Muckle-Wells syndrome

Summary

Muckle-Wells syndrome (MONDO:0008633) is a disease with 1 cohort gene and 10 clinical trials. Top therapeutic interventions include canakinumab, rilonacept, and gevokizumab.

At a glance

• Prevalence: <1 / 1 000 000 (Europe) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 256
• Phenotypes (HPO): 37
• Clinical trials: 10

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

37 HPO clinical features (Orphanet curated; top 37 by frequency):

HPO ID	Term	Frequency
HP:0000408	Progressive sensorineural hearing impairment	Very frequent (80-99%)
HP:0000509	Conjunctivitis	Very frequent (80-99%)
HP:0000554	Uveitis	Very frequent (80-99%)
HP:0000988	Skin rash	Very frequent (80-99%)
HP:0001369	Arthritis	Very frequent (80-99%)
HP:0001744	Splenomegaly	Very frequent (80-99%)
HP:0001769	Broad foot	Very frequent (80-99%)
HP:0002240	Hepatomegaly	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0006824	Cranial nerve paralysis	Very frequent (80-99%)
HP:0100534	Episcleritis	Very frequent (80-99%)
HP:0000100	Nephrotic syndrome	Frequent (30-79%)
HP:0000112	Nephropathy	Frequent (30-79%)
HP:0001025	Urticaria	Frequent (30-79%)
HP:0001917	Renal amyloidosis	Frequent (30-79%)
HP:0001939	Abnormality of metabolism/homeostasis	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0000078	Abnormality of the genital system	Occasional (5-29%)
HP:0000174	Abnormal palate morphology	Occasional (5-29%)
HP:0000256	Macrocephaly	Occasional (5-29%)
HP:0000366	Abnormality of the nose	Occasional (5-29%)
HP:0000501	Glaucoma	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000823	Delayed puberty	Occasional (5-29%)
HP:0001608	Abnormality of the voice	Occasional (5-29%)
HP:0001761	Pes cavus	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0001945	Fever	Occasional (5-29%)
HP:0002091	Restrictive ventilatory defect	Occasional (5-29%)
HP:0002633	Vasculitis	Occasional (5-29%)
HP:0003326	Myalgia	Occasional (5-29%)
HP:0004299	Hernia of the abdominal wall	Occasional (5-29%)
HP:0004322	Short stature	Occasional (5-29%)
HP:0008064	Ichthyosis	Occasional (5-29%)
HP:0011107	Recurrent aphthous stomatitis	Occasional (5-29%)
HP:0100490	Camptodactyly of finger	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Muckle-Wells syndrome
Mondo ID	MONDO:0008633
OMIM	191900
Orphanet	575
DOID	DOID:0050854
ICD-11	1983358487
NCIT	C119054
SNOMED CT	402417009
UMLS	C0268390
MedGen	120634
GARD	0008472
MedDRA	10064569
NORD	1459
Is cancer (heuristic)	no

Also known as: Muckle Wells syndrome · Muckle-Wells syndrome · MWS · neutrophilic urticaria · urticaria, deafness and amyloidosis

Data availability: 256 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › Muckle-Wells syndrome

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, autosomal dominant Ehlers-Danlos syndrome, vascular type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid syndrome

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

256 retrieved; paginated sample, class counts are floors:

144 uncertain significance, 42 conflicting classifications of pathogenicity, 27 benign/likely benign, 19 benign, 12 likely benign, 5 pathogenic, 4 pathogenic/likely pathogenic, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1188124	NM_001243133.2(NLRP3):c.2575T>C (p.Tyr859His)	NLRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4370	NM_001243133.2(NLRP3):c.1316C>T (p.Ala439Val)	NLRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4373	NM_001243133.2(NLRP3):c.1055C>T (p.Ala352Val)	NLRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4374	NM_001243133.2(NLRP3):c.778C>T (p.Arg260Ter)	NLRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
4377	NM_001243133.2(NLRP3):c.907G>A (p.Asp303Asn)	NLRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
4379	NM_001243133.2(NLRP3):c.1058T>C (p.Leu353Pro)	NLRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
97909	NM_001243133.2(NLRP3):c.1043C>T (p.Thr348Met)	NLRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
97960	NM_001243133.2(NLRP3):c.2576A>G (p.Tyr859Cys)	NLRP3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
97987	NM_001243133.2(NLRP3):c.931G>A (p.Glu311Lys)	NLRP3	Pathogenic	criteria provided, multiple submitters, no conflicts
2579697	NM_001243133.2(NLRP3):c.1712T>G (p.Leu571Trp)	NLRP3	Likely pathogenic	no assertion criteria provided
4375	NM_001243133.2(NLRP3):c.1705G>C (p.Gly569Arg)	NLRP3	Likely pathogenic	criteria provided, single submitter
97953	NM_001243133.2(NLRP3):c.1985T>C (p.Met662Thr)	NLRP3	Likely pathogenic	criteria provided, single submitter
1058144	NM_001243133.2(NLRP3):c.1371G>T (p.Glu457Asp)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
138532	NM_001243133.2(NLRP3):c.1584C>T (p.Ala528=)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
138534	NM_001243133.2(NLRP3):c.2118C>T (p.Leu706=)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1446237	NM_001243133.2(NLRP3):c.2273T>C (p.Val758Ala)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1548717	NM_001243133.2(NLRP3):c.1650G>A (p.Lys550=)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1980828	NM_001243133.2(NLRP3):c.800A>G (p.Gln267Arg)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234288	NM_001243133.2(NLRP3):c.404G>A (p.Arg135His)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234290	NM_001243133.2(NLRP3):c.2176A>G (p.Ser726Gly)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234291	NM_001243133.2(NLRP3):c.2425G>A (p.Gly809Ser)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234304	NM_001243133.2(NLRP3):c.2611G>A (p.Ala871Thr)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234305	NM_001243133.2(NLRP3):c.2738C>T (p.Thr913Met)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234451	NM_001243133.2(NLRP3):c.2761A>G (p.Thr921Ala)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
245593	NM_001243133.2(NLRP3):c.208G>A (p.Val70Met)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
259561	NM_001243133.2(NLRP3):c.2107C>A (p.Gln703Lys)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296934	NM_001243133.2(NLRP3):c.-122T>C	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296938	NM_001243133.2(NLRP3):c.28A>C (p.Arg10=)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296939	NM_001243133.2(NLRP3):c.194C>G (p.Ala65Gly)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
296940	NM_001243133.2(NLRP3):c.203T>C (p.Met68Thr)	NLRP3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 4 · 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
NLRP3	Supportive	Autosomal dominant	Muckle-Wells syndrome	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NLRP3	Orphanet:1451	CINCA syndrome
NLRP3	Orphanet:47045	Familial cold urticaria
NLRP3	Orphanet:575	Muckle-Wells syndrome
NLRP3	Orphanet:647815	Keratitis fugax hereditaria

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
NLRP3	HGNC:16400	ENSG00000162711	Q96P20	NACHT, LRR and PYD domains-containing protein 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLRP3	NACHT, LRR and PYD domains-containing protein 3	Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis.

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)
NLRP3	Other/Unknown	no		Leu-rich_rpt, DAPIN, NACHT_NTPase

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
NLRP3	172	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NLRP3	3,797

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NLRP3	Q96P20	24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
The NLRP3 inflammasome	1	671.8×	0.005	NLRP3
Purinergic signaling in leishmaniasis infection	1	423.0×	0.005	NLRP3
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.005	NLRP3
Metalloprotease DUBs	1	300.5×	0.005	NLRP3
SARS-CoV-1 activates/modulates innate immune responses	1	271.9×	0.005	NLRP3
Cytoprotection by HMOX1	1	184.2×	0.006	NLRP3
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	89.2×	0.011	NLRP3

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
detection of biotic stimulus	1	4213.0×	0.003	NLRP3
negative regulation of acute inflammatory response	1	2407.4×	0.003	NLRP3
positive regulation of type 2 immune response	1	2407.4×	0.003	NLRP3
NLRP3 inflammasome complex assembly	1	2407.4×	0.003	NLRP3
positive regulation of T-helper 2 cell differentiation	1	2106.5×	0.003	NLRP3
osmosensory signaling pathway	1	1532.0×	0.003	NLRP3
positive regulation of T-helper 2 cell cytokine production	1	1532.0×	0.003	NLRP3
pattern recognition receptor signaling pathway	1	991.3×	0.004	NLRP3
positive regulation of interleukin-4 production	1	561.7×	0.005	NLRP3
negative regulation of interleukin-1 beta production	1	510.7×	0.005	NLRP3
pyroptotic inflammatory response	1	510.7×	0.005	NLRP3
negative regulation of non-canonical NF-kappaB signal transduction	1	510.7×	0.005	NLRP3
positive regulation of interleukin-1 beta production	1	259.3×	0.008	NLRP3
positive regulation of non-canonical NF-kappaB signal transduction	1	255.3×	0.008	NLRP3
defense response	1	216.1×	0.008	NLRP3
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.008	NLRP3
cellular response to virus	1	200.6×	0.008	NLRP3
regulation of inflammatory response	1	168.5×	0.009	NLRP3
protein maturation	1	163.6×	0.009	NLRP3
positive regulation of inflammatory response	1	145.3×	0.010	NLRP3
negative regulation of inflammatory response	1	137.0×	0.010	NLRP3
protein homooligomerization	1	122.1×	0.010	NLRP3
cellular response to lipopolysaccharide	1	98.0×	0.012	NLRP3
inflammatory response	1	37.7×	0.031	NLRP3
innate immune response	1	33.6×	0.033	NLRP3
apoptotic process	1	28.7×	0.038	NLRP3
signal transduction	1	16.1×	0.065	NLRP3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	NLRP3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) 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
NLRP3	CLOMIPHENE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NLRP3	11	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NLRP3	534	Binding:527, Functional:6, ADMET:1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NLRP3	534

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

11 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)
CLOMIPHENE	4	NLRP3
GLYBURIDE	4	NLRP3
CURCUMIN	3	NLRP3
JT-001	3	NLRP3
TRICLOCARBAN	2	NLRP3
CLIOXANIDE	2	NLRP3
DAPANSUTRILE	2	NLRP3
USNOFLAST	2	NLRP3
INZOMELID	1	NLRP3
BMS-986299	1	NLRP3
NT-0796	1	NLRP3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NLRP3
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: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	6
Not specified	2
PHASE2	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00288704	PHASE3	COMPLETED	Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)
NCT00465985	PHASE3	COMPLETED	Efficacy, Safety, and Tolerability of ACZ885 in Patients With Muckle-Wells Syndrome
NCT00685373	PHASE3	COMPLETED	Efficacy and Safety of ACZ885 in Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
NCT00991146	PHASE3	COMPLETED	Efficacy and Safety Study of Canakinumab Administered for 6 Months (24 Weeks) in Japanese Patients With Cryopyrin-associated Periodic Syndromes Followed by an Extension Phase
NCT01302860	PHASE3	COMPLETED	Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
NCT01576367	PHASE3	COMPLETED	Efficacy, Safety and Tolerability of ACZ885 in Pediatric Patients With the Following Cryopyrin-associated Periodic Syndromes: Familial Cold Autoinflammatory Syndrome, Muckle-Wells Syndrome, or Neonatal Onset Multisystem Inflammatory Disease
NCT01045772	PHASE2	COMPLETED	Safety and Tolerability of Rilonacept in Muckle-Wells Syndrome (MWS) or Schnitzler Syndrome (SchS)
NCT01211977	PHASE1/PHASE2	WITHDRAWN	A Pilot Study of XOMA 052 in Familial Cold Autoinflammatory Syndrome / Muckle-Wells Syndrome and Behcet’s Disease
NCT06544018	Not specified	RECRUITING	Circadian Rhythm Deregulation in Patients With CAPS
NCT01952275	Not specified	UNKNOWN	Observational Study of the Genetic Architecture of Neutrophil-Mediated Inflammatory Skin Diseases

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CANAKINUMAB	4	5
RILONACEPT	4	2
GEVOKIZUMAB	3	1