Granulomatosis with polyangiitis

disease

On this page

Also known as ANCA-associated vasculitisGPAgranulomatosis - Wegener'sMidline granulomatosisnecrotizing respiratory granulomatosispauci-immune glomerulonephritis associated with granulomatosis with polyangiitisWegener granulomatosisWegener's granulomatosisWegener's syndromeWg

Summary

Granulomatosis with polyangiitis (MONDO:0012105) is a disease with 12 cohort genes (6 GWAS associations across 5 studies) and 157 clinical trials. Top therapeutic interventions include cyclophosphamide anhydrous, azathioprine, and rituximab.

At a glance

Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
Cohort genes: 12
GWAS associations: 6
Phenotypes (HPO): 80
Clinical trials: 157

Clinical features

Epidemiology

Prevalence records

25 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.85	Europe	Validated
Point prevalence	1-9 / 100 000	9	Europe	Validated
Annual incidence	1-9 / 100 000	1	United Kingdom	Validated
Annual incidence	1-9 / 1 000 000	0.86	Germany	Validated
Annual incidence	1-9 / 100 000	1.19	Sweden	Validated
Annual incidence	1-9 / 1 000 000	0.49	Spain	Validated
Annual incidence	1-9 / 100 000	1	Norway	Validated
Annual incidence	1-9 / 1 000 000	0.93	Finland	Validated
Annual incidence	1-9 / 1 000 000	0.21	Lithuania	Validated
Annual incidence	1-9 / 1 000 000	0.66	Greece	Validated
Annual incidence	1-9 / 1 000 000	0.24	Italy	Validated
Annual incidence	1-9 / 1 000 000	0.46	Canada	Validated
Annual incidence	1-9 / 1 000 000	0.21	Japan	Validated
Annual incidence	<1 / 1 000 000	0.037	Taiwan, Province of China	Validated
Annual incidence	1-9 / 100 000	1.3	United States	Validated
Point prevalence	1-5 / 10 000	16	Sweden	Validated
Point prevalence	1-9 / 100 000	2.37	France	Validated
Point prevalence	1-9 / 100 000	9.51	Norway	Validated
Point prevalence	1-9 / 100 000	9.5	Australia	Validated
Point prevalence	1-9 / 100 000	9.35	New Zealand	Validated

Signs & symptoms

Clinical features (HPO)

80 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000163	Abnormal oral cavity morphology	Very frequent (80-99%)
HP:0000246	Sinusitis	Very frequent (80-99%)
HP:0000366	Abnormality of the nose	Very frequent (80-99%)
HP:0000388	Otitis media	Very frequent (80-99%)
HP:0000421	Epistaxis	Very frequent (80-99%)
HP:0000790	Hematuria	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002113	Pulmonary infiltrates	Very frequent (80-99%)
HP:0002205	Recurrent respiratory infections	Very frequent (80-99%)
HP:0002633	Vasculitis	Very frequent (80-99%)
HP:0002637	Cerebral ischemia	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0002955	Granulomatosis	Very frequent (80-99%)
HP:0002960	Autoimmunity	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0100820	Glomerulopathy	Very frequent (80-99%)
HP:0000093	Proteinuria	Frequent (30-79%)
HP:0000099	Glomerulonephritis	Frequent (30-79%)
HP:0000579	Nasolacrimal duct obstruction	Frequent (30-79%)
HP:0000864	Abnormality of the hypothalamus-pituitary axis	Frequent (30-79%)
HP:0000988	Skin rash	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0002017	Nausea and vomiting	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002093	Respiratory insufficiency	Frequent (30-79%)
HP:0002105	Hemoptysis	Frequent (30-79%)
HP:0002206	Pulmonary fibrosis	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0005764	Polyarticular arthritis	Frequent (30-79%)
HP:0006510	Chronic pulmonary obstruction	Frequent (30-79%)
HP:0006535	Recurrent intrapulmonary hemorrhage	Frequent (30-79%)
HP:0009830	Peripheral neuropathy	Frequent (30-79%)
HP:0011227	Elevated circulating C-reactive protein concentration	Frequent (30-79%)
HP:0012649	Increased inflammatory response	Frequent (30-79%)
HP:0012735	Cough	Frequent (30-79%)
HP:0032230	Cytoplasmic antineutrophil antibody positivity	Frequent (30-79%)
HP:0033557	Anti-proteinase 3 antibody positivity	Frequent (30-79%)
HP:0033559	Anti-myeloperoxidase antibody positivity	Frequent (30-79%)
HP:0034104	Anti-neutrophil elastase antibody positivity	Frequent (30-79%)
HP:0100532	Scleritis	Frequent (30-79%)
HP:0100533	Inflammatory abnormality of the eye	Frequent (30-79%)
HP:0100539	Periorbital edema	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0200034	Papule	Frequent (30-79%)
HP:0000024	Prostatitis	Occasional (5-29%)
HP:0000071	Ureteral stenosis	Occasional (5-29%)
HP:0000083	Renal insufficiency	Occasional (5-29%)
HP:0000126	Hydronephrosis	Occasional (5-29%)
HP:0000389	Chronic otitis media	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	granulomatosis with polyangiitis
Mondo ID	MONDO:0012105
EFO	EFO:0005297
MeSH	D014890
OMIM	608710
Orphanet	900
DOID	DOID:12132
ICD-10-CM	M31.3
ICD-11	1020056159
NCIT	C123111, C3444
SNOMED CT	195353004
UMLS	C3495801
MedGen	811223
GARD	0007880
MedDRA	10047888
NORD	1840
Is cancer (heuristic)	no

Also known as: ANCA-associated vasculitis · GPA · granulomatosis - Wegener’s · granulomatosis with polyangiitis · Midline granulomatosis · necrotizing respiratory granulomatosis · pauci-immune glomerulonephritis associated with granulomatosis with polyangiitis · Wegener granulomatosis · Wegener’s granulomatosis · Wegener’s syndrome · Wg

Data availability: 6 GWAS associations (5 studies) · 13 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › urinary system disorder › kidney disorder › nephritis › glomerulonephritis › granulomatosis with polyangiitis

Subtypes (1): eosinophilic granulomatosis with polyangiitis

Genetics & variants

GWAS landscape

6 GWAS associations across 5 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9277554	2e-50	HLA-DPB1	C	4.17
rs26595	2e-08	COMMD10 - SEMA6A-AS1	T	1.35
rs595018	2e-07	MS4A10 - CCDC86-AS1	A	1.46
rs7503953	2e-07	RNU6-1264P - BTF3P14	A	1.5
rs1949829	4e-07	CICP17 - ROBO2P1	T	1.78
rs4862110	2e-06	TENM3 - DCTD	C	1.44

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002159	Xie G	2013	459	1,503	Association of granulomatosis with polyangiitis (Wegener’s) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis.
GCST002160	Xie G	2013	459	1,503	Association of granulomatosis with polyangiitis (Wegener’s) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis.
GCST90482042	Verma A	2024	243	451,162	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436167	Zhou W	2018	186	400,595	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST90044018	Jiang L	2021	135	456,213	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	6
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	3
intergenic_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9277554	6	33087761	C>G,T	0.292	3_prime_UTR_variant	HLA-DPB1	2e-50	Tier 2: splice/UTR
rs26595	5	116423793	G>A,C,T	0.44	intergenic_variant	COMMD10 - SEMA6A-AS1	2e-08	Tier 4: intronic/intergenic
rs595018	11	60824803	T>A,C,G	0.216	intron_variant	MS4A10 - CCDC86-AS1	2e-07	Tier 4: intronic/intergenic
rs7503953	17	6238357	A>C,T	0.171	intron_variant	RNU6-1264P - BTF3P14	2e-07	Tier 4: intronic/intergenic
rs1949829	7	51470190	C>T	0.055	intergenic_variant	CICP17 - ROBO2P1	4e-07	Tier 4: intronic/intergenic
rs4862110	4	182829876	T>A,C	0.174	intron_variant	TENM3 - DCTD	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
HLA-DPB1	HLA-DPB1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL11A2	Orphanet:1427	Autosomal recessive otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:166100	Autosomal dominant otospondylomegaepiphyseal dysplasia
COL11A2	Orphanet:2021	Fibrochondrogenesis
COL11A2	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A2	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
HLA-DPB1	Orphanet:133	Chronic beryllium disease
HLA-DPB1	Orphanet:900	Granulomatosis with polyangiitis

Cohort genes → proteins

12 cohort genes, 11 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	12

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RING1	HGNC:10018	ENSG00000204227	Q06587	E3 ubiquitin-protein ligase RING1	gwas
RXRB	HGNC:10478	ENSG00000204231	P28702	Retinoic acid receptor RXR-beta	gwas
SEMA6A	HGNC:10738	ENSG00000092421	Q9H2E6	Semaphorin-6A	gwas
COL11A2	HGNC:2187	ENSG00000204248	P13942	Collagen alpha-2(XI) chain	gwas
COBL	HGNC:22199	ENSG00000106078	O75128	Protein cordon-bleu	gwas
DCTD	HGNC:2710	ENSG00000129187	P32321	Deoxycytidylate deaminase	gwas
CCDC86	HGNC:28359	ENSG00000110104	Q9H6F5	Coiled-coil domain-containing protein 86	gwas
WSCD1	HGNC:29060	ENSG00000179314	Q658N2	Sialate:O-sulfotransferase 1	gwas
HSD17B8	HGNC:3554	ENSG00000204228	Q92506	(3R)-3-hydroxyacyl-CoA dehydrogenase	gwas
HLA-DOA	HGNC:4936	ENSG00000204252	P06340	HLA class II histocompatibility antigen, DO alpha chain	gwas
HLA-DPB1	HGNC:4940	ENSG00000223865	P04440	HLA class II histocompatibility antigen, DP beta 1 chain	gwas
HLA-DPB2	HGNC:4941	ENSG00000224557		major histocompatibility complex, class II, DP beta 2 (pseudogene)	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RING1	E3 ubiquitin-protein ligase RING1	Constitutes one of the E3 ubiquitin-protein ligases that mediate monoubiquitination of ‘Lys-119’ of histone H2A, thereby playing a central role in histone code and gene regulation.
RXRB	Retinoic acid receptor RXR-beta	Receptor for retinoic acid.
SEMA6A	Semaphorin-6A	Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling.
COL11A2	Collagen alpha-2(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
COBL	Protein cordon-bleu	Plays an important role in the reorganization of the actin cytoskeleton.
DCTD	Deoxycytidylate deaminase	Catalyzes the deamination of dCMP to dUMP, providing the nucleoside monophosphate substrate for the thymidylate synthase/TYMS.
CCDC86	Coiled-coil domain-containing protein 86	Required for proper chromosome segregation during mitosis and error-free mitotic progression.
WSCD1	Sialate:O-sulfotransferase 1	Sialate:O-sulfotransferase which catalyzes 8-O-sulfation at the Sia-glycan level using 3’-phosphoadenosine 5’-phosphosulfate (PAPS) as a donor, forming 8-O-sulfated Sia (Sia8S)-glycans.
HSD17B8	(3R)-3-hydroxyacyl-CoA dehydrogenase	Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS).
HLA-DOA	HLA class II histocompatibility antigen, DO alpha chain	Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells.
HLA-DPB1	HLA class II histocompatibility antigen, DP beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.

Protein-family classification

Druggable: 4 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.33

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
Nuclear receptor	1	32.2×	0.184
Antibody/Immunoglobulin	2	4.9×	0.185
Scaffold/PPI	1	1.4×	0.788
Enzyme (other)	1	1.0×	0.788
Other/Unknown	6	0.9×	0.788
Transcription factor	1	0.7×	0.788

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RING1	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
RXRB	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
SEMA6A	Scaffold/PPI	no		Semap_dom, Plexin_repeat, WD40/YVTN_repeat-like_dom_sf
COL11A2	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
COBL	Other/Unknown	no		WH2_dom, Cordon-bleu_ubiquitin_domain, COBL-like
DCTD	Other/Unknown	no		CMP_dCMP_dom, dCMP_deaminase-rel, APOBEC/CMP_deaminase_Zn-bd
CCDC86	Other/Unknown	no		CCDC86
WSCD1	Other/Unknown	no		Sulfotransferase_dom, WSC_carb-bd, P-loop_NTPase
HSD17B8	Enzyme (other)	yes	1.1.1.100	SDR_fam, Sc_DH/Rdtase_CS, NAD(P)-bd_dom_sf
HLA-DOA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB2	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

8 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)	12
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	4
inferior vagus X ganglion	3
lymph node	3
adenohypophysis	2
pituitary gland	2
right lobe of thyroid gland	2
lateral globus pallidus	2
male germ line stem cell (sensu Vertebrata) in testis	2
vermiform appendix	2
mucosa of stomach	1
adrenal tissue	1
parotid gland	1
left adrenal gland	1
right adrenal gland	1
stromal cell of endometrium	1
left testis	1
primordial germ cell in gonad	1
right testis	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RING1	133	ubiquitous	marker	pituitary gland, adenohypophysis, right lobe of thyroid gland
RXRB	134	ubiquitous	yes	right lobe of thyroid gland, granulocyte, mucosa of stomach
SEMA6A	266	ubiquitous	marker	inferior vagus X ganglion, adrenal tissue, lateral globus pallidus
COL11A2	134	broad	yes	pituitary gland, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis
COBL	255	broad	marker	inferior vagus X ganglion, parotid gland, lateral globus pallidus
DCTD	285	ubiquitous	marker	stromal cell of endometrium, right adrenal gland, left adrenal gland
CCDC86	277	ubiquitous	yes	left testis, right testis, primordial germ cell in gonad
WSCD1	207	broad	yes	ventricular zone, ganglionic eminence, inferior vagus X ganglion
HSD17B8	133	ubiquitous	marker	body of pancreas, right lobe of liver, right uterine tube
HLA-DOA	133	broad	marker	lymph node, vermiform appendix, granulocyte
HLA-DPB1	135	ubiquitous	marker	granulocyte, lymph node, vermiform appendix
HLA-DPB2	121	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, lymph node, granulocyte

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HSD17B8	3,680
RING1	2,846
COL11A2	1,583
COBL	1,439
SEMA6A	1,384
CCDC86	1,352
RXRB	1,313
WSCD1	898
HLA-DOA	891
DCTD	847

Intra-cohort edges

A	B	Sources
COL11A2	HSD17B8	string_interaction
COL11A2	RING1	string_interaction
COL11A2	RXRB	string_interaction
HSD17B8	RING1	string_interaction
HSD17B8	RXRB	string_interaction
RING1	RXRB	string_interaction

Structural data

PDB: 8 · AlphaFold-only: 3 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CCDC86	Q9H6F5	10
HLA-DPB1	P04440	10
RXRB	P28702	7
HSD17B8	Q92506	3
SEMA6A	Q9H2E6	1
COBL	O75128	1
DCTD	P32321	1
HLA-DOA	P06340	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WSCD1	Q658N2	77.87
RING1	Q06587	72.69
COL11A2	P13942	50.18

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 49. Enrichment computed across 12 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NR1H2 & NR1H3 regulate gene expression to limit cholesterol uptake	1	285.5×	0.043	RXRB
NR1H2 & NR1H3 regulate gene expression linked to triglyceride lipolysis in adipose	1	285.5×	0.043	RXRB
NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis	1	285.5×	0.043	RXRB
MHC class II antigen presentation	2	22.3×	0.043	HLA-DOA, HLA-DPB1
NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis	1	178.4×	0.055	RXRB
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis	1	142.8×	0.057	RXRB
SUMOylation of DNA methylation proteins	1	84.0×	0.062	RING1
Translocation of ZAP-70 to Immunological synapse	1	79.3×	0.062	HLA-DPB1
Other semaphorin interactions	1	75.1×	0.062	SEMA6A
Phosphorylation of CD3 and TCR zeta chains	1	68.0×	0.062	HLA-DPB1
Co-inhibition by PD-1	1	64.9×	0.062	HLA-DPB1
Fatty acyl-CoA biosynthesis	1	54.9×	0.062	HSD17B8
Signaling by Retinoic Acid	1	51.0×	0.062	RXRB
Semaphorin interactions	1	49.2×	0.062	SEMA6A
NR1H2 and NR1H3-mediated signaling	1	49.2×	0.062	RXRB
MET activates PTK2 signaling	1	47.6×	0.062	COL11A2
Interconversion of nucleotide di- and triphosphates	1	44.6×	0.062	DCTD
Generation of second messenger molecules	1	43.3×	0.062	HLA-DPB1
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	38.6×	0.063	RXRB
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	1	37.6×	0.063	RING1
Transcriptional Regulation by E2F6	1	36.6×	0.063	RING1
Collagen chain trimerization	1	32.4×	0.068	COL11A2
SUMOylation of transcription cofactors	1	30.4×	0.068	RING1
SUMOylation of RNA binding proteins	1	29.7×	0.068	RING1
Developmental Lineage of Pancreatic Ductal Cells	1	28.6×	0.068	COL11A2
Assembly of collagen fibrils and other multimeric structures	1	25.0×	0.071	COL11A2
Nuclear Receptor transcription pathway	1	25.0×	0.071	RXRB
Regulation of PTEN gene transcription	1	22.3×	0.075	RING1
Collagen degradation	1	22.0×	0.075	COL11A2
Collagen biosynthesis and modifying enzymes	1	21.3×	0.075	COL11A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	2	210.7×	0.003	HLA-DOA, HLA-DPB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	2	108.7×	0.004	HLA-DOA, HLA-DPB1
positive regulation of immune response	2	96.3×	0.004	HLA-DOA, HLA-DPB1
positive regulation of T cell activation	2	88.7×	0.004	HLA-DOA, HLA-DPB1
negative regulation of cell adhesion involved in sprouting angiogenesis	1	1685.2×	0.008	SEMA6A
negative regulation of antigen processing and presentation of peptide antigen via MHC class II	1	842.6×	0.012	HLA-DOA
dUMP biosynthetic process	1	842.6×	0.012	DCTD
nucleoside salvage	1	561.7×	0.014	DCTD
collateral sprouting in absence of injury	1	561.7×	0.014	COBL
pyrimidine nucleotide metabolic process	1	421.3×	0.016	DCTD
somite specification	1	337.0×	0.016	COBL
dTMP biosynthetic process	1	337.0×	0.016	DCTD
soft palate development	1	337.0×	0.016	COL11A2
positive regulation of vitamin D receptor signaling pathway	1	280.9×	0.016	RXRB
mitotic nuclear division	1	280.9×	0.016	CCDC86
embryonic axis specification	1	240.7×	0.016	COBL
floor plate development	1	240.7×	0.016	COBL
ventricular cardiac muscle cell differentiation	1	240.7×	0.016	RXRB
actin filament network formation	1	187.2×	0.020	COBL
notochord development	1	168.5×	0.020	COBL
adaptive immune response	2	16.9×	0.020	HLA-DOA, HLA-DPB1
maternal placenta development	1	153.2×	0.020	RXRB
estrogen biosynthetic process	1	153.2×	0.020	HSD17B8
negative regulation of vascular endothelial growth factor signaling pathway	1	129.6×	0.022	SEMA6A
negative regulation of sprouting angiogenesis	1	129.6×	0.022	SEMA6A
regulation of T cell differentiation	1	120.4×	0.023	HLA-DOA
protein heterotetramerization	1	105.3×	0.024	HSD17B8
positive regulation of dendrite development	1	99.1×	0.024	COBL
positive regulation of ruffle assembly	1	99.1×	0.024	COBL
positive regulation of neuron migration	1	99.1×	0.024	SEMA6A

Therapeutics

Drugs indicated for this disease

2 approved, 9 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Avacopan	Approved (phase 4)
Rituximab	Approved (phase 4)
Abatacept	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Depemokimab	Phase 3 (in late-stage trials)
Gusperimus	Phase 3 (in late-stage trials)
Mepolizumab	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Prednisone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Blisibimod, Daclizumab, Etanercept, Infliximab, Prednisolone, Vilobelimab.

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 11

Druggability breadth: 4 of 12 evidence-associated genes (33%) 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
RXRB	BEXAROTENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RXRB	6	4
RING1	0	0
SEMA6A	0	0
COL11A2	0	0
COBL	0	0
DCTD	0	0
CCDC86	0	0
WSCD1	0	0
HSD17B8	0	0
HLA-DOA	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BEXAROTENE	4	RXRB
OXAPROZIN	4	RXRB
TRETINOIN	4	RXRB
ALITRETINOIN	4	RXRB
PIRINIXIC ACID	2	RXRB
IRX-4204	2	RXRB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
RXRB	211	Binding:183, Functional:28
DCTD	5	Binding:5
RING1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HSD17B8	1.1.1.100	3-oxoacyl-[acyl-carrier-protein] reductase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RXRB	211

Pharmacogenomics

Cohort genes with a PharmGKB record: 12; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

6 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)
BEXAROTENE	4	RXRB
OXAPROZIN	4	RXRB
TRETINOIN	4	RXRB
ALITRETINOIN	4	RXRB
PIRINIXIC ACID	2	RXRB
IRX-4204	2	RXRB

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RXRB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	3	HSD17B8, HLA-DOA, HLA-DPB1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	8	RING1, SEMA6A, COL11A2, COBL, DCTD, CCDC86, WSCD1, HLA-DPB2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL11A2	0	RXRB
RING1	1	—
SEMA6A	0	—
COBL	0	—
DCTD	5	—
CCDC86	0	—
WSCD1	0	—
HSD17B8	0	—
HLA-DOA	0	—
HLA-DPB1	0	—
HLA-DPB2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 157.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	64
PHASE2	24
PHASE3	16
PHASE4	15
PHASE1	14
EARLY_PHASE1	12
PHASE1/PHASE2	7
PHASE2/PHASE3	5

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05962840	PHASE4	RECRUITING	Efficacy and Safety for Rituximab Combined With Telitacicept in the Treatment of ANCA-associated Vasculitis (TTCAAVREM)
NCT05965284	PHASE4	RECRUITING	Efficacy and Safety for Telitacicept in the Remission Maintenance Treatment of ANCA-associated Vasculitis (TTCAZAREM)
NCT06611696	PHASE4	RECRUITING	Avacopan vs Reduced-dose Glucocorticoids in ANCA-associated Vasculitis
NCT07035834	PHASE4	NOT_YET_RECRUITING	SGLT-2 Inhibitors on Albuminuria in Chronic Kidney Disease Patients With Lupus Nephritis and ANCA- Associated Vasculitis
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT07451847	PHASE4	NOT_YET_RECRUITING	Comparison of a Strategy Based on Clinico-biological Monitoring Versus Pre-emptive Rituximab Treatment in Cases of ANCA Reappearance in Granulomatosis With Polyangiitis and Microscopic Polyangiitis.
NCT00307671	PHASE4	COMPLETED	Treatment of Necrotizing Vasculitides for Patients Older Than 65 Years
NCT00747461	PHASE4	TERMINATED	Interventional Cryotherapy for the Eradication of Benign Airway Disease (ICE the BAD)
NCT01405807	PHASE4	UNKNOWN	Alemtuzumab for ANCA Associated Refractory Vasculitis
NCT02115997	PHASE4	COMPLETED	A Study Evaluating the Safety and Efficacy of Rituximab in Combination With Glucocorticoids in Participants With Wegener’s Granulomatosis or Microscopic Polyangitis
NCT02169219	PHASE4	COMPLETED	Pilot Study of Short-Course Glucocorticoids and Rituximab for Treatment of ANCA-Associated Vasculitis
NCT02198248	PHASE4	UNKNOWN	Low-dose Glucocorticoid Vasculitis Induction Study
NCT02626845	PHASE4	TERMINATED	Rituximab for the Otolaryngologic Manifestations of Granulomatosis With Polyangiitis
NCT04316494	PHASE4	TERMINATED	Hydroxychloroquine in ANCA Vasculitis Evaluation
NCT04944524	PHASE4	UNKNOWN	Comparison of Tofacitinib and Methotrexate in the Maintained Treatment of GPA
NCT01933724	PHASE3	ACTIVE_NOT_RECRUITING	The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach
NCT04871191	PHASE3	RECRUITING	Study of Salvage Therapy to Treat Patients With Granulomatosis With Polyangiitis
NCT05946564	PHASE3	RECRUITING	A Trial to Evaluate the Efficacy of Pioglitazone to Promote Renal Tolerance in ANCA-associated Vasculitis - RENATO Trial
NCT06983821	PHASE3	RECRUITING	Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW)
NCT07168161	PHASE3	RECRUITING	BDB-001 Phase III Trial in ANCA-Associated Vasculitis
NCT07176546	PHASE2/PHASE3	NOT_YET_RECRUITING	TAVNEOS for Otolaryngologic Manifestations of Granulomatosis With Polyangiitis
NCT07373262	PHASE3	NOT_YET_RECRUITING	Avacopan Added to Standard-of-care Therapy in ANCA-associated Vasculitis With Severe Kidney Involvement
NCT00005007	PHASE2/PHASE3	COMPLETED	Etanercept for Wegener’s Granulomatosis
NCT00103792	PHASE3	COMPLETED	Mycophenolate Mofetil for Treatment of Relapses of Wegener’s Disease or Microscopic Polyangiitis (MPA)
NCT00104299	PHASE2/PHASE3	COMPLETED	Rituximab for the Treatment of Wegener’s Granulomatosis and Microscopic Polyangiitis
NCT00138983	PHASE3	COMPLETED	Prevention of Glucocorticoid-Induced Osteoporosis in Rheumatic Diseases: Alendronate Versus Alfacalcidol.
NCT00430105	PHASE2/PHASE3	COMPLETED	Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides
NCT00748644	PHASE3	COMPLETED	Efficacy Study of Two Treatments in the Remission of Vasculitis
NCT00987389	PHASE3	COMPLETED	Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis
NCT01408836	PHASE2/PHASE3	TERMINATED	Plasma Exchange for Renal Vasculitis
NCT01697267	PHASE3	COMPLETED	Rituximab Vasculitis Maintenance Study
NCT01731561	PHASE3	COMPLETED	Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis
NCT01940094	PHASE3	COMPLETED	The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach
NCT02108860	PHASE3	COMPLETED	Abatacept for the Treatment of Relapsing, Non-Severe, Granulomatosis With Polyangiitis (Wegener’s)
NCT02994927	PHASE3	COMPLETED	A Phase 3 Clinical Trial of CCX168 (Avacopan) in Patients With ANCA-Associated Vasculitis
NCT03942887	PHASE3	UNKNOWN	Exploring Durable Remission With Rituximab in Antineutrophil Cytoplasmic Antibody(ANCA)-Associated Vasculitis
NCT03919435	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	TEMPO Study: Trimethoprim-Sulfamethoxazole in Granulomatosis With Polyangiitis
NCT05630612	PHASE2	ACTIVE_NOT_RECRUITING	ETA and AT1 Antagonism in ANCA-vasculitis (SPARVASC)
NCT06685042	PHASE1/PHASE2	RECRUITING	Anti-CD19 CAR T-Cell Therapy in Refractory Systemic Autoimmune Diseases
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CYCLOPHOSPHAMIDE ANHYDROUS	4	13
AZATHIOPRINE	4	8
RITUXIMAB	4	6
TOFACITINIB	4	6
AVACOPAN	4	5
ABATACEPT	4	3
METHYLPREDNISOLONE	4	2
PREDNISONE	4	2
ALEMTUZUMAB	4	1
BELIMUMAB	4	1
DACLIZUMAB	4	1
ETANERCEPT	4	1
HYDROXYCHLOROQUINE	4	1
LEFLUNOMIDE	4	1
METHOTREXATE	4	1
MYCOPHENOLATE MOFETIL	4	1
SPARSENTAN	4	1
SULFAMETHOXAZOLE	4	1
TRIMETHOPRIM	4	1
VALACYCLOVIR	4	1
TELITACICEPT	3	2
BLISIBIMOD	3	1
GUSPERIMUS	3	1
VILOBELIMAB	3	1
YELLOW FEVER VACCINE	3	1
AB-101	2	1
INTERLEUKIN-10	2	1
RAPCABTAGENE AUTOLEUCEL	2	1
CHEMBL15720	0	2
CHEMBL426	0	1

Cohort genes: RING1, RXRB, SEMA6A, COL11A2, COBL, DCTD, CCDC86, WSCD1, HSD17B8, HLA-DOA, HLA-DPB1
Drugs: Cyclophosphamide, Azathioprine, Rituximab, Tofacitinib, Avacopan, Abatacept, Methylprednisolone, Prednisone, Alemtuzumab, Belimumab, Daclizumab, Etanercept, Hydroxychloroquine, Leflunomide, Methotrexate, Mycophenolate Mofetil, Sparsentan, Sulfamethoxazole, Trimethoprim, Valacyclovir, Telitacicept, Blisibimod, Gusperimus, Vilobelimab, Yellow Fever Vaccine