Porokeratosis 9, multiple types

Summary

Porokeratosis 9, multiple types (MONDO:0014713) is a disease caused by FDPS (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FDPS (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	porokeratosis 9, multiple types
Mondo ID	MONDO:0014713
OMIM	616631
UMLS	C4225262
MedGen	894586
GARD	0016146
Is cancer (heuristic)	no

Also known as: FDPS porokeratosis (disease) · POROK9 · porokeratosis (disease) caused by mutation in FDPS · porokeratosis 9, multiple types · porokeratosis 9, multiple types; POROK9

Data availability: 3 ClinVar variants · 4 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 9, 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 7, multiple types, porokeratosis 8, 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

ClinVar germline variants

3 retrieved; paginated sample, class counts are floors:

3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
217746	NM_002004.4(FDPS):c.536G>A (p.Arg179Gln)	FDPS	Pathogenic	no assertion criteria provided
217747	NM_002004.4(FDPS):c.481-1776_847-143del	FDPS	Pathogenic	no assertion criteria provided
217748	NM_002004.4(FDPS):c.684+1G>A	FDPS	Pathogenic	no assertion criteria provided

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
FDPS	Strong	Autosomal dominant	porokeratosis 9, multiple types	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FDPS	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
FDPS	HGNC:3631	ENSG00000160752	P14324	Farnesyl pyrophosphate synthase	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FDPS	Farnesyl pyrophosphate synthase	Key enzyme in isoprenoid biosynthesis which catalyzes the formation of farnesyl diphosphate (FPP), a precursor for several classes of essential metabolites including sterols, dolichols, carotenoids, and ubiquinones.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FDPS	Enzyme (other)	yes	2.5.1.1	Polyprenyl_synt, Isoprenoid_synthase_dom_sf, Polyprenyl_synt_CS

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
adrenal tissue	1
mucosa of transverse colon	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FDPS	294	ubiquitous	marker	adrenal tissue, ventricular zone, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FDPS	2,771

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FDPS	P14324	92

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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
Lanosterol biosynthesis	1	761.3×	0.003	FDPS
Activation of gene expression by SREBF (SREBP)	1	259.6×	0.004	FDPS

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
geranyl diphosphate biosynthetic process	1	8426.0×	2e-04	FDPS
trans, trans-farnesyl diphosphate biosynthetic process	1	8426.0×	2e-04	FDPS
cholesterol biosynthetic process	1	421.3×	0.002	FDPS

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
FDPS	MINODRONIC ACID

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FDPS	12	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MINODRONIC ACID	4	FDPS
ZOLEDRONIC ACID	4	FDPS
ALENDRONATE SODIUM	4	FDPS
PAMIDRONIC ACID	4	FDPS
ALENDRONIC ACID	4	FDPS
RISEDRONIC ACID	4	FDPS
ZOLEDRONIC ACID ANHYDROUS	4	FDPS
IBANDRONIC ACID	4	FDPS
NERIDRONIC ACID	3	FDPS
PYROPHOSPHORIC ACID	2	FDPS
INCADRONIC ACID	2	FDPS
PIRIDRONIC ACID	2	FDPS

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FDPS	182	Binding:177, ADMET:3, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FDPS	2.5.1.1, 2.5.1.10	dimethylallyltranstransferase, (2E,6E)-farnesyl diphosphate synthase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
FDPS	182

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

12 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.

Compound	Max phase	Cohort target (bioactivity)
MINODRONIC ACID	4	FDPS
ZOLEDRONIC ACID	4	FDPS
ALENDRONATE SODIUM	4	FDPS
PAMIDRONIC ACID	4	FDPS
ALENDRONIC ACID	4	FDPS
RISEDRONIC ACID	4	FDPS
ZOLEDRONIC ACID ANHYDROUS	4	FDPS
IBANDRONIC ACID	4	FDPS
NERIDRONIC ACID	3	FDPS
PYROPHOSPHORIC ACID	2	FDPS
INCADRONIC ACID	2	FDPS
PIRIDRONIC ACID	2	FDPS

Druggability pyramid

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

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

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.