Human Gene MVK (uc001toz.4)
  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 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr12:110,011,500-110,035,071)mRNA (may differ from genome)Protein (202 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblExonPrimerGeneCardsGeneNetworkH-INV
HGNCLynxMalacardsMGIneXtProtPubMed
ReactomeTreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MVK
CDC HuGE Published Literature: MVK
Positive Disease Associations: HDL cholesterol , mevalonate kinase deficiency , Neuroblastoma
Related Studies:
  1. HDL cholesterol
    Kathiresan ,et al. 2008, Common variants at 30 loci contribute to polygenic dyslipidemia, Nature genetics 2009 41- 1 : 56-65. [PubMed 19060906]
  2. 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]
  3. 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.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: MVK
Diseases sorted by gene-association score: mevalonic aciduria* (1723), hyper-igd syndrome* (1680), porokeratosis 3, multiple types* (1330), porokeratosis 1, multiple types* (247), porokeratosis* (230), relapsing fever (24), periodic fever, familial (19), familial mediterranean fever, ar (16), linear porokeratosis (11), pyoderma gangrenosum (10), peroxisomal disease (9), punctate porokeratosis (9), rhizomelic chondrodysplasia punctata (9), blau syndrome (9), cervical adenitis (8), nonsyndromic retinitis pigmentosa (8), cinca syndrome (7), pharyngitis (4), intestinal obstruction (4), autosomal recessive disease (3), retinitis pigmentosa (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 27.14 RPKM in Testis
Total median expression: 449.30 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -193.10474-0.407 Picture PostScript Text
3' UTR -309.80689-0.450 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013750 - GHMP_kinase_C_dom
IPR006204 - GHMP_kinase_N_dom
IPR006203 - GHMP_knse_ATP-bd_CS
IPR006205 - Mev_gal_kin
IPR006206 - Mevalonate/galactokinase
IPR020568 - Ribosomal_S5_D2-typ_fold
IPR014721 - Ribosomal_S5_D2-typ_fold_subgr

Pfam Domains:
PF08544 - GHMP kinases C terminal

SCOP Domains:
54211 - Ribosomal protein S5 domain 2-like
55060 - GHMP Kinase, C-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2R3V - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q03426
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000287 magnesium ion binding
GO:0004496 mevalonate kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0042802 identical protein binding

Biological Process:
GO:0006629 lipid metabolic process
GO:0006694 steroid biosynthetic process
GO:0006695 cholesterol biosynthetic process
GO:0008202 steroid metabolic process
GO:0008203 cholesterol metabolic process
GO:0008299 isoprenoid biosynthetic process
GO:0016126 sterol biosynthetic process
GO:0016310 phosphorylation
GO:0019287 isopentenyl diphosphate biosynthetic process, mevalonate pathway
GO:0045540 regulation of cholesterol biosynthetic process
GO:0050728 negative regulation of inflammatory response

Cellular Component:
GO:0005737 cytoplasm
GO:0005777 peroxisome
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  LF383524 - JP 2014500723-A/191027: Polycomb-Associated Non-Coding RNAs.
LF206924 - JP 2014500723-A/14427: Polycomb-Associated Non-Coding RNAs.
M88468 - Homo sapiens mevalonate kinase mRNA, complete cds.
AB209722 - Homo sapiens mRNA for mevalonate kinase variant protein.
AK315678 - Homo sapiens cDNA, FLJ96772, Homo sapiens mevalonate kinase (mevalonic aciduria) (MVK), mRNA.
AK293130 - Homo sapiens cDNA FLJ57872 complete cds, highly similar to Mevalonate kinase (EC 2.7.1.36).
AK295338 - Homo sapiens cDNA FLJ57879 complete cds, highly similar to Mevalonate kinase (EC 2.7.1.36).
BC016140 - Homo sapiens mevalonate kinase, mRNA (cDNA clone MGC:9001 IMAGE:3921543), complete cds.
X75311 - H.sapiens /Hepatitis B virus fusion mRNA for mevalonate kinase.
LF359385 - JP 2014500723-A/166888: Polycomb-Associated Non-Coding RNAs.
AB463115 - Synthetic construct DNA, clone: pF1KB5046, Homo sapiens MVK gene for mevalonate kinase, without stop codon, in Flexi system.
DQ891089 - Synthetic construct clone IMAGE:100003719; FLH169250.01X; RZPDo839A0396D mevalonate kinase (mevalonic aciduria) (MVK) gene, encodes complete protein.
DQ894271 - Synthetic construct Homo sapiens clone IMAGE:100008731; FLH169246.01L; RZPDo839A0395D mevalonate kinase (mevalonic aciduria) (MVK) gene, encodes complete protein.
KJ891657 - Synthetic construct Homo sapiens clone ccsbBroadEn_01051 MVK gene, encodes complete protein.
KJ905231 - Synthetic construct Homo sapiens clone ccsbBroadEn_14705 MVK gene, encodes complete protein.
KR709345 - Synthetic construct Homo sapiens clone CCSBHm_00000727 MVK (MVK) mRNA, encodes complete protein.
KR709346 - Synthetic construct Homo sapiens clone CCSBHm_00000739 MVK (MVK) mRNA, encodes complete protein.
KR709347 - Synthetic construct Homo sapiens clone CCSBHm_00000744 MVK (MVK) mRNA, encodes complete protein.
KR709348 - Synthetic construct Homo sapiens clone CCSBHm_00000763 MVK (MVK) mRNA, encodes complete protein.
CU677575 - Synthetic construct Homo sapiens gateway clone IMAGE:100017178 5' read MVK mRNA.
KU178205 - Homo sapiens mevalonate kinase isoform 1 (MVK) mRNA, partial cds.
KU178206 - Homo sapiens mevalonate kinase isoform 2 (MVK) mRNA, partial cds, alternatively spliced.
AF217536 - Homo sapiens truncated mevalonate kinase mRNA, partial cds, alternatively spliced.
LF359387 - JP 2014500723-A/166890: Polycomb-Associated Non-Coding RNAs.
AK023087 - Homo sapiens cDNA FLJ13025 fis, clone NT2RP3000875, highly similar to MEVALONATE KINASE (EC 2.7.1.36).
JD121973 - Sequence 102997 from Patent EP1572962.
JD320840 - Sequence 301864 from Patent EP1572962.
JD071610 - Sequence 52634 from Patent EP1572962.
JD457029 - Sequence 438053 from Patent EP1572962.
JD475791 - Sequence 456815 from Patent EP1572962.
JD488322 - Sequence 469346 from Patent EP1572962.
JD493923 - Sequence 474947 from Patent EP1572962.
JD254383 - Sequence 235407 from Patent EP1572962.
JD526574 - Sequence 507598 from Patent EP1572962.
JD340399 - Sequence 321423 from Patent EP1572962.
JD460677 - Sequence 441701 from Patent EP1572962.
JD424407 - Sequence 405431 from Patent EP1572962.
JD467980 - Sequence 449004 from Patent EP1572962.
JD162974 - Sequence 143998 from Patent EP1572962.
JD288038 - Sequence 269062 from Patent EP1572962.
JD076025 - Sequence 57049 from Patent EP1572962.
LF359391 - JP 2014500723-A/166894: Polycomb-Associated Non-Coding RNAs.
JD416622 - Sequence 397646 from Patent EP1572962.
JD239813 - Sequence 220837 from Patent EP1572962.
JD416579 - Sequence 397603 from Patent EP1572962.
JD224516 - Sequence 205540 from Patent EP1572962.
MA619101 - JP 2018138019-A/191027: Polycomb-Associated Non-Coding RNAs.
MA442501 - JP 2018138019-A/14427: Polycomb-Associated Non-Coding RNAs.
MA594962 - JP 2018138019-A/166888: Polycomb-Associated Non-Coding RNAs.
MA594964 - JP 2018138019-A/166890: Polycomb-Associated Non-Coding RNAs.
MA594968 - JP 2018138019-A/166894: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00900 - Terpenoid backbone biosynthesis
hsa01100 - Metabolic pathways
hsa04146 - Peroxisome

Reactome (by CSHL, EBI, and GO)

Protein Q03426 (Reactome details) participates in the following event(s):

R-HSA-191380 Mevalonate is phosphorylated to mevalonate-5-phosphate
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
R-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-191273 Cholesterol biosynthesis
R-HSA-8957322 Metabolism of steroids
R-HSA-556833 Metabolism of lipids
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: AK293130, KIME_HUMAN, Q03426
UCSC ID: uc001toz.4
RefSeq Accession: NM_000431
Protein: Q03426 (aka KIME_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene MVK:
rp-overview (Nonsyndromic Retinitis Pigmentosa Overview)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: AK293130.1
exon count: 9CDS single in 3' UTR: no RNA size: 1120
ORF size: 609CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 808.50frame shift in genome: no % Coverage: 99.82
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.