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Kinase Fusion Gene:CASP8_STRADB |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: CASP8_STRADB | KinaseFusionDB ID: KFG935 | FusionGDB2.0 ID: KFG935 | Hgene | Tgene | Gene symbol | CASP8 | STRADB | Gene ID | 841 | 55437 | |
| Gene name | caspase 8 | STE20 related adaptor beta | ||||||||||
| Synonyms | ALPS2B|CAP4|Casp-8|FLICE|MACH|MCH5 | ALS2CR2|CALS-21|ILPIP|ILPIPA|PAPK|PRO1038 | ||||||||||
| Cytomap | 2q33.1 | 2q33.1 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | caspase-8FADD-homologous ICE/CED-3-like proteaseFADD-like ICEICE-like apoptotic protease 5MACH-alpha-1/2/3 proteinMACH-beta-1/2/3/4 proteinMORT1-associated ced-3 homologapoptotic cysteine proteaseapoptotic protease Mch-5caspase 8, apoptosis-relat | STE20-related kinase adapter protein betaILP-interacting protein ILPIPASTE20-related kinase adaptor betaSTRAD betaamyotrophic lateral sclerosis 2 (juvenile) chromosome region, candidate 2amyotrophic lateral sclerosis 2 chromosomal region candidate ge | ||||||||||
| Modification date | 20240411 | 20240305 | ||||||||||
| UniProtAcc | Q14790 | Q9C0K7 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000490682, ENST00000358485, ENST00000264274, ENST00000264275, ENST00000392258, ENST00000392259, ENST00000392266, ENST00000432109, ENST00000323492, | ENST00000194530, ENST00000488196, ENST00000392249, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: CASP8 [Title/Abstract] AND STRADB [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CASP8(202098835)-STRADB(202334676), # 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 | CASP8 | GO:0006508 | proteolysis | 12888622 |
| Hgene | CASP8 | GO:0030335 | positive regulation of cell migration | 18216014 |
| Hgene | CASP8 | GO:0036462 | TRAIL-activated apoptotic signaling pathway | 21785459 |
| Hgene | CASP8 | GO:0045862 | positive regulation of proteolysis | 18387192 |
| Hgene | CASP8 | GO:0051604 | protein maturation | 16916640|33852854|35594856 |
| Hgene | CASP8 | GO:0060546 | negative regulation of necroptotic process | 31827280 |
| Hgene | CASP8 | GO:0097191 | extrinsic apoptotic signaling pathway | 21785459|35446120 |
| Hgene | CASP8 | GO:0097202 | activation of cysteine-type endopeptidase activity | 18387192 |
| Tgene | STRADB | GO:0006468 | protein phosphorylation | 14517248 |
| Tgene | STRADB | GO:0006611 | protein export from nucleus | 14517248 |
| Tgene | STRADB | GO:0032147 | activation of protein kinase activity | 14517248 |
| Kinase Fusion gene breakpoints across CASP8 (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 STRADB (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-LN-A49O-01A | CASP8 | chr2 | 202098835 | STRADB | chr2 | 202334676 |
| ChimerDB4 | TCGA-LN-A49O | CASP8 | chr2 | 202098835 | STRADB | chr2 | 202337677 |
| ChimerDB4 | TCGA-LN-A49O | CASP8 | chr2 | 202098835 | STRADB | chr2 | 202337678 |
| ChimerDB4 | TCGA-JW-A5VG-01A | CASP8 | chr2 | 202098835 | STRADB | chr2 | 202319469 |
| ChimerDB4 | TCGA-LN-A49O | CASP8 | chr2 | 202123105 | STRADB | chr2 | 202334676 |
| CCLE | HCC2218 | CASP8 | chr2 | 202098835 | STRADB | chr2 | 202340342 |
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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/:202098835/:202334676) - 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 |
| CASP8 | STRADB |
| FUNCTION: Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood (PubMed:23516580, PubMed:8681376, PubMed:8681377, PubMed:9006941, PubMed:9184224, PubMed:8962078, PubMed:35446120, PubMed:35338844). Initiator protease that induces extrinsic apoptosis by mediating cleavage and activation of effector caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death (PubMed:23516580, PubMed:8681376, PubMed:8681377, PubMed:9006941, PubMed:9184224, PubMed:8962078, PubMed:35446120, PubMed:35338844). Cleaves and activates effector caspases CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10 (PubMed:8962078, PubMed:9006941, PubMed:16916640). Binding to the adapter molecule FADD recruits it to either receptor TNFRSF6/FAS mediated or TNFRSF1A (PubMed:8681376, PubMed:8681377). The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation (PubMed:9184224). The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases (PubMed:9184224). Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC (PubMed:9184224). In addition to extrinsic apoptosis, also acts as a negative regulator of necroptosis: acts by cleaving RIPK1 at 'Asp-324', which is crucial to inhibit RIPK1 kinase activity, limiting TNF-induced apoptosis, necroptosis and inflammatory response (PubMed:31827280, PubMed:31827281). Also able to initiate pyroptosis by mediating cleavage and activation of gasdermin-C and -D (GSDMC and GSDMD, respectively): gasdermin cleavage promotes release of the N-terminal moiety that binds to membranes and forms pores, triggering pyroptosis (PubMed:32929201, PubMed:34012073). Initiates pyroptosis following inactivation of MAP3K7/TAK1 (By similarity). Also acts as a regulator of innate immunity by mediating cleavage and inactivation of N4BP1 downstream of TLR3 or TLR4, thereby promoting cytokine production (By similarity). May participate in the Granzyme B (GZMB) cell death pathways (PubMed:8755496). Cleaves PARP1 and PARP2 (PubMed:8681376). {ECO:0000250|UniProtKB:O89110, ECO:0000269|PubMed:16916640, ECO:0000269|PubMed:23516580, ECO:0000269|PubMed:31827280, ECO:0000269|PubMed:31827281, ECO:0000269|PubMed:32929201, ECO:0000269|PubMed:34012073, ECO:0000269|PubMed:35338844, ECO:0000269|PubMed:35446120, ECO:0000269|PubMed:8681376, ECO:0000269|PubMed:8681377, ECO:0000269|PubMed:8755496, ECO:0000269|PubMed:8962078, ECO:0000269|PubMed:9006941, ECO:0000269|PubMed:9184224}.; FUNCTION: [Isoform 5]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 6]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 7]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex (Probable). Acts as an inhibitor of the caspase cascade (PubMed:12010809). {ECO:0000269|PubMed:12010809, ECO:0000305|PubMed:8681376}.; FUNCTION: [Isoform 8]: Lacks the catalytic site and may interfere with the pro-apoptotic activity of the complex. {ECO:0000305|PubMed:8681376}. | FUNCTION: Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation (By similarity). {ECO:0000250, ECO:0000269|PubMed:14517248}. |
| 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 CASP8_STRADB |
| 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 |
| 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 |
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Related Drugs to CASP8_STRADB |
| 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 CASP8-STRADB 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 CASP8_STRADB |
| 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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