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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:FKBP5-TMPRSS2

Fusion Gene and Fusion Protein Summary

check button Fusion gene summary
Fusion partner gene informationFusion gene name: FKBP5-TMPRSS2
FusionPDB ID: 30519
FusionGDB2.0 ID: 30519
HgeneTgene
Gene symbol

FKBP5

TMPRSS2

Gene ID

2289

7113

Gene nameFKBP prolyl isomerase 5transmembrane serine protease 2
SynonymsAIG6|FKBP51|FKBP54|P54|PPIase|Ptg-10PP9284|PRSS10
Cytomap

6p21.31

21q22.3

Type of geneprotein-codingprotein-coding
Descriptionpeptidyl-prolyl cis-trans isomerase FKBP551 kDa FK506-binding protein51 kDa FKBP54 kDa progesterone receptor-associated immunophilinFF1 antigenFK506 binding protein 5FKBP-51HSP90-binding immunophilinPPIase FKBP5T-cell FK506-binding proteinandrogtransmembrane protease serine 2epitheliasinserine protease 10transmembrane protease, serine 2
Modification date2020032920200313
UniProtAcc

Q13451

Main function of 5'-partner protein: FUNCTION: Immunophilin protein with PPIase and co-chaperone activities (PubMed:11350175). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded (PubMed:12538866). Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). {ECO:0000269|PubMed:11350175, ECO:0000269|PubMed:12538866, ECO:0000269|PubMed:28147277}.

O15393

Main function of 5'-partner protein: FUNCTION: Plasma membrane-anchored serine protease that participates in proteolytic cascades of relevance for the normal physiologic function of the prostate (PubMed:25122198). Androgen-induced TMPRSS2 activates several substrates that include pro-hepatocyte growth factor/HGF, the protease activated receptor-2/F2RL1 or matriptase/ST14 leading to extracellular matrix disruption and metastasis of prostate cancer cells (PubMed:15537383, PubMed:26018085, PubMed:25122198). In addition, activates trigeminal neurons and contribute to both spontaneous pain and mechanical allodynia (By similarity). {ECO:0000250|UniProtKB:Q9JIQ8, ECO:0000269|PubMed:15537383, ECO:0000269|PubMed:25122198, ECO:0000269|PubMed:26018085}.; FUNCTION: (Microbial infection) Facilitates human coronaviruses SARS-CoV and SARS-CoV-2 infections via two independent mechanisms, proteolytic cleavage of ACE2 receptor which promotes viral uptake, and cleavage of coronavirus spike glycoproteins which activates the glycoprotein for host cell entry (PubMed:24227843, PubMed:32142651, PubMed:32404436, PubMed:34159616, PubMed:33051876). Upon SARS-CoV-2 infection, increases syncytia formation by accelerating the fusion process (PubMed:34159616, PubMed:33051876). Proteolytically cleaves and activates the spike glycoproteins of human coronavirus 229E (HCoV-229E) and human coronavirus EMC (HCoV-EMC) and the fusion glycoproteins F0 of Sendai virus (SeV), human metapneumovirus (HMPV), human parainfluenza 1, 2, 3, 4a and 4b viruses (HPIV). Essential for spread and pathogenesis of influenza A virus (strains H1N1, H3N2 and H7N9); involved in proteolytic cleavage and activation of hemagglutinin (HA) protein which is essential for viral infectivity. {ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21325420, ECO:0000269|PubMed:23536651, ECO:0000269|PubMed:23966399, ECO:0000269|PubMed:24027332, ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32404436, ECO:0000269|PubMed:33051876, ECO:0000269|PubMed:34159616}.
Ensembl transtripts involved in fusion geneENST idsENST00000357266, ENST00000536438, 
ENST00000539068, ENST00000542713, 
ENST00000540787, 
ENST00000497881, 
ENST00000332149, ENST00000398585, 
ENST00000458356, 
Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0)* DoF score16 X 11 X 9=158428 X 34 X 5=4760
# samples 1635
** MAII scorelog2(16/1584*10)=-3.30742852519225
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
log2(35/4760*10)=-3.76553474636298
possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs).
DoF>8 and MAII<0
Fusion gene context

PubMed: FKBP5 [Title/Abstract] AND TMPRSS2 [Title/Abstract] AND fusion [Title/Abstract]

Fusion neoantigen context

PubMed: FKBP5 [Title/Abstract] AND TMPRSS2 [Title/Abstract] AND neoantigen [Title/Abstract]

Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0)TMPRSS2(42880008)-FKBP5(35565184), # samples:2
TMPRSS2(42866283)-FKBP5(35565187), # samples:2
FKBP5(35586873)-TMPRSS2(42861520), # samples:1
Anticipated loss of major functional domain due to fusion event.FKBP5-TMPRSS2 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.
FKBP5-TMPRSS2 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.
FKBP5-TMPRSS2 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.
FKBP5-TMPRSS2 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.
TMPRSS2-FKBP5 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.
TMPRSS2-FKBP5 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.
TMPRSS2-FKBP5 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF.
TMPRSS2-FKBP5 seems lost the major protein functional domain in Hgene 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
HgeneFKBP5

GO:0061077

chaperone-mediated protein folding

11350175

TgeneTMPRSS2

GO:0006508

proteolysis

21068237|24227843

TgeneTMPRSS2

GO:0046598

positive regulation of viral entry into host cell

21068237|24227843



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/chr6:42880008/chr21:35565184)
- 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 FKBP5 (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 TMPRSS2 (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)
ENST00000539068FKBP5chr635586873-ENST00000332149TMPRSS2chr2142861520-35437112031951582
ENST00000539068FKBP5chr635586873-ENST00000398585TMPRSS2chr2142861520-35417112031951582
ENST00000539068FKBP5chr635586873-ENST00000458356TMPRSS2chr2142861520-20857112031951582
ENST00000536438FKBP5chr635586873-ENST00000332149TMPRSS2chr2142861520-36568243162064582
ENST00000536438FKBP5chr635586873-ENST00000398585TMPRSS2chr2142861520-36548243162064582
ENST00000536438FKBP5chr635586873-ENST00000458356TMPRSS2chr2142861520-21988243162064582
ENST00000357266FKBP5chr635586873-ENST00000332149TMPRSS2chr2142861520-34936611531901582
ENST00000357266FKBP5chr635586873-ENST00000398585TMPRSS2chr2142861520-34916611531901582
ENST00000357266FKBP5chr635586873-ENST00000458356TMPRSS2chr2142861520-20356611531901582
ENST00000542713FKBP5chr635586873-ENST00000332149TMPRSS2chr2142861520-34986661581906582
ENST00000542713FKBP5chr635586873-ENST00000398585TMPRSS2chr2142861520-34966661581906582
ENST00000542713FKBP5chr635586873-ENST00000458356TMPRSS2chr2142861520-20406661581906582

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
ENST00000539068ENST00000332149FKBP5chr635586873-TMPRSS2chr2142861520-0.0013112460.99868876
ENST00000539068ENST00000398585FKBP5chr635586873-TMPRSS2chr2142861520-0.0013229160.9986771
ENST00000539068ENST00000458356FKBP5chr635586873-TMPRSS2chr2142861520-0.0016092940.9983907
ENST00000536438ENST00000332149FKBP5chr635586873-TMPRSS2chr2142861520-0.0015539620.99844605
ENST00000536438ENST00000398585FKBP5chr635586873-TMPRSS2chr2142861520-0.0015703970.9984296
ENST00000536438ENST00000458356FKBP5chr635586873-TMPRSS2chr2142861520-0.0025178410.99748224
ENST00000357266ENST00000332149FKBP5chr635586873-TMPRSS2chr2142861520-0.0013242730.99867564
ENST00000357266ENST00000398585FKBP5chr635586873-TMPRSS2chr2142861520-0.0013373520.9986626
ENST00000357266ENST00000458356FKBP5chr635586873-TMPRSS2chr2142861520-0.0016353110.99836475
ENST00000542713ENST00000332149FKBP5chr635586873-TMPRSS2chr2142861520-0.0013277220.99867225
ENST00000542713ENST00000398585FKBP5chr635586873-TMPRSS2chr2142861520-0.0013404390.9986595
ENST00000542713ENST00000458356FKBP5chr635586873-TMPRSS2chr2142861520-0.0016274030.9983726

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 FKBP5-TMPRSS2

check button +/-13 AA sequence from the breakpoints of the fusion protein sequences.
HgeneHchrHbpTgeneTchrTbpLength(fusion protein)BP in fusion proteinPeptide
FKBP5chr635586873TMPRSS2chr2142861520661170GYSNPNEGATVEKTKKALCITLTLGT
FKBP5chr635586873TMPRSS2chr2142861520666170GYSNPNEGATVEKTKKALCITLTLGT
FKBP5chr635586873TMPRSS2chr2142861520711170GYSNPNEGATVEKTKKALCITLTLGT
FKBP5chr635586873TMPRSS2chr2142861520824170GYSNPNEGATVEKTKKALCITLTLGT

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Potential FusionNeoAntigen Information of FKBP5-TMPRSS2 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.
FKBP5-TMPRSS2_35586873_42861520.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)
FKBP5-TMPRSS2chr635586873chr2142861520661HLA-A30:08KTKKALCIT0.98340.59321221
FKBP5-TMPRSS2chr635586873chr2142861520661HLA-A30:08KTKKALCITL0.99280.81961222
FKBP5-TMPRSS2chr635586873chr2142861520661HLA-A30:01KTKKALCIT0.98590.78441221
FKBP5-TMPRSS2chr635586873chr2142861520661HLA-B07:13TVEKTKKAL0.78470.7465918
FKBP5-TMPRSS2chr635586873chr2142861520661HLA-A30:01KTKKALCITL0.99350.91411222

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Potential FusionNeoAntigen Information of FKBP5-TMPRSS2 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 FKBP5-TMPRSS2

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
1727EGATVEKTKKALCIFKBP5TMPRSS2chr635586873chr2142861520661

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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FKBP5-TMPRSS2

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-B14:023BVN1727EGATVEKTKKALCI-7.9962-8.1096
HLA-B14:023BVN1727EGATVEKTKKALCI-5.70842-6.74372
HLA-B52:013W391727EGATVEKTKKALCI-6.83737-6.95077
HLA-B52:013W391727EGATVEKTKKALCI-4.4836-5.5189
HLA-A11:014UQ21727EGATVEKTKKALCI-10.0067-10.1201
HLA-A11:014UQ21727EGATVEKTKKALCI-9.03915-10.0745
HLA-A24:025HGA1727EGATVEKTKKALCI-6.56204-6.67544
HLA-A24:025HGA1727EGATVEKTKKALCI-5.42271-6.45801
HLA-B44:053DX81727EGATVEKTKKALCI-7.85648-8.89178
HLA-B44:053DX81727EGATVEKTKKALCI-5.3978-5.5112
HLA-A02:016TDR1727EGATVEKTKKALCI-3.37154-4.40684

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Vaccine Design for the FusionNeoAntigens of FKBP5-TMPRSS2

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
FKBP5-TMPRSS2chr635586873chr21428615201221KTKKALCITAAAAGACTAAGAAAGCACTGTGCATCA
FKBP5-TMPRSS2chr635586873chr21428615201222KTKKALCITLAAAAGACTAAGAAAGCACTGTGCATCACCT
FKBP5-TMPRSS2chr635586873chr2142861520918TVEKTKKALCAACAGTAGAAAAGACTAAGAAAGCAC

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 FKBP5-TMPRSS2

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
N/AFKBP5-TMPRSS2chr635586873ENST00000357266chr2142861520ENST00000332149HM245391

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Potential target of CAR-T therapy development for FKBP5-TMPRSS2

check button Predicted 3D structure. We used RoseTTAFold.
185_FKBP5-TMPRSS2_cee42_pred.pdb


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
TgeneTMPRSS2chr6:35586873chr21:42861520ENST0000033214921485_1050493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein
TgeneTMPRSS2chr6:35586873chr21:42861520ENST0000045835621485_1050493.0TransmembraneHelical%3B Signal-anchor for type II membrane protein

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
FKBP5chr635586873ENST00000357266TMPRSS2chr2142861520ENST00000332149

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Related Drugs to FKBP5-TMPRSS2

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 FKBP5-TMPRSS2

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
TgeneTMPRSS2C0033578Prostatic Neoplasms4CTD_human
TgeneTMPRSS2C0376358Malignant neoplasm of prostate4CTD_human