GeneBe

PMVK

protein-coding

phosphomevalonate kinase

Gene summary

This gene encodes a peroxisomal enzyme that is a member of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family of ATP-dependent enzymes. The encoded protein catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate, which is the fifth step in the mevalonate pathway of isoprenoid biosynthesis. Mutations in this gene are linked to certain types of porokeratosis including disseminated superficial porokeratosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

MANE transcript

NM_006556.4

Inheritance

AD, AR

ClinVar variants

P:7U:35B:7

Top phenotype

Porokeratosis 1, multiple types

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr1:154,924,740-154,936,719

External References & Databases

Ensembl (ENSG00000163344)NCBI Gene (10654)OMIM (607622)HGNC:9141GenCCUniProt (Q15126)AlphaFoldClinVar (PMVK)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

porokeratosis 1, Mibelli typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008290

Submitter: Labcorp Genetics (formerly Invitae)

porokeratosis of MibelliSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019141

Submitter: Orphanet

autoinflammatory syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019751

Submitter: Ambry Genetics

porokeratosis 1, Mibelli typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008290

Submitter: Ambry Genetics

autoinflammatory syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0019751

Submitter: PanelApp Australia

porokeratosis 1, Mibelli typeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0008290

Submitter: PanelApp Australia

porokeratosis 1, Mibelli typeMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0008290

Submitter: Ambry Genetics

porokeratosis 1, Mibelli typeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008290

Submitter: G2P

Clinical Genomic Database (CGD)

Porokeratosis 1, multiple typesAD

Manifestation: Dermatologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26202976Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PMVK variants in ClinVar

8 Conditions Cataloged
Inborn genetic diseasesTotal: 30
not providedTotal: 9
Porokeratosis 1, Mibelli typeTotal: 6
Linear porokeratosisTotal: 3
PMVK-related disorderTotal: 2
Primary ciliary dyskinesiaTotal: 1
not specifiedTotal: 1
PMVK-associated autoinflammatory disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006556.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
1
clinvar
33
clinvar
4
clinvar
1
clinvar
 39
nonsense
1
clinvar
3
clinvar
1
clinvar
 5
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
1
clinvar
1
clinvar
 2
Total25356149

Highest pathogenic variant AF is 0.00032227478

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_006556.4RefSeqNP_006547.15MANE Select
ENST00000368467.4EnsemblENSP00000357452.35MANE Select
NM_001323011.3RefSeqNP_001309940.15Standard
NM_001323012.3RefSeqNP_001309941.13Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Mevalonate pathway
  • Peroxisome - Homo sapiens (human)
  • Terpenoid backbone biosynthesis - Homo sapiens (human)
  • Simvastatin Action Pathway
  • Pravastatin Action Pathway

Biological Process

  • cholesterol biosynthetic process
  • sterol biosynthetic process
  • phosphorylation
  • isopentenyl diphosphate biosynthetic process, mevalonate pathway
  • regulation of cholesterol biosynthetic process

Molecular Function

  • phosphomevalonate kinase activity
  • ATP binding

Cellular Component

  • peroxisome
  • cytosol
  • membrane
  • extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000368467
Coding exons
5
Length
12258
Individuals with no LoFs
125691
Homozygous LoFs
0
Heterozygous LoFs
56
Defined
125747
p
0.000223
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.754971200.8070.000007461235
Missense (PolyPhen)3844.2870.85803468
Synonymous1.113948.90.7980.00000289377
Loss of Function0.666810.30.7765.25e-7106

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000540.00052rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish0.0000490.000046rare
European (Non-Finnish)0.000270.00026rare
South Asian0.000130.00013rare
Other0.000340.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease
DISEASE: Porokeratosis 1, multiple types (POROK1) [MIM:175800]: 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:26202976, ECO:0000269|PubMed:27052676}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.159

Intolerance Scores

LoFtool
0.772
RVIS EVS
0.59
RVIS percentile EVS
82.51

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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