Porokeratosis 7, multiple types

Summary

Porokeratosis 7, multiple types (MONDO:0013868) is a disease caused by MVD (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: MVD (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	porokeratosis 7, multiple types
Mondo ID	MONDO:0013868
OMIM	614714
UMLS	C3553549
MedGen	766463
GARD	0015838
Is cancer (heuristic)	no

Also known as: POROK7 · porokeratosis 7, disseminated superficial actinic type · porokeratosis 7, multiple types

Data availability: 13 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › keratosis › porokeratosis › disseminated superficial actinic porokeratosis › porokeratosis 7, multiple types

Related subtypes (6): porokeratosis 3, disseminated superficial actinic type, porokeratosis 4, disseminated superficial actinic type, porokeratosis 5, disseminated superficial actinic type, porokeratosis 6, disseminated superficial actinic type, porokeratosis 8, disseminated superficial actinic type, porokeratosis 9, multiple types

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

13 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 4 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1301637	NM_002461.3(MVD):c.141+1del	MVD	Pathogenic	criteria provided, single submitter
1323302	NM_002461.3(MVD):c.1013+1G>T	MVD	Pathogenic	criteria provided, single submitter
253039	NM_002461.3(MVD):c.746T>C (p.Phe249Ser)	MVD	Pathogenic	criteria provided, multiple submitters, no conflicts
253040	NM_002461.3(MVD):c.875A>G (p.Asn292Ser)	MVD	Pathogenic	criteria provided, single submitter
3779982	NM_002461.3(MVD):c.1014-1G>T	MVD	Likely pathogenic	criteria provided, single submitter
1344813	NM_002461.3(MVD):c.70+5G>A	LOC130059740	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2358332	NM_002461.3(MVD):c.688G>A (p.Glu230Lys)	MVD	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3891765	NM_002461.3(MVD):c.2T>G (p.Met1Arg)	LOC130059740	Uncertain significance	criteria provided, single submitter
1342402	NM_002461.3(MVD):c.1013+5G>T	MVD	Uncertain significance	criteria provided, single submitter
3891764	NM_002461.3(MVD):c.233G>A (p.Arg78Gln)	MVD	Uncertain significance	criteria provided, single submitter
4279894	NM_002461.3(MVD):c.1092del (p.Gly365fs)	MVD	Uncertain significance	criteria provided, single submitter
638465	NM_002461.3(MVD):c.128T>C (p.Leu43Pro)	MVD	Uncertain significance	criteria provided, single submitter
1321178	NM_002461.3(MVD):c.232C>A (p.Arg78=)	MVD	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
MVD	Strong	Autosomal dominant	porokeratosis 7, multiple types	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MVD	Orphanet:79152	Disseminated superficial actinic porokeratosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MVD	HGNC:7529	ENSG00000167508	P53602	Diphosphomevalonate decarboxylase	gencc,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).

Protein-family classification

Druggable: 1 · 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	27.7×	0.036

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

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MVD	1,189

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MVD	P53602	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of dolichyl-phosphate	1	1631.4×	0.006	MVD
Cholesterol biosynthesis	1	1142.0×	0.006	MVD
Lanosterol biosynthesis	1	761.3×	0.006	MVD
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	317.2×	0.008	MVD
Synthesis of substrates in N-glycan biosythesis	1	292.8×	0.008	MVD
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.008	MVD
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	207.6×	0.009	MVD
Metabolism of steroids	1	137.6×	0.012	MVD
Asparagine N-linked glycosylation	1	60.1×	0.024	MVD
Metabolism of lipids	1	31.6×	0.041	MVD
Post-translational protein modification	1	19.2×	0.062	MVD
Metabolism of proteins	1	12.4×	0.086	MVD
Metabolism	1	11.6×	0.086	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 1 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	1	5617.3×	7e-04	MVD
isoprenoid biosynthetic process	1	1685.2×	0.001	MVD
cholesterol biosynthetic process	1	421.3×	0.003	MVD
positive regulation of cell population proliferation	1	33.6×	0.030	MVD

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	MVD
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MVD	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.