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 | Fusion Gene Summary |
| Fusion Gene ORF analysis |
| Fusion Genomic Features |
| Fusion Protein Features |
| Fusion Gene Sequence |
| Fusion Gene PPI analysis |
| Related Drugs |
| Related Diseases |
Fusion gene:CDK2-ALK (FusionGDB2 ID:15231) |
Fusion Gene Summary for CDK2-ALK |
 Fusion gene summary |
| Fusion gene information | Fusion gene name: CDK2-ALK | Fusion gene ID: 15231 | Hgene | Tgene | Gene symbol | CDK2 | ALK | Gene ID | 1017 | 238 |
| Gene name | cyclin dependent kinase 2 | ALK receptor tyrosine kinase | |
| Synonyms | CDKN2|p33(CDK2) | CD246|NBLST3 | |
| Cytomap | 12q13.2 | 2p23.2-p23.1 | |
| Type of gene | protein-coding | protein-coding | |
| Description | cyclin-dependent kinase 2cdc2-related protein kinasecell division protein kinase 2p33 protein kinase | ALK tyrosine kinase receptorCD246 antigenanaplastic lymphoma receptor tyrosine kinasemutant anaplastic lymphoma kinase | |
| Modification date | 20200313 | 20200329 | |
| UniProtAcc | P24941 | Q96BT7 | |
| Ensembl transtripts involved in fusion gene | ENST00000556656, ENST00000266970, ENST00000354056, ENST00000440311, ENST00000553376, | ENST00000389048, ENST00000431873, ENST00000498037, | |
| Fusion gene scores | * DoF score | 4 X 4 X 2=32 | 56 X 74 X 20=82880 |
| # samples | 4 | 57 | |
| ** MAII score | log2(4/32*10)=0.321928094887362 effective Gene in Pan-Cancer Fusion Genes (eGinPCFGs). DoF>8 and MAII>0 | log2(57/82880*10)=-7.18391827352181 possibly effective Gene in Pan-Cancer Fusion Genes (peGinPCFGs). DoF>8 and MAII<0 | |
| Context | PubMed: CDK2 [Title/Abstract] AND ALK [Title/Abstract] AND fusion [Title/Abstract] | ||
| Most frequent breakpoint | CDK2(56365031)-ALK(29448431), # samples:2 | ||
| Anticipated loss of major functional domain due to fusion event. | CDK2-ALK seems lost the major protein functional domain in Hgene partner, which is a epigenetic factor due to the frame-shifted ORF. CDK2-ALK seems lost the major protein functional domain in Hgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. CDK2-ALK seems lost the major protein functional domain in Hgene partner, which is a kinase due to the frame-shifted ORF. CDK2-ALK seems lost the major protein functional domain in Hgene partner, which is a tumor suppressor due to the frame-shifted ORF. CDK2-ALK seems lost the major protein functional domain in Tgene partner, which is a CGC due to the frame-shifted ORF. CDK2-ALK seems lost the major protein functional domain in Tgene partner, which is a IUPHAR drug target due to the frame-shifted ORF. CDK2-ALK 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 | CDK2 | GO:0006468 | protein phosphorylation | 12944431|28666995 |
| Hgene | CDK2 | GO:0008284 | positive regulation of cell proliferation | 10767298 |
| Hgene | CDK2 | GO:0016572 | histone phosphorylation | 11746698 |
| Hgene | CDK2 | GO:0018105 | peptidyl-serine phosphorylation | 23184662 |
| Hgene | CDK2 | GO:0060968 | regulation of gene silencing | 20935635 |
| Tgene | ALK | GO:0016310 | phosphorylation | 9174053 |
| Tgene | ALK | GO:0046777 | protein autophosphorylation | 9174053 |
| Fusion gene breakpoints across CDK2 (5'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Fusion gene breakpoints across ALK (3'-gene) * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| 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 | SKCM | TCGA-WE-A8K4-01A | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
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Fusion Gene ORF analysis for CDK2-ALK |
| Open reading frame (ORF) analsis of fusion genes based on Ensembl gene isoform structure. * Click on the break point to see the gene structure around the break point region using the UCSC Genome Browser. |
| ORF | Henst | Tenst | Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand |
| 3UTR-3CDS | ENST00000556656 | ENST00000389048 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 3UTR-intron | ENST00000556656 | ENST00000431873 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 3UTR-intron | ENST00000556656 | ENST00000498037 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000266970 | ENST00000431873 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000266970 | ENST00000498037 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000354056 | ENST00000431873 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000354056 | ENST00000498037 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000440311 | ENST00000431873 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000440311 | ENST00000498037 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000553376 | ENST00000431873 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| 5CDS-intron | ENST00000553376 | ENST00000498037 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| Frame-shift | ENST00000266970 | ENST00000389048 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| Frame-shift | ENST00000354056 | ENST00000389048 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| Frame-shift | ENST00000440311 | ENST00000389048 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| Frame-shift | ENST00000553376 | ENST00000389048 | CDK2 | chr12 | 56365031 | + | ALK | chr2 | 29448431 | - |
| ORFfinder result based on the fusion transcript sequence of in-frame fusion genes. |
| 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) |
| 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 |
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Fusion Genomic Features for CDK2-ALK |
| FusionAI prediction of the potential fusion gene breakpoint based on the pre-mature RNA sequence context (+/- 5kb of individual partner genes, total 20kb length sequence). FusionAI is a fusion gene breakpoint classifier based on convolutional neural network by comparing the fusion positive and negative sequence context of ~ 20K fusion gene data. From here, we can have the relative potentency of the 20K genomic sequence how individual sequnce will be likely used as the gene fusion breakpoints. |
| Hgene | Hchr | Hbp | Hstrand | Tgene | Tchr | Tbp | Tstrand | 1-p | p (fusion gene breakpoint) |
| Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions. We integrated a total of 44 different types of human genomic feature loci information across five big categories including virus integration sites, repeats, structural variants, chromatin states, and gene expression regulation. More details are in help page. |
| Distribution of 44 human genomic features loci across 20kb length fusion breakpoint regions that are ovelapped with the top 1% feature importance score regions. More details are in help page. |
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Fusion Protein Features for CDK2-ALK |
| Four levels of functional features of fusion genes Go to FGviewer search page for the most frequent breakpoint (https://ccsmweb.uth.edu/FGviewer/:56365031/:29448431) - 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 |
| CDK2 | ALK |
| FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Triggers duplication of centrosomes and DNA. Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates CDK2AP2 (PubMed:12944431). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878}. | FUNCTION: Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain (PubMed:20123966, PubMed:20308323, PubMed:31079898). Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA (PubMed:20123966, PubMed:20308323). Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys)(PubMed:20308323). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly) (PubMed:21285950). Required for normal survival after DNA damage (PubMed:20308323). May inhibit apoptosis and promote cell survival and angiogenesis (PubMed:19293182). {ECO:0000269|PubMed:19293182, ECO:0000269|PubMed:20123966, ECO:0000269|PubMed:20308323, ECO:0000269|PubMed:21285950, ECO:0000269|PubMed:31079898}. |
| 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. |
| - In-frame and 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 |
| - In-frame and 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 |
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Fusion Gene Sequence for CDK2-ALK |
| For in-frame fusion transcripts, we provide the fusion transcript sequences and fusion amino acid sequences. To have fusion amino acid sequence, we ran ORFfinder and chose the longest ORF among the all predicted ones. |
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Fusion Gene PPI Analysis for CDK2-ALK |
| 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 (BIOGRID-3.4.160) |
| Hgene | Hgene's interactors | Tgene | Tgene's interactors |
| - Retained PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Still interaction with |
| - Lost PPIs in in-frame fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
| - Retained PPIs, but lost function due to frame-shift fusion. |
| Partner | Gene | Hbp | Tbp | ENST | Strand | BPexon | TotalExon | Protein feature loci | *BPloci | TotalLen | Interaction lost with |
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Related Drugs for CDK2-ALK |
| Drugs targeting genes involved in this fusion gene. (DrugBank Version 5.1.8 2021-05-08) |
| Partner | Gene | UniProtAcc | DrugBank ID | Drug name | Drug activity | Drug type | Drug status |
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Related Diseases for CDK2-ALK |
| Diseases associated with fusion partners. (DisGeNet 4.0) |
| Partner | Gene | Disease ID | Disease name | # pubmeds | Source |
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