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Fusion Protein:KLC1-BTK |
Fusion Gene and Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: KLC1-BTK | FusionPDB ID: 42824 | FusionGDB2.0 ID: 42824 | Hgene | Tgene | Gene symbol | KLC1 | BTK | Gene ID | 3831 | 695 |
| Gene name | kinesin light chain 1 | Bruton tyrosine kinase | |
| Synonyms | KLC|KNS2|KNS2A | AGMX1|AT|ATK|BPK|IGHD3|IMD1|PSCTK1|XLA | |
| Cytomap | 14q32.33 | Xq22.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | kinesin light chain 1kinesin 2 60/70kDamedulloblastoma antigen MU-MB-2.50 | tyrosine-protein kinase BTKB-cell progenitor kinaseBruton agammaglobulinemia tyrosine kinaseBruton's tyrosine kinaseagammaglobulinaemia tyrosine kinasedominant-negative kinase-deficient Brutons tyrosine kinasetruncated Bruton agammaglobulinemia tyro | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | Q07866 Main function of 5'-partner protein: FUNCTION: Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport. The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity. | Q06187 Main function of 5'-partner protein: FUNCTION: Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis. {ECO:0000269|PubMed:11606584, ECO:0000269|PubMed:16415872, ECO:0000269|PubMed:16517732, ECO:0000269|PubMed:16738337, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:9012831}. | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000246489, ENST00000334553, ENST00000347839, ENST00000348520, ENST00000380038, ENST00000389744, ENST00000445352, ENST00000452929, ENST00000553286, ENST00000554280, ENST00000555836, ENST00000557450, ENST00000557575, | ENST00000464567, ENST00000308731, ENST00000372880, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 9 X 12 X 6=648 | 2 X 2 X 2=8 |
| # samples | 16 | 2 | |
| ** MAII score | log2(16/648*10)=-2.01792190799726 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(2/8*10)=1.32192809488736 | |
| Fusion gene context | PubMed: KLC1 [Title/Abstract] AND BTK [Title/Abstract] AND fusion [Title/Abstract] | ||
| Fusion neoantigen context | PubMed: KLC1 [Title/Abstract] AND BTK [Title/Abstract] AND neoantigen [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | KLC1(104129264)-BTK(100604944), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | KLC1-BTK 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. KLC1-BTK 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. KLC1-BTK seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. KLC1-BTK seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. KLC1-BTK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. KLC1-BTK seems lost the major protein functional domain in Tgene partner, which is a kinase due to the frame-shifted ORF. KLC1-BTK seems lost the major protein functional domain in Tgene partner, which is a tumor suppressor 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 |
| Tgene | BTK | GO:0018108 | peptidyl-tyrosine phosphorylation | 11606584 |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/chr14:104129264/chrX:100604944) - 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 KLC1 (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 BTK (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) |
| ENST00000348520 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1626 | 1116 | 319 | 1152 | 277 |
| ENST00000380038 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1600 | 1090 | 293 | 1126 | 277 |
| ENST00000389744 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1576 | 1066 | 269 | 1102 | 277 |
| ENST00000557575 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1566 | 1056 | 259 | 1092 | 277 |
| ENST00000553286 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1566 | 1056 | 259 | 1092 | 277 |
| ENST00000347839 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1566 | 1056 | 259 | 1092 | 277 |
| ENST00000555836 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1566 | 1056 | 259 | 1092 | 277 |
| ENST00000334553 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1566 | 1056 | 259 | 1092 | 277 |
| ENST00000246489 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1562 | 1052 | 255 | 1088 | 277 |
| ENST00000557450 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1562 | 1052 | 255 | 1088 | 277 |
| ENST00000554280 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1562 | 1052 | 255 | 1088 | 277 |
| ENST00000452929 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1562 | 1052 | 255 | 1088 | 277 |
| ENST00000445352 | KLC1 | chr14 | 104129264 | + | ENST00000372880 | BTK | chrX | 100604944 | - | 1500 | 990 | 199 | 1026 | 275 |
| 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 |
| ENST00000348520 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002563315 | 0.9974367 |
| ENST00000380038 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002434778 | 0.99756527 |
| ENST00000389744 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002591987 | 0.997408 |
| ENST00000557575 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002682817 | 0.99731714 |
| ENST00000553286 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002682817 | 0.99731714 |
| ENST00000347839 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002682817 | 0.99731714 |
| ENST00000555836 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002682817 | 0.99731714 |
| ENST00000334553 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002682817 | 0.99731714 |
| ENST00000246489 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.0026395 | 0.9973605 |
| ENST00000557450 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.0026395 | 0.9973605 |
| ENST00000554280 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.0026395 | 0.9973605 |
| ENST00000452929 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.0026395 | 0.9973605 |
| ENST00000445352 | ENST00000372880 | KLC1 | chr14 | 104129264 | + | BTK | chrX | 100604944 | - | 0.002420116 | 0.9975799 |
| 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 KLC1-BTK |
| +/-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 KLC1-BTK 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 KLC1-BTK 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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 KLC1-BTK |
| 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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