Mevalonate kinase (MVK)

Mevalonate kinase is an essential cytosolic enzyme encoded by the *MVK* gene that catalyzes the phosphorylation of mevalonic acid to 5-phosphomevalonate, an early and regulatory step in the mevalonate pathway leading to cholesterol, steroid hormone, and isoprenoid biosynthesis. Deficiency of this enzyme, caused by pathogenic MVK gene variants, underlies a spectrum of rare metabolic autoinflammatory diseases ranging from hyperimmunoglobulinemia D syndrome (HIDS) to mevalonic aciduria (MVA), characterized by recurrent fever, systemic inflammation, neurological involvement, and other features. The enzyme is not a classic receptor, but is a pharmacologically relevant enzyme with therapeutic importance in rare diseases, and is targeted indirectly by metabolic and immunomodulatory therapies

Other names

MKmevalonate kinase 1LH receptor mRNA-binding proteinLRBPMVLKKIME_HUMANPOROK3

Statins inhibit upstream HMG-CoA reductase, reducing substrate (mevalonate) accumulation, but can worsen isoprenoid deficiency in patients with enzyme deficiency; IL-1 inhibitors block downstream inflammation caused by metabolic dysregulation from MVK mutations; IL-6 and TNF inhibitors target downstream inflammatory pathways activated in MKD