VRK3 Gene

Name	vaccinia related kinase 3
Description	This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVaccinia‐related kinase 3 (VRK3) plays a critical neuroprotective role by modulating ERK signaling. It promotes the nuclear transport of heat shock protein 70 (HSP70), thereby enhancing the activity of the vaccinia H1‐related phosphatase (VHR) to suppress excessive ERK activation induced by glutamate or oxidative stress. In addition, oxidative stress triggers cyclin‐dependent kinase 5 (CDK5)–mediated phosphorylation of VRK3, which further stabilizes the interaction between VRK3 and VHR to attenuate pro‐apoptotic signaling. Moreover, under oxidative conditions, the E3 ubiquitin ligase RNF144a facilitates VRK3 degradation by polyubiquitylation after its redistribution from the nucleus, thereby lifting its inhibitory effect on ERK and sensitizing cells to apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its neuroprotective functions, VRK3 exhibits active kinase properties that extend to the regulation of the cell cycle and chromatin dynamics. Studies have demonstrated that VRK3 phosphorylates the nuclear envelope protein barrier‐to‐autointegration factor (BAF), which is thought to facilitate chromatin dissociation from the nuclear envelope during interphase. Large‐scale proteomic and interactome analyses further implicate VRK3 in vital processes such as DNA repair, RNA processing, and cell proliferation. Notably, VRK3 has emerged as an essential factor in pediatric diffuse intrinsic pontine glioma (DIPG), where its repression not only halts tumor cell growth but also specifically induces cell death in certain DIPG models, underscoring VRK3’s potential as a promising therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural investigations have revealed that VRK3 possesses an unusually rigid and stable active site that remains well ordered regardless of the presence or binding mode of divalent cations, setting it apart from its active kinase relatives. Furthermore, VRK3 influences broader physiological processes by modulating the subcellular distribution of circadian clock components, such as CRY1, which in turn affects the amplitude and period of circadian rhythms. These findings collectively highlight the multifaceted roles of VRK3 in orchestrating key cellular signaling events, cell cycle progression, and the regulation of complex rhythmic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Haengjin Song, Wanil Kim, Sung-Hoon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "VRK3-mediated nuclear localization of HSP70 prevents glutamate excitotoxicity-induced apoptosis and Aβ accumulation via enhancement of ERK phosphatase VHR activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep38452"}], "href": "https://doi.org/10.1038/srep38452"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27941812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27941812"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Haengjin Song, Wanil Kim, Jung-Hyun Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep28634"}], "href": "https://doi.org/10.1038/srep28634"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27346674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27346674"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Seung Hyun Han, Kyong-Tai Kim "}, {"type": "b", "children": [{"type": "t", "text": "RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.247304"}], "href": "https://doi.org/10.1242/jcs.247304"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33067254"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33067254"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Choon-Ho Park, Hye Guk Ryu, Seong-Hoon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Presumed pseudokinase VRK3 functions as a BAF kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2015.04.007"}], "href": "https://doi.org/10.1016/j.bbamcr.2015.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25899223"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25899223"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Claudia Silva-Evangelista, Emilie Barret, Virginie Ménez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A kinome-wide shRNA screen uncovers vaccinia-related kinase 3 (VRK3) as an essential gene for diffuse intrinsic pontine glioma survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-019-0884-5"}], "href": "https://doi.org/10.1038/s41388-019-0884-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31324890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31324890"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Namgyu Lee, Dae-Kyum Kim, Seung Hyun Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.14348/molcells.2017.0108"}], "href": "https://doi.org/10.14348/molcells.2017.0108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28927264"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28927264"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ting Fu, Hong Ren, Jiajing Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of bivalent cations in structural stabilities of new drug targets--vaccinia-related kinases (VRK) from molecular dynamics simulations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Pharm Des (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1381612811319120014"}], "href": "https://doi.org/10.2174/1381612811319120014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23082977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23082977"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nayoung Park, Jieun Song, Seongsu Jeong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.04.057"}], "href": "https://doi.org/10.1016/j.bbrc.2017.04.057"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28412365"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28412365"}]}]}]}
Proteins	VRK3_HUMAN
NCBI Gene ID	51231
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

VRK3 has 5,403 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 116 datasets.

Click the + buttons to view associations for VRK3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

VRK3 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by VRK3 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of VRK3 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of VRK3 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of VRK3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of VRK3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of VRK3 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of VRK3 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of VRK3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of VRK3 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of VRK3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of VRK3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of VRK3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with VRK3 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with VRK3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with VRK3 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of VRK3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of VRK3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of VRK3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of VRK3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of VRK3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing VRK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing VRK3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with VRK3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with VRK3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of VRK3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with VRK3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with VRK3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by VRK3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with VRK3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with VRK3 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with VRK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with VRK3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at VRK3 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of VRK3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of VRK3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing VRK3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD High Level Gene-Disease Associations	diseases associated with VRK3 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of VRK3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with VRK3 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing VRK3 from the GeneSigDB Published Gene Signatures dataset.