95077
HLA-B52:013W395759LVAKWKGAVPLIQS-4.4836-5.5189
HLA-A11:014UQ25759LVAKWKGAVPLIQS-10.0067-10.1201
HLA-A11:014UQ25759LVAKWKGAVPLIQS-9.03915-10.0745
HLA-A24:025HGA5759LVAKWKGAVPLIQS-6.56204-6.67544
HLA-A24:025HGA5759LVAKWKGAVPLIQS-5.42271-6.45801
HLA-B44:053DX85759LVAKWKGAVPLIQS-7.85648-8.89178
HLA-B44:053DX85759LVAKWKGAVPLIQS-5.3978-5.5112
HLA-A02:016TDR5759LVAKWKGAVPLIQS-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of TSEN2-KLK2

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
TSEN2-KLK2chr312533716chr19513779771121KGAVPLIQSRGGAAAGGTGCCGTGCCCCTCATCCAGTCTC
TSEN2-KLK2chr312533716chr19513779771221GAVPLIQSRAAGGTGCCGTGCCCCTCATCCAGTCTC
TSEN2-KLK2chr312533716chr1951377977817AKWKGAVPLTTGCTAAATGGAAAGGTGCCGTGCCCC
TSEN2-KLK2chr312533716chr1951377977918KWKGAVPLICTAAATGGAAAGGTGCCGTGCCCCTCA

check button mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs.
Fusion geneHchrHbpTchrTbpStart in +/-13AAEnd in +/-13AAFusionNeoAntigen peptideFusionNEoAntigen RNA sequence
TSEN2-KLK2chr312533716chr1951377977217SDPKLVAKWKGAVPLTTTCAGATCCTAAACTGGTTGCTAAATGGAAAGGTGCCGTGCCCC
TSEN2-KLK2chr312533716chr1951377977318DPKLVAKWKGAVPLICAGATCCTAAACTGGTTGCTAAATGGAAAGGTGCCGTGCCCCTCA
TSEN2-KLK2chr312533716chr1951377977621LVAKWKGAVPLIQSRAACTGGTTGCTAAATGGAAAGGTGCCGTGCCCCTCATCCAGTCTC
TSEN2-KLK2chr312533716chr1951377977722VAKWKGAVPLIQSRITGGTTGCTAAATGGAAAGGTGCCGTGCCCCTCATCCAGTCTCGGA

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Information of the samples that have these potential fusion neoantigens of TSEN2-KLK2

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
PRADTSEN2-KLK2chr312533716ENST00000284995chr1951377977ENST00000325321TCGA-G9-6378

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Potential target of CAR-T therapy development for TSEN2-KLK2

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 TSEN2-KLK2

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 TSEN2-KLK2

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
TgeneKLK2C0033578Prostatic Neoplasms2CTD_human
TgeneKLK2C0376358Malignant neoplasm of prostate2CTD_human