MVK

Protein identityUniProt · HPA

UniProt accession

Q03426

Gene

MVK

Ensembl

ENSG00000110921

Chromosome

12

Canonical length

396 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Vesicles,Cytosol

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

396 residues, UniProt reviewed canonical sequence.

>Q03426|MVK
     1  MLSEVLLVSA PGKVILHGEH AVVHGKVALA VSLNLRTFLR LQPHSNGKVD LSLPNIGIKR
    61  AWDVARLQSL DTSFLEQGDV TTPTSEQVEK LKEVAGLPDD CAVTERLAVL AFLYLYLSIC
   121  RKQRALPSLD IVVWSELPPG AGLGSSAAYS VCLAAALLTV CEEIPNPLKD GDCVNRWTKE
   181  DLELINKWAF QGERMIHGNP SGVDNAVSTW GGALRYHQGK ISSLKRSPAL QILLTNTKVP
   241  RNTRALVAGV RNRLLKFPEI VAPLLTSIDA ISLECERVLG EMGEAPAPEQ YLVLEELIDM
   301  NQHHLNALGV GHASLDQLCQ VTRARGLHSK LTGAGGGGCG ITLLKPGLEQ PEVEATKQAL
   361  TSCGFDCLET SIGAPGVSIH SATSLDSRVQ QALDGL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MVK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.24

Highest tissue expression

59 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MVK.

Disease | AllUniProt

Conditions MVK is implicated in, by any mechanism.

• Mevalonic aciduria (MEVA) MIM:610377
• Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) MIM:260920
• Porokeratosis 3, multiple types (POROK3) MIM:175900

Disease | GeneticClinVar

112 pathogenic / likely-pathogenic of 796 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hyperimmunoglobulin D with periodic fever
• Mevalonic aciduria
• Porokeratosis 3, disseminated superficial actinic type
• MVK-related disorder
• Autoinflammatory syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.55

gnomAD pLI

0.17

gnomAD missense Z

0.94

DepMap mean gene effect

-0.78

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cholesterol biosynthetic process
• isopentenyl diphosphate biosynthetic process, mevalonate pathway
• isoprenoid biosynthetic process
• negative regulation of inflammatory response

Molecular functions

• ATP binding
• identical protein binding
• magnesium ion binding
• mevalonate kinase activity

Cellular components

• cytosol
• peroxisome

Protein domainsUniProt · Pfam · InterPro

• GHMP kinase, ATP-binding, conserved site
• GHMP kinase N-terminal domain
• GHMP kinase, C-terminal domain
• Small ribosomal subunit protein uS5 domain 2-type fold, subgroup
• Ribosomal protein uS5 domain 2-type superfamily
• GHMP kinase, C-terminal domain superfamily
• GHMP kinases N terminal domain
• GHMP kinases C terminal
• Mevalonate kinase

KeywordsUniProt

• ATP-binding
• Cataract
• Cholesterol biosynthesis
• Cholesterol metabolism
• Cytoplasm
• Kinase
• Lipid biosynthesis
• Lipid metabolism
• Magnesium
• Metal-binding
• Nucleotide-binding
• Peroxisome
• Steroid biosynthesis
• Steroid metabolism
• Sterol biosynthesis
• Sterol metabolism
• Transferase