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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
MVK
mevalonate kinase
Chromosome 12 Β· 12q24.11
NCBI Gene: 4598Ensembl: ENSG00000110921.14HGNC: HGNC:7530UniProt: B2RDU6
123PubMed Papers
23Diseases
0Drugs
111Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mevalonate kinase activityprotein bindingcholesterol biosynthetic processisoprenoid biosynthetic processhyperimmunoglobulinemia D with periodic fevermevalonic aciduriaporokeratosis 3, disseminated superficial actinic typeVitamin B12-responsive methylmalonic acidemia type cblB
✦AI Summary

MVK encodes mevalonate kinase, a cytosolic enzyme that catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, representing a critical regulatory step in isoprenoid and cholesterol biosynthesis 12. The enzyme requires ATP and magnesium ion cofactors and participates in the mevalonate pathway for isopentenyl diphosphate production 3. Beyond lipid metabolism, MVK function extends to innate immune regulation, as GO annotations indicate its involvement in negative regulation of inflammatory responses. MVK deficiency causes mevalonate kinase deficiency (MKD), a rare monogenic systemic autoinflammatory disorder characterized by disrupted isoprenoid biosynthesis and dysregulated cellular processes 45. MKD represents one of four historical monogenic autoinflammatory diseases, alongside familial Mediterranean fever, cryopyrinopathies, and TNF receptor-associated periodic syndrome 5. Additional disease associations include hyperimmunoglobulinemia D and periodic fever syndrome, and porokeratosis. The clinical significance of MVK lies in understanding autoinflammatory pathogenesis and developing therapeutic strategies targeting the mevalonate pathway for metabolic and immunological diseases. Recent therapeutic advances focus on modulating downstream components of the pathway rather than direct MVK manipulation.

Sources cited
1
MVK catalyzes phosphorylation of mevalonate in isoprenoid and cholesterol biosynthesis
PMID: 11278915
2
MVK catalyzes phosphorylation of mevalonate in isoprenoid and cholesterol biosynthesis
PMID: 18302342
3
MVK mutations cause mevalonate kinase deficiency, a rare autoinflammatory disorder affecting isoprenoid biosynthesis and cellular processes
PMID: 39600705
4
MVK mutations are associated with mevalonate kinase deficiency, one of four historical monogenic systemic autoinflammatory diseases
PMID: 32546426
5
MVK (mevalonate kinase) participates in the mevalonate pathway for isoprenoid synthesis and lipid metabolism regulation
PMID: 32432943
Disease Associationsβ“˜23
hyperimmunoglobulinemia D with periodic feverOpen Targets
0.85Strong
mevalonic aciduriaOpen Targets
0.84Strong
porokeratosis 3, disseminated superficial actinic typeOpen Targets
0.75Strong
methylmalonic aciduria, cblB typeOpen Targets
0.55Moderate
Vitamin B12-responsive methylmalonic acidemia type cblBOpen Targets
0.55Moderate
neurodegenerative diseaseOpen Targets
0.53Moderate
autoinflammatory syndromeOpen Targets
0.52Moderate
Retinal dystrophyOpen Targets
0.51Moderate
genetic disorderOpen Targets
0.47Moderate
methylmalonic acidemiaOpen Targets
0.39Weak
retinitis pigmentosaOpen Targets
0.37Weak
mevalonate kinase deficiencyOpen Targets
0.37Weak
disseminated superficial actinic porokeratosisOpen Targets
0.37Weak
porokeratosis of MibelliOpen Targets
0.37Weak
Abnormality of the skeletal systemOpen Targets
0.23Weak
Alzheimer diseaseOpen Targets
0.20Weak
cataractOpen Targets
0.20Weak
coronary artery diseaseOpen Targets
0.20Weak
Age-related cataractOpen Targets
0.20Weak
hearing lossOpen Targets
0.16Weak
Hyperimmunoglobulinemia D and periodic fever syndromeUniProt
Mevalonic aciduriaUniProt
Porokeratosis 3, multiple typesUniProt
Pathogenic Variants111
NM_000431.4(MVK):c.1129G>A (p.Val377Ile)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|not provided|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|MVK-related disorder|Porokeratosis 3, disseminated superficial actinic type|Autoinflammatory syndrome|Inborn genetic diseases|Mevalonic aciduria|Retinal dystrophy|autosomal recessive MVK-related disorders
β˜…β˜…β˜†β˜†2026β†’ Residue 377
NM_000431.4(MVK):c.803T>C (p.Ile268Thr)Pathogenic
Mevalonic aciduria|Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|not provided|not specified|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|Autoinflammatory syndrome|MVK-related disorder|Inborn genetic diseases|Retinal dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 268
NM_000431.4(MVK):c.421del (p.Ala141fs)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2026β†’ Residue 141
NM_000431.4(MVK):c.1000G>A (p.Ala334Thr)Pathogenic
Mevalonic aciduria|Hyperimmunoglobulin D with periodic fever|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|Retinal dystrophy
β˜…β˜…β˜†β˜†2026β†’ Residue 334
NM_000431.4(MVK):c.829C>T (p.Arg277Cys)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2026β†’ Residue 277
NM_000431.4(MVK):c.1139A>G (p.His380Arg)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria|MVK-related disorder|Deficiency of mevalonate kinase
β˜…β˜…β˜†β˜†2026β†’ Residue 380
NM_000431.4(MVK):c.644G>A (p.Arg215Gln)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria
β˜…β˜…β˜†β˜†2026β†’ Residue 215
NM_000431.4(MVK):c.346T>C (p.Tyr116His)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|See cases|MVK-related disorder
β˜…β˜…β˜†β˜†2026β†’ Residue 116
NM_000431.4(MVK):c.613A>G (p.Asn205Asp)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|Autoinflammatory syndrome|Mevalonic aciduria
β˜…β˜…β˜†β˜†2026β†’ Residue 205
NM_000431.4(MVK):c.608T>C (p.Val203Ala)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|Deficiency of mevalonate kinase
β˜…β˜…β˜†β˜†2025β†’ Residue 203
NM_000431.4(MVK):c.794T>G (p.Leu265Arg)Likely pathogenic
Hyperimmunoglobulin D with periodic fever|Retinal dystrophy|Mevalonic aciduria
β˜…β˜…β˜†β˜†2025β†’ Residue 265
NM_000431.4(MVK):c.59A>C (p.His20Pro)Pathogenic
Mevalonic aciduria|Hyperimmunoglobulin D with periodic fever|not provided|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2025β†’ Residue 20
NM_000431.4(MVK):c.277_283del (p.Glu93fs)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2025β†’ Residue 93
NM_000431.4(MVK):c.564G>A (p.Trp188Ter)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|Autoinflammatory syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 188
NM_000431.4(MVK):c.709A>T (p.Thr237Ser)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria
β˜…β˜…β˜†β˜†2025β†’ Residue 237
NM_000431.4(MVK):c.1162C>T (p.Arg388Ter)Pathogenic
Hyperimmunoglobulin D with periodic fever|not provided|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever|MVK-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 388
NM_000431.4(MVK):c.943_944del (p.Leu315fs)Pathogenic
not provided|Mevalonic aciduria|Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever;Porokeratosis 3, disseminated superficial actinic type
β˜…β˜…β˜†β˜†2025β†’ Residue 315
NM_000431.4(MVK):c.928G>A (p.Val310Met)Pathogenic
Mevalonic aciduria|Hyperimmunoglobulin D with periodic fever|not provided|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever|Autoinflammatory syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 310
NM_000431.4(MVK):c.604G>A (p.Gly202Arg)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria|Porokeratosis 3, disseminated superficial actinic type|not provided|Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2025β†’ Residue 202
NM_000431.4(MVK):c.1006G>A (p.Gly336Ser)Pathogenic
Hyperimmunoglobulin D with periodic fever|Mevalonic aciduria|Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever
β˜…β˜…β˜†β˜†2025β†’ Residue 336
View on ClinVar β†—
Related Genes
SQLEProtein interaction100%HSD17B7Protein interaction100%TM7SF2Protein interaction100%MSMO1Protein interaction100%SC5DProtein interaction99%SREBF2Protein interaction92%
Tissue Expression6 tissues
Liver
100%
Brain
21%
Ovary
19%
Bone Marrow
19%
Lung
18%
Heart
16%
Gene Interaction Network
Click a node to explore
MVKSQLEHSD17B7TM7SF2MSMO1SC5DSREBF2
PROTEIN STRUCTURE
Preparing viewer…
PDB2R3V Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.98LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.75 [0.57–0.98]
RankingsWhere MVK stands among ~20K protein-coding genes
  • #3,829of 20,598
    Most Researched123 Β· top quartile
  • #709of 5,498
    Most Pathogenic Variants111 Β· top quartile
  • #9,431of 17,882
    Most Constrained (LOEUF)0.98
Genes detectedMVK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.
PMID: 34102137
Lancet Β· 2021
1.00
2
Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated
PMID: 37870968
N Engl J Med Β· 2023
0.90
3
Head and neck cancer.
PMID: 18486742
Lancet Β· 2008
0.80
4
PMID: 20301590
0.70
5
Systemic autoinflammatory diseases: Clinical state of the art.
PMID: 32546426
Best Pract Res Clin Rheumatol Β· 2020
0.60