PMVK

phosphomevalonate kinase

Basic information

Region (hg38): 1:154924739-154936719

Links

ENSG00000163344 ∙ NCBI:10654 ∙ OMIM:607622 ∙ HGNC:9141 ∙ Uniprot:Q15126 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Porokeratosis 1, multiple types	AD	General	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	Dermatologic	26202976

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	1
missense			12	2	1	15
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					6	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)
1-154925085-A-C			Benign (Jun 20, 2021)
1-154925143-G-A		Inborn genetic diseases	Uncertain significance (May 30, 2022)
1-154925157-AG-A		Porokeratosis 1, Mibelli type	Pathogenic (Jul 23, 2015)
1-154925181-C-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
1-154925258-G-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
1-154926359-G-A		Inborn genetic diseases	Uncertain significance (Sep 26, 2023)
1-154926360-T-A			Likely benign (Nov 01, 2022)
1-154926383-C-A		Inborn genetic diseases	Uncertain significance (Mar 15, 2024)
1-154926384-G-A		Porokeratosis 1, Mibelli type	Pathogenic (Jul 23, 2015)
1-154926398-G-A		PMVK-associated autoinflammatory disorder	Uncertain significance (-)
1-154926405-C-G		Inborn genetic diseases	Uncertain significance (Jul 13, 2021)
1-154926405-C-T		Inborn genetic diseases	Uncertain significance (Jul 26, 2021)
1-154926417-G-A		Linear porokeratosis	Likely pathogenic (May 01, 2019)
1-154926423-C-T			Benign (Jun 10, 2021)
1-154926441-G-A		Inborn genetic diseases	Uncertain significance (Jul 21, 2021)
1-154926467-C-T		Linear porokeratosis	Likely pathogenic (May 01, 2019)
1-154928774-A-AAAAT			Benign (Jun 19, 2021)
1-154928774-A-AAAATAAAT			Benign (Jun 21, 2021)
1-154929049-A-G		PMVK-related disorder	Benign/Likely benign (Oct 22, 2019)
1-154929113-C-G		Inborn genetic diseases	Uncertain significance (Nov 09, 2022)
1-154929156-C-A		Inborn genetic diseases	Uncertain significance (Sep 12, 2023)
1-154932364-T-C		PMVK-related disorder	Benign (Jun 10, 2021)
1-154932407-G-C		Inborn genetic diseases	Uncertain significance (Jul 28, 2021)
1-154932703-A-G			Benign (Jun 20, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PMVK	protein_coding	protein_coding	ENST00000368467	5	12258

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000271	0.550	125691	0	56	125747	0.000223

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.754	97	120	0.807	0.00000746	1235
Missense in Polyphen		38	44.287	0.85803		468
Synonymous	1.11	39	48.9	0.798	0.00000289	377
Loss of Function	0.666	8	10.3	0.776	5.25e-7	106

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000541	0.000541
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000495	0.0000462
European (Non-Finnish)	0.000270	0.000264
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000337	0.000326

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

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

Mouse Genome Informatics

• Gene name: Pmvk

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