Disseminated superficial actinic porokeratosis

Summary

Disseminated superficial actinic porokeratosis (MONDO:0019212) is a disease (an umbrella term covering 7 Mondo subtypes) with 5 cohort genes. The dominant Reactome pathway is Lanosterol biosynthesis (3 cohort genes).

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 5
• ClinVar variants: 1
• Phenotypes (HPO): 4

Clinical features

Signs & symptoms

Clinical features (HPO)

4 HPO clinical features (Orphanet curated; top 4 by frequency):

HPO ID	Term	Frequency
HP:0200044	Porokeratosis	Very frequent (80-99%)
HP:0000992	Cutaneous photosensitivity	Frequent (30-79%)
HP:0000989	Pruritus	Occasional (5-29%)
HP:0002860	Squamous cell carcinoma	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	disseminated superficial actinic porokeratosis
Mondo ID	MONDO:0019212
Orphanet	79152
ICD-10-CM	L56.5
ICD-11	1828294192
SNOMED CT	41495000
UMLS	C0265970
MedGen	120561
GARD	0010983
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant · 5 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (3): porokeratosis plantaris palmaris et disseminata, porokeratosis of Mibelli, linear porokeratosis

Subtypes (7): 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, 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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
3780611	NM_022082.4(SLC17A9):c.1118-2A>G	SLC17A9	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 7 · 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
FDPS	Strong	Autosomal dominant	porokeratosis 9, multiple types	5
MVD	Strong	Autosomal dominant	porokeratosis 7, multiple types	5
SART3	Moderate	Autosomal dominant	disseminated superficial actinic porokeratosis	3
SLC17A9	Supportive	Autosomal dominant	disseminated superficial actinic porokeratosis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC17A9	Orphanet:79152	Disseminated superficial actinic porokeratosis
FDPS	Orphanet:79152	Disseminated superficial actinic porokeratosis
MVD	Orphanet:79152	Disseminated superficial actinic porokeratosis
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

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC17A9	HGNC:16192	ENSG00000101194	Q9BYT1	Voltage-gated purine nucleotide uniporter SLC17A9	gencc,clinvar
SART3	HGNC:16860	ENSG00000075856	Q15020	Spliceosome associated factor 3, U4/U6 recycling protein	gencc
FDPS	HGNC:3631	ENSG00000160752	P14324	Farnesyl pyrophosphate synthase	gencc
MVD	HGNC:7529	ENSG00000167508	P53602	Diphosphomevalonate decarboxylase	gencc
MVK	HGNC:7530	ENSG00000110921	Q03426	Mevalonate kinase	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC17A9	Voltage-gated purine nucleotide uniporter SLC17A9	Voltage-gated ATP nucleotide uniporter that can also transport the purine nucleotides ADP and GTP.
SART3	Spliceosome associated factor 3, U4/U6 recycling protein	U6 snRNP-binding protein that functions as a recycling factor of the splicing machinery.
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.
MVD	Diphosphomevalonate decarboxylase	Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP).
MVK	Mevalonate kinase	Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.8

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	2	11.1×	0.048
Transporter	1	15.6×	0.125
Enzyme (other)	1	2.4×	0.471
Other/Unknown	1	0.4×	0.983

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC17A9	Transporter	yes		Sugar_transporter_CS, MFS, MFS_dom
SART3	Other/Unknown	no		RRM_dom, HAT, LSM_interact
FDPS	Enzyme (other)	yes	2.5.1.1	Polyprenyl_synt, Isoprenoid_synthase_dom_sf, Polyprenyl_synt_CS
MVD	Kinase	yes	4.1.1.33	Mev_decarb, Ribsml_uS5_D2-typ_fold_subgr, Ribosomal_Su5_D2-typ_SF
MVK	Kinase	yes	2.7.1.36	GHMP_knse_ATP-bd_CS, GHMP_kinase_N_dom, Mev_gal_kin

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lobe of liver	2
liver	1
stromal cell of endometrium	1
endothelial cell	1
secondary oocyte	1
tendon of biceps brachii	1
adrenal tissue	1
mucosa of transverse colon	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
lower esophagus mucosa	1
metanephros cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC17A9	194	ubiquitous	marker	right lobe of liver, liver, stromal cell of endometrium
SART3	296	ubiquitous	marker	endothelial cell, secondary oocyte, tendon of biceps brachii
FDPS	294	ubiquitous	marker	adrenal tissue, ventricular zone, mucosa of transverse colon
MVD	189	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
MVK	271	ubiquitous	marker	lower esophagus mucosa, right lobe of liver, metanephros cortex

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MVK	3,424
SART3	3,318
FDPS	2,771
MVD	1,189
SLC17A9	912

Intra-cohort edges

A	B	Sources
FDPS	MVD	string_interaction
FDPS	MVK	string_interaction
MVD	MVK	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FDPS	P14324	92
SART3	Q15020	9
MVD	P53602	1
MVK	Q03426	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC17A9	Q9BYT1	89.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 5 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Lanosterol biosynthesis	3	761.3×	2e-08	FDPS, MVD, MVK
Activation of gene expression by SREBF (SREBP)	3	259.6×	3e-07	FDPS, MVD, MVK
Cholesterol biosynthesis	2	761.3×	9e-06	MVD, MVK
Regulation of cholesterol biosynthesis by SREBP (SREBF)	2	211.5×	9e-05	MVD, MVK
Metabolism of steroids	2	91.7×	4e-04	MVD, MVK
Synthesis of dolichyl-phosphate	1	543.8×	0.004	MVD
Metabolism of lipids	2	21.0×	0.005	MVD, MVK
Synthesis of substrates in N-glycan biosythesis	1	97.6×	0.017	MVD
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1	69.2×	0.021	MVD
Metabolism	2	7.7×	0.027	MVD, MVK
Asparagine N-linked glycosylation	1	20.0×	0.058	MVD
Post-translational protein modification	1	6.4×	0.161	MVD
Metabolism of proteins	1	4.1×	0.223	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 5 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	2246.9×	2e-06	MVD, MVK
cholesterol biosynthetic process	3	252.8×	2e-06	FDPS, MVD, MVK
isoprenoid biosynthetic process	2	674.1×	2e-05	MVD, MVK
purine nucleotide import into lysosome	1	3370.4×	0.001	SLC17A9
guanine nucleotide transmembrane transport	1	3370.4×	0.001	SLC17A9
geranyl diphosphate biosynthetic process	1	1685.2×	0.002	FDPS
trans, trans-farnesyl diphosphate biosynthetic process	1	1685.2×	0.002	FDPS
regulation of RNA metabolic process	1	561.7×	0.005	SART3
ADP transport	1	421.3×	0.005	SLC17A9
transcription elongation-coupled chromatin remodeling	1	421.3×	0.005	SART3
ATP export	1	337.0×	0.006	SLC17A9
ATP transport	1	280.9×	0.007	SLC17A9
spliceosomal tri-snRNP complex assembly	1	224.7×	0.008	SART3
lysosomal protein catabolic process	1	210.7×	0.008	SLC17A9
homeostasis of number of cells	1	134.8×	0.011	SART3
hematopoietic stem cell proliferation	1	129.6×	0.011	SART3
spliceosomal snRNP assembly	1	116.2×	0.012	SART3
cell morphogenesis	1	31.5×	0.040	SART3
nucleosome assembly	1	28.1×	0.041	SART3
negative regulation of inflammatory response	1	27.4×	0.041	MVK
mRNA splicing, via spliceosome	1	18.3×	0.059	SART3
regulation of gene expression	1	16.7×	0.061	SART3
positive regulation of cell population proliferation	1	6.7×	0.140	MVD

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
SLC17A9	0	0
SART3	0	0
MVD	0	0
MVK	0	0

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): 3.

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

Symbol	Assays	Type breakdown
FDPS	182	Binding:177, ADMET:3, Functional:2
MVD	3	Binding:3
SART3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FDPS	2.5.1.1, 2.5.1.10	dimethylallyltranstransferase, (2E,6E)-farnesyl diphosphate synthase
MVD	4.1.1.33	diphosphomevalonate decarboxylase
MVK	2.7.1.36	mevalonate kinase

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: 5; 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	2	MVD, MVK
D	Druggable family + AlphaFold only, no drug	1	SLC17A9
E	Difficult family or no structure, no drug	1	SART3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MVD	3	FDPS
MVK	0	FDPS
SLC17A9	0	—
SART3	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.