Linear porokeratosis

Summary

Linear porokeratosis (MONDO:0023246) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	linear porokeratosis
Mondo ID	MONDO:0023246
ICD-11	1622319802
SNOMED CT	238631008
UMLS	C0302319
MedGen	81293
GARD	0009515
Is cancer (heuristic)	no

Also known as: Congenital facial linear porokeratosis (type) · Porokeratosis, Linear · Zosteriform porokeratosis

Data availability: 5 ClinVar variants.

Disease family

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

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

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

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

3 likely pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1012741	NM_006556.4(PMVK):c.79G>T (p.Glu27Ter)	PMVK	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1344672	NM_002461.3(MVD):c.811_815del (p.Phe271fs)	MVD	Likely pathogenic	no assertion criteria provided
1344669	NM_006556.4(PMVK):c.329G>A (p.Arg110Gln)	PMVK	Likely pathogenic	no assertion criteria provided
1344671	NM_006556.4(PMVK):c.379C>T (p.Gln127Ter)	PMVK	Likely pathogenic	no assertion criteria provided
1344813	NM_002461.3(MVD):c.70+5G>A	LOC130059740	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MVD	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
MVD	HGNC:7529	ENSG00000167508	P53602	Diphosphomevalonate decarboxylase	clinvar
PMVK	HGNC:9141	ENSG00000163344	Q15126	Phosphomevalonate kinase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MVD	Diphosphomevalonate decarboxylase	Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP).
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)
MVD	Kinase	yes	4.1.1.33	Mev_decarb, Ribsml_uS5_D2-typ_fold_subgr, Ribosomal_Su5_D2-typ_SF
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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
apex of heart	1
lower esophagus mucosa	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MVD	189	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar 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
PMVK	1,326
MVD	1,189

Intra-cohort edges

A	B	Sources
MVD	PMVK	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MVD	P53602	1
PMVK	Q15126	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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×	2e-05	MVD, PMVK
Activation of gene expression by SREBF (SREBP)	2	259.6×	9e-05	MVD, PMVK
Synthesis of dolichyl-phosphate	1	815.7×	0.005	MVD
Cholesterol biosynthesis	1	571.0×	0.006	MVD
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	158.6×	0.015	MVD
Synthesis of substrates in N-glycan biosythesis	1	146.4×	0.015	MVD
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	103.8×	0.018	MVD
Metabolism of steroids	1	68.8×	0.024	MVD
Asparagine N-linked glycosylation	1	30.1×	0.048	MVD
Metabolism of lipids	1	15.8×	0.081	MVD
Post-translational protein modification	1	9.6×	0.120	MVD
Metabolism of proteins	1	6.2×	0.165	MVD
Metabolism	1	5.8×	0.165	MVD

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	MVD, PMVK
cholesterol biosynthetic process	2	421.3×	2e-05	MVD, PMVK
isoprenoid biosynthetic process	1	842.6×	0.001	MVD
sterol biosynthetic process	1	842.6×	0.001	PMVK
response to cholesterol	1	842.6×	0.001	PMVK
positive regulation of cell population proliferation	1	16.8×	0.059	MVD

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MVD	0	0
PMVK	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
MVD	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MVD	4.1.1.33	diphosphomevalonate decarboxylase
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	MVD, 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)
MVD	3	—
PMVK	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.