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Kinase Fusion Gene:RIPK1_NQO2 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: RIPK1_NQO2 | KinaseFusionDB ID: KFG5381 | FusionGDB2.0 ID: KFG5381 | Hgene | Tgene | Gene symbol | RIPK1 | NQO2 | Gene ID | 8737 | 4835 | |
| Gene name | receptor interacting serine/threonine kinase 1 | N-ribosyldihydronicotinamide:quinone dehydrogenase 2 | ||||||||||
| Synonyms | AIEFL|IMD57|RIP|RIP-1|RIP1 | DHQV|DIA6|NMOR2|QR2 | ||||||||||
| Cytomap | 6p25.2 | 6p25.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | receptor-interacting serine/threonine-protein kinase 1cell death protein RIPreceptor (TNFRSF)-interacting serine-threonine kinase 1receptor-interacting protein 1receptor-interacting protein kinase 1serine/threonine-protein kinase RIP | ribosyldihydronicotinamide dehydrogenase [quinone]N-ribosyldihydronicotinamide:quinone reductase 2NAD(P)H dehydrogenase, quinone 2NAD(P)H menadione oxidoreductase-1, dioxin-inducible-2NAD(P)H quinone dehydrogenase 2NRH:quinone oxidoreductase 2quinon | ||||||||||
| Modification date | 20240305 | 20240411 | ||||||||||
| UniProtAcc | Q13546 | P16083 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000479389, ENST00000259808, ENST00000380409, ENST00000541791, | ENST00000338130, ENST00000380430, ENST00000380441, ENST00000380454, ENST00000380455, ENST00000606474, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: RIPK1 [Title/Abstract] AND NQO2 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | RIPK1(3089891)-NQO2(3006702), # 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 | RIPK1 | GO:0010628 | positive regulation of gene expression | 26020802 |
| Hgene | RIPK1 | GO:0030163 | protein catabolic process | 17389591 |
| Hgene | RIPK1 | GO:0032757 | positive regulation of interleukin-8 production | 16127453 |
| Hgene | RIPK1 | GO:0032760 | positive regulation of tumor necrosis factor production | 16127453 |
| Hgene | RIPK1 | GO:0035556 | intracellular signal transduction | 26020802 |
| Hgene | RIPK1 | GO:0036289 | peptidyl-serine autophosphorylation | 23473668 |
| Hgene | RIPK1 | GO:0043065 | positive regulation of apoptotic process | 8612133|17389591 |
| Hgene | RIPK1 | GO:0043123 | positive regulation of canonical NF-kappaB signal transduction | 17389591 |
| Hgene | RIPK1 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 16127453|17389591 |
| Hgene | RIPK1 | GO:0046330 | positive regulation of JNK cascade | 17389591 |
| Hgene | RIPK1 | GO:0046777 | protein autophosphorylation | 8612133 |
| Hgene | RIPK1 | GO:0071356 | cellular response to tumor necrosis factor | 17389591 |
| Hgene | RIPK1 | GO:0097191 | extrinsic apoptotic signaling pathway | 7538908 |
| Hgene | RIPK1 | GO:1903800 | positive regulation of miRNA processing | 26020802 |
| Tgene | NQO2 | GO:1901662 | quinone catabolic process | 18254726 |
| Kinase Fusion gene breakpoints across RIPK1 (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 NQO2 (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-AN-A0FJ-01A | RIPK1 | chr6 | 3089891 | NQO2 | chr6 | 3006702 |
| CCLE | SIHA | RIPK1 | chr6 | 3085642 | NQO2 | chr6 | 3017118 |
| CCLE | EBC-1 | RIPK1 | chr6 | 3081350 | NQO2 | chr6 | 3026987 |
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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/:3089891/:3006702) - 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 |
| RIPK1 | NQO2 |
| FUNCTION: Serine-threonine kinase which is a key regulator of TNF-mediated apoptosis, necroptosis and inflammatory pathways (PubMed:32657447, PubMed:31827280, PubMed:31827281, PubMed:17703191, PubMed:24144979). Exhibits kinase activity-dependent functions that regulate cell death and kinase-independent scaffold functions regulating inflammatory signaling and cell survival (PubMed:11101870, PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Has kinase-independent scaffold functions: upon binding of TNF to TNFR1, RIPK1 is recruited to the TNF-R1 signaling complex (TNF-RSC also known as complex I) where it acts as a scaffold protein promoting cell survival, in part, by activating the canonical NF-kappa-B pathway (By similarity). Kinase activity is essential to regulate necroptosis and apoptosis, two parallel forms of cell death: upon activation of its protein kinase activity, regulates assembly of two death-inducing complexes, namely complex IIa (RIPK1-FADD-CASP8), which drives apoptosis, and the complex IIb (RIPK1-RIPK3-MLKL), which drives necroptosis (By similarity). RIPK1 is required to limit CASP8-dependent TNFR1-induced apoptosis (By similarity). In normal conditions, RIPK1 acts as an inhibitor of RIPK3-dependent necroptosis, a process mediated by RIPK3 component of complex IIb, which catalyzes phosphorylation of MLKL upon induction by ZBP1 (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Inhibits RIPK3-mediated necroptosis via FADD-mediated recruitment of CASP8, which cleaves RIPK1 and limits TNF-induced necroptosis (PubMed:19524512, PubMed:19524513, PubMed:29440439, PubMed:30988283). Required to inhibit apoptosis and necroptosis during embryonic development: acts by preventing the interaction of TRADD with FADD thereby limiting aberrant activation of CASP8 (By similarity). In addition to apoptosis and necroptosis, also involved in inflammatory response by promoting transcriptional production of pro-inflammatory cytokines, such as interleukin-6 (IL6) (PubMed:31827280, PubMed:31827281). Phosphorylates RIPK3: RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation (PubMed:19524513). Phosphorylates DAB2IP at 'Ser-728' in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade (PubMed:17389591, PubMed:15310755). Required for ZBP1-induced NF-kappa-B activation in response to DNA damage (By similarity). {ECO:0000250|UniProtKB:Q60855, ECO:0000269|PubMed:11101870, ECO:0000269|PubMed:15310755, ECO:0000269|PubMed:17389591, ECO:0000269|PubMed:17703191, ECO:0000269|PubMed:19524512, ECO:0000269|PubMed:19524513, ECO:0000269|PubMed:24144979, ECO:0000269|PubMed:29440439, ECO:0000269|PubMed:30988283, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32657447}. | FUNCTION: The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. {ECO:0000269|PubMed:18254726}. |
| 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 RIPK1_NQO2 |
| 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 |
| RIPK1 | Q13546 | human | RIPK1 | Q13546 | S15 | NVIKMkssDFLEsAE | |
| RIPK1 | Q13546 | human | RIPK1 | Q13546 | S166 | LAsFkMWskLNNEEH | PK_Tyr_Ser-Thr |
| RIPK1 | Q13546 | human | DAB2IP | Q5VWQ8 | S728 | PsPARsSsYSEANEP | DUF3498 |
| RIPK1 | Q13546 | human | RIPK1 | Q13546 | S14 | LNVIKMkssDFLEsA | |
| RIPK1 | Q13546 | human | RIPK1 | Q13546 | S20 | kssDFLEsAELDsGG | PK_Tyr_Ser-Thr |
| RIPK1 | Q13546 | human | RIPK1 | Q13546 | S161 | IADLGLAsFkMWskL | PK_Tyr_Ser-Thr |
| 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 |
| RIPK1 | ID | Description | 0.00e+00 |
| RIPK1 | GO:0043124 | negative regulation of canonical NF-kappaB signal transduction | 2.31e-03 |
| RIPK1 | GO:0046330 | positive regulation of JNK cascade | 2.90e-03 |
| RIPK1 | GO:0032874 | positive regulation of stress-activated MAPK cascade | 2.90e-03 |
| RIPK1 | GO:0070304 | positive regulation of stress-activated protein kinase signaling cascade | 2.90e-03 |
| RIPK1 | GO:0046328 | regulation of JNK cascade | 2.90e-03 |
| RIPK1 | GO:2001235 | positive regulation of apoptotic signaling pathway | 2.92e-03 |
| RIPK1 | GO:0007254 | JNK cascade | 3.17e-03 |
| RIPK1 | GO:0032872 | regulation of stress-activated MAPK cascade | 3.32e-03 |
| RIPK1 | GO:0070302 | regulation of stress-activated protein kinase signaling cascade | 3.32e-03 |
| RIPK1 | GO:0097191 | extrinsic apoptotic signaling pathway | 3.64e-03 |
| RIPK1 | GO:0051403 | stress-activated MAPK cascade | 3.64e-03 |
| RIPK1 | GO:0031098 | stress-activated protein kinase signaling cascade | 3.64e-03 |
| RIPK1 | GO:0071356 | cellular response to tumor necrosis factor | 3.64e-03 |
| RIPK1 | GO:0034612 | response to tumor necrosis factor | 3.92e-03 |
| RIPK1 | GO:0043122 | regulation of canonical NF-kappaB signal transduction | 3.92e-03 |
| RIPK1 | GO:0007249 | canonical NF-kappaB signal transduction | 4.71e-03 |
| RIPK1 | GO:2001233 | regulation of apoptotic signaling pathway | 7.67e-03 |
| RIPK1 | GO:0051090 | regulation of DNA-binding transcription factor activity | 7.67e-03 |
| RIPK1 | GO:0043410 | positive regulation of MAPK cascade | 9.65e-03 |
| RIPK1 | GO:0031349 | positive regulation of defense response | 9.65e-03 |
| RIPK1 | GO:0062100 | positive regulation of programmed necrotic cell death | 1.42e-02 |
| RIPK1 | GO:0030948 | negative regulation of vascular endothelial growth factor receptor signaling pathway | 1.42e-02 |
| RIPK1 | GO:0070103 | regulation of interleukin-6-mediated signaling pathway | 1.42e-02 |
| RIPK1 | GO:1900103 | positive regulation of endoplasmic reticulum unfolded protein response | 1.42e-02 |
| RIPK1 | GO:0021819 | layer formation in cerebral cortex | 1.42e-02 |
| RIPK1 | GO:1903265 | positive regulation of tumor necrosis factor-mediated signaling pathway | 1.42e-02 |
| RIPK1 | GO:1903894 | regulation of IRE1-mediated unfolded protein response | 1.42e-02 |
| RIPK1 | GO:0034144 | negative regulation of toll-like receptor 4 signaling pathway | 1.42e-02 |
| RIPK1 | GO:0060148 | positive regulation of post-transcriptional gene silencing | 1.42e-02 |
| RIPK1 | GO:1900370 | positive regulation of post-transcriptional gene silencing by RNA | 1.42e-02 |
| RIPK1 | GO:2000637 | positive regulation of miRNA-mediated gene silencing | 1.42e-02 |
| RIPK1 | GO:0032239 | regulation of nucleobase-containing compound transport | 1.42e-02 |
| RIPK1 | GO:0045651 | positive regulation of macrophage differentiation | 1.42e-02 |
| RIPK1 | GO:1900006 | positive regulation of dendrite development | 1.42e-02 |
| RIPK1 | GO:1903798 | regulation of miRNA processing | 1.42e-02 |
| RIPK1 | GO:0007252 | I-kappaB phosphorylation | 1.42e-02 |
| RIPK1 | GO:0070920 | regulation of regulatory ncRNA processing | 1.42e-02 |
| RIPK1 | GO:1900747 | negative regulation of vascular endothelial growth factor signaling pathway | 1.42e-02 |
| RIPK1 | GO:0044070 | regulation of monoatomic anion transport | 1.46e-02 |
| RIPK1 | GO:1902548 | negative regulation of cellular response to vascular endothelial growth factor stimulus | 1.47e-02 |
| RIPK1 | GO:2001224 | positive regulation of neuron migration | 1.47e-02 |
| RIPK1 | GO:0036498 | IRE1-mediated unfolded protein response | 1.47e-02 |
| RIPK1 | GO:0090128 | regulation of synapse maturation | 1.47e-02 |
| RIPK1 | GO:0060546 | negative regulation of necroptotic process | 1.58e-02 |
| RIPK1 | GO:0062099 | negative regulation of programmed necrotic cell death | 1.62e-02 |
| RIPK1 | GO:0034260 | negative regulation of GTPase activity | 1.64e-02 |
| RIPK1 | GO:0045649 | regulation of macrophage differentiation | 1.64e-02 |
| RIPK1 | GO:0070102 | interleukin-6-mediated signaling pathway | 1.64e-02 |
| RIPK1 | GO:0021801 | cerebral cortex radial glia-guided migration | 1.64e-02 |
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Related Drugs to RIPK1_NQO2 |
| 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 RIPK1-NQO2 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 RIPK1_NQO2 |
| 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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