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Kinase Fusion Gene:TLK2_THRA |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: TLK2_THRA | KinaseFusionDB ID: KFG6591 | FusionGDB2.0 ID: KFG6591 | Hgene | Tgene | Gene symbol | TLK2 | THRA | Gene ID | 11011 | 7067 | |
| Gene name | tousled like kinase 2 | thyroid hormone receptor alpha | ||||||||||
| Synonyms | HsHPK|MRD57|PKU-ALPHA | AR7|CHNG6|EAR7|ERB-T-1|ERBA|ERBA1|NR1A1|THRA1|THRA2|THRalpha|THRalpha1|THRalpha2|TRalpha|TRalpha1|TRalpha2|c-ERBA-1|c-erbA | ||||||||||
| Cytomap | 17q23.2 | 17q21.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | serine/threonine-protein kinase tousled-like 2 | thyroid hormone receptor alphaEAR-7ERBA-related 7V-erbA-related protein 7c-erbA protooncogenec-erbA-alphanuclear receptor subfamily 1 group A member 1thyroid hormone receptor alpha 1thyroid hormone receptor, alpha (erythroblastic leukemia viral (v | ||||||||||
| Modification date | 20240403 | 20240411 | ||||||||||
| UniProtAcc | Q86UE8 | Q9Y2W1 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000326270, ENST00000343388, ENST00000346027, ENST00000542523, ENST00000582809, ENST00000577616, | ENST00000264637, ENST00000394121, ENST00000450525, ENST00000546243, ENST00000584985, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: TLK2 [Title/Abstract] AND THRA [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | TLK2(60613698)-THRA(38240088), # samples:2 | |||||||||||
| 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 | TLK2 | GO:0006468 | protein phosphorylation | 12660173 |
| Hgene | TLK2 | GO:0006974 | DNA damage response | 12660173 |
| Hgene | TLK2 | GO:0018105 | peptidyl-serine phosphorylation | 20016786 |
| Hgene | TLK2 | GO:0035556 | intracellular signal transduction | 12660173 |
| Hgene | TLK2 | GO:0071480 | cellular response to gamma radiation | 12660173 |
| Hgene | TLK2 | GO:1902275 | regulation of chromatin organization | 12660173 |
| Tgene | THRA | GO:0006357 | regulation of transcription by RNA polymerase II | 18052923 |
| Tgene | THRA | GO:0006366 | transcription by RNA polymerase II | 8710870|9653119 |
| Tgene | THRA | GO:0009755 | hormone-mediated signaling pathway | 18052923 |
| Tgene | THRA | GO:0017055 | negative regulation of RNA polymerase II transcription preinitiation complex assembly | 8524305 |
| Tgene | THRA | GO:0045892 | negative regulation of DNA-templated transcription | 8710870 |
| Tgene | THRA | GO:2000143 | negative regulation of DNA-templated transcription initiation | 8524305 |
| Kinase Fusion 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. |
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| Kinase Fusion gene breakpoints across THRA (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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Kinase Fusion Gene Sample Information |
| Kinase Fusion gene information. |
| Kinase Fusion gene information from four resources (ChiTars 5.0, ChimerDB 4.0, COSMIC, and CCLE) * All genome coordinats were lifted-over on hg19. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| Source | Sample | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp |
| ChimerDB4 | TCGA-FD-A43P-01A | TLK2 | chr17 | 60613698 | THRA | chr17 | 38240088 |
| ChimerDB4 | TCGA-FD-A43P | TLK2 | chr17 | 60613698 | THRA | chr17 | 38240087 |
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Kinase Fusion ORF Analysis |
| Kinase Fusion information from ORFfinder translation from full-length transcript sequence from KinaseFusionDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Seq length (transcript) | Seq length (amino acids) |
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Kinase Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from KinaseFusionDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >Henst_Tenst_Hgene_Hchr_Hbp_Tgene_Tchr_Tbp_length(fusion AA)_AAseq |
Multiple Sequence Alignment of All Fusion Protein Isoforms |
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Kinase Fusion Protein Functional Features |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr17:60613698/chr17:38240088) - 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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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| TLK2 | THRA |
| FUNCTION: Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (PubMed:9427565, PubMed:10523312, PubMed:11470414, PubMed:12660173, PubMed:12955071, PubMed:29955062, PubMed:33323470). Phosphorylates the chromatin assembly factors ASF1A and ASF1B (PubMed:11470414, PubMed:20016786, PubMed:29955062, PubMed:35136069). Phosphorylation of ASF1A prevents its proteasome-mediated degradation, thereby enhancing chromatin assembly (PubMed:20016786). Negative regulator of amino acid starvation-induced autophagy (PubMed:22354037). {ECO:0000269|PubMed:10523312, ECO:0000269|PubMed:11470414, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:20016786, ECO:0000269|PubMed:22354037, ECO:0000269|PubMed:29955062, ECO:0000269|PubMed:33323470, ECO:0000269|PubMed:35136069, ECO:0000269|PubMed:9427565}. | FUNCTION: Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798). {ECO:0000269|PubMed:20123736, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:22424773, ECO:0000269|PubMed:23525231, ECO:0000269|PubMed:24043798}. |
| 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, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained domain in the 5'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
| - Retained domain in the 3'-partner of fusion protein (protein functional feature from UniProt). |
| Partner | Hgeneene | Hbp | Tgeneene | Tbp | ENST | BPexon | TotalExon | Protein feature loci | BPloci | TotalLen | Feature | Note |
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Kinase-Substrate Information of TLK2_THRA |
| Phosphorylation target of the kinase (phosphosite, 03-17-2024) |
| Kinase | Kinase UniProt Acc | Kinase species | Substrate | Substrate UniProt Acc | Substrate phosphorylated residues | Substrate phosphorylated sites (+/-7AA) | Domain |
| TLK2 | Q86UE8 | human | ASF1B | Q9NVP2 | S198 | PGLLPENsMDCI___ | |
| TLK2 | Q86UE8 | human | ASF1A | Q9Y294 | S192 | GWSTSENsLNVMLES |
| Biological Network Integration of This Kinase and Substrates (GeneMANIA website) |
| Enriched GO biological processes of the phosphorylation target genes of the kinase |
| Kinase | GOID | GO term | P.adjust |
| TLK2 | ID | Description | 0.00e+00 |
| TLK2 | GO:0006334 | nucleosome assembly | 4.25e-04 |
| TLK2 | GO:0034728 | nucleosome organization | 4.25e-04 |
| TLK2 | GO:0065004 | protein-DNA complex assembly | 8.59e-04 |
| TLK2 | GO:0140861 | DNA repair-dependent chromatin remodeling | 6.29e-03 |
| TLK2 | GO:0001835 | blastocyst hatching | 6.29e-03 |
| TLK2 | GO:0035188 | hatching | 6.29e-03 |
| TLK2 | GO:0071684 | organism emergence from protective structure | 6.29e-03 |
| TLK2 | GO:0031297 | replication fork processing | 1.04e-02 |
| TLK2 | GO:0045005 | DNA-templated DNA replication maintenance of fidelity | 1.05e-02 |
| TLK2 | GO:0001824 | blastocyst development | 1.96e-02 |
| TLK2 | GO:0006261 | DNA-templated DNA replication | 2.47e-02 |
| TLK2 | GO:0001649 | osteoblast differentiation | 3.60e-02 |
| TLK2 | GO:0006260 | DNA replication | 3.60e-02 |
| TLK2 | GO:0001701 | in utero embryonic development | 4.65e-02 |
| TLK2 | GO:0042692 | muscle cell differentiation | 4.65e-02 |
| TLK2 | GO:0001503 | ossification | 4.65e-02 |
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Related Drugs to TLK2_THRA |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
| Distribution of the number of studies mentioning TLK2-THRA and kinase inhibitors the PubMed Abstract (04-01-2024) |
| Fusion gene - drug pair 1 | Fusion gene - drug pair 2 | PMID | Publication date | DOI | Study title |
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Related Diseases to TLK2_THRA |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Related diseases from the literature mentioned this fusion gene and drug. (PubMed, 04-01-2024) |
| MeSH ID | MeSH term |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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Clinical Trials of the Found Drugs/Small Molecules |
| Statistics of the Clinical Trials of the Found Kinase Inibitors from clinicaltrials.gov (06-17-2024) |
| Clinical Trials from clinicaltrials.gov (06-17-2024) |
| Fusion Gene | Kinase Inhibitor | NCT ID | Study Status | Phases | Disease | # Enrolment | Date |
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