MVK

Chr 12ARAD

mevalonate kinase

Also known as: LRBP, MK, MVLK, POROK3

NCBI Gene: 4598 ENSG00000110921 UniProt: Q03426 OMIM: 251170

This gene encodes mevalonate kinase, a peroxisomal enzyme that catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate in isoprenoid and cholesterol biosynthesis. Mutations cause autosomal recessive mevalonic aciduria with early-onset psychomotor retardation, failure to thrive, hepatosplenomegaly, and recurrent fevers, as well as the milder hyper-IgD syndrome with periodic fever episodes, lymphadenopathy, and arthralgia. The gene also causes autosomal dominant porokeratosis, a skin condition with multiple clinical variants.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyper-IgD syndromeMIM #260920

Mevalonic aciduriaMIM #610377

Porokeratosis 3, multiple typesMIM #175900

UniProtHyperimmunoglobulinemia D and periodic fever syndrome

Clinical highlights

Gene-disease validity (ClinGen)

mevalonate kinase deficiency · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.55

LOEUF

LOF

Mechanism· G2P

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GeneReview available — MVK