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Kinase Fusion Gene:PRIM2_CDK12 |
Kinase Fusion Protein Summary |
Kinase Fusion gene summary |
Kinase Fusion partner gene information | Kinase Fusion gene name: PRIM2_CDK12 | KinaseFusionDB ID: KFG4853 | FusionGDB2.0 ID: KFG4853 | Hgene | Tgene | Gene symbol | PRIM2 | CDK12 | Gene ID | 5558 | 51755 | |
Gene name | DNA primase subunit 2 | cyclin dependent kinase 12 | ||||||||||
Synonyms | PRIM2A|p58 | CRK7|CRKR|CRKRS | ||||||||||
Cytomap | 6p11.2 | 17q12 | ||||||||||
Type of gene | protein-coding | protein-coding | ||||||||||
Description | DNA primase large subunitDNA primase 58 kDa subunitprimase (DNA) subunit 2primase, DNA, polypeptide 2 (58kDa) | 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 | 20240411 | 20240403 | ||||||||||
UniProtAcc | P49643 | Q9NYV4 | ||||||||||
Ensembl transtripts involved in fusion gene | ENST ids | ENST00000607273, ENST00000389488, | ENST00000430627, ENST00000447079, ENST00000559545, | |||||||||
Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: PRIM2 [Title/Abstract] AND CDK12 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) |
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 | PRIM2 | GO:0006269 | DNA replication, synthesis of primer | 8026492 |
Hgene | PRIM2 | GO:0006270 | DNA replication initiation | 26975377 |
Tgene | CDK12 | GO:0006366 | transcription by RNA polymerase II | 22988298 |
Tgene | CDK12 | GO:0032968 | positive regulation of transcription elongation by RNA polymerase II | 22988298 |
Tgene | CDK12 | GO:0046777 | protein autophosphorylation | 11683387 |
Kinase Fusion gene breakpoints across PRIM2 (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 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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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 |
CCLE | KYSE-410 | PRIM2 | chr6 | 57246966 | CDK12 | chr17 | 37680927 |
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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/:/:) - 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. |
Main function of each fusion partner protein. (from UniProt) |
Hgene | Tgene |
PRIM2 | CDK12 |
FUNCTION: Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:9705292, PubMed:17893144, PubMed:25550159, PubMed:26975377). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144, PubMed:25550159). Binds RNA:DNA duplex and coordinates the catalytic activities of PRIM1 and POLA2 during primase-to-polymerase switch. {ECO:0000250|UniProtKB:P09884, ECO:0000250|UniProtKB:P33610, ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377, ECO:0000269|PubMed:9705292}. | 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 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 PRIM2_CDK12 |
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 |
CDK12 | Q9NYV4 | human | PAK2 | Q13177 | T134 | LkFyDsNtVkQKyLs | |
CDK12 | Q9NYV4 | human | POLR2A | P24928 | S1616 | TPQSPSysPtsPsYS | RNA_pol_Rpb1_R |
CDK12 | Q9NYV4 | human | PAK2 | Q13177 | T169 | TEAPAVVtEEEDDDE | |
CDK12 | Q9NYV4 | human | TP63 | Q9H3D4-2 | S68 | TFDALsPsPAIPSNT | |
CDK12 | Q9NYV4 | human | POLR2A | P24928 | S1619 | SPSysPtsPsYSPTS | RNA_pol_Rpb1_R |
CDK12 | Q9NYV4 | human | TP63 | Q9H3D4-2 | S66 | SSTFDALsPsPAIPS | |
CDK12 | Q9NYV4 | human | TP63 | Q9H3D4-2 | S301 | TSIKKRRsPDDELLY | P53_tetramer |
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 |
CDK12 | ID | Description | 0.00e+00 |
CDK12 | GO:2001235 | positive regulation of apoptotic signaling pathway | 2.92e-02 |
CDK12 | GO:2001233 | regulation of apoptotic signaling pathway | 2.92e-02 |
CDK12 | GO:0060525 | prostate glandular acinus development | 2.92e-02 |
CDK12 | GO:2000271 | positive regulation of fibroblast apoptotic process | 2.92e-02 |
CDK12 | GO:0060601 | lateral sprouting from an epithelium | 2.92e-02 |
CDK12 | GO:0060742 | epithelial cell differentiation involved in prostate gland development | 2.92e-02 |
CDK12 | GO:0035112 | genitalia morphogenesis | 2.92e-02 |
CDK12 | GO:0043589 | skin morphogenesis | 2.92e-02 |
CDK12 | GO:1904672 | regulation of somatic stem cell population maintenance | 2.92e-02 |
CDK12 | GO:0034333 | adherens junction assembly | 2.92e-02 |
CDK12 | GO:0045605 | negative regulation of epidermal cell differentiation | 2.92e-02 |
CDK12 | GO:0045683 | negative regulation of epidermis development | 2.92e-02 |
CDK12 | GO:0010838 | positive regulation of keratinocyte proliferation | 2.92e-02 |
CDK12 | GO:0033147 | negative regulation of intracellular estrogen receptor signaling pathway | 2.92e-02 |
CDK12 | GO:0060572 | morphogenesis of an epithelial bud | 2.92e-02 |
CDK12 | GO:0030540 | female genitalia development | 2.92e-02 |
CDK12 | GO:0036342 | post-anal tail morphogenesis | 2.92e-02 |
CDK12 | GO:2000269 | regulation of fibroblast apoptotic process | 2.92e-02 |
CDK12 | GO:0048485 | sympathetic nervous system development | 2.92e-02 |
CDK12 | GO:0150105 | protein localization to cell-cell junction | 2.92e-02 |
CDK12 | GO:1900118 | negative regulation of execution phase of apoptosis | 2.92e-02 |
CDK12 | GO:0002223 | stimulatory C-type lectin receptor signaling pathway | 2.92e-02 |
CDK12 | GO:1990840 | response to lectin | 2.92e-02 |
CDK12 | GO:1990858 | cellular response to lectin | 2.92e-02 |
CDK12 | GO:0060571 | morphogenesis of an epithelial fold | 2.92e-02 |
CDK12 | GO:0030859 | polarized epithelial cell differentiation | 2.92e-02 |
CDK12 | GO:0044346 | fibroblast apoptotic process | 2.92e-02 |
CDK12 | GO:0060740 | prostate gland epithelium morphogenesis | 2.92e-02 |
CDK12 | GO:0035116 | embryonic hindlimb morphogenesis | 2.92e-02 |
CDK12 | GO:0060512 | prostate gland morphogenesis | 2.92e-02 |
CDK12 | GO:0006353 | DNA-templated transcription termination | 2.92e-02 |
CDK12 | GO:1900117 | regulation of execution phase of apoptosis | 2.92e-02 |
CDK12 | GO:0031069 | hair follicle morphogenesis | 2.92e-02 |
CDK12 | GO:0035115 | embryonic forelimb morphogenesis | 2.92e-02 |
CDK12 | GO:0051497 | negative regulation of stress fiber assembly | 2.92e-02 |
CDK12 | GO:0061436 | establishment of skin barrier | 2.92e-02 |
CDK12 | GO:0009954 | proximal/distal pattern formation | 2.92e-02 |
CDK12 | GO:0008340 | determination of adult lifespan | 2.92e-02 |
CDK12 | GO:0033146 | regulation of intracellular estrogen receptor signaling pathway | 2.92e-02 |
CDK12 | GO:0032232 | negative regulation of actin filament bundle assembly | 2.92e-02 |
CDK12 | GO:0035137 | hindlimb morphogenesis | 2.92e-02 |
CDK12 | GO:0033144 | negative regulation of intracellular steroid hormone receptor signaling pathway | 2.92e-02 |
CDK12 | GO:0048730 | epidermis morphogenesis | 2.92e-02 |
CDK12 | GO:0045616 | regulation of keratinocyte differentiation | 3.09e-02 |
CDK12 | GO:0035136 | forelimb morphogenesis | 3.09e-02 |
CDK12 | GO:0042771 | intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | 3.14e-02 |
CDK12 | GO:0033120 | positive regulation of RNA splicing | 3.14e-02 |
CDK12 | GO:0048483 | autonomic nervous system development | 3.14e-02 |
CDK12 | GO:0010837 | regulation of keratinocyte proliferation | 3.14e-02 |
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Related Drugs to PRIM2_CDK12 |
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 PRIM2-CDK12 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 PRIM2_CDK12 |
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 |