porokeratosis of Mibelli

Summary

porokeratosis of Mibelli (MONDO:0019141) is a disease with 2 cohort genes.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• Phenotypes (HPO): 5

Clinical features

Signs & symptoms

Clinical features (HPO)

5 HPO clinical features (Orphanet curated; top 5 by frequency):

HPO ID	Term	Frequency
HP:0000962	Hyperkeratosis	Very frequent (80-99%)
HP:0008065	Aplasia/Hypoplasia of the skin	Very frequent (80-99%)
HP:0200044	Porokeratosis	Very frequent (80-99%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0000992	Cutaneous photosensitivity	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	porokeratosis of Mibelli
Mondo ID	MONDO:0019141
Orphanet	735
SNOMED CT	80432009
UMLS	C0949506
MedGen	181842
GARD	0004438
Is cancer (heuristic)	no

Data availability: 2 GenCC gene-disease records.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › porokeratosis › porokeratosis of Mibelli

Related subtypes (3): porokeratosis plantaris palmaris et disseminata, disseminated superficial actinic porokeratosis, linear porokeratosis

Subtypes (2): porokeratosis 1, Mibelli type, porokeratosis 3, disseminated superficial actinic type

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
MVK	Definitive	Autosomal dominant	porokeratosis 3, disseminated superficial actinic type	10
PMVK	Definitive	Autosomal dominant	porokeratosis 1, Mibelli type	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MVK	Orphanet:29	Mevalonic aciduria
MVK	Orphanet:343	Hyperimmunoglobulinemia D with periodic fever
MVK	Orphanet:735	Porokeratosis of Mibelli
MVK	Orphanet:79152	Disseminated superficial actinic porokeratosis
PMVK	Orphanet:735	Porokeratosis of Mibelli

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MVK	HGNC:7530	ENSG00000110921	Q03426	Mevalonate kinase	gencc
PMVK	HGNC:9141	ENSG00000163344	Q15126	Phosphomevalonate kinase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MVK	Mevalonate kinase	Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.
PMVK	Phosphomevalonate kinase	Catalyzes the reversible ATP-dependent phosphorylation of mevalonate 5-phosphate to produce mevalonate diphosphate and ADP, a key step in the mevalonic acid mediated biosynthesis of isopentenyl diphosphate and other polyisoprenoid metaboli…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MVK	Kinase	yes	2.7.1.36	GHMP_knse_ATP-bd_CS, GHMP_kinase_N_dom, Mev_gal_kin
PMVK	Enzyme (other)	yes	2.7.4.2	Pmev_kin_anim, P-loop_NTPase

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	2
right lobe of liver	2
metanephros cortex	1
apex of heart	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MVK	271	ubiquitous	marker	lower esophagus mucosa, right lobe of liver, metanephros cortex
PMVK	283	ubiquitous	marker	apex of heart, lower esophagus mucosa, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MVK	3,424
PMVK	1,326

Intra-cohort edges

A	B	Sources
MVK	PMVK	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MVK	Q03426	1
PMVK	Q15126	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Lanosterol biosynthesis	2	761.3×	1e-05	MVK, PMVK
Activation of gene expression by SREBF (SREBP)	2	259.6×	5e-05	MVK, PMVK
Cholesterol biosynthesis	1	571.0×	0.004	MVK
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	158.6×	0.011	MVK
Metabolism of steroids	1	68.8×	0.020	MVK
Metabolism of lipids	1	15.8×	0.073	MVK
Metabolism	1	5.8×	0.165	MVK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
isopentenyl diphosphate biosynthetic process, mevalonate pathway	2	5617.3×	1e-07	MVK, PMVK
cholesterol biosynthetic process	2	421.3×	2e-05	MVK, PMVK
isoprenoid biosynthetic process	1	842.6×	0.001	MVK
sterol biosynthetic process	1	842.6×	0.001	PMVK
response to cholesterol	1	842.6×	0.001	PMVK
negative regulation of inflammatory response	1	68.5×	0.015	MVK

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MVK	0	0
PMVK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MVK	2.7.1.36	mevalonate kinase
PMVK	2.7.4.2	phosphomevalonate kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MVK, PMVK
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MVK	0	—
PMVK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.