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Fusion Protein:CASC3-CDK12 |
Fusion Protein Summary |
 Fusion gene summary |
| Fusion partner gene information | Fusion gene name: CASC3-CDK12 | FusionPDB ID: 13145 | FusionGDB2.0 ID: 13145 | Hgene | Tgene | Gene symbol | CASC3 | CDK12 | Gene ID | 22794 | 51755 |
| Gene name | CASC3 exon junction complex subunit | cyclin dependent kinase 12 | |
| Synonyms | BTZ|MLN51 | CRK7|CRKR|CRKRS | |
| Cytomap | 17q21.1 | 17q12 | |
| Type of gene | protein-coding | protein-coding | |
| Description | protein CASC3MLN 51barentszcancer susceptibility 3cancer susceptibility candidate 3cancer susceptibility candidate gene 3 proteinmetastatic lymph node 51metastatic lymph node gene 51 proteinprotein barentsz | cyclin-dependent kinase 12CDC2-related protein kinase 7Cdc2-related kinase, arginine/serine-richcell division cycle 2-related protein kinase 7cell division protein kinase 12 | |
| Modification date | 20200313 | 20200313 | |
| UniProtAcc | O15234 | Q9NYV4 | |
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000264645, | ENST00000559545, ENST00000430627, ENST00000447079, |
| Fusion gene scores for assessment (based on all fusion genes of FusionGDB 2.0) | * DoF score | 21 X 10 X 10=2100 | 36 X 30 X 14=15120 |
| # samples | 28 | 55 | |
| ** MAII score | log2(28/2100*10)=-2.90689059560852 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | log2(55/15120*10)=-4.78088271069641 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context (manual curation of fusion genes in FusionPDB) | PubMed: CASC3 [Title/Abstract] AND CDK12 [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | CASC3(38297860)-CDK12(37680926), # samples:1 CASC3(38297860)-CDK12(37680927), # samples:1 CASC3(38297860)-CDK12(37686884), # samples:1 | ||
| Anticipated loss of major functional domain due to fusion event. | CASC3-CDK12 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. CASC3-CDK12 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. CASC3-CDK12 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. CASC3-CDK12 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. CASC3-CDK12 seems lost the major protein functional domain in Hgene partner, which is a cell metabolism gene due to the frame-shifted ORF. CASC3-CDK12 seems lost the major protein functional domain in Hgene partner, which is a essential gene due to the frame-shifted ORF. CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a essential gene due to the frame-shifted ORF. CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. CASC3-CDK12 seems lost the major protein functional domain in Tgene partner, which is a kinase 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 | CASC3 | GO:0000398 | mRNA splicing, via spliceosome | 29301961 |
| Tgene | CDK12 | GO:0046777 | protein autophosphorylation | 11683387 |
| Fusion gene breakpoints across CASC3 (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 CDK12 (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 Gene Sample Information |
| Fusion gene information from FusionGDB2.0. |
| Fusion gene information from two resources (ChiTars 5.0 and ChimerDB 4.0) * 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 | Disease | Sample | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| ChimerDB4 | STAD | TCGA-BR-4366-01A | CASC3 | chr17 | 38297860 | - | CDK12 | chr17 | 37686884 | + |
| ChimerDB4 | STAD | TCGA-CD-A486-01A | CASC3 | chr17 | 38297860 | + | CDK12 | chr17 | 37680927 | + |
| ChimerDB4 | STAD | TCGA-CD-A486 | CASC3 | chr17 | 38297860 | + | CDK12 | chr17 | 37680926 | + |
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Fusion ORF Analysis |
| 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) |
| ENST00000264645 | CASC3 | chr17 | 38297860 | - | ENST00000430627 | CDK12 | chr17 | 37686884 | + | 2370 | 523 | 576 | 1208 | 210 |
| 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 |
| ENST00000264645 | ENST00000430627 | CASC3 | chr17 | 38297860 | - | CDK12 | chr17 | 37686884 | + | 0.104445025 | 0.89555496 |
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Fusion Amino Acid Sequences |
| For individual full-length fusion transcript sequence from FusionPDB, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
| >FusionGDB ID_FusionGDB isoform ID_FGname_Hgene_Hchr_Hbp_Henst_Tgene_Tchr_Tbp_Tenst_length(fusion AA) seq_BP >13145_13145_1_CASC3-CDK12_CASC3_chr17_38297860_ENST00000264645_CDK12_chr17_37686884_ENST00000430627_length(amino acids)=210AA_BP= MVEGDLSSAPQELNPAVTAALLQLLSQPEAEPPGHLPHEHQALRPMEYSTRPRPNRTYGNTDGPETGFSAIDTDERNSGPALTESLVQTL VKNRTFSGSLSHLGESSSYQGTGSVQFPGDQDLRFARVPLALHPVVGQPFLKAEGSSNSVVHAETKLQNYGELGPGTTGASSSGAGLHWG -------------------------------------------------------------- |
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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/chr17:38297860/chr17:37680926) - 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 |
| CASC3 | CDK12 |
| FUNCTION: Required for pre-mRNA splicing as component of the spliceosome (PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays a role in the stress response by participating in cytoplasmic stress granules assembly and by favoring cell recovery following stress. Component of the dendritic ribonucleoprotein particles (RNPs) in hippocampal neurons. May play a role in mRNA transport. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) and poly(U) RNA homopolymer. {ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:17652158, ECO:0000269|PubMed:28502770, ECO:0000269|PubMed:29301961}. | FUNCTION: Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors. {ECO:0000269|PubMed:11683387, ECO:0000269|PubMed:19651820, ECO:0000269|PubMed:20952539, ECO:0000269|PubMed:22012619, ECO:0000269|PubMed:24662513}. |
| 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 protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 41_46 | 99.0 | 1130.6666666666667 | Compositional bias | Note=Poly-Gly |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 1266_1280 | 1253.3333333333333 | 1482.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 1266_1280 | 0 | 1491.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 407_413 | 0 | 1491.0 | Compositional bias | Note=Poly-Ala | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 535_540 | 0 | 1491.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 727_1020 | 0 | 1491.0 | Domain | Protein kinase | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 733_741 | 0 | 1491.0 | Nucleotide binding | Note=ATP | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000447079 | 0 | 14 | 814_819 | 0 | 1491.0 | Nucleotide binding | Note=ATP |
| - Not-retained protein feature among the 13 regional features. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Protein feature | Protein feature note |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 95_131 | 99.0 | 1130.6666666666667 | Coiled coil | Ontology_term=ECO:0000255 |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 392_395 | 99.0 | 1130.6666666666667 | Compositional bias | Note=Poly-Pro |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 425_428 | 99.0 | 1130.6666666666667 | Compositional bias | Note=Poly-Pro |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 643_648 | 99.0 | 1130.6666666666667 | Compositional bias | Note=Poly-Pro |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 692_695 | 99.0 | 1130.6666666666667 | Compositional bias | Note=Poly-Pro |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 204_210 | 99.0 | 1130.6666666666667 | Motif | Nuclear localization signal 1 |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 254_262 | 99.0 | 1130.6666666666667 | Motif | Nuclear localization signal 2 |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 462_466 | 99.0 | 1130.6666666666667 | Motif | Note=Nuclear export signal |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 137_283 | 99.0 | 1130.6666666666667 | Region | Note=Sufficient to form the EJC |
| Hgene | CASC3 | chr17:38297860 | chr17:37686884 | ENST00000264645 | - | 3 | 14 | 377_703 | 99.0 | 1130.6666666666667 | Region | Note=Necessary for localization in cytoplasmic stress granules |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 407_413 | 1253.3333333333333 | 1482.0 | Compositional bias | Note=Poly-Ala | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 535_540 | 1253.3333333333333 | 1482.0 | Compositional bias | Note=Poly-Pro | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 727_1020 | 1253.3333333333333 | 1482.0 | Domain | Protein kinase | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 733_741 | 1253.3333333333333 | 1482.0 | Nucleotide binding | Note=ATP | |
| Tgene | CDK12 | chr17:38297860 | chr17:37686884 | ENST00000430627 | 12 | 14 | 814_819 | 1253.3333333333333 | 1482.0 | Nucleotide binding | Note=ATP |
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Fusion Protein-Protein Interaction |
| Go to ChiPPI (Chimeric Protein-Protein interactions) to see the chimeric PPI interaction in |
| Protein-protein interactors with each fusion partner protein in wild-type from validated records (BIOGRID-3.4.160) |
| Gene | PPI interactors |
| Protein-protein interactors based on sequence similarity (STRING) |
| Gene | STRING network |
| CASC3 | |
| CDK12 |
| - Retained interactions in fusion protein (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost interactions due to fusion (protein functional feature from UniProt). |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs to CASC3-CDK12 |
| 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 CASC3-CDK12 |
| 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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