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Kinase Fusion Gene:HIF1A_VRK1 |
Kinase Fusion Protein Summary |
 Kinase Fusion gene summary |
| Kinase Fusion partner gene information | Kinase Fusion gene name: HIF1A_VRK1 | KinaseFusionDB ID: KFG2675 | FusionGDB2.0 ID: KFG2675 | Hgene | Tgene | Gene symbol | HIF1A | VRK1 | Gene ID | 3091 | 7443 | |
| Gene name | hypoxia inducible factor 1 subunit alpha | VRK serine/threonine kinase 1 | ||||||||||
| Synonyms | HIF-1-alpha|HIF-1A|HIF-1alpha|HIF1|HIF1-ALPHA|MOP1|PASD8|bHLHe78 | HMNR10|PCH1|PCH1A | ||||||||||
| Cytomap | 14q23.2 | 14q32.2 | ||||||||||
| Type of gene | protein-coding | protein-coding | ||||||||||
| Description | hypoxia-inducible factor 1-alphaARNT interacting proteinPAS domain-containing protein 8basic-helix-loop-helix-PAS protein MOP1class E basic helix-loop-helix protein 78hypoxia inducible factor 1 alpha subunithypoxia inducible factor 1, alpha subunit | serine/threonine-protein kinase VRK1vaccinia related kinase 1vaccinia virus B1R-related kinase 1 | ||||||||||
| Modification date | 20240416 | 20240416 | ||||||||||
| UniProtAcc | Q16665 | Q99986 | ||||||||||
| Ensembl transtripts involved in fusion gene | ENST ids | ENST00000323441, ENST00000337138, ENST00000394997, ENST00000539097, ENST00000557206, ENST00000557538, | ENST00000216639, ENST00000555067, | |||||||||
| Context (manual curation of fusion genes in KinaseFusionDB) | PubMed: HIF1A [Title/Abstract] AND VRK1 [Title/Abstract] AND fusion [Title/Abstract] | |||||||||||
| Most frequent breakpoint (based on all fusion genes of FusionGDB 2.0) | HIF1A(62162557)-VRK1(97299804), # samples:3 | |||||||||||
| 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 | HIF1A | GO:0000302 | response to reactive oxygen species | 32697943 |
| Hgene | HIF1A | GO:0001666 | response to hypoxia | 11782478 |
| Hgene | HIF1A | GO:0001666 | response to hypoxia | 8756616|9887100|15261140|18419598 |
| Hgene | HIF1A | GO:0001678 | intracellular glucose homeostasis | 30125331 |
| Hgene | HIF1A | GO:0006110 | regulation of glycolytic process | 32697943 |
| Hgene | HIF1A | GO:0006355 | regulation of DNA-templated transcription | 11782478 |
| Hgene | HIF1A | GO:0006355 | regulation of DNA-templated transcription | 15261140 |
| Hgene | HIF1A | GO:0010468 | regulation of gene expression | 18419598|32697943 |
| Hgene | HIF1A | GO:0010573 | vascular endothelial growth factor production | 12958148 |
| Hgene | HIF1A | GO:0010575 | positive regulation of vascular endothelial growth factor production | 8756616 |
| Hgene | HIF1A | GO:0010628 | positive regulation of gene expression | 15459207|24244340 |
| Hgene | HIF1A | GO:0032364 | intracellular oxygen homeostasis | 16956324 |
| Hgene | HIF1A | GO:0034599 | cellular response to oxidative stress | 8089148|8387214 |
| Hgene | HIF1A | GO:0045893 | positive regulation of DNA-templated transcription | 9887100|25043030 |
| Hgene | HIF1A | GO:0045944 | positive regulation of transcription by RNA polymerase II | 7539918|8089148|8387214|11573933|22735262|32697943 |
| Hgene | HIF1A | GO:0046886 | positive regulation of hormone biosynthetic process | 1448077 |
| Hgene | HIF1A | GO:0070101 | positive regulation of chemokine-mediated signaling pathway | 17178876 |
| Hgene | HIF1A | GO:0071456 | cellular response to hypoxia | 11573933|19528298|20889502|22735262 |
| Hgene | HIF1A | GO:0098586 | cellular response to virus | 32697943 |
| Hgene | HIF1A | GO:1900017 | positive regulation of cytokine production involved in inflammatory response | 32697943 |
| Hgene | HIF1A | GO:1902895 | positive regulation of miRNA transcription | 19782034 |
| Hgene | HIF1A | GO:1903377 | negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway | 24899725 |
| Tgene | VRK1 | GO:0006974 | DNA damage response | 33076429 |
| Tgene | VRK1 | GO:0046777 | protein autophosphorylation | 21543316|22194607 |
| Tgene | VRK1 | GO:0090166 | Golgi disassembly | 19103756 |
| Tgene | VRK1 | GO:0120187 | positive regulation of protein localization to chromatin | 33076429 |
| Kinase Fusion gene breakpoints across HIF1A (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 VRK1 (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 |
| ChimerDB4 | TCGA-R8-A6MK-01A | HIF1A | chr14 | 62162557 | VRK1 | chr14 | 97299804 |
| ChimerDB4 | TCGA-R8-A6MK | HIF1A | chr14 | 62162557 | VRK1 | chr14 | 97299803 |
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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/:62162557/:97299804) - 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 |
| HIF1A | VRK1 |
| FUNCTION: Functions as a master transcriptional regulator of the adaptive response to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:18658046, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia (PubMed:11292861, PubMed:11566883, PubMed:15465032, PubMed:16973622, PubMed:17610843, PubMed:20624928, PubMed:22009797, PubMed:9887100, PubMed:30125331). Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease (PubMed:22009797). Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Activation requires recruitment of transcriptional coactivators such as CREBBP and EP300 (PubMed:9887100, PubMed:16543236). Activity is enhanced by interaction with NCOA1 and/or NCOA2 (PubMed:10594042). Interaction with redox regulatory protein APEX1 seems to activate CTAD and potentiates activation by NCOA1 and CREBBP (PubMed:10202154, PubMed:10594042). Involved in the axonal distribution and transport of mitochondria in neurons during hypoxia (PubMed:19528298). {ECO:0000250|UniProtKB:Q61221, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:10594042, ECO:0000269|PubMed:11292861, ECO:0000269|PubMed:11566883, ECO:0000269|PubMed:15465032, ECO:0000269|PubMed:16543236, ECO:0000269|PubMed:16973622, ECO:0000269|PubMed:17610843, ECO:0000269|PubMed:18658046, ECO:0000269|PubMed:19528298, ECO:0000269|PubMed:20624928, ECO:0000269|PubMed:22009797, ECO:0000269|PubMed:30125331, ECO:0000269|PubMed:9887100}.; FUNCTION: (Microbial infection) Upon infection by human coronavirus SARS-CoV-2, is required for induction of glycolysis in monocytes and the consequent pro-inflammatory state (PubMed:32697943). In monocytes, induces expression of ACE2 and cytokines such as IL1B, TNF, IL6, and interferons (PubMed:32697943). Promotes human coronavirus SARS-CoV-2 replication and monocyte inflammatory response (PubMed:32697943). {ECO:0000269|PubMed:32697943}. | FUNCTION: Serine/threonine kinase involved in cell cycle, nuclear condensation and transcription regulation (PubMed:14645249, PubMed:18617507, PubMed:19103756). Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation (PubMed:19103756). Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2 (PubMed:10951572). Phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (PubMed:16495336). Phosphorylates ATF2 which activates its transcriptional activity (PubMed:15105425). {ECO:0000269|PubMed:10951572, ECO:0000269|PubMed:14645249, ECO:0000269|PubMed:15105425, ECO:0000269|PubMed:16495336, ECO:0000269|PubMed:18617507, ECO:0000269|PubMed:19103756, ECO:0000269|PubMed:33076429}. |
| 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 HIF1A_VRK1 |
| 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 |
| VRK1 | Q99986 | human | VRK1 | Q99986 | S376 | GVEDTEWsNtQtEEA | |
| VRK1 | Q99986 | human | COIL | P38432 | S184 | NEEAKRKsPKKKEKC | Coilin_N |
| VRK1 | Q99986 | human | TP53 | P04637 | T18 | EPPLsQEtFsDLWkL | P53_TAD |
| VRK1 | Q99986 | human | H3C1 | P68431 | T3 | _____ArtkQtArks | Histone |
| VRK1 | Q99986 | human | H3C1 | P68431 | S10 | tkQtArkstGGkAPr | Histone |
| VRK1 | Q99986 | human | ATF2 | P15336 | T73 | ADQtPtPtRFLkNCE | |
| VRK1 | Q99986 | human | BANF1 | O75531 | S4 | ____MttsQkHRDFV | BAF |
| VRK1 | Q99986 | human | BANF1 | O75531 | T3 | _____MttsQkHRDF | BAF |
| VRK1 | Q99986 | human | VRK1 | Q99986 | T386 | QtEEAIQtRSRTRKR | |
| VRK1 | Q99986 | human | JUN | P05412 | S73 | VGLLkLAsPELERLI | Jun |
| VRK1 | Q99986 | human | ATF2 | P15336 | S62 | FGPARNDsVIVADQt | |
| VRK1 | Q99986 | human | H2AC17 | P0C0S8 | T120 | AVLLPkktEsHHkAk | Histone_H2A_C |
| VRK1 | Q99986 | human | JUN | P05412 | S63 | kNsDLLtsPDVGLLk | Jun |
| VRK1 | Q99986 | human | NR1I2 | O75469 | S350 | MQAISLFsPDRPGVL | Hormone_recep |
| VRK1 | Q99986 | human | BANF1 | O75531 | T2 | ______MttsQkHRD | BAF |
| VRK1 | Q99986 | human | KAT5 | Q92993 | T158 | VEVVsPAtPVPSETA | |
| VRK1 | Q99986 | human | VRK1 | Q99986 | T355 | GLkAKTItKKRKKEI |
| 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 |
| VRK1 | ID | Description | 0.00e+00 |
| VRK1 | GO:1901522 | positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus | 4.76e-03 |
| VRK1 | GO:0006979 | response to oxidative stress | 4.76e-03 |
| VRK1 | GO:0006978 | DNA damage respons | 3.85e-05 |
| VRK1 | GO:0042772 | DNA damage respons | 4.30e-05 |
| VRK1 | GO:1903008 | organelle disassembly | 4.76e-03 |
| VRK1 | GO:0009267 | cellular response to starvation | 7.64e-03 |
| VRK1 | GO:0042770 | signal transduction in response to DNA damage | 7.98e-03 |
| VRK1 | GO:0043618 | regulation of transcription from RNA polymerase II promoter in response to stress | 8.43e-03 |
| VRK1 | GO:0060218 | hematopoietic stem cell differentiation | 8.43e-03 |
| VRK1 | GO:0042594 | response to starvation | 8.43e-03 |
| VRK1 | GO:0045815 | transcription initiation-coupled chromatin remodeling | 8.43e-03 |
| VRK1 | GO:0043620 | regulation of DNA-templated transcription in response to stress | 8.43e-03 |
| VRK1 | GO:0040029 | epigenetic regulation of gene expression | 8.44e-03 |
| VRK1 | GO:0071763 | nuclear membrane organization | 8.77e-03 |
| VRK1 | GO:0031669 | cellular response to nutrient levels | 8.77e-03 |
| VRK1 | GO:0035794 | positive regulation of mitochondrial membrane permeability | 8.77e-03 |
| VRK1 | GO:0034599 | cellular response to oxidative stress | 8.77e-03 |
| VRK1 | GO:1902108 | regulation of mitochondrial membrane permeability involved in apoptotic process | 8.77e-03 |
| VRK1 | GO:0009299 | mRNA transcription | 8.77e-03 |
| VRK1 | GO:0042149 | cellular response to glucose starvation | 8.77e-03 |
| VRK1 | GO:1905710 | positive regulation of membrane permeability | 8.77e-03 |
| VRK1 | GO:1902895 | positive regulation of miRNA transcription | 8.77e-03 |
| VRK1 | GO:0006998 | nuclear envelope organization | 8.89e-03 |
| VRK1 | GO:0031668 | cellular response to extracellular stimulus | 8.89e-03 |
| VRK1 | GO:0046902 | regulation of mitochondrial membrane permeability | 1.07e-02 |
| VRK1 | GO:0030217 | T cell differentiation | 1.07e-02 |
| VRK1 | GO:2000630 | positive regulation of miRNA metabolic process | 1.10e-02 |
| VRK1 | GO:0062197 | cellular response to chemical stress | 1.10e-02 |
| VRK1 | GO:2000144 | positive regulation of DNA-templated transcription initiation | 1.16e-02 |
| VRK1 | GO:1902893 | regulation of miRNA transcription | 1.19e-02 |
| VRK1 | GO:0061614 | miRNA transcription | 1.19e-02 |
| VRK1 | GO:0030330 | DNA damage respons | 6.51e-04 |
| VRK1 | GO:0090559 | regulation of membrane permeability | 1.22e-02 |
| VRK1 | GO:2000142 | regulation of DNA-templated transcription initiation | 1.34e-02 |
| VRK1 | GO:0006970 | response to osmotic stress | 1.34e-02 |
| VRK1 | GO:0044773 | mitotic DNA damage checkpoint signaling | 1.37e-02 |
| VRK1 | GO:0006289 | nucleotide-excision repair | 1.40e-02 |
| VRK1 | GO:2000628 | regulation of miRNA metabolic process | 1.40e-02 |
| VRK1 | GO:0044774 | mitotic DNA integrity checkpoint signaling | 1.40e-02 |
| VRK1 | GO:0140747 | regulation of ncRNA transcription | 1.53e-02 |
| VRK1 | GO:0007178 | transmembrane receptor protein serine/threonine kinase signaling pathway | 1.58e-02 |
| VRK1 | GO:0030098 | lymphocyte differentiation | 1.76e-02 |
| VRK1 | GO:0016032 | viral process | 1.76e-02 |
| VRK1 | GO:0010586 | miRNA metabolic process | 1.82e-02 |
| VRK1 | GO:0008637 | apoptotic mitochondrial changes | 1.91e-02 |
| VRK1 | GO:0090398 | cellular senescence | 1.91e-02 |
| VRK1 | GO:0022037 | metencephalon development | 1.97e-02 |
| VRK1 | GO:0042752 | regulation of circadian rhythm | 1.97e-02 |
| VRK1 | GO:1903131 | mononuclear cell differentiation | 2.10e-02 |
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Related Drugs to HIF1A_VRK1 |
| 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 HIF1A-VRK1 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 HIF1A_VRK1 |
| 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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