Cutaneous polyarteritis nodosa

Summary

Cutaneous polyarteritis nodosa (MONDO:0018592) is a disease with 1 cohort gene and 2 clinical trials. Top therapeutic interventions include azathioprine, colchicine, and dapsone.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cutaneous polyarteritis nodosa
Mondo ID	MONDO:0018592
Orphanet	439729
ICD-11	1752423171
NCIT	C117295
SNOMED CT	239926000
UMLS	C0343190
MedGen	83358
GARD	0007415
Is cancer (heuristic)	no

Also known as: cutaneous PAN · cutaneous periarteritis nodosa

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › arteritis › polyarteritis nodosa › primary polyarteritis nodosa › cutaneous polyarteritis nodosa

Related subtypes (2): single-organ polyarteritis nodosa, systemic polyarteritis nodosa

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
180526	NM_005902.4(SMAD3):c.1129G>A (p.Val377Ile)	SMAD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMAD3	Orphanet:284984	Aneurysm-osteoarthritis syndrome
SMAD3	Orphanet:60030	Loeys-Dietz syndrome
SMAD3	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

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
SMAD3	HGNC:6769	ENSG00000166949	P84022	SMAD family member 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMAD3	SMAD family member 3	Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SMAD3	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_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
cartilage tissue	1
hindlimb stylopod muscle	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMAD3	288	ubiquitous	marker	tendon of biceps brachii, cartilage tissue, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMAD3	6,440

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMAD3	P84022	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 54. 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
Loss of Function of SMAD4 in Cancer	1	3806.7×	0.003	SMAD3
SMAD4 MH2 Domain Mutants in Cancer	1	3806.7×	0.003	SMAD3
SMAD2/3 MH2 Domain Mutants in Cancer	1	3806.7×	0.003	SMAD3
Loss of Function of TGFBR1 in Cancer	1	2284.0×	0.003	SMAD3
RUNX3 regulates BCL2L11 (BIM) transcription	1	2284.0×	0.003	SMAD3
Loss of Function of SMAD2/3 in Cancer	1	1903.3×	0.003	SMAD3
Signaling by TGF-beta Receptor Complex in Cancer	1	1903.3×	0.003	SMAD3
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	1903.3×	0.003	SMAD3
TGFBR1 KD Mutants in Cancer	1	1903.3×	0.003	SMAD3
RUNX3 regulates CDKN1A transcription	1	1631.4×	0.003	SMAD3
Formation of axial mesoderm	1	815.7×	0.005	SMAD3
Signaling by Activin	1	761.3×	0.005	SMAD3
Formation of definitive endoderm	1	713.8×	0.005	SMAD3
FOXO-mediated transcription of cell cycle genes	1	671.8×	0.005	SMAD3
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	671.8×	0.005	SMAD3
Germ layer formation at gastrulation	1	671.8×	0.005	SMAD3
NOTCH4 Intracellular Domain Regulates Transcription	1	571.0×	0.005	SMAD3
Interleukin-37 signaling	1	519.1×	0.005	SMAD3
Signaling by NODAL	1	496.5×	0.005	SMAD3
Signaling by NOTCH4	1	496.5×	0.005	SMAD3
TGFBR3 expression	1	456.8×	0.006	SMAD3
Downregulation of TGF-beta receptor signaling	1	407.9×	0.006	SMAD3
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	380.7×	0.006	SMAD3
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	368.4×	0.006	SMAD3
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	368.4×	0.006	SMAD3
Signaling by TGFBR3	1	368.4×	0.006	SMAD3
FOXO-mediated transcription	1	335.9×	0.006	SMAD3
TGF-beta receptor signaling activates SMADs	1	326.3×	0.006	SMAD3
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	308.6×	0.006	SMAD3
Interleukin-1 family signaling	1	271.9×	0.006	SMAD3

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
negative regulation of lung blood pressure	1	16852.0×	0.003	SMAD3
regulation of miRNA transcription	1	16852.0×	0.003	SMAD3
positive regulation of transforming growth factor beta3 production	1	8426.0×	0.004	SMAD3
paraxial mesoderm morphogenesis	1	5617.3×	0.004	SMAD3
immune system development	1	4213.0×	0.004	SMAD3
regulation of transforming growth factor beta2 production	1	4213.0×	0.004	SMAD3
regulation of striated muscle tissue development	1	2808.7×	0.004	SMAD3
trophoblast cell migration	1	2407.4×	0.004	SMAD3
transdifferentiation	1	2106.5×	0.004	SMAD3
pericardium development	1	1872.4×	0.004	SMAD3
positive regulation of extracellular matrix assembly	1	1872.4×	0.004	SMAD3
negative regulation of cardiac muscle hypertrophy in response to stress	1	1872.4×	0.004	SMAD3
response to angiotensin	1	1872.4×	0.004	SMAD3
embryonic foregut morphogenesis	1	1685.2×	0.004	SMAD3
negative regulation of osteoblast proliferation	1	1532.0×	0.004	SMAD3
response to alcohol	1	1532.0×	0.004	SMAD3
positive regulation of positive chemotaxis	1	1404.3×	0.004	SMAD3
primary miRNA processing	1	1296.3×	0.004	SMAD3
negative regulation of cytosolic calcium ion concentration	1	1296.3×	0.004	SMAD3
negative regulation of wound healing	1	1296.3×	0.004	SMAD3
nodal signaling pathway	1	1123.5×	0.004	SMAD3
lens fiber cell differentiation	1	1053.2×	0.004	SMAD3
osteoblast development	1	991.3×	0.004	SMAD3
regulation of epithelial cell proliferation	1	936.2×	0.004	SMAD3
activin receptor signaling pathway	1	887.0×	0.004	SMAD3
regulation of dendritic spine morphogenesis	1	842.6×	0.004	SMAD3
regulation of transforming growth factor beta receptor signaling pathway	1	802.5×	0.004	SMAD3
positive regulation of chondrocyte differentiation	1	802.5×	0.004	SMAD3
developmental growth	1	732.7×	0.004	SMAD3
SMAD protein signal transduction	1	732.7×	0.004	SMAD3

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
SMAD3	FLUORESCEIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMAD3	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUORESCEIN	4	SMAD3
ELLAGIC ACID	2	SMAD3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMAD3	24	Binding:18, Functional:6

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

2 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)
FLUORESCEIN	4	SMAD3
ELLAGIC ACID	2	SMAD3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SMAD3
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: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02939573	PHASE2	RECRUITING	A Randomized Multicenter Study for Isolated Skin Vasculitis
NCT05168475	PHASE2	TERMINATED	Biologics in Refractory Vasculitis: A Trial of Biologic Therapy for Refractory Primary Non-ANCA Associated Vasculitis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AZATHIOPRINE	4	1
COLCHICINE	4	1
DAPSONE	4	1