Description: Homo sapiens mevalonate kinase (MVK), transcript variant 1, mRNA. RefSeq Summary (NM_000431): 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]. Transcript (Including UTRs) Position: hg19 chr12:110,011,500-110,035,071 Size: 23,572 Total Exon Count: 9 Strand: + Coding Region Position: hg19 chr12:110,023,882-110,034,382 Size: 10,501 Coding Exon Count: 6
ID:KIME_HUMAN DESCRIPTION: RecName: Full=Mevalonate kinase; Short=MK; EC=2.7.1.36; FUNCTION: May be a regulatory site in cholesterol biosynthetic pathway. CATALYTIC ACTIVITY: ATP + (R)-mevalonate = ADP + (R)-5- phosphomevalonate. ENZYME REGULATION: Farnesyl- and geranyl-pyrophosphates are competitive inhibitors. PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate: step 1/3. SUBUNIT: Homodimer. INTERACTION: Self; NbExp=2; IntAct=EBI-740630, EBI-740630; SUBCELLULAR LOCATION: Cytoplasm. DISEASE: 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. DISEASE: 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. SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase subfamily. SEQUENCE CAUTION: Sequence=CAA53059.1; Type=Erroneous initiation; Note=Translation N-terminally shortened; WEB RESOURCE: Name=INFEVERS; Note=Repertory of FMF and hereditary autoinflammatory disorders mutations; URL="http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=3"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/MVK";
HDL cholesterol Kathiresan ,et al. 2008, Common variants at 30 loci contribute to polygenic dyslipidemia, Nature genetics 2009 41- 1 : 56-65.
[PubMed 19060906]
HDL cholesterol Willer ,et al. 2008, Newly identified loci that influence lipid concentrations and risk of coronary artery disease, Nature genetics 2008 40- 2 : 161-9.
[PubMed 18193043]
mevalonate kinase deficiency Houten, S. M. et al. 2003, Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands., European journal of human genetics. 2003 Feb;11(2):196-200.
[PubMed 12634869]
This predicts a disease incidence between1 in 5196 and 1 in 53 656, which is far more than actually observed. Although under-diagnosis ofpatients with MK deficiency remains possible, this discrepancy probably is due to a reduced penetrance of V377I homozygosity. Analysis of the distribution of the V377I allele within patients carrying MVK mutations revealed that this was not according to the Hardy-Weinberg equilibrium principle, most probably due to an under-representation of V377I homozygotes in HIDS. Homozygotes for V377I might exhibit a much milder phenotype of MK deficiency or no disease-phenotype at all.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q03426
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.