2r3v

Structural highlights

Disease

KIME_HUMAN Defects in MVK are the cause of mevalonic aciduria (MEVA) [MIM:610377. It is an accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia.^{[1] [2] [3] [4] [5]} Defects in MVK are the cause of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) [MIM:260920. HIDS is an autosomal recessive disease characterized by recurrent episodes of unexplained high fever associated with skin rash, diarrhea, adenopathy (swollen, tender lymph nodes), athralgias and/or arthritis. Concentration of IgD, and often IgA, are above normal.^{[6] [7] [8] [9] [10]}

Function

KIME_HUMAN May be a regulatory site in cholesterol biosynthetic pathway.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Mevalonate kinase

References

1. ↑ Schafer BL, Bishop RW, Kratunis VJ, Kalinowski SS, Mosley ST, Gibson KM, Tanaka RD. Molecular cloning of human mevalonate kinase and identification of a missense mutation in the genetic disease mevalonic aciduria. J Biol Chem. 1992 Jul 5;267(19):13229-38. PMID:1377680
2. ↑ Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJ, Waterham HR. Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet. 2001 Apr;9(4):253-9. PMID:11313768 doi:10.1038/sj.ejhg.5200595
3. ↑ Hinson DD, Ross RM, Krisans S, Shaw JL, Kozich V, Rolland MO, Divry P, Mancini J, Hoffmann GF, Gibson KM. Identification of a mutation cluster in mevalonate kinase deficiency, including a new mutation in a patient of Mennonite ancestry. Am J Hum Genet. 1999 Aug;65(2):327-35. PMID:10417275 doi:S0002-9297(07)62049-7
4. ↑ Houten SM, Romeijn GJ, Koster J, Gray RG, Darbyshire P, Smit GP, de Klerk JB, Duran M, Gibson KM, Wanders RJ, Waterham HR. Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis. Hum Mol Genet. 1999 Aug;8(8):1523-8. PMID:10401001
5. ↑ Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, Grateau G, Delpech M. Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet. 2001 Apr;9(4):260-6. PMID:11313769 doi:10.1038/sj.ejhg.5200614
6. ↑ Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJ, Waterham HR. Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet. 2001 Apr;9(4):253-9. PMID:11313768 doi:10.1038/sj.ejhg.5200595
7. ↑ Cuisset L, Drenth JP, Simon A, Vincent MF, van der Velde Visser S, van der Meer JW, Grateau G, Delpech M. Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet. 2001 Apr;9(4):260-6. PMID:11313769 doi:10.1038/sj.ejhg.5200614
8. ↑ Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet. 1999 Jun;22(2):175-7. PMID:10369261 doi:10.1038/9691
9. ↑ Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet. 1999 Jun;22(2):178-81. PMID:10369262 doi:10.1038/9696
10. ↑ D'Osualdo A, Picco P, Caroli F, Gattorno M, Giacchino R, Fortini P, Corona F, Tommasini A, Salvi G, Specchia F, Obici L, Meini A, Ricci A, Seri M, Ravazzolo R, Martini A, Ceccherini I. MVK mutations and associated clinical features in Italian patients affected with autoinflammatory disorders and recurrent fever. Eur J Hum Genet. 2005 Mar;13(3):314-20. PMID:15536479 doi:5201323
11. ↑ Fu Z, Voynova NE, Herdendorf TJ, Miziorko HM, Kim JJ. Biochemical and structural basis for feedback inhibition of mevalonate kinase and isoprenoid metabolism. Biochemistry. 2008 Mar 25;47(12):3715-24. Epub 2008 Feb 27. PMID:18302342 doi:10.1021/bi7024386