MVK

Chr 12ARAD

mevalonate kinase

Also known as: LRBP, MK, MVLK, POROK3

This gene encodes mevalonate kinase, a peroxisomal enzyme that catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate in isoprenoid and cholesterol biosynthesis. Mutations cause autosomal recessive mevalonic aciduria with early-onset psychomotor retardation, failure to thrive, hepatosplenomegaly, and recurrent fevers, as well as the milder hyper-IgD syndrome with periodic fever episodes, lymphadenopathy, and arthralgia. The gene also causes autosomal dominant porokeratosis, a skin condition with multiple clinical variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.553 OMIM phenotypes
Clinical SummaryMVK
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Gene-Disease Validity (ClinGen)
mevalonate kinase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.55LOEUF
pLI 0.167
Z-score 3.02
OE 0.26 (0.130.55)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.94Z-score
OE missense 0.82 (0.730.93)
183 obs / 222.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.130.55)
00.351.4
Missense OE0.82 (0.730.93)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 5 / 19.3Missense obs/exp: 183 / 222.5Syn Z: 0.88
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMVK-related porokeratosis, multiple typesOTHERAD
definitiveMVK-related mevalonic aciduriaLOFAR
definitiveMVK-related hyper-IgD syndromeLOFAR
DN
0.7132th %ile
GOF
0.5954th %ile
LOF
0.2775th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MVK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗