MVK Gene

Name	mevalonate kinase
Description	This gene encodes the peroxisomal enzyme mevalonate kinase. Mevalonate is a key intermediate, and mevalonate kinase a key early enzyme, in isoprenoid and sterol synthesis. Mevalonate kinase deficiency caused by mutation of this gene results in mevalonic aciduria, a disease characterized psychomotor retardation, failure to thrive, hepatosplenomegaly, anemia and recurrent febrile crises. Defects in this gene also cause hyperimmunoglobulinaemia D and periodic fever syndrome, a disorder characterized by recurrent episodes of fever associated with lymphadenopathy, arthralgia, gastrointestinal dismay and skin rash. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMevalonate kinase (MVK) is the essential enzyme in the isoprenoid and cholesterol biosynthetic pathway, catalyzing the ATP‐dependent phosphorylation of mevalonate. Structural and biochemical studies have defined its catalytic site—with key residues required for substrate binding and for feedback inhibition by downstream metabolites such as farnesyl diphosphate—and demonstrated that MVK functions exclusively in the cytosol to regulate the generation of sterol and non‐sterol isoprenoids. In fibroblasts from affected individuals, even modest temperature elevations have been shown to further destabilize mutant MVK, thereby impairing enzyme maturation and reducing mevalonate flux, while compensatory increases in pathway enzymes help maintain metabolite levels despite deficient MVK activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its canonical kinase activity, MVK has been unexpectedly implicated in post‐transcriptional regulation. It was identified as the luteinizing hormone receptor (LHR) mRNA binding protein (LRBP) in ovarian cells, and detailed mutational and binding studies have shown that an intact enzyme active site is required for MVK to interact with LHR mRNA and suppress its translation. Moreover, hormone‐induced signaling cascades that elevate MVK/LRBP levels subsequently contribute to LHR mRNA down‐regulation, linking cellular metabolic status with reproductive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPathogenic mutations in the MVK gene lead to a spectrum of disorders collectively known as mevalonate kinase deficiency (MKD), which includes the severe mevalonic aciduria and the milder hyper‐immunoglobulinemia D and periodic fever syndrome. In these conditions, reduced enzyme activity compromises the production of critical isoprenoid intermediates needed for protein prenylation; this defect perturbs the modification and function of small GTPases, thereby contributing to autoinflammatory phenotypes. In the skin, MVK’s role has also been highlighted in disseminated superficial actinic porokeratosis (DSAP), wherein mutations disturb keratinocyte differentiation and reduce resistance to ultraviolet‐induced apoptosis. Consistent with these pathogenic mechanisms, both clinical and in‐vitro studies have underscored a direct relation between mutated MVK, impaired isoprenoid synthesis, and inflammatory as well as dermatologic manifestations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sander M Houten, Joost Frenkel, Ger T Rijkers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/11.25.3115"}], "href": "https://doi.org/10.1093/hmg/11.25.3115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12444096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12444096"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sander M Houten, Marit S Schneiders, Ronald J A Wanders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of isoprenoid/cholesterol biosynthesis in cells from mevalonate kinase-deficient patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M206564200"}], "href": "https://doi.org/10.1074/jbc.M206564200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12477733"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12477733"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sander M Houten, Christiaan S van Woerden, Frits A Wijburg, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Mevalonate kinase deficiency: Evidence for a phenotypic continuum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.wnl.0000115390.33405.f7"}], "href": "https://doi.org/10.1212/01.wnl.0000115390.33405.f7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15037710"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15037710"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sheng-Quan Zhang, Tao Jiang, Min Li, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The farnesyltransferase inhibitors tipifarnib and lonafarnib inhibit cytokines secretion in a cellular model of mevalonate kinase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatr Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1203/PDR.0b013e31821b581c"}], "href": "https://doi.org/10.1203/PDR.0b013e31821b581c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21430599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21430599"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Akiharu Kubo, Takashi Sasaki, Hisato Suzuki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Clonal Expansion of Second-Hit Cells with Somatic Recombinations or C>T Transitions Form Porokeratosis in MVD or MVK Mutant Heterozygotes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jid.2019.05.020"}], "href": "https://doi.org/10.1016/j.jid.2019.05.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31207227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31207227"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Kang Zeng, Qi-Guo Zhang, Li Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Splicing mutation in MVK is a cause of porokeratosis of Mibelli."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Dermatol Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00403-014-1465-7"}], "href": "https://doi.org/10.1007/s00403-014-1465-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24781643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24781643"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Wen-sheng Lu, Xiao-dong Zheng, Xiu-hua Yao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel MVK missense mutation in one Chinese family with disseminated superficial actinic porokeratosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-014-3609-4"}], "href": "https://doi.org/10.1007/s11033-014-3609-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25059119"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25059119"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Marcia A Munoz, Julie Jurczyluk, Anna Simon, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Clinical, genetic, and therapeutic diversity in 2 patients with severe mevalonate kinase deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pediatrics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1542/peds.2010-2192"}], "href": "https://doi.org/10.1542/peds.2010-2192"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22271696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22271696"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Geeta Madathil Govindaraj, Abhinav Jain, Geetha Peethambaran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectrum of clinical features and genetic variants in mevalonate kinase (MVK) gene of South Indian families suffering from Hyperimmunoglobulin D Syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0237999"}], "href": "https://doi.org/10.1371/journal.pone.0237999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32822427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32822427"}]}]}]}
Synonyms	MVLK, LRBP, POROK3
Proteins	KIME_HUMAN
NCBI Gene ID	4598
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MVK has 8,362 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 137 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

MVK Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MVK gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MVK gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 MVK 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 MVK 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 MVK 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 MVK 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 MVK 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 MVK 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 MVK 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 MVK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MVK 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 MVK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MVK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MVK 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 MVK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MVK 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 MVK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MVK gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with MVK gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of MVK gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing MVK protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MVK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MVK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MVK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MVK 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 MVK 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 MVK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MVK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with MVK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with MVK gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with MVK gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MVK protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DGIdb Drug Targets 2026	interacting drugs for MVK protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving MVK gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving MVK gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with MVK gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MVK 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 MVK 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 MVK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MVK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.