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Kinase Fusion Gene:DYRK1A_CLK3 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: DYRK1A_CLK3 | KinaseFusionDB ID: KFG1775 | FusionGDB2.0 ID: KFG1775 | Hgene | Tgene | Gene symbol | DYRK1A | CLK3 | Gene ID | 1859 | 1198 | |
Gene name | dual specificity tyrosine phosphorylation regulated kinase 1A | CDC like kinase 3 | ||||||||||
Synonyms | DYRK|DYRK1|HP86|MNB|MNBH|MRD7 | PHCLK3|PHCLK3/152 | ||||||||||
Cytomap | 21q22.13 | 15q24.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | dual specificity tyrosine-phosphorylation-regulated kinase 1AMNB/DYRK protein kinasedual specificity YAK1-related kinasedual specificity tyrosine-(Y)-phosphorylation regulated kinase 1Amnb protein kinase homolog hp86protein kinase minibrain homologs | dual specificity protein kinase CLK3 | ||||||||||
Modification date | 20240411 | 20240305 | ||||||||||
UniProtAcc | Q13627 | P49761 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000321219, ENST00000338785, ENST00000339659, ENST00000398956, ENST00000398960, ENST00000451934, ENST00000455387, ENST00000462274, | ENST00000348245, ENST00000352989, ENST00000345005, ENST00000395066, ENST00000564353, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: DYRK1A [Title/Abstract] AND CLK3 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | DYRK1A(38817557)-CLK3(74919753), # samples:1 |
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 | DYRK1A | GO:0018108 | peptidyl-tyrosine phosphorylation | 9748265 |
Hgene | DYRK1A | GO:0033120 | positive regulation of RNA splicing | 28377597 |
Hgene | DYRK1A | GO:0038083 | peptidyl-tyrosine autophosphorylation | 24327345 |
Hgene | DYRK1A | GO:0090310 | negative regulation of DNA methylation-dependent heterochromatin formation | 24820035 |
Tgene | CLK3 | GO:0006468 | protein phosphorylation | 9637771 |
Tgene | CLK3 | GO:0043484 | regulation of RNA splicing | 9637771 |
Kinase Fusion gene breakpoints across DYRK1A (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 CLK3 (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 |
ChiTaRS5.0 | BF884316 | DYRK1A | chr21 | 38817557 | CLK3 | chr15 | 74919753 |
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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/:38817557/:74919753) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
DYRK1A | CLK3 |
FUNCTION: Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities (PubMed:21127067, PubMed:8769099, PubMed:30773093, PubMed:20981014, PubMed:23665168). Exhibits a substrate preference for proline at position P+1 and arginine at position P-3 (PubMed:23665168). Plays an important role in double-strand breaks (DSBs) repair following DNA damage (PubMed:31024071). Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR) (PubMed:30773093). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (PubMed:25620562, PubMed:29849146). May play a role in a signaling pathway regulating nuclear functions of cell proliferation (PubMed:14500717). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Has pro-survival function and negatively regulates the apoptotic process (By similarity). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1 (By similarity). This in turn inhibits p53/TP53 activity and apoptosis (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 at 'Thr-434' (By similarity). {ECO:0000250|UniProtKB:Q61214, ECO:0000250|UniProtKB:Q63470, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:20981014, ECO:0000269|PubMed:21127067, ECO:0000269|PubMed:23665168, ECO:0000269|PubMed:25620562, ECO:0000269|PubMed:29849146, ECO:0000269|PubMed:30773093, ECO:0000269|PubMed:31024071, ECO:0000269|PubMed:8769099}. | FUNCTION: Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex. May be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing and can cause redistribution of SR proteins from speckles to a diffuse nucleoplasmic distribution. Phosphorylates SRSF1 and SRSF3. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. {ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:9637771}. |
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 DYRK1A_CLK3 |
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 |
CLK3 | P49761 | human | USP13 | Q92995 | Y708 | EPLTMPGyGGAASAG | UCH |
DYRK1A | Q13627 | human | MAPT | P10636-8 | S199 | GDRsGyssPGsPGtP | |
DYRK1A | Q13627 | human | MAPT | P10636-8 | S396 | GAEIVyKsPVVsGDt | |
DYRK1A | Q13627 | human | MAPT | P10636-8 | S404 | PVVsGDtsPRHLsNV | |
DYRK1A | Q13627 | human | TRAF3 | Q13114 | S75 | CGHRFCEsCMAALLS | |
DYRK1A | Q13627 | human | MEF2D | Q14814 | S251 | NkVIPAksPPPPtHS | |
DYRK1A | Q13627 | human | CCNL2 | Q96S94 | S369 | AKkAkADsPVNGLPK | |
DYRK1A | Q13627 | human | CCND1 | P24385 | T286 | EEVDLACtPtDVRDV | |
DYRK1A | Q13627 | human | AMPH | P49418 | S295 | PARPRsPsQTRKGPP | |
DYRK1A | Q13627 | human | FOXO1 | Q12778 | S329 | stIsGRLsPIMtEQD | |
DYRK1A | Q13627 | human | PLK2 | Q9NYY3 | S358 | VPDFHLSsPAKNFFK | |
DYRK1A | Q13627 | human | CDKL5 | O76039 | S308 | RLLDRsPsRSAKRkP | |
DYRK1A | Q13627 | human | CCNL2 | Q96S94 | S330 | LDGtsGFsPAPKLVE | |
DYRK1A | Q13627 | human | SNCA | P37840 | S87 | ktVEGAGsIAAATGF | Synuclein |
DYRK1A | Q13627 | human | DNM1 | Q05193 | S857 | AsPSRPEsPRPPFDL | |
DYRK1A | Q13627 | human | RCAN1 | P53805 | S167 | FLIsPPAsPPVGWKQ | Calcipressin |
DYRK1A | Q13627 | human | MAPT | P10636-8 | S202 | sGyssPGsPGtPGsR | |
DYRK1A | Q13627 | human | TRAF3 | Q13114 | T29 | HTDRSAGtPVFVPEQ | |
DYRK1A | Q13627 | human | AMPH | P49418 | T310 | VPPLPKVtPtKELQQ | |
DYRK1A | Q13627 | human | MAPT | P10636-8 | T217 | sRtPsLPtPPtREPK | |
DYRK1A | Q13627 | human | RCAN1 | P53805 | T247 | QtRRPEYtPIHLS__ | |
DYRK1A | Q13627 | human | POLR2A | P24928 | S1616 | TPQSPSysPtsPsYS | RNA_pol_Rpb1_R |
DYRK1A | Q13627 | human | GLI1 | P08151 | S408 | GPLPRAPsISTVEPk | |
DYRK1A | Q13627 | human | DYRK1A | Q13627 | S529 | SNSGRARsDPtHQHR | |
DYRK1A | Q13627 | human | NFATC1 | O95644 | S261 | ARssRPAsPCNKRKY | |
DYRK1A | Q13627 | human | AMPH | P49418 | S293 | PAPARPRsPsQTRKG | |
DYRK1A | Q13627 | human | SF3B1 | O75533 | T273 | AtPGRGDtPGHAtPG | |
DYRK1A | Q13627 | human | NFATC1 | O95644 | S409 | LsPTSYMsPTLPALD | |
DYRK1A | Q13627 | human | MAPT | P10636-8 | T212 | tPGsRsRtPsLPtPP | |
DYRK1A | Q13627 | human | CCNL2 | Q96S94 | S338 | PAPKLVEsPKEGKGs | |
DYRK1A | Q13627 | human | LIN52 | Q52LA3 | S28 | FEKLDRAsPDLWPEQ | LIN52 |
DYRK1A | Q13627 | human | POLR2A | P24928 | S1619 | SPSysPtsPsYSPTS | RNA_pol_Rpb1_R |
DYRK1A | Q13627 | human | SPRY2 | O43597 | T75 | KPAPRPStQHkHERL | |
DYRK1A | Q13627 | human | NFATC1 | O95644 | S403 | WAkPKPLsPTSYMsP | |
DYRK1A | Q13627 | human | TP53 | P04637 | S15 | PsVEPPLsQEtFsDL | P53_TAD |
DYRK1A | Q13627 | human | MAPT | P10636-8 | T205 | ssPGsPGtPGsRsRt | |
DYRK1A | Q13627 | human | SF3B1 | O75533 | T434 | PARkLtAtPtPLGGM | SF3b1 |
DYRK1A | Q13627 | human | MAPT | P10636-8 | S422 | GsIDMVDsPQLAtLA | |
DYRK1A | Q13627 | human | TRAF3 | Q13114 | S9 | ESSKKMDsPGALQTN | |
DYRK1A | Q13627 | human | NFATC1 | O95644 | S278 | NGRQPPYsPHHsPTP | |
DYRK1A | Q13627 | human | AMPH | P49418 | T312 | PLPKVtPtKELQQEN |
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 |
CLK3 | ID | Description | 0.00e+00 |
CLK3 | GO:1904294 | positive regulation of ERAD pathway | 7.31e-03 |
CLK3 | GO:1904292 | regulation of ERAD pathway | 7.31e-03 |
CLK3 | GO:0030318 | melanocyte differentiation | 7.31e-03 |
CLK3 | GO:0070536 | protein K63-linked deubiquitination | 7.31e-03 |
CLK3 | GO:0050931 | pigment cell differentiation | 7.31e-03 |
CLK3 | GO:1905898 | positive regulation of response to endoplasmic reticulum stress | 7.31e-03 |
CLK3 | GO:0048066 | developmental pigmentation | 8.71e-03 |
CLK3 | GO:1905897 | regulation of response to endoplasmic reticulum stress | 1.19e-02 |
CLK3 | GO:0036503 | ERAD pathway | 1.19e-02 |
CLK3 | GO:0016579 | protein deubiquitination | 1.19e-02 |
CLK3 | GO:0043473 | pigmentation | 1.19e-02 |
CLK3 | GO:1901800 | positive regulation of proteasomal protein catabolic process | 1.19e-02 |
CLK3 | GO:0070646 | protein modification by small protein removal | 1.21e-02 |
CLK3 | GO:1903052 | positive regulation of proteolysis involved in protein catabolic process | 1.21e-02 |
CLK3 | GO:0061136 | regulation of proteasomal protein catabolic process | 1.56e-02 |
CLK3 | GO:0045732 | positive regulation of protein catabolic process | 1.56e-02 |
CLK3 | GO:0050821 | protein stabilization | 1.56e-02 |
CLK3 | GO:1903050 | regulation of proteolysis involved in protein catabolic process | 1.59e-02 |
CLK3 | GO:0034976 | response to endoplasmic reticulum stress | 1.71e-02 |
CLK3 | GO:0031647 | regulation of protein stability | 1.93e-02 |
CLK3 | GO:0045862 | positive regulation of proteolysis | 1.93e-02 |
CLK3 | GO:0010506 | regulation of autophagy | 1.93e-02 |
CLK3 | GO:0042176 | regulation of protein catabolic process | 1.93e-02 |
DYRK1A | ID | Description | 0.00e+00 |
DYRK1A | GO:0031571 | mitotic G1 DNA damage checkpoint signaling | 2.28e-03 |
DYRK1A | GO:0044819 | mitotic G1/S transition checkpoint signaling | 2.28e-03 |
DYRK1A | GO:0032886 | regulation of microtubule-based process | 2.51e-03 |
DYRK1A | GO:2000377 | regulation of reactive oxygen species metabolic process | 4.85e-03 |
DYRK1A | GO:0010506 | regulation of autophagy | 5.92e-03 |
DYRK1A | GO:0031113 | regulation of microtubule polymerization | 5.92e-03 |
DYRK1A | GO:0042770 | signal transduction in response to DNA damage | 5.92e-03 |
DYRK1A | GO:2000379 | positive regulation of reactive oxygen species metabolic process | 5.92e-03 |
DYRK1A | GO:0006979 | response to oxidative stress | 5.92e-03 |
DYRK1A | GO:0048488 | synaptic vesicle endocytosis | 5.92e-03 |
DYRK1A | GO:0140238 | presynaptic endocytosis | 5.92e-03 |
DYRK1A | GO:0030330 | DNA damage respons | 6.04e-05 |
DYRK1A | GO:0051348 | negative regulation of transferase activity | 6.36e-03 |
DYRK1A | GO:0031115 | negative regulation of microtubule polymerization | 6.36e-03 |
DYRK1A | GO:0036465 | synaptic vesicle recycling | 6.36e-03 |
DYRK1A | GO:0044773 | mitotic DNA damage checkpoint signaling | 6.36e-03 |
DYRK1A | GO:0072593 | reactive oxygen species metabolic process | 6.36e-03 |
DYRK1A | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 6.36e-03 |
DYRK1A | GO:0044774 | mitotic DNA integrity checkpoint signaling | 6.36e-03 |
DYRK1A | GO:0046785 | microtubule polymerization | 6.39e-03 |
DYRK1A | GO:0050804 | modulation of chemical synaptic transmission | 6.39e-03 |
DYRK1A | GO:0099177 | regulation of trans-synaptic signaling | 6.39e-03 |
DYRK1A | GO:0031110 | regulation of microtubule polymerization or depolymerization | 6.39e-03 |
DYRK1A | GO:1902807 | negative regulation of cell cycle G1/S phase transition | 6.39e-03 |
DYRK1A | GO:0034599 | cellular response to oxidative stress | 6.39e-03 |
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Related Drugs to DYRK1A_CLK3 |
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 DYRK1A-CLK3 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 DYRK1A_CLK3 |
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 |