MVK

mevalonate kinase

Basic information

Region (hg38): 12:109573254-109598125

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 (Definitive), mode of inheritance: Mitochondrial
• mevalonic aciduria (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mevalonic aciduria; Hyper-IgD syndrome	AR	Allergy/Immunology/Infectious	In 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 phase	Allergy/Immunology/Infectious; Dermatologic; Biochemical; Gastrointestinal; Neurologic; Ophthalmologic	6144826; 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.

• not provided (151 variants)
• Hyperimmunoglobulin D with periodic fever (141 variants)
• Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever (83 variants)
• Mevalonic aciduria (65 variants)
• Porokeratosis 3, disseminated superficial actinic type;Hyperimmunoglobulin D with periodic fever;Mevalonic aciduria (56 variants)
• Hyperimmunoglobulin D with periodic fever;Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria (42 variants)
• not specified (41 variants)
• Porokeratosis 3, disseminated superficial actinic type;Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever (40 variants)
• Autoinflammatory syndrome (37 variants)
• Mevalonic aciduria;Hyperimmunoglobulin D with periodic fever;Porokeratosis 3, disseminated superficial actinic type (37 variants)
• Hyperimmunoglobulin D with periodic fever;Mevalonic aciduria;Porokeratosis 3, disseminated superficial actinic type (34 variants)
• Inborn genetic diseases (17 variants)
• MVK-related condition (6 variants)
• MVK-Related Disorders (4 variants)
• Porokeratosis 3, disseminated superficial actinic type (3 variants)
• Hyperimmunoglobulin D with periodic fever;Mevalonic aciduria (2 variants)
• Methylmalonic acidemia (1 variants)
• Nemaline myopathy 5 (1 variants)
• See cases (1 variants)
• Retinal dystrophy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			9	63	3	75
missense	12	20	127	2		161
nonsense	6	1				7
start loss						0
frameshift	9	5				14
inframe indel						0
splice donor/acceptor (+/-2bp)		5	1			6
splice region		1	13	14	3	31
non coding			17	43	45	105
Total	27	31	154	108	48

Highest pathogenic variant AF is 0.000171

Variants in MVK

This is a list of pathogenic ClinVar variants found in the MVK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-109573327-C-T		Methylmalonic aciduria, cblB type	Likely benign (Nov 17, 2023)
12-109573330-TC-T		Methylmalonic aciduria, cblB type	Likely benign (Dec 13, 2023)
12-109573333-C-T		Methylmalonic aciduria, cblB type	Likely benign (Jun 05, 2023)
12-109573337-A-C		Methylmalonic aciduria, cblB type	Likely benign (Jun 26, 2022)
12-109573340-C-T		Methylmalonic aciduria, cblB type	Likely benign (Oct 12, 2023)
12-109573345-A-T		Methylmalonic aciduria, cblB type	Likely pathogenic (Jul 09, 2023)
12-109573346-C-A		Methylmalonic aciduria, cblB type	Likely pathogenic (Jun 14, 2023)
12-109573349-G-A		Methylmalonic aciduria, cblB type	Likely benign (Oct 26, 2022)
12-109573355-G-A		Methylmalonic aciduria, cblB type	Likely benign (Aug 30, 2023)
12-109573364-GC-G		Methylmalonic aciduria, cblB type	Pathogenic (May 29, 2023)
12-109573365-C-T		Methylmalonic aciduria, cblB type	Uncertain significance (Apr 10, 2020)
12-109573369-G-A		Methylmalonic aciduria, cblB type	Likely pathogenic (Jan 25, 2023)
12-109573370-A-C		Methylmalonic aciduria, cblB type	Likely benign (Jul 23, 2022)
12-109573373-G-A		Methylmalonic aciduria, cblB type	Likely benign (Jun 20, 2021)
12-109573373-G-T		Methylmalonic aciduria, cblB type	Likely benign (Jun 13, 2022)
12-109573373-GC-G		Methylmalonic aciduria, cblB type	Likely pathogenic (Mar 21, 2018)
12-109573376-G-A		Methylmalonic aciduria, cblB type	Likely benign (Nov 16, 2019)
12-109573379-G-A		Methylmalonic aciduria, cblB type	Likely benign (Jul 07, 2023)
12-109573382-C-T		Methylmalonic aciduria, cblB type • MMAB-related disorder	Conflicting classifications of pathogenicity (Nov 27, 2023)
12-109573390-G-A		Methylmalonic aciduria, cblB type	Conflicting classifications of pathogenicity (Jan 29, 2024)
12-109573393-G-A		Methylmalonic aciduria, cblB type	Uncertain significance (-)
12-109573394-A-T		Methylmalonic aciduria, cblB type	Pathogenic (Jun 01, 2021)
12-109573397-C-T		Methylmalonic aciduria, cblB type	Likely benign (Nov 20, 2023)
12-109573402-G-A		Inborn genetic diseases • Methylmalonic aciduria, cblB type	Uncertain significance (Apr 22, 2022)
12-109573403-C-T		Methylmalonic aciduria, cblB type	Likely benign (Nov 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MVK	protein_coding	protein_coding	ENST00000228510	10	24008

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.167	0.833	125732	0	16	125748	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.941	183	222	0.823	0.0000142	2511
Missense in Polyphen		51	73.866	0.69044		845
Synonymous	0.883	91	102	0.889	0.00000721	859
Loss of Function	3.02	5	19.3	0.259	9.38e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000307	0.000304
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.0000449	0.0000439
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mvk

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