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Kinase Fusion Gene:HAP1_CDK12 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: HAP1_CDK12 | KinaseFusionDB ID: KFG2640 | FusionGDB2.0 ID: KFG2640 | Hgene | Tgene | Gene symbol | HAP1 | CDK12 | Gene ID | 9001 | 51755 | |
| Gene name | huntingtin associated protein 1 | cyclin dependent kinase 12 | ||||||||||
| Synonyms | HAP2|HIP5|HLP|hHLP1 | CRK7|CRKR|CRKRS | ||||||||||
| Cytomap | 17q21.2 | 17q12 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | huntingtin-associated protein 1HAP-1epididymis secretory sperm binding proteinhuntingtin-associated protein 2neuroan 1 | 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 | 20240305 | 20240403 | ||||||||||
| UniProtAcc | P54257 | Q9NYV4 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000393939, ENST00000347901, ENST00000310778, ENST00000341193, | ENST00000430627, ENST00000447079, ENST00000559545, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: HAP1 [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 |
| 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 HAP1 (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 | CCLF_UPGI_0068_T | HAP1 | chr17 | 39883305 | CDK12 | chr17 | 37682117 |
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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. |
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| Main function of each fusion partner protein. (from UniProt) |
| Hgene | Tgene |
| HAP1 | CDK12 |
| FUNCTION: Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17). {ECO:0000269|PubMed:18922795}. | 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 HAP1_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 HAP1_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 HAP1-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 HAP1_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 |
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