Related Experiment Video
Updated: Jun 4, 2026
Characterization of In Vitro Differentiation of Human Primary Keratinocytes by RNA-Seq Analysis
Published on: May 16, 2020
Transcriptomic and proteomic analysis of MVK variant sites in two subtypes of porokeratosis
Shuqin Lai1, Wenjie Zhu2, Chunli Lin1
1Department of Dermatology, Joint Organization of Jiangxi Clinical Medicine Research Center for Dermatology, First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi, People's Republic of China.
Abstract:
Porokeratosis (PK) encompasses genetically heterogeneous keratinization disorders, with disseminated superficial actinic porokeratosis (DSAP) and porokeratosis ptychotropica (PPt) as distinct subtypes. Although MVK is a known causative gene, how different variants drive distinct phenotypes remains unclear. Through whole-exome sequencing of two DSAP patients, we identified an MVK variant (c.439G > A, p.Ala147Thr) cataloged as likely pathogenic in ClinVar yet uncharacterized functionally in DSAP keratinocytes. A previously reported PPt-associated variant (c.64G > A) was included for comparison. We established HaCaT cells stably overexpressing each mutant via lentiviral transduction and validated expression by qPCR and Western blot. Integrated transcriptomic and proteomic analyses identified differentially expressed genes (DEGs) and proteins (DEPs) across MVK439 versus control, MVK64 versus control, and MVK439 versus MVK64 groups, followed by GO and KEGG enrichment. Transcriptomic profiling revealed 231, 1,849, and 2,329 DEGs in the respective comparisons. Proteomic screening identified 2,673 DEPs, with 42 shared across all groups, 77 specifically associated with c.439G > A, and 832 linked to c.64G > A. Integrated analysis suggested IL12A and pIgR as potential contributors to c.439G > A-driven DSAP, while CXCL11, CXCL9, and TNFRSF12A may mediate c.64G > A-induced PPt. These findings offer new insights into MVK function and PK pathogenesis, warranting validation in larger cohorts.
Insights
Genetic variants in the MVK gene cause distinct porokeratosis (PK) subtypes. This study functionally characterized MVK variants, revealing specific molecular pathways involved in disseminated superficial actinic porokeratosis (DSAP) and porokeratosis ptychotropica (PPt).
Area of Science:
- Genetics
- Molecular Biology
- Dermatology
Background:
- Porokeratosis (PK) is a group of heterogeneous keratinization disorders.
- The MVK gene is implicated in PK, but how its variants lead to distinct phenotypes is unclear.
Purpose of the Study:
- To functionally characterize a novel MVK variant (c.439G>A) associated with disseminated superficial actinic porokeratosis (DSAP).
- To compare its molecular effects with a known MVK variant (c.64G>A) linked to porokeratosis ptychotropica (PPt).
Main Methods:
- Whole-exome sequencing identified MVK variants.
- HaCaT cells were engineered to overexpress MVK mutants.
- Integrated transcriptomic and proteomic analyses were performed.
Main Results:
- Transcriptomic profiling revealed significant differentially expressed genes (DEGs) for each MVK variant compared to controls and between variants.
- Proteomic screening identified thousands of differentially expressed proteins (DEPs), with unique profiles for each MVK variant.
- Specific genes (IL12A, pIgR) were linked to the c.439G>A variant (DSAP), and others (CXCL11, CXCL9, TNFRSF12A) to the c.64G>A variant (PPt).
Conclusions:
- The study provides functional insights into MVK gene variants and their roles in PK pathogenesis.
- Distinct MVK variants may drive specific PK subtypes through unique molecular mechanisms.
- Further validation in larger patient cohorts is warranted.
