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Kinase Fusion Gene:CLOCK_PDGFRA |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CLOCK_PDGFRA | KinaseFusionDB ID: KFG1347 | FusionGDB2.0 ID: KFG1347 | Hgene | Tgene | Gene symbol | CLOCK | PDGFRA | Gene ID | 9575 | 5156 | |
| Gene name | clock circadian regulator | platelet derived growth factor receptor alpha | ||||||||||
| Synonyms | KAT13D|bHLHe8 | CD140A|PDGFR-2|PDGFR2 | ||||||||||
| Cytomap | 4q12 | 4q12 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | circadian locomoter output cycles protein kaputcircadian locomoter output cycles kaput proteinclass E basic helix-loop-helix protein 8clock homolog | platelet-derived growth factor receptor alphaCD140 antigen-like family member ACD140a antigenPDGF-R-alphaalpha-type platelet-derived growth factor receptorplatelet-derived growth factor receptor 2platelet-derived growth factor receptor, alpha polype | ||||||||||
| Modification date | 20240407 | 20240416 | ||||||||||
| UniProtAcc | O15516 | P16234 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000309964, ENST00000381322, ENST00000513440, ENST00000506923, | ENST00000257290, ENST00000508170, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CLOCK [Title/Abstract] AND PDGFRA [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CLOCK(56376079)-PDGFRA(55153597), # samples:3 | |||||||||||
| 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 | CLOCK | GO:0006473 | protein acetylation | 28985504 |
| Hgene | CLOCK | GO:0032922 | circadian regulation of gene expression | 10864977|23229515|24005054 |
| Hgene | CLOCK | GO:0042753 | positive regulation of circadian rhythm | 12738229|23229515 |
| Hgene | CLOCK | GO:0045893 | positive regulation of DNA-templated transcription | 10864977|23229515|23785138 |
| Hgene | CLOCK | GO:0051775 | response to redox state | 11441146 |
| Hgene | CLOCK | GO:0071479 | cellular response to ionizing radiation | 21659603 |
| Tgene | PDGFRA | GO:0008284 | positive regulation of cell population proliferation | 10806482 |
| Tgene | PDGFRA | GO:0010544 | negative regulation of platelet activation | 8188664 |
| Tgene | PDGFRA | GO:0018108 | peptidyl-tyrosine phosphorylation | 2536956|8188664 |
| Tgene | PDGFRA | GO:0030335 | positive regulation of cell migration | 17470632 |
| Tgene | PDGFRA | GO:0034614 | cellular response to reactive oxygen species | 24190966 |
| Tgene | PDGFRA | GO:0038091 | positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway | 17470632 |
| Tgene | PDGFRA | GO:0046777 | protein autophosphorylation | 2536956|8188664 |
| Tgene | PDGFRA | GO:0048008 | platelet-derived growth factor receptor signaling pathway | 2536956|10806482 |
| Tgene | PDGFRA | GO:0048146 | positive regulation of fibroblast proliferation | 10806482 |
| Kinase Fusion gene breakpoints across CLOCK (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Kinase Fusion gene breakpoints across PDGFRA (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-69-7979-01A | CLOCK | chr4 | 56376079 | PDGFRA | chr4 | 55153597 |
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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/:56376079/:55153597) - 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 |
| CLOCK | PDGFRA |
| FUNCTION: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Regulates the circadian expression of ICAM1, VCAM1, CCL2, THPO and MPL and also acts as an enhancer of the transactivation potential of NF-kappaB. Plays an important role in the homeostatic regulation of sleep. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1, KLF10 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The CLOCK-BMAL2 heterodimer activates the transcription of SERPINE1/PAI1 and BHLHE40/DEC1. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence (PubMed:23229515). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (PubMed:23229515). The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3' (PubMed:23229515). CLOCK has an intrinsic acetyltransferase activity, which enables circadian chromatin remodeling by acetylating histones and nonhistone proteins, including its own partner BMAL1. Represses glucocorticoid receptor NR3C1/GR-induced transcriptional activity by reducing the association of NR3C1/GR to glucocorticoid response elements (GREs) via the acetylation of multiple lysine residues located in its hinge region (PubMed:21980503). The acetyltransferase activity of CLOCK is as important as its transcription activity in circadian control. Acetylates metabolic enzymes IMPDH2 and NDUFA9 in a circadian manner. Facilitated by BMAL1, rhythmically interacts and acetylates argininosuccinate synthase 1 (ASS1) leading to enzymatic inhibition of ASS1 as well as the circadian oscillation of arginine biosynthesis and subsequent ureagenesis (PubMed:28985504). Drives the circadian rhythm of blood pressure through transcriptional activation of ATP1B1 (By similarity). {ECO:0000250|UniProtKB:O08785, ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:18587630, ECO:0000269|PubMed:21659603, ECO:0000269|PubMed:21980503, ECO:0000269|PubMed:22284746, ECO:0000269|PubMed:23229515, ECO:0000269|PubMed:23785138, ECO:0000269|PubMed:24005054, ECO:0000269|PubMed:28985504}. | FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:10734113, ECO:0000269|PubMed:10947961, ECO:0000269|PubMed:11297552, ECO:0000269|PubMed:12522257, ECO:0000269|PubMed:1646396, ECO:0000269|PubMed:17087943, ECO:0000269|PubMed:1709159, ECO:0000269|PubMed:17141222, ECO:0000269|PubMed:20972453, ECO:0000269|PubMed:21224473, ECO:0000269|PubMed:21596750, ECO:0000269|PubMed:2554309, ECO:0000269|PubMed:8188664, ECO:0000269|PubMed:8760137, ECO:0000269|PubMed:8943348}. |
| 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 CLOCK_PDGFRA |
| 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 |
| PDGFRA | P16234 | human | PDGFRA | P16234 | Y1018 | RLSADsGyIIPLPDI | |
| PDGFRA | P16234 | human | PDGFRA | P16234 | Y572 | IsPDGHEyIyVDPMQ | |
| PDGFRA | P16234 | human | PDGFRA | P16234 | Y988 | RVDSDNAyIGVtyKN | |
| PDGFRA | P16234 | human | CCDC88C | Q9P219 | Y2025 | PQTVWyEyGCV____ | |
| PDGFRA | P16234 | human | SRC | P12931 | Y419 | RLIEDNEytARQGAk | PK_Tyr_Ser-Thr |
| PDGFRA | P16234 | human | PDGFRA | P16234 | Y574 | PDGHEyIyVDPMQLP |
| 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 |
| PDGFRA | ID | Description | 0.00e+00 |
| PDGFRA | GO:0031648 | protein destabilization | 4.83e-03 |
| PDGFRA | GO:0022602 | ovulation cycle process | 4.83e-03 |
| PDGFRA | GO:0048008 | platelet-derived growth factor receptor signaling pathway | 4.83e-03 |
| PDGFRA | GO:0042698 | ovulation cycle | 5.44e-03 |
| PDGFRA | GO:0008585 | female gonad development | 7.79e-03 |
| PDGFRA | GO:0046545 | development of primary female sexual characteristics | 7.79e-03 |
| PDGFRA | GO:0046660 | female sex differentiation | 7.79e-03 |
| PDGFRA | GO:0042476 | odontogenesis | 7.79e-03 |
| PDGFRA | GO:0030168 | platelet activation | 7.79e-03 |
| PDGFRA | GO:0048565 | digestive tract development | 7.79e-03 |
| PDGFRA | GO:0055123 | digestive system development | 8.41e-03 |
| PDGFRA | GO:0034614 | cellular response to reactive oxygen species | 8.57e-03 |
| PDGFRA | GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 9.76e-03 |
| PDGFRA | GO:0046777 | protein autophosphorylation | 1.07e-02 |
| PDGFRA | GO:0000302 | response to reactive oxygen species | 1.07e-02 |
| PDGFRA | GO:0031032 | actomyosin structure organization | 1.07e-02 |
| PDGFRA | GO:0002064 | epithelial cell development | 1.07e-02 |
| PDGFRA | GO:0070374 | positive regulation of ERK1 and ERK2 cascade | 1.07e-02 |
| PDGFRA | GO:0007596 | blood coagulation | 1.07e-02 |
| PDGFRA | GO:0050817 | coagulation | 1.07e-02 |
| PDGFRA | GO:0007599 | hemostasis | 1.07e-02 |
| PDGFRA | GO:0008406 | gonad development | 1.07e-02 |
| PDGFRA | GO:0045137 | development of primary sexual characteristics | 1.07e-02 |
| PDGFRA | GO:0051896 | regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.11e-02 |
| PDGFRA | GO:0034599 | cellular response to oxidative stress | 1.13e-02 |
| PDGFRA | GO:0060828 | regulation of canonical Wnt signaling pathway | 1.14e-02 |
| PDGFRA | GO:0018108 | peptidyl-tyrosine phosphorylation | 1.20e-02 |
| PDGFRA | GO:0018212 | peptidyl-tyrosine modification | 1.20e-02 |
| PDGFRA | GO:0007548 | sex differentiation | 1.21e-02 |
| PDGFRA | GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1.21e-02 |
| PDGFRA | GO:0048511 | rhythmic process | 1.21e-02 |
| PDGFRA | GO:0048608 | reproductive structure development | 1.21e-02 |
| PDGFRA | GO:0061458 | reproductive system development | 1.21e-02 |
| PDGFRA | GO:0070372 | regulation of ERK1 and ERK2 cascade | 1.21e-02 |
| PDGFRA | GO:0060070 | canonical Wnt signaling pathway | 1.21e-02 |
| PDGFRA | GO:0062197 | cellular response to chemical stress | 1.21e-02 |
| PDGFRA | GO:0031647 | regulation of protein stability | 1.24e-02 |
| PDGFRA | GO:0070371 | ERK1 and ERK2 cascade | 1.24e-02 |
| PDGFRA | GO:0033674 | positive regulation of kinase activity | 1.24e-02 |
| PDGFRA | GO:0030111 | regulation of Wnt signaling pathway | 1.24e-02 |
| PDGFRA | GO:0050878 | regulation of body fluid levels | 1.40e-02 |
| PDGFRA | GO:0006979 | response to oxidative stress | 1.61e-02 |
| PDGFRA | GO:0140694 | non-membrane-bounded organelle assembly | 1.61e-02 |
| PDGFRA | GO:0051347 | positive regulation of transferase activity | 1.61e-02 |
| PDGFRA | GO:0042060 | wound healing | 1.61e-02 |
| PDGFRA | GO:0035332 | positive regulation of hippo signaling | 1.61e-02 |
| PDGFRA | GO:0036093 | germ cell proliferation | 1.61e-02 |
| PDGFRA | GO:0071803 | positive regulation of podosome assembly | 1.61e-02 |
| PDGFRA | GO:0048732 | gland development | 1.61e-02 |
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Related Drugs to CLOCK_PDGFRA |
| 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 CLOCK-PDGFRA 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 CLOCK_PDGFRA |
| 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 |
| Tgene | PDGFRA | C0238198 | Gastrointestinal Stromal Tumors | 10 | CGI;CLINGEN;CTD_human;GENOMICS_ENGLAND;ORPHANET;UNIPROT |
| Tgene | PDGFRA | C3179349 | Gastrointestinal Stromal Sarcoma | 9 | CLINGEN;CTD_human;ORPHANET |
| Tgene | PDGFRA | C0346421 | Chronic eosinophilic leukemia | 4 | ORPHANET |
| Tgene | PDGFRA | C0206141 | Idiopathic Hypereosinophilic Syndrome | 3 | CTD_human;GENOMICS_ENGLAND |
| Tgene | PDGFRA | C0006413 | Burkitt Lymphoma | 2 | ORPHANET |
| Tgene | PDGFRA | C0206142 | Eosinophilic leukemia | 2 | CTD_human |
| Tgene | PDGFRA | C0206143 | Loeffler's Endocarditis | 2 | CTD_human |
| Tgene | PDGFRA | C1292769 | Precursor B-cell lymphoblastic leukemia | 2 | ORPHANET |
| Tgene | PDGFRA | C1540912 | Hypereosinophilic syndrome | 2 | CGI;CTD_human |
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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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