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Fusion Protein:TMPRSS2-PHF12 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: TMPRSS2-PHF12 | FusionPDB ID: 92399 | FusionGDB2.0 ID: 92399 | Hgene | Tgene | Gene symbol | TMPRSS2 | PHF12 | Gene ID | 7113 | 57649 |
| Gene name | transmembrane serine protease 2 | PHD finger protein 12 | |
| Synonyms | PP9284|PRSS10 | PF1 | |
| Cytomap | 21q22.3 | 17q11.2 | |
| Type of gene | protein-coding | protein-coding | |
| Description | transmembrane protease serine 2epitheliasinserine protease 10transmembrane protease, serine 2 | PHD finger protein 12PHD factor 1PHD zinc finger transcription factor | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | 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 gene | ENST ids | ENST00000332149, ENST00000398585, ENST00000458356, ENST00000497881, | ENST00000577226, ENST00000268756, ENST00000582655, ENST00000332830, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 40 X 73 X 10=29200 | 10 X 9 X 6=540 |
| # samples | 130 | 14 | |
| ** MAII score | log2(130/29200*10)=-4.48938484073892 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(14/540*10)=-1.94753258010586 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Fusion gene context | PubMed: TMPRSS2 [Title/Abstract] AND PHF12 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: TMPRSS2 [Title/Abstract] AND PHF12 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | TMPRSS2(42860321)-PHF12(27235899), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | TMPRSS2-PHF12 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-PHF12 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-PHF12 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-PHF12 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-PHF12 seems lost the major protein functional domain in Hgene partner, which is a CGC due to the frame-shifted ORF. TMPRSS2-PHF12 seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. TMPRSS2-PHF12 seems lost the major protein functional domain in Tgene partner, which is a epigenetic factor due to the frame-shifted ORF. TMPRSS2-PHF12 seems lost the major protein functional domain in Tgene partner, which is a essential gene 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) |
| Gene ontology of each fusion partner gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Hgene | TMPRSS2 | GO:0006508 | proteolysis | 21068237|24227843 |
| Hgene | TMPRSS2 | GO:0046598 | positive regulation of viral entry into host cell | 21068237|24227843 |
| Tgene | PHF12 | GO:0000122 | negative regulation of transcription by RNA polymerase II | 22048773 |
| Tgene | PHF12 | GO:0045892 | negative regulation of transcription, DNA-templated | 11390640 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr21:42860321/chr17:27235899) - 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. |
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| Retention 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. |
| Fusion gene breakpoints across TMPRSS2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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| Fusion gene breakpoints across PHF12 (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
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Fusion Amino Acid Sequences |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000332149 | TMPRSS2 | chr21 | 42860321 | - | ENST00000332830 | PHF12 | chr17 | 27235899 | - | 2169 | 580 | 135 | 1235 | 366 |
| ENST00000398585 | TMPRSS2 | chr21 | 42860321 | - | ENST00000332830 | PHF12 | chr17 | 27235899 | - | 2206 | 617 | 40 | 1272 | 410 |
| DeepORF 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. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000332149 | ENST00000332830 | TMPRSS2 | chr21 | 42860321 | - | PHF12 | chr17 | 27235899 | - | 0.000729267 | 0.99927074 |
| ENST00000398585 | ENST00000332830 | TMPRSS2 | chr21 | 42860321 | - | PHF12 | chr17 | 27235899 | - | 0.001095551 | 0.99890447 |
| 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 TMPRSS2-PHF12 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
| TMPRSS2 | chr21 | 42860321 | PHF12 | chr17 | 27235899 | 580 | 148 | VSHCPGGEDENRCVQRKEVQARAVFY |
| TMPRSS2 | chr21 | 42860321 | PHF12 | chr17 | 27235899 | 617 | 192 | VSHCPGGEDENRCVQRKEVQARAVFY |
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Potential FusionNeoAntigen Information of TMPRSS2-PHF12 in HLA I |
| 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. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of TMPRSS2-PHF12 in HLA II |
| 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. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of TMPRSS2-PHF12 |
| 3D 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. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of TMPRSS2-PHF12 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of TMPRSS2-PHF12 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of TMPRSS2-PHF12 |
| 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 type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for TMPRSS2-PHF12 |
| Predicted 3D structure. We used RoseTTAFold. |
| Retention 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'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | TMPRSS2 | chr21:42860321 | chr17:27235899 | ENST00000332149 | - | 5 | 14 | 85_105 | 148 | 493.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
| Hgene | TMPRSS2 | chr21:42860321 | chr17:27235899 | ENST00000398585 | - | 5 | 14 | 85_105 | 185 | 530.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
| Hgene | TMPRSS2 | chr21:42860321 | chr17:27235899 | ENST00000458356 | - | 5 | 14 | 85_105 | 148 | 493.0 | Transmembrane | Helical%3B Signal-anchor for type II membrane protein |
| 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. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to TMPRSS2-PHF12 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to TMPRSS2-PHF12 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
| Hgene | TMPRSS2 | C0033578 | Prostatic Neoplasms | 4 | CTD_human |
| Hgene | TMPRSS2 | C0376358 | Malignant neoplasm of prostate | 4 | CTD_human |
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