Polyarteritis nodosa

Summary

Polyarteritis nodosa (MONDO:0019170) is a disease with 1 cohort gene (9 GWAS associations across 7 studies) and 22 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, azathioprine, and methotrexate.

At a glance

• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• GWAS associations: 9
• ClinVar variants: 1
• Phenotypes (HPO): 28
• Clinical trials: 22

Clinical features

Epidemiology

Prevalence records

9 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	3.16	Europe	Validated
Annual incidence	1-9 / 1 000 000	0.11	Australia	Validated
Annual incidence	1-9 / 1 000 000	0.62	Spain	Validated
Annual incidence	<1 / 1 000 000	0.04	Germany	Validated
Point prevalence	1-9 / 100 000	3.1	Sweden	Validated
Point prevalence	1-9 / 100 000	3.07	France	Validated
Point prevalence	1-9 / 100 000	3.3	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.9	United Kingdom	Not yet validated
Annual incidence	<1 / 1 000 000	0.05	Norway	Not yet validated

Signs & symptoms

Clinical features (HPO)

28 HPO clinical features (Orphanet curated; top 28 by frequency):

HPO ID	Term	Frequency
HP:0011121	Abnormal skin morphology	Very frequent (80-99%)
HP:0000077	Abnormality of the kidney	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002829	Arthralgia	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0005764	Polyarticular arthritis	Frequent (30-79%)
HP:0009830	Peripheral neuropathy	Frequent (30-79%)
HP:0011227	Elevated circulating C-reactive protein concentration	Frequent (30-79%)
HP:0031003	Polyneuritis	Frequent (30-79%)
HP:0033260	Livedo racemosa	Frequent (30-79%)
HP:0000707	Abnormality of the nervous system	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0000965	Cutis marmorata	Occasional (5-29%)
HP:0001482	Subcutaneous nodule	Occasional (5-29%)
HP:0001701	Pericarditis	Occasional (5-29%)
HP:0002011	Morphological central nervous system abnormality	Occasional (5-29%)
HP:0002027	Abdominal pain	Occasional (5-29%)
HP:0002088	Abnormal lung morphology	Occasional (5-29%)
HP:0003390	Sensory axonal neuropathy	Occasional (5-29%)
HP:0010783	Erythema	Occasional (5-29%)
HP:0011024	Abnormality of the gastrointestinal tract	Occasional (5-29%)
HP:0030680	Abnormal cardiovascular system morphology	Occasional (5-29%)
HP:0030880	Raynaud phenomenon	Occasional (5-29%)
HP:0200042	Skin ulcer	Occasional (5-29%)
HP:0000478	Abnormality of the eye	Very rare (<1-4%)
HP:0001638	Cardiomyopathy	Very rare (<1-4%)
HP:0002102	Pleuritis	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	polyarteritis nodosa
Mondo ID	MONDO:0019170
MeSH	D010488
Orphanet	767
DOID	DOID:9810
ICD-10-CM	M30.0
ICD-11	1419332129
NCIT	C26847
SNOMED CT	155441006
UMLS	C0031036
MedGen	14681
GARD	0007360
MedDRA	10036024
NORD	1588
Is cancer (heuristic)	no

Also known as: classic polyarteritis nodosa · classical polyarteritis nodosa · Küssmaul-Maier disease · PAN · panarteritis nodosa · periarteritis · periarteritis nodosa · polyarteritis · polyarteritis nodosa

Data availability: 1 ClinVar variant · 9 GWAS associations (7 studies) · 1 GenCC gene-disease record · 12 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

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

Related subtypes (6): cerebral arteritis, granulomatous angiitis, juvenile temporal arteritis, Takayasu arteritis, microscopic polyangiitis, endarteritis

Subtypes (2): primary polyarteritis nodosa, secondary polyarteritis nodosa

Genetics & variants

GWAS landscape

9 GWAS associations across 7 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs561877564	6e-14	Y_RNA - DPY19L4	T	3.13
rs552784808	2e-12	TRPC1	G	3.32
rs535102440	2e-12	C5orf67 - MAP3K1	G	3.26
rs574444037	6e-12	LINC02725	T	2.3
rs546028699	8e-12	RNU6-983P - LINC01724	C	2.31
rs561179602	1e-11	LINC01798	A	2.1
rs887106336	2e-11	EHD3 - RPL21P70	C	3.63
rs144374102	3e-11	LINC01539, LINC01905	G	1.23
rs118182813	5e-08	PRB4 - PRB1	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90478028	Verma A	2024	2,132	447,316	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436166	Zhou W	2018	828	400,595	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90651709	Liu TY	2025	784	228,546	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90480213	Verma A	2024	443	121,040	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482041	Verma A	2024	443	121,040	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90482040	Verma A	2024	233	59,496	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90474050	UK Biobank Whole-Genome Sequencing Consortium	2025	213	458,227	Whole-genome sequencing of 490,640 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	9

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	8
unknown	1

Functional consequences

Consequence	Count
intron_variant	6
intergenic_variant	3

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs561877564	8	94715527	T>C	0.001	intergenic_variant	Y_RNA - DPY19L4	6e-14	Tier 4: intronic/intergenic
rs552784808	3	142735857	G>C	0	intron_variant	TRPC1	2e-12	Tier 4: intronic/intergenic
rs535102440	5	56675768	G>A,T	0	intron_variant	C5orf67 - MAP3K1	2e-12	Tier 4: intronic/intergenic
rs574444037	11	128138423	T>C	0.003	intron_variant	LINC02725	6e-12	Tier 4: intronic/intergenic
rs546028699	1	194998811	C>T	0.001	intergenic_variant	RNU6-983P - LINC01724	8e-12	Tier 4: intronic/intergenic
rs561179602	2	66985476	A>T	0.001	intron_variant	LINC01798	1e-11	Tier 4: intronic/intergenic
rs887106336	2	31281363	C>T	0	intron_variant	EHD3 - RPL21P70	2e-11	Tier 4: intronic/intergenic
rs144374102	18	56126774	G>A,C	0.003	intron_variant	LINC01539, LINC01905	3e-11	Tier 4: intronic/intergenic
rs118182813	12	11340707	A>G		intergenic_variant	PRB4 - PRB1	5e-08	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
973523	NM_001282225.2(ADA2):c.-46-108_542+142del	ADA2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
ADA2	Moderate	Autosomal recessive	polyarteritis nodosa	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ADA2	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:404553	Deficiency of adenosine deaminase 2
ADA2	Orphanet:820	Sneddon syndrome

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
ADA2	HGNC:1839	ENSG00000093072	Q9NZK5	Adenosine deaminase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ADA2	Adenosine deaminase 2	Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.

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)
ADA2	Enzyme (other)	yes	3.5.4.4	A_deaminase_dom, Ado/ade_deaminase, ADGF

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
leukocyte	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADA2	254	ubiquitous	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADA2	1,808

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ADA2	Q9NZK5	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
Surfactant metabolism	1	368.4×	0.014	ADA2
Innate Immune System	1	25.5×	0.072	ADA2
Neutrophil degranulation	1	23.1×	0.072	ADA2
Immune System	1	13.0×	0.081	ADA2
Metabolism of proteins	1	12.4×	0.081	ADA2

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
inosine biosynthetic process	1	5617.3×	2e-04	ADA2
adenosine catabolic process	1	4213.0×	2e-04	ADA2

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ADA2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ADA2	3.5.4.4	adenosine deaminase

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	ADA2
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)
ADA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 22.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	15
PHASE2	4
PHASE4	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00307671	PHASE4	COMPLETED	Treatment of Necrotizing Vasculitides for Patients Older Than 65 Years
NCT00400075	PHASE4	UNKNOWN	CHUSPAN PAN BP Treatment of Polyarteritis Nodosa and Microscopic Polyangiitis Without Poor-Prognosis Factors
NCT00647166	PHASE3	COMPLETED	Association Corticosteroid/Azathioprine in Microscopic Polyangiitis/ Polyarteritis Nodosa or Eosinophilic Granulomatosis With Polyangiitis (Churg Strauss Syndrome)
NCT00001457	PHASE2	COMPLETED	Lamivudine for Chronic Hepatitis B
NCT00751517	PHASE2	UNKNOWN	Cyclophosphamide Versus Methotrexate for Remission Maintenance in Systemic Necrotizing Vasculitides
NCT03482479	PHASE2	COMPLETED	Low Dose Naltrexone to Improve Physical Health in Patients With Vasculitis
NCT05168475	PHASE2	TERMINATED	Biologics in Refractory Vasculitis: A Trial of Biologic Therapy for Refractory Primary Non-ANCA Associated Vasculitis
NCT01241305	Not specified	RECRUITING	One-Time DNA Study for Vasculitis
NCT02257866	Not specified	RECRUITING	Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
NCT02593565	Not specified	RECRUITING	Vasculitis Pregnancy Registry
NCT02967068	Not specified	RECRUITING	VCRC Tissue Repository
NCT03004326	Not specified	RECRUITING	Clinical Transcriptomics in Systemic Vasculitis (CUTIS)
NCT00006055	Not specified	UNKNOWN	Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases
NCT00315406	Not specified	COMPLETED	Determining Disease Activity Biomarkers in Individuals With Polyarteritis Nodosa
NCT01066208	Not specified	UNKNOWN	American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Diagnostic and Classification Criteria for Primary Systemic Vasculitis
NCT02006134	Not specified	UNKNOWN	Pediatric Vasculitis Initiative
NCT02176070	Not specified	COMPLETED	Reproductive Health in Men and Women With Vasculitis
NCT02190916	Not specified	COMPLETED	Vasculitis Illness Perception (VIP) Study
NCT02190929	Not specified	COMPLETED	Educational Needs of Patients With Systemic Vasculitis
NCT02190942	Not specified	COMPLETED	VCRC Patient Contact Registry Patient-Reported Data Validation Study
NCT02476292	Not specified	COMPLETED	Impact of Vasculitis on Employment and Income
NCT03410290	Not specified	COMPLETED	Journey of Patients With Vasculitis From First Symptom to Diagnosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	7
AZATHIOPRINE	4	3
METHOTREXATE	4	1
METHYLPREDNISOLONE	4	1
MYCOPHENOLATE MOFETIL	4	1
PREDNISONE	4	1
CHEMBL15720	0	1
CHEMBL426	0	1