Rare genetic inflammatory skin disorders

Gene: PMVK

Green List (high evidence)

Comment on list classification: There are at least 13 unrelated individuals reported in literature with germline heterozygous variants in PMVK, diagnosed with a type of porokeratosis. Based on the available evidence, PMVK should be promoted to Green for Rare genetic inflammatory skin disorders.

Created: 31 Dec 2025, 1:46 p.m. | Last Modified: 31 Dec 2025, 1:46 p.m.

Panel Version: 4.9

Porokeratosis is characterised by keratotic lesions with an atrophic center rimmed by an elevated border. Disease onset is mostly in childhood or adolescence.

PMID: 26202976 Zhang et al. 2015
Screened 12 isoprenoid genes in 134 Chinese probands with porokeratosis and identified PMVK mutations:
9 unrelated cases (some cases sporadic some familial). PMVK variants detected: c.1A>G, p.Met1?; c.94A>T, p.Arg32*; c.205A>G, p.Lys69Glu; c.312G>A, p.Trp104*; c.412C>T, p.Arg138*; c.550del, p.Leu184*.

PMID: 27052676 Wang et al 2016
Investigated the genetic basis of Disseminated Superficial Porokeratosis (DSP) in 2 five-generation Chinese families with members affected by DSP. Identified a nonsense variation c.412C>T (p.Arg138*) in PMVK in both families through WES. Age of onset: mostly between 5-10 yo.

PMID: 37315547 Zhang et al., 2023
Identified a novel heterozygous missense variant, c.207G>T (p. Lys69Asn) in PMVK in a Chinese pedigree with 4 individuals affected by porokeratosis. Patients presented with keratotic lesions in childhood / adolescence. Only 4 genes were sequenced: MVK, MVD, PMVK, and FDPS.

PMID: 41296516 Narula et al., 2025 (online ahead of print)
20-year-old Indian man, presented with persistent non-pruritic skin lesions since childhood: skin-coloured papules on the scrotum and pigmented annular plaques over the forearms, dorsum of the foot, elbows, knees, and buttocks. Heterozygous for NM_006556.4: c.412C>T (p.Arg138*) - same variant as reported in PMID: 27052676.

This gene is NOT predicted to be LoF intolerant (pLI = 0.02, LOEUF = 0.87).
PMVK is associated with AD Porokeratosis 1, multiple types MIM:175800 in OMIM (accessed 3rd Dec 2025).
Sources: Literature

Created: 31 Dec 2025, 1:45 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Porokeratosis 1, multiple types, OMIM:175800; porokeratosis, MONDO:0006602

Publications

• 26202976
• 27052676
• 37315547
• 41296516