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Kinase Fusion Gene:CDK8_ATP8A2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CDK8_ATP8A2 | KinaseFusionDB ID: KFG1198 | FusionGDB2.0 ID: KFG1198 | Hgene | Tgene | Gene symbol | CDK8 | ATP8A2 | Gene ID | 1024 | 51761 | |
| Gene name | cyclin dependent kinase 8 | ATPase phospholipid transporting 8A2 | ||||||||||
| Synonyms | IDDHBA|K35 | ATP|ATPIB|CAMRQ4|IB|ML-1 | ||||||||||
| Cytomap | 13q12.13 | 13q12.13 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | cyclin-dependent kinase 8CDK8 protein kinasecell division protein kinase 8mediator complex subunit CDK8mediator of RNA polymerase II transcription subunit CDK8protein kinase K35 | phospholipid-transporting ATPase IBATPase, aminophospholipid transporter, class I, type 8A, member 2ATPase, aminophospholipid transporter-like, class I, type 8A, member 2P4-ATPase flippase complex alpha subunit ATP8A2probable phospholipid-transporting | ||||||||||
| Modification date | 20240403 | 20240403 | ||||||||||
| UniProtAcc | P49336 | Q9NTI2 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000381527, ENST00000536792, ENST00000480323, | ENST00000491840, ENST00000255283, ENST00000381655, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CDK8 [Title/Abstract] AND ATP8A2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CDK8(26928017)-ATP8A2(26402256), # 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 |
| Kinase Fusion gene breakpoints across CDK8 (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 ATP8A2 (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-L5-A8NW-01A | CDK8 | chr13 | 26928017 | ATP8A2 | chr13 | 26402256 |
| ChimerDB4 | TCGA-L5-A8NW | CDK8 | chr13 | 26928017 | ATP8A2 | chr13 | 26402255 |
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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/chr13:26928017/chr13:26402256) - 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 |
| CDK8 | ATP8A2 |
| FUNCTION: Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex. Phosphorylates CCNH leading to down-regulation of the TFIIH complex and transcriptional repression. Recruited through interaction with MAML1 to hyperphosphorylate the intracellular domain of NOTCH, leading to its degradation. {ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:30905399}. | FUNCTION: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (By similarity). Able to translocate phosphatidylserine, but not phosphatidylcholine (PubMed:34403372). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE) (By similarity). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP (By similarity). ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth (By similarity). Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes (By similarity). May be involved in vesicle trafficking in neuronal cells (By similarity). Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival (By similarity). {ECO:0000250|UniProtKB:C7EXK4, ECO:0000269|PubMed:34403372, ECO:0000305|PubMed:31397519}. |
| 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 CDK8_ATP8A2 |
| 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 |
| CDK8 | P49336 | human | STAT1 | P42224 | S727 | TDNLLPMsPEEFDEV | STAT1_TAZ2bind |
| CDK8 | P49336 | human | SMAD1 | Q15797 | S195 | PNSSYPNsPGSSSSt | |
| CDK8 | P49336 | human | SMAD1 | Q15797 | S187 | NSHPFPHsPNSSYPN | |
| CDK8 | P49336 | human | E2F1 | Q01094 | S375 | PVDEDRLsPLVAADS | |
| CDK8 | P49336 | human | H3C1 | P68431 | S10 | tkQtArkstGGkAPr | Histone |
| CDK8 | P49336 | human | SMAD1 | Q15797 | S206 | SSStYPHsPTSSDPG | |
| CDK8 | P49336 | human | CCNH | P51946 | S304 | yEDDDyVsKKsKHEE | |
| CDK8 | P49336 | human | SMAD1 | Q15797 | S214 | PTSSDPGsPFQMPAD | |
| CDK8 | P49336 | human | SMAD3 | P84022 | T179 | PQSNIPEtPPPGYLS | |
| CDK8 | P49336 | human | SMAD3 | P84022 | S213 | NLsPNPMsPAHNNLD | |
| CDK8 | P49336 | human | NOTCH1 | P46531 | S2513 | EHPFLtPsPEsPDQW | |
| CDK8 | P49336 | human | NOTCH1 | P46531 | T2511 | VPEHPFLtPsPEsPD | |
| CDK8 | P49336 | human | SMAD3 | P84022 | S208 | DAGsPNLsPNPMsPA | |
| CDK8 | P49336 | human | CCNH | P51946 | S5 | ___MYHNsSQkRHWT | |
| CDK8 | P49336 | human | NOTCH1 | P46531 | S2516 | FLtPsPEsPDQWsss |
| 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 |
| CDK8 | ID | Description | 0.00e+00 |
| CDK8 | GO:0072073 | kidney epithelium development | 1.11e-04 |
| CDK8 | GO:0001822 | kidney development | 8.05e-04 |
| CDK8 | GO:0072001 | renal system development | 8.05e-04 |
| CDK8 | GO:0007440 | foregut morphogenesis | 1.12e-03 |
| CDK8 | GO:0045667 | regulation of osteoblast differentiation | 2.60e-03 |
| CDK8 | GO:0060039 | pericardium development | 2.60e-03 |
| CDK8 | GO:0031053 | primary miRNA processing | 2.60e-03 |
| CDK8 | GO:1901201 | regulation of extracellular matrix assembly | 2.60e-03 |
| CDK8 | GO:0061036 | positive regulation of cartilage development | 4.50e-03 |
| CDK8 | GO:0043276 | anoikis | 4.50e-03 |
| CDK8 | GO:0010614 | negative regulation of cardiac muscle hypertrophy | 4.50e-03 |
| CDK8 | GO:0033002 | muscle cell proliferation | 4.50e-03 |
| CDK8 | GO:0003161 | cardiac conduction system development | 4.50e-03 |
| CDK8 | GO:0014741 | negative regulation of muscle hypertrophy | 4.50e-03 |
| CDK8 | GO:0001649 | osteoblast differentiation | 4.50e-03 |
| CDK8 | GO:0048762 | mesenchymal cell differentiation | 4.50e-03 |
| CDK8 | GO:0014706 | striated muscle tissue development | 4.50e-03 |
| CDK8 | GO:0061448 | connective tissue development | 5.07e-03 |
| CDK8 | GO:0085029 | extracellular matrix assembly | 5.07e-03 |
| CDK8 | GO:0035196 | miRNA processing | 5.07e-03 |
| CDK8 | GO:0035850 | epithelial cell differentiation involved in kidney development | 5.07e-03 |
| CDK8 | GO:0048546 | digestive tract morphogenesis | 5.27e-03 |
| CDK8 | GO:1902895 | positive regulation of miRNA transcription | 5.68e-03 |
| CDK8 | GO:0060485 | mesenchyme development | 5.80e-03 |
| CDK8 | GO:0030857 | negative regulation of epithelial cell differentiation | 5.80e-03 |
| CDK8 | GO:0061005 | cell differentiation involved in kidney development | 5.80e-03 |
| CDK8 | GO:0072132 | mesenchyme morphogenesis | 5.80e-03 |
| CDK8 | GO:0010718 | positive regulation of epithelial to mesenchymal transition | 5.80e-03 |
| CDK8 | GO:0060038 | cardiac muscle cell proliferation | 5.80e-03 |
| CDK8 | GO:0045599 | negative regulation of fat cell differentiation | 5.81e-03 |
| CDK8 | GO:1903053 | regulation of extracellular matrix organization | 5.81e-03 |
| CDK8 | GO:2000630 | positive regulation of miRNA metabolic process | 5.81e-03 |
| CDK8 | GO:0001947 | heart looping | 5.81e-03 |
| CDK8 | GO:0045668 | negative regulation of osteoblast differentiation | 5.81e-03 |
| CDK8 | GO:0001756 | somitogenesis | 5.81e-03 |
| CDK8 | GO:0010611 | regulation of cardiac muscle hypertrophy | 5.81e-03 |
| CDK8 | GO:0014743 | regulation of muscle hypertrophy | 5.81e-03 |
| CDK8 | GO:0051148 | negative regulation of muscle cell differentiation | 5.81e-03 |
| CDK8 | GO:0061371 | determination of heart left/right asymmetry | 5.81e-03 |
| CDK8 | GO:1902893 | regulation of miRNA transcription | 5.81e-03 |
| CDK8 | GO:0003143 | embryonic heart tube morphogenesis | 5.81e-03 |
| CDK8 | GO:0061614 | miRNA transcription | 5.81e-03 |
| CDK8 | GO:0061035 | regulation of cartilage development | 5.83e-03 |
| CDK8 | GO:0009880 | embryonic pattern specification | 5.97e-03 |
| CDK8 | GO:0001707 | mesoderm formation | 5.97e-03 |
| CDK8 | GO:0050678 | regulation of epithelial cell proliferation | 5.97e-03 |
| CDK8 | GO:0007178 | transmembrane receptor protein serine/threonine kinase signaling pathway | 5.97e-03 |
| CDK8 | GO:0048332 | mesoderm morphogenesis | 5.97e-03 |
| CDK8 | GO:0060537 | muscle tissue development | 6.27e-03 |
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Related Drugs to CDK8_ATP8A2 |
| 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 CDK8-ATP8A2 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 CDK8_ATP8A2 |
| 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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