PMVK

phosphomevalonate kinase

Basic information

Region (hg38): 1:154924740-154936719

Links

ENSG00000163344NCBI:10654OMIM:607622HGNC:9141Uniprot:Q15126AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • porokeratosis 1, Mibelli type (Moderate), mode of inheritance: AD
  • porokeratosis of Mibelli (Supportive), mode of inheritance: AD
  • porokeratosis 1, Mibelli type (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Porokeratosis 1, multiple typesADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic26202976

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PMVK 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
1
clinvar
1
missense
12
clinvar
2
clinvar
1
clinvar
15
nonsense
1
clinvar
1
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
6
clinvar
6
Total 0 1 12 2 8

Variants in PMVK

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

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

Position Type Phenotype Significance ClinVar
1-154925080-GC-G Benign (Jun 20, 2021)1259917
1-154925085-A-C Benign (Jun 20, 2021)1254973
1-154925143-G-A Inborn genetic diseases Uncertain significance (May 30, 2022)2247763
1-154925157-AG-A Porokeratosis 1, Mibelli type Pathogenic (Jul 23, 2015)253042
1-154925181-C-T Inborn genetic diseases Uncertain significance (Jun 24, 2022)2296534
1-154925258-G-T Inborn genetic diseases Uncertain significance (Oct 05, 2022)2317218
1-154926359-G-A Inborn genetic diseases Uncertain significance (Sep 26, 2023)3215871
1-154926360-T-A Likely benign (Nov 01, 2022)2639382
1-154926383-C-A Inborn genetic diseases Uncertain significance (Mar 15, 2024)3308121
1-154926384-G-A Porokeratosis 1, Mibelli type Pathogenic (Jul 23, 2015)253041
1-154926398-G-A PMVK-associated autoinflammatory disorder Uncertain significance (-)3062336
1-154926405-C-G Inborn genetic diseases Uncertain significance (Jul 13, 2021)2236501
1-154926405-C-T Inborn genetic diseases Uncertain significance (Jul 26, 2021)2351691
1-154926417-G-A Linear porokeratosis Likely pathogenic (May 01, 2019)1344671
1-154926423-C-T Benign (Jun 10, 2021)1180221
1-154926441-G-A Inborn genetic diseases Uncertain significance (May 27, 2022)2222469
1-154926467-C-T Linear porokeratosis Likely pathogenic (May 01, 2019)1344669
1-154928774-A-AAAAT Benign (Jun 19, 2021)1257436
1-154928774-A-AAAATAAAT Benign (Jun 21, 2021)1270881
1-154929049-A-G PMVK-related disorder Likely benign (Nov 07, 2016)377095
1-154929113-C-G Inborn genetic diseases Uncertain significance (Nov 09, 2022)2323082
1-154929156-C-A Inborn genetic diseases Uncertain significance (Sep 12, 2023)2622769
1-154932364-T-C PMVK-related disorder Benign (Jun 10, 2021)1278538
1-154932407-G-C Inborn genetic diseases Uncertain significance (Jul 28, 2021)2239778
1-154932703-A-G Benign (Jun 20, 2021)1227224

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
PMVKprotein_codingprotein_codingENST00000368467 512258
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.00002710.5501256910561257470.000223
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.754971200.8070.000007461235
Missense in Polyphen3844.2870.85803468
Synonymous1.113948.90.7980.00000289377
Loss of Function0.666810.30.7765.25e-7106

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0005410.000541
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.00004950.0000462
European (Non-Finnish)0.0002700.000264
Middle Eastern0.00005440.0000544
South Asian0.0001310.000131
Other0.0003370.000326

dbNSFP

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.;
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
0.159

Intolerance Scores

loftool
0.772
rvis_EVS
0.59
rvis_percentile_EVS
82.51

Haploinsufficiency Scores

pHI
0.134
hipred
N
hipred_score
0.208
ghis
0.449

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.999

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Pmvk
Phenotype

Gene ontology

Biological process
cholesterol biosynthetic process;sterol biosynthetic process;phosphorylation;isopentenyl diphosphate biosynthetic process, mevalonate pathway;regulation of cholesterol biosynthetic process;response to cholesterol
Cellular component
peroxisome;cytosol;membrane;extracellular exosome
Molecular function
phosphomevalonate kinase activity;ATP binding