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Kinase Fusion Gene:NUAK1_C12orf65 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: NUAK1_C12orf65 | KinaseFusionDB ID: KFG4304 | FusionGDB2.0 ID: KFG4304 | Hgene | Tgene | Gene symbol | NUAK1 | C12orf65 | Gene ID | 9891 | 91574 | |
| Gene name | NUAK family kinase 1 | mitochondrial translation release factor in rescue | ||||||||||
| Synonyms | ARK5 | C12orf65|COXPD7|SPG55|mtRF-R | ||||||||||
| Cytomap | 12q23.3 | 12q24.31 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | NUAK family SNF1-like kinase 1AMP-activated protein kinase family member 5AMPK-related protein kinase 5NUAK family, SNF1-like kinase, 1omphalocele kinase 1 | mitochondrial translation release factor in rescueprobable peptide chain release factor C12orf65, mitochondrial | ||||||||||
| Modification date | 20240305 | 20240403 | ||||||||||
| UniProtAcc | O60285 | Q9H3J6 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000261402, | ENST00000253233, ENST00000366329, ENST00000429587, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: NUAK1 [Title/Abstract] AND C12orf65 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | NUAK1(106477642)-C12orf65(123738194), # 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 | NUAK1 | GO:0006468 | protein phosphorylation | 25329316 |
| Hgene | NUAK1 | GO:0030155 | regulation of cell adhesion | 20354225 |
| Hgene | NUAK1 | GO:0035507 | regulation of myosin-light-chain-phosphatase activity | 20354225 |
| Hgene | NUAK1 | GO:2000772 | regulation of cellular senescence | 19927127 |
| Tgene | C12orf65 | GO:0072344 | rescue of stalled ribosome | 33243891 |
| Kinase Fusion gene breakpoints across NUAK1 (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 C12orf65 (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-PC-A5DN-01A | NUAK1 | chr12 | 106477642 | C12orf65 | chr12 | 123738194 |
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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/:106477642/:123738194) - 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 |
| NUAK1 | C12orf65 |
| FUNCTION: Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression. Phosphorylates ATM, CASP6, LATS1, PPP1R12A and p53/TP53. Acts as a regulator of cellular senescence and cellular ploidy by mediating phosphorylation of 'Ser-464' of LATS1, thereby controlling its stability. Controls cell adhesion by regulating activity of the myosin protein phosphatase 1 (PP1) complex. Acts by mediating phosphorylation of PPP1R12A subunit of myosin PP1: phosphorylated PPP1R12A then interacts with 14-3-3, leading to reduced dephosphorylation of myosin MLC2 by myosin PP1. May be involved in DNA damage response: phosphorylates p53/TP53 at 'Ser-15' and 'Ser-392' and is recruited to the CDKN1A/WAF1 promoter to participate in transcription activation by p53/TP53. May also act as a tumor malignancy-associated factor by promoting tumor invasion and metastasis under regulation and phosphorylation by AKT1. Suppresses Fas-induced apoptosis by mediating phosphorylation of CASP6, thereby suppressing the activation of the caspase and the subsequent cleavage of CFLAR. Regulates UV radiation-induced DNA damage response mediated by CDKN1A. In association with STK11, phosphorylates CDKN1A in response to UV radiation and contributes to its degradation which is necessary for optimal DNA repair (PubMed:25329316). {ECO:0000269|PubMed:12409306, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15060171, ECO:0000269|PubMed:15273717, ECO:0000269|PubMed:19927127, ECO:0000269|PubMed:20354225, ECO:0000269|PubMed:21317932, ECO:0000269|PubMed:25329316}. | FUNCTION: Part of a mitoribosome-associated quality control pathway that prevents aberrant translation by responding to interruptions during elongation (PubMed:33243891). As heterodimer with MTRES1, ejects the unfinished nascent chain and peptidyl transfer RNA (tRNA), respectively, from stalled ribosomes. Recruitment of mitoribosome biogenesis factors to these quality control intermediates suggests additional roles for MTRES1 and MTRF during mitoribosome rescue (PubMed:33243891). {ECO:0000269|PubMed:33243891}. |
| 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 NUAK1_C12orf65 |
| 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 |
| NUAK1 | O60285 | human | CDKN1A | P38936 | S146 | GRkRRQtsMTDFyHs | |
| NUAK1 | O60285 | human | PPP1R12A | O14974 | S472 | AGVTRsAssPRLsss | |
| NUAK1 | O60285 | human | MAPT | P10636-8 | S262 | NVKskIGstENLkHQ | Tubulin-binding |
| NUAK1 | O60285 | human | CASP6 | P55212 | S257 | TLVNRKVsQRRVDFc | Peptidase_C14 |
| NUAK1 | O60285 | human | TP53 | P04637 | S392 | FktEGPDsD______ | |
| NUAK1 | O60285 | human | PPP1R12A | O14974 | S910 | sLLGRsGsysyLEER | |
| NUAK1 | O60285 | human | LATS1 | O95835 | S464 | NIPVRsNsFNNPLGN | |
| NUAK1 | O60285 | human | MAPT | P10636-8 | S356 | rVQskIGsLDNItHV | Tubulin-binding |
| NUAK1 | O60285 | human | PPP1R12A | O14974 | S445 | LGLRktGsyGALAEI | |
| NUAK1 | O60285 | human | TP53 | P04637 | S15 | PsVEPPLsQEtFsDL | P53_TAD |
| 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 |
| NUAK1 | ID | Description | 0.00e+00 |
| NUAK1 | GO:0043086 | negative regulation of catalytic activity | 4.01e-05 |
| NUAK1 | GO:0051348 | negative regulation of transferase activity | 9.49e-05 |
| NUAK1 | GO:2000379 | positive regulation of reactive oxygen species metabolic process | 1.94e-04 |
| NUAK1 | GO:0072332 | intrinsic apoptotic signaling pathway by p53 class mediator | 2.49e-04 |
| NUAK1 | GO:0045936 | negative regulation of phosphate metabolic process | 2.49e-04 |
| NUAK1 | GO:0010563 | negative regulation of phosphorus metabolic process | 2.49e-04 |
| NUAK1 | GO:0062100 | positive regulation of programmed necrotic cell death | 4.33e-04 |
| NUAK1 | GO:2000377 | regulation of reactive oxygen species metabolic process | 7.02e-04 |
| NUAK1 | GO:0044839 | cell cycle G2/M phase transition | 7.02e-04 |
| NUAK1 | GO:0090399 | replicative senescence | 7.02e-04 |
| NUAK1 | GO:0006977 | DNA damage respons | 1.29e-05 |
| NUAK1 | GO:0033673 | negative regulation of kinase activity | 8.93e-04 |
| NUAK1 | GO:0045736 | negative regulation of cyclin-dependent protein serine/threonine kinase activity | 8.93e-04 |
| NUAK1 | GO:1904030 | negative regulation of cyclin-dependent protein kinase activity | 8.93e-04 |
| NUAK1 | GO:0071480 | cellular response to gamma radiation | 1.06e-03 |
| NUAK1 | GO:0010165 | response to X-ray | 1.06e-03 |
| NUAK1 | GO:0031571 | mitotic G1 DNA damage checkpoint signaling | 1.06e-03 |
| NUAK1 | GO:0044819 | mitotic G1/S transition checkpoint signaling | 1.06e-03 |
| NUAK1 | GO:0072593 | reactive oxygen species metabolic process | 1.09e-03 |
| NUAK1 | GO:0000082 | G1/S transition of mitotic cell cycle | 1.30e-03 |
| NUAK1 | GO:2000279 | negative regulation of DNA biosynthetic process | 1.52e-03 |
| NUAK1 | GO:0044843 | cell cycle G1/S phase transition | 1.62e-03 |
| NUAK1 | GO:0062098 | regulation of programmed necrotic cell death | 1.65e-03 |
| NUAK1 | GO:0042771 | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | 1.92e-03 |
| NUAK1 | GO:0034504 | protein localization to nucleus | 1.96e-03 |
| NUAK1 | GO:0097193 | intrinsic apoptotic signaling pathway | 1.96e-03 |
| NUAK1 | GO:0070266 | necroptotic process | 1.96e-03 |
| NUAK1 | GO:0042326 | negative regulation of phosphorylation | 1.96e-03 |
| NUAK1 | GO:0048638 | regulation of developmental growth | 1.96e-03 |
| NUAK1 | GO:0006913 | nucleocytoplasmic transport | 1.96e-03 |
| NUAK1 | GO:0051169 | nuclear transport | 1.96e-03 |
| NUAK1 | GO:0010332 | response to gamma radiation | 2.00e-03 |
| NUAK1 | GO:0010823 | negative regulation of mitochondrion organization | 2.02e-03 |
| NUAK1 | GO:0097300 | programmed necrotic cell death | 2.62e-03 |
| NUAK1 | GO:0034605 | cellular response to heat | 3.09e-03 |
| NUAK1 | GO:0045786 | negative regulation of cell cycle | 3.19e-03 |
| NUAK1 | GO:0071479 | cellular response to ionizing radiation | 3.23e-03 |
| NUAK1 | GO:0001558 | regulation of cell growth | 3.23e-03 |
| NUAK1 | GO:0043254 | regulation of protein-containing complex assembly | 3.23e-03 |
| NUAK1 | GO:0030330 | DNA damage respons | 2.19e-04 |
| NUAK1 | GO:0031400 | negative regulation of protein modification process | 3.41e-03 |
| NUAK1 | GO:0072594 | establishment of protein localization to organelle | 3.86e-03 |
| NUAK1 | GO:0000079 | regulation of cyclin-dependent protein serine/threonine kinase activity | 3.86e-03 |
| NUAK1 | GO:0044773 | mitotic DNA damage checkpoint signaling | 3.87e-03 |
| NUAK1 | GO:0044772 | mitotic cell cycle phase transition | 3.88e-03 |
| NUAK1 | GO:1904029 | regulation of cyclin-dependent protein kinase activity | 3.89e-03 |
| NUAK1 | GO:2000134 | negative regulation of G1/S transition of mitotic cell cycle | 3.91e-03 |
| NUAK1 | GO:0044774 | mitotic DNA integrity checkpoint signaling | 3.92e-03 |
| NUAK1 | GO:0048145 | regulation of fibroblast proliferation | 3.95e-03 |
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Related Drugs to NUAK1_C12orf65 |
| 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 NUAK1-C12orf65 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 NUAK1_C12orf65 |
| 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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