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Kinase Fusion Gene:CLK3_MUC2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CLK3_MUC2 | KinaseFusionDB ID: KFG1341 | FusionGDB2.0 ID: KFG1341 | Hgene | Tgene | Gene symbol | CLK3 | MUC2 | Gene ID | 1198 | 4583 | |
| Gene name | CDC like kinase 3 | mucin 2, oligomeric mucus/gel-forming | ||||||||||
| Synonyms | PHCLK3|PHCLK3/152 | MLP|MUC-2|SMUC | ||||||||||
| Cytomap | 15q24.1 | 11p15.5 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | dual specificity protein kinase CLK3 | mucin-2mucin 2, intestinal/tracheal | ||||||||||
| Modification date | 20240305 | 20240403 | ||||||||||
| UniProtAcc | P49761 | Q02817 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000395066, ENST00000345005, ENST00000348245, ENST00000352989, ENST00000564353, | ENST00000359061, ENST00000441003, ENST00000333592, ENST00000361558, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CLK3 [Title/Abstract] AND MUC2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CLK3(74907758)-MUC2(1092784), # 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 | CLK3 | GO:0006468 | protein phosphorylation | 9637771 |
| Hgene | CLK3 | GO:0043484 | regulation of RNA splicing | 9637771 |
| Tgene | MUC2 | GO:0010273 | detoxification of copper ion | 36206754 |
| Kinase Fusion gene breakpoints across CLK3 (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 MUC2 (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-AA-3819-01A | CLK3 | chr15 | 74907758 | MUC2 | chr11 | 1092784 |
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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/:74907758/:1092784) - 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 |
| CLK3 | MUC2 |
| 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}. | FUNCTION: Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces (PubMed:17058067, PubMed:19432394, PubMed:33031746). Major constituent of the colon mucus, which is mainly formed by large polymeric networks of MUC2 secreted by goblet cells that cover the exposed surfaces of intestine (PubMed:19432394, PubMed:33031746). MUC2 networks form hydrogels that guard the underlying epithelium from pathogens and other hazardous matter entering from the outside world, while permitting nutrient absorption and gas exchange (PubMed:33031746, PubMed:36206754). Acts as a divalent copper chaperone that protects intestinal cells from copper toxicity and facilitates nutritional copper unptake into cells (PubMed:36206754). Binds both Cu(2+) and its reduced form, Cu(1+), at two juxtaposed binding sites: Cu(2+), once reduced to Cu(1+) by vitamin C (ascorbate) or other dietary antioxidants, transits to the other binding site (PubMed:36206754). MUC2-bound Cu(1+) is protected from oxidation in aerobic environments, and can be released for nutritional delivery to cells (PubMed:36206754). Mucin gels store antimicrobial molecules that participate in innate immunity (PubMed:33031746). Mucin glycoproteins also house and feed the microbiome, lubricate tissue surfaces, and may facilitate the removal of contaminants and waste products from the body (PubMed:33031746). Goblet cells synthesize two forms of MUC2 mucin that differ in branched chain O-glycosylation and the site of production in the colon: a (1) 'thick' mucus that wraps the microbiota to form fecal pellets is produced in the proximal, ascending colon (By similarity). 'Thick' mucus transits along the descending colon and is lubricated by a (2) 'thin' MUC2 mucus produced in the distal colon which adheres to the 'thick' mucus (By similarity). {ECO:0000250|UniProtKB:Q80Z19, ECO:0000269|PubMed:17058067, ECO:0000269|PubMed:19432394, ECO:0000269|PubMed:33031746, ECO:0000269|PubMed:36206754}. |
| 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 CLK3_MUC2 |
| 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 |
| 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 |
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Related Drugs to CLK3_MUC2 |
| 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 CLK3-MUC2 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 CLK3_MUC2 |
| 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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