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Fusion Protein:FGF13-NLRP3 |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: FGF13-NLRP3 | FusionPDB ID: 30216 | FusionGDB2.0 ID: 30216 | Hgene | Tgene | Gene symbol | FGF13 | NLRP3 | Gene ID | 2258 | 114548 |
| Gene name | fibroblast growth factor 13 | NLR family pyrin domain containing 3 | |
| Synonyms | FGF-13|FGF2|FHF-2|FHF2|LINC00889 | AGTAVPRL|AII|AVP|C1orf7|CIAS1|CLR1.1|DFNA34|FCAS|FCAS1|FCU|KEFH|MWS|NALP3|PYPAF1 | |
| Cytomap | Xq26.3-q27.1 | 1q44 | |
| Type of gene | protein-coding | protein-coding | |
| Description | fibroblast growth factor 13fibroblast growth factor homologous factor 2 | NACHT, LRR and PYD domains-containing protein 3NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3NACHT, LRR and PYD containing protein 3PYRIN-containing APAF1-like protein 1caterpiller protein 1.1cold autoinflammatory syndrome 1 protei | |
| Modification date | 20200313 | 20200315 | |
| UniProtAcc | Q92913 Main function of 5'-partner protein: FUNCTION: Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules (By similarity). Through its action on microtubules, may participate in the refinement of axons by negatively regulating axonal and leading processes branching (By similarity). Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus (By similarity). May regulate voltage-gated sodium channels transport and function (PubMed:15282281). May also play a role in MAPK signaling (By similarity). Required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons (By similarity). {ECO:0000250|UniProtKB:P70377, ECO:0000269|PubMed:15282281}. | Q96P20 Main function of 5'-partner protein: FUNCTION: As the sensor component of the NLRP3 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP3, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu (PubMed:28847925). Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (PubMed:23871209). Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity). {ECO:0000250|UniProtKB:Q8R4B8, ECO:0000269|PubMed:22801494, ECO:0000269|PubMed:23871209, ECO:0000269|PubMed:28847925, ECO:0000305|PubMed:23305783}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000370603, ENST00000441825, ENST00000305414, ENST00000315930, ENST00000541469, | ENST00000474792, ENST00000336119, ENST00000348069, ENST00000366496, ENST00000366497, ENST00000391827, ENST00000391828, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 10 X 5 X 4=200 | 2 X 2 X 2=8 |
| # samples | 9 | 2 | |
| ** MAII score | log2(9/200*10)=-1.15200309344505 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(2/8*10)=1.32192809488736 | |
| Fusion gene context | PubMed: FGF13 [Title/Abstract] AND NLRP3 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: FGF13 [Title/Abstract] AND NLRP3 [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | FGF13(137939674)-NLRP3(247611707), # samples:3 | ||
| Anticipated loss of major functional domain due to fusion event. | FGF13-NLRP3 seems lost the major protein functional domain in Hgene partner, which is a CGC by not retaining the major functional domain in the partially deleted in-frame ORF. FGF13-NLRP3 seems lost the major protein functional domain in Hgene partner, which is a essential gene by not retaining the major functional domain in the partially deleted in-frame ORF. FGF13-NLRP3 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. FGF13-NLRP3 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. | ||
| * DoF score (Degree of Frequency) = # partners X # break points X # cancer types ** MAII score (Major Active Isofusion Index) = log2(# samples/DoF score*10) |
| 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 | FGF13 | GO:0000165 | MAPK cascade | 12244047 |
| Tgene | NLRP3 | GO:0032088 | negative regulation of NF-kappaB transcription factor activity | 14662828 |
| Tgene | NLRP3 | GO:0043280 | positive regulation of cysteine-type endopeptidase activity involved in apoptotic process | 15030775 |
| Tgene | NLRP3 | GO:0050718 | positive regulation of interleukin-1 beta secretion | 15030775 |
| Tgene | NLRP3 | GO:0051092 | positive regulation of NF-kappaB transcription factor activity | 19158675 |
| Tgene | NLRP3 | GO:0071222 | cellular response to lipopolysaccharide | 28847925 |
| Tgene | NLRP3 | GO:1901223 | negative regulation of NIK/NF-kappaB signaling | 14662828 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chrX:137939674/chr1:247611707) - 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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| Retention analysis results 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, are available here. |
| Fusion gene breakpoints across FGF13 (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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| Fusion gene breakpoints across NLRP3 (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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Fusion Amino Acid Sequences |
| Fusion information from ORFfinder translation from full-length transcript sequence from FusionPDB. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | Seq length (transcript) | BP loci (transcript) | Predicted start (transcript) | Predicted stop (transcript) | Seq length (amino acids) |
| ENST00000441825 | FGF13 | chrX | 137939674 | - | ENST00000391827 | NLRP3 | chr1 | 247611707 | + | 268 | 168 | 2 | 211 | 69 |
| DeepORF prediction of the coding potential based on the fusion transcript sequence of in-frame fusion genes. DeepORF is a coding potential classifier based on convolutional neural network by comparing the real Ribo-seq data. If the no-coding score < 0.5 and coding score > 0.5, then the in-frame fusion transcript is predicted as being likely translated. |
| Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | No-coding score | Coding score |
| ENST00000441825 | ENST00000391827 | FGF13 | chrX | 137939674 | - | NLRP3 | chr1 | 247611707 | + | 0.87220156 | 0.12779847 |
| Predicted full-length fusion amino acid sequences. For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among all the predicted ones. |
Get the fusion protein sequences from here. |
| Fusion protein sequence information is available in the fasta format. >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP |
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Fusion Protein Breakpoint Sequences for FGF13-NLRP3 |
| +/-13 AA sequence from the breakpoints of the fusion protein sequences. |
| Hgene | Hchr | Hbp | Tgene | Tchr | Tbp | Length(fusion protein) | BP in fusion protein | Peptide |
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Potential FusionNeoAntigen Information of FGF13-NLRP3 in HLA I |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCpan v4.1 (%rank<0.5) and deepHLApan v1.1 (immunogenic score>0.5) |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA I | FusionNeoAntigen peptide | Binding score | Immunogenic score | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Potential FusionNeoAntigen Information of FGF13-NLRP3 in HLA II |
| Multiple sequence alignments of the potential FusionNeoAntigens per fusion breakpoints. If the MSA is empty, then it means that there were predicted fusion neoantigens in this fusion breakpoint, but those predicted fusion neoantigens were not across the breakpoint, which is not fusion-specific. |
| Potential FusionNeoAntigen Information * We used NetMHCIIpan v4.1 (%rank<0.5). |
| Fusion gene | Hchr | Hbp | Tgene | Tchr | Tbp | HLA II | FusionNeoAntigen peptide | Neoantigen start (at BP 13) | Neoantigen end (at BP 13) |
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Fusion breakpoint peptide structures of FGF13-NLRP3 |
| 3D structures of the fusion breakpoint peptide of 14AA sequence that have potential fusion neoantigens * The minimum length of the amino acid sequence in RoseTTAFold is 14AA. Here, we predicted the 14AA fusion protein breakpoint sequence not the fusion neoantigen peptide, which is shorter than 14 AA. |
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Filtering FusionNeoAntigens Through Checking the Interaction with HLAs in 3D of FGF13-NLRP3 |
| Virtual screening between 25 HLAs (from PDB) and FusionNeoAntigens * We used Glide to predict the interaction between HLAs and neoantigens. |
| HLA allele | PDB ID | File name | BPseq | Docking score | Glide score |
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Vaccine Design for the FusionNeoAntigens of FGF13-NLRP3 |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-Is. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide sequence | FusionNeoAntigen RNA sequence |
| mRNA and peptide sequences of FusionNeoAntigens that have potential interaction with HLA-IIs. |
| Fusion gene | Hchr | Hbp | Tchr | Tbp | Start in +/-13AA | End in +/-13AA | FusionNeoAntigen peptide | FusionNEoAntigen RNA sequence |
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Information of the samples that have these potential fusion neoantigens of FGF13-NLRP3 |
| These samples were reported as having these fusion breakpoints. For individual breakpoints, we checked the open reading frames considering multiple gene isoforms and chose the in-frame fusion genes only. Then, we made fusion protein sequences and predicted the fusion neoantigens. These fusion-positive samples may have these potential fusion neoantigens. |
| Cancer type | Fusion gene | Hchr | Hbp | Henst | Tchr | Tbp | Tenst | Sample |
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Potential target of CAR-T therapy development for FGF13-NLRP3 |
| Predicted 3D structure. We used RoseTTAFold. |
| 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, to provide the retention of the transmembrane domain, we only show the protein feature retention information of those transmembrane features * Minus value of BPloci means that the break point is located before the CDS. |
| - In-frame and retained 'Transmembrane'. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Subcellular localization prediction of the transmembrane domain retained fusion proteins * We used DeepLoc 1.0. The order of the X-axis of the barplot is as follows: Entry_ID, Localization, Type, Nucleus, Cytoplasm, Extracellular, Mitochondrion, Cell_membrane, Endoplasmic_reticulum, Plastid, Golgi.apparatus, Lysosome.Vacuole, Peroxisome. Y-axis is the output score of DeepLoc. Clicking the image will open a new tab with a large image. |
| Hgene | Hchr | Hbp | Henst | Tgene | Tchr | Tbp | Tenst | DeepLoc result |
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Related Drugs to FGF13-NLRP3 |
| Drugs used for this fusion-positive patient. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Drug | Source | PMID |
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Related Diseases to FGF13-NLRP3 |
| Diseases that have this fusion gene. (Manual curation of PubMed, 04-30-2022 + MyCancerGenome) |
| Hgene | Tgene | Disease | Source | PMID |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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