GeneBe

MVK

mevalonate kinase

Basic information

Region (hg38): 12:109573255-109598125

Links

ENSG00000110921 ∙ NCBI:4598 ∙ OMIM:251170 ∙ HGNC:7530 ∙ Uniprot:Q03426 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • mevalonic aciduria (Supportive), mode of inheritance: AR
  • hyperimmunoglobulinemia D with periodic fever (Supportive), mode of inheritance: AR
  • porokeratosis of Mibelli (Supportive), mode of inheritance: AD
  • disseminated superficial actinic porokeratosis (Supportive), mode of inheritance: AD
  • porokeratosis 3, disseminated superficial actinic type (Strong), mode of inheritance: AD
  • hyperimmunoglobulinemia D with periodic fever (Definitive), mode of inheritance: AR
  • mevalonic aciduria (Strong), mode of inheritance: AR
  • mevalonic aciduria (Definitive), mode of inheritance: AR
  • porokeratosis 3, disseminated superficial actinic type (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Mevalonic aciduria; Hyper-IgD syndromeARAllergy/Immunology/InfectiousIn Mevalonic aciduria, diagnosis can be challenging, and effective treatment is available with specific agents (eg, steroids, leukotriene receptor antagonists); In Hyper-IgD syndrome, accurate diagnosis may be beneficial in order to avoid unnecessary surgery for suspected appendicitis/acute abdomen; Medical treatment (eg, corticosteroids, leukotriene receptor inhibitors) during the acute phase can be effective, as well as medical treatment in the non-acute phaseAllergy/Immunology/Infectious; Dermatologic; Biochemical; Gastrointestinal; Neurologic; Ophthalmologic6144826; 3012338; 8386351; 8190036; 8973873; 10369262; 10369261; 11313769; 11742050; 15149516; 15457465; 15536479; 16835861; 18409191; 20194276; 21399979; 21548022; 22159817; 22246419; 22271696; 22983302; 34525209; 35525811

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MVK gene.

  • Hyperimmunoglobulin_D_with_periodic_fever (589 variants)
  • Mevalonic_aciduria (548 variants)
  • Porokeratosis_3,_disseminated_superficial_actinic_type (542 variants)
  • not_provided (148 variants)
  • not_specified (45 variants)
  • Inborn_genetic_diseases (34 variants)
  • Autoinflammatory_syndrome (33 variants)
  • Retinal_dystrophy (20 variants)
  • MVK-related_disorder (20 variants)
  • Deficiency_of_mevalonate_kinase (7 variants)
  • Nemaline_myopathy_6 (1 variants)
  • Nemaline_myopathy_5 (1 variants)
  • See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MVK gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000431.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
166
clinvar
1
clinvar
 175
missense
11
clinvar
37
clinvar
213
clinvar
4
clinvar
1
clinvar
 266
nonsense
13
clinvar
3
clinvar
 16
start loss
2
1
 3
frameshift
22
clinvar
12
clinvar
6
clinvar
 40
splice donor/acceptor (+/-2bp)
2
clinvar
9
clinvar
4
clinvar
 15
Total 50 61 232 170 2

Highest pathogenic variant AF is 0.0020969014

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MVKprotein_codingprotein_codingENST00000228510 1024008
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.1670.8331257320161257480.0000636
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.9411832220.8230.00001422511
Missense in Polyphen5173.8660.69044845
Synonymous0.883911020.8890.00000721859
Loss of Function3.02519.30.2599.38e-7227

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003070.000304
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00009240.0000924
European (Non-Finnish)0.00004490.0000439
Middle Eastern0.000.00
South Asian0.00009800.0000980
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis (PubMed:9325256, PubMed:18302342). {ECO:0000269|PubMed:18302342, ECO:0000269|PubMed:9325256}.;
Disease
DISEASE: Mevalonic aciduria (MEVA) [MIM:610377]: Accumulation of mevalonic acid which causes a variety of symptoms such as psychomotor retardation, dysmorphic features, cataracts, hepatosplenomegaly, lymphadenopathy, anemia, hypotonia, myopathy, and ataxia. {ECO:0000269|PubMed:10401001, ECO:0000269|PubMed:10417275, ECO:0000269|PubMed:11313768, ECO:0000269|PubMed:11313769, ECO:0000269|PubMed:1377680}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) [MIM:260920]: Autosomal recessive disease characterized by recurrent episodes of unexplained high fever associated with skin rash, diarrhea, adenopathy (swollen, tender lymph nodes), arthralgias and/or arthritis. Concentration of IgD, and often IgA, are above normal. {ECO:0000269|PubMed:10369261, ECO:0000269|PubMed:10369262, ECO:0000269|PubMed:11313768, ECO:0000269|PubMed:11313769, ECO:0000269|PubMed:15536479}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Porokeratosis 3, multiple types (POROK3) [MIM:175900]: A form of porokeratosis, a disorder of faulty keratinization characterized by one or more atrophic patches surrounded by a distinctive hyperkeratotic ridgelike border called the cornoid lamella. The keratotic lesions can progress to overt cutaneous neoplasms, typically squamous cell carcinomas. Multiple clinical variants of porokeratosis are recognized, including porokeratosis of Mibelli, linear porokeratosis, disseminated superficial actinic porokeratosis, palmoplantar porokeratosis, and punctate porokeratosis. Different clinical presentations can be observed among members of the same family. Individuals expressing more than one variant have also been reported. {ECO:0000269|PubMed:22983302, ECO:0000269|PubMed:24781643}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Mevalonate pathway;Peroxisome - Homo sapiens (human);Terpenoid backbone biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Cholesterol Biosynthesis;Activation of gene expression by SREBF (SREBP);Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Squalene and cholesterol biosynthesis;Metabolism;superpathway of cholesterol biosynthesis;Metabolism of steroids;Steroids metabolism;Cholesterol biosynthesis;Activation of gene expression by SREBF (SREBP);mevalonate pathway;superpathway of geranylgeranyldiphosphate biosynthesis I (via mevalonate) (Consensus)

Recessive Scores

pRec
0.318

Intolerance Scores

loftool
0.0698
rvis_EVS
-0.2
rvis_percentile_EVS
38.98

Haploinsufficiency Scores

pHI
0.0425
hipred
Y
hipred_score
0.554
ghis
0.564

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.997

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Mvk
Phenotype

Gene ontology

Biological process
cholesterol biosynthetic process;isoprenoid biosynthetic process;phosphorylation;isopentenyl diphosphate biosynthetic process, mevalonate pathway;regulation of cholesterol biosynthetic process;negative regulation of inflammatory response
Cellular component
peroxisome;cytosol
Molecular function
magnesium ion binding;mevalonate kinase activity;protein binding;ATP binding;identical protein binding