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Kinase Fusion Gene:MLKL_GRHL1 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: MLKL_GRHL1 | KinaseFusionDB ID: KFG3901 | FusionGDB2.0 ID: KFG3901 | Hgene | Tgene | Gene symbol | MLKL | GRHL1 | Gene ID | 197259 | 29841 | |
Gene name | mixed lineage kinase domain like pseudokinase | grainyhead like transcription factor 1 | ||||||||||
Synonyms | hMLKL | LBP32|MGR|NH32|TFCP2L2 | ||||||||||
Cytomap | 16q23.1 | 2p25.1 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | mixed lineage kinase domain-like protein | grainyhead-like protein 1 homologLBP protein 32grainyhead-like 1mammalian grainyheadtranscription factor CP2-like 2transcription factor LBP-32 | ||||||||||
Modification date | 20240411 | 20240403 | ||||||||||
UniProtAcc | Q8NB16 | Q9NZI5 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000306247, ENST00000308807, | ENST00000324883, ENST00000324907, ENST00000405379, ENST00000480736, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: MLKL [Title/Abstract] AND GRHL1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | MLKL(74707850)-GRHL1(10142405), # 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 | MLKL | GO:0070207 | protein homotrimerization | 24316671 |
Hgene | MLKL | GO:0097528 | execution phase of necroptosis | 24316671 |
Tgene | GRHL1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 12175488|35013237 |
Kinase Fusion gene breakpoints across MLKL (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 GRHL1 (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 | CB048029 | MLKL | chr16 | 74707850 | GRHL1 | chr2 | 10142405 |
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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/:74707850/:10142405) - 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 |
MLKL | GRHL1 |
FUNCTION: Pseudokinase that plays a key role in TNF-induced necroptosis, a programmed cell death process (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Does not have protein kinase activity (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). Activated following phosphorylation by RIPK3, leading to homotrimerization, localization to the plasma membrane and execution of programmed necrosis characterized by calcium influx and plasma membrane damage (PubMed:22265413, PubMed:22265414, PubMed:22421439, PubMed:24316671). In addition to TNF-induced necroptosis, necroptosis can also take place in the nucleus in response to orthomyxoviruses infection: following activation by ZBP1, MLKL is phosphorylated by RIPK3 in the nucleus, triggering disruption of the nuclear envelope and leakage of cellular DNA into the cytosol.following ZBP1 activation, which senses double-stranded Z-RNA structures, nuclear RIPK3 catalyzes phosphorylation and activation of MLKL, promoting disruption of the nuclear envelope and leakage of cellular DNA into the cytosol (By similarity). Binds to highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which is essential for its necroptotic function (PubMed:29883610). {ECO:0000250|UniProtKB:Q9D2Y4, ECO:0000269|PubMed:22265413, ECO:0000269|PubMed:22265414, ECO:0000269|PubMed:22421439, ECO:0000269|PubMed:24316671, ECO:0000269|PubMed:29883610}. | FUNCTION: Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, nor functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity). May play a role in regulating glucose homeostasis and insulin signaling. {ECO:0000250|UniProtKB:Q921D9, ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:29309642, ECO:0000269|PubMed:35013237}.; FUNCTION: [Isoform 1]: Functions as a transcription activator. {ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:29309642}.; FUNCTION: [Isoform 2]: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed. {ECO:0000269|PubMed:12175488}. |
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 MLKL_GRHL1 |
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 |
MLKL | Q8NB16 | human | CNR2 | P34972 | S352 | kITPWPDsRDLDLSD |
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 |
MLKL | ID | Description | 0.00e+00 |
MLKL | GO:0033004 | negative regulation of mast cell activation | 9.03e-03 |
MLKL | GO:0001975 | response to amphetamine | 9.03e-03 |
MLKL | GO:0032228 | regulation of synaptic transmissio | 1.85e-03 |
MLKL | GO:0014075 | response to amine | 9.03e-03 |
MLKL | GO:0050805 | negative regulation of synaptic transmission | 9.03e-03 |
MLKL | GO:0007187 | G protein-coupled receptor signaling pathwa | 2.97e-03 |
MLKL | GO:0045576 | mast cell activation | 9.51e-03 |
MLKL | GO:0001508 | action potential | 1.81e-02 |
MLKL | GO:0007189 | adenylate cyclase-activating G protein-coupled receptor signaling pathway | 1.81e-02 |
MLKL | GO:0002695 | negative regulation of leukocyte activation | 2.01e-02 |
MLKL | GO:0050866 | negative regulation of cell activation | 2.01e-02 |
MLKL | GO:0030595 | leukocyte chemotaxis | 2.01e-02 |
MLKL | GO:0002274 | myeloid leukocyte activation | 2.01e-02 |
MLKL | GO:0007188 | adenylate cyclase-modulating G protein-coupled receptor signaling pathway | 2.01e-02 |
MLKL | GO:0060326 | cell chemotaxis | 2.49e-02 |
MLKL | GO:0032496 | response to lipopolysaccharide | 2.52e-02 |
MLKL | GO:0002237 | response to molecule of bacterial origin | 2.54e-02 |
MLKL | GO:0050900 | leukocyte migration | 2.60e-02 |
MLKL | GO:0042391 | regulation of membrane potential | 2.60e-02 |
MLKL | GO:0006935 | chemotaxis | 2.60e-02 |
MLKL | GO:0042330 | taxis | 2.60e-02 |
MLKL | GO:0050804 | modulation of chemical synaptic transmission | 2.60e-02 |
MLKL | GO:0099177 | regulation of trans-synaptic signaling | 2.60e-02 |
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Related Drugs to MLKL_GRHL1 |
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 MLKL-GRHL1 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 MLKL_GRHL1 |
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 |