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MVK
mevalonate kinase
The MVK gene provides instructions for the mevalonate kinase enzyme, which plays a crucial role in the production of cholesterol and other essential cellular substances. The MVK gene encodes the mevalonate kinase enzyme, an important component of the mevalonate pathway.
MVK is located on the long (q) arm of chromosome 12, at band 12q24.11. Arm ratio per GRCh38 - banding schematic.
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Overview
The MVK gene is responsible for producing the mevalonate kinase enzyme. This enzyme is a key player in the mevalonate pathway, a metabolic route essential for creating several vital biological molecules. These include cholesterol, steroid hormones, and bile acids, which are involved in diverse bodily functions from development to fat digestion.
Beyond these, mevalonate kinase also contributes to the production of other compounds necessary for fundamental cellular processes such as cell growth, maturation, structural integrity, gene regulation, and protein synthesis.
What the gene does
The mevalonate kinase enzyme, encoded by the MVK gene, facilitates the conversion of mevalonic acid into mevalonate-5-phosphate. This reaction represents the second step in the mevalonate pathway. This pathway is critical for synthesising cholesterol, which is subsequently converted into steroid hormones important for development and reproduction, and bile acids used in fat digestion.
Furthermore, the mevalonate pathway, and thus the mevalonate kinase enzyme, is involved in generating other isoprenoid compounds. These compounds are essential for various cellular activities, including cell proliferation, differentiation, maintaining the cytoskeleton, regulating gene expression, and modifying proteins.
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Chromosome location
The MVK gene is located on chromosome 12. Specifically, its chromosomal address is band 12q24.11. The gene provides the genetic blueprint for a protein consisting of 396 amino acids.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the MVK gene can affect the function of the mevalonate kinase enzyme, potentially disrupting the mevalonate pathway. These genetic changes can range from single nucleotide substitutions to larger deletions or insertions, impacting enzyme activity and the subsequent production of essential molecules.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1126G>A | p.Gly376Ser | Pathogenic/Likely pathogenic | ★★☆☆ | Mevalonic aciduria |
c.207_208del | p.Leu70fs | Pathogenic | ★★☆☆ | Mevalonic aciduria |
c.349_350del | p.Leu117fs | Pathogenic/Likely pathogenic | ★★☆☆ | Hyperimmunoglobulin D with periodic fever |
c.560_561del | p.Lys187fs | Pathogenic | ★★☆☆ | Porokeratosis 3, disseminated superficial actinic type |
c.58C>A | p.His20Asn | Pathogenic | ★★☆☆ | Mevalonic aciduria |
c.643C>T | p.Arg215Ter | Pathogenic | ★★☆☆ | Mevalonic aciduria |
c.830G>A | p.Arg277His | Pathogenic/Likely pathogenic | ★★☆☆ | Autoinflammatory syndrome |
c.904C>T | p.Gln302Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Mevalonic aciduria |
c.943_944del | p.Leu315fs | Pathogenic/Likely pathogenic | ★★☆☆ | Mevalonic aciduria |
c.976G>A | p.Gly326Arg | Pathogenic/Likely pathogenic | ★★☆☆ | Mevalonic aciduria |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the MVK gene are primarily associated with mevalonate kinase deficiency. This condition presents with a spectrum of severity, including hyperimmunoglobulinemia D syndrome (HIDS), which is generally less severe, and mevalonic aciduria (MVA), representing a more severe form.
Inheritance pattern
Conditions caused by pathogenic MVK variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The MVK gene is assessed across several NHS Genomic Medicine Service national panels in the UK, indicating its clinical relevance for a range of conditions. It is included in panels for 'Autoinflammatory disorders', 'Likely inborn error of metabolism', and 'Periodic fever syndromes', among others.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the role of the mevalonate kinase enzyme?
The mevalonate kinase enzyme, produced from the MVK gene, converts mevalonic acid into mevalonate-5-phosphate. This is a critical step in the mevalonate pathway, which is responsible for synthesising cholesterol, steroid hormones, bile acids, and other compounds essential for cell function.
What is mevalonate kinase deficiency?
Mevalonate kinase deficiency is an inherited metabolic disorder caused by pathogenic variants in the MVK gene. It can manifest in varying severities, from hyperimmunoglobulinemia D syndrome (HIDS) to the more severe mevalonic aciduria (MVA), affecting the body's ability to produce essential molecules from the mevalonate pathway.
How is the MVK gene inherited?
The MVK gene is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the gene, one from each parent, to develop a condition associated with MVK gene variants.
References
- Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clinical biochemistry. 2007. PMID: 17467679
- Haas D, Hoffmann GF. Mevalonate kinase deficiencies: from mevalonic aciduria to hyperimmunoglobulinemia D syndrome. Orphanet journal of rare diseases. 2006. PMID: 16722536
- Mandey SH, Schneiders MS, Koster J. Mutational spectrum and genotype-phenotype correlations in mevalonate kinase deficiency. Human mutation. 2006. PMID: 16835861