Vitiligo-associated multiple autoimmune disease susceptibility 1

Summary

Vitiligo-associated multiple autoimmune disease susceptibility 1 (MONDO:0011684) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	vitiligo-associated multiple autoimmune disease susceptibility 1
Mondo ID	MONDO:0011684
OMIM	606579
UMLS	C1847835
MedGen	335788
Is cancer (heuristic)	no

Also known as: VAMAS1 · vitiligo-associated multiple autoimmune disease susceptibility 1 · vitiligo-associated multiple autoimmune disease susceptibility type 1

Data availability: 13 ClinVar variants.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › vitiligo-associated multiple autoimmune disease susceptibility 1

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, multiple sclerosis, susceptibility to, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

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

13 retrieved; paginated sample, class counts are floors:

7 uncertain significance, 3 benign/likely benign, 2 likely benign, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
714854	NM_033004.4(NLRP1):c.2841G>C (p.Arg947Ser)	NLRP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1481575	NM_005546.4(ITK):c.1562C>T (p.Pro521Leu)	ITK	Uncertain significance	criteria provided, single submitter
1016715	NM_033004.4(NLRP1):c.439C>T (p.Arg147Cys)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1366760	NM_033004.4(NLRP1):c.164C>T (p.Ser55Leu)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1369278	NM_033004.4(NLRP1):c.4097G>A (p.Arg1366His)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1441287	NM_033004.4(NLRP1):c.3338C>T (p.Thr1113Met)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442888	NM_033004.4(NLRP1):c.1040T>G (p.Val347Gly)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3582339	NM_033004.4(NLRP1):c.2960G>A (p.Arg987Gln)	NLRP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1097101	NM_033004.4(NLRP1):c.3228C>T (p.Asp1076=)	NLRP1	Likely benign	criteria provided, multiple submitters, no conflicts
4163	NM_033004.4(NLRP1):c.464T>A (p.Leu155His)	NLRP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
734173	NM_033004.4(NLRP1):c.272-7C>G	NLRP1	Likely benign	criteria provided, multiple submitters, no conflicts
770795	NM_033004.4(NLRP1):c.316G>A (p.Gly106Arg)	NLRP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
808209	NM_033004.4(NLRP1):c.923G>A (p.Arg308Gln)	NLRP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NLRP1	Orphanet:352662	Corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome
ITK	Orphanet:538963	Combined immunodeficiency due to ITK deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NLRP1	HGNC:14374	ENSG00000091592	Q9C000	NACHT, LRR and PYD domains-containing protein 1	clinvar
ITK	HGNC:6171	ENSG00000113263	Q08881	Tyrosine-protein kinase ITK/TSK	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NLRP1	NACHT, LRR and PYD domains-containing protein 1	Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis.
ITK	Tyrosine-protein kinase ITK/TSK	Tyrosine kinase that plays an essential role in regulation of the adaptive immune response.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NLRP1	Other/Unknown	no		CARD, Leu-rich_rpt, DAPIN
ITK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
monocyte	1
mononuclear cell	1
blood	1
thymus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NLRP1	203	ubiquitous	marker	granulocyte, monocyte, mononuclear cell
ITK	198	broad	marker	granulocyte, thymus, blood

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITK	2,670
NLRP1	1,544

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITK	Q08881	37
NLRP1	Q9C000	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
The NLRP1 inflammasome	1	1903.3×	0.004	NLRP1
TCR signaling	1	248.3×	0.012	ITK
FCERI mediated Ca+2 mobilization	1	178.4×	0.012	ITK
Generation of second messenger molecules	1	173.0×	0.012	ITK
Fc epsilon receptor (FCERI) signaling	1	135.9×	0.012	ITK
Adaptive Immune System	1	14.9×	0.088	ITK
Innate Immune System	1	12.8×	0.088	ITK
Immune System	1	6.5×	0.148	ITK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
NLRP1 inflammasome complex assembly	1	8426.0×	0.003	NLRP1
NK T cell differentiation	1	2106.5×	0.007	ITK
gamma-delta T cell activation	1	1053.2×	0.007	ITK
self proteolysis	1	766.0×	0.007	NLRP1
response to muramyl dipeptide	1	702.2×	0.007	NLRP1
cellular response to UV-B	1	702.2×	0.007	NLRP1
pattern recognition receptor signaling pathway	1	495.6×	0.008	NLRP1
pyroptotic inflammatory response	1	255.3×	0.012	NLRP1
activation of innate immune response	1	240.7×	0.012	NLRP1
signal transduction	2	16.1×	0.012	NLRP1, ITK
B cell receptor signaling pathway	1	200.6×	0.013	ITK
intrinsic apoptotic signaling pathway	1	179.3×	0.013	NLRP1
cellular defense response	1	159.0×	0.014	ITK
positive regulation of cytokine production	1	135.9×	0.014	ITK
positive regulation of interleukin-1 beta production	1	129.6×	0.014	NLRP1
T cell activation	1	129.6×	0.014	ITK
antiviral innate immune response	1	113.9×	0.015	NLRP1
neuron apoptotic process	1	92.6×	0.017	NLRP1
regulation of inflammatory response	1	84.3×	0.018	NLRP1
T cell receptor signaling pathway	1	75.9×	0.019	ITK
positive regulation of inflammatory response	1	72.6×	0.019	NLRP1
protein homooligomerization	1	61.1×	0.022	NLRP1
defense response to bacterium	1	54.0×	0.023	NLRP1
adaptive immune response	1	42.1×	0.028	ITK
regulation of apoptotic process	1	41.7×	0.028	NLRP1
defense response to virus	1	34.7×	0.032	NLRP1
intracellular signal transduction	1	19.1×	0.054	ITK
inflammatory response	1	18.9×	0.054	NLRP1
apoptotic process	1	14.3×	0.068	NLRP1

Therapeutics

Drug target analysis

Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 0

Druggability breadth: 2 of 2 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
NLRP1	PERHEXILINE MALEATE
ITK	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ITK	39	4
NLRP1	2	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PERHEXILINE MALEATE	4	NLRP1
DITHIAZANINE IODIDE	4	NLRP1
FEDRATINIB	4	ITK
AXITINIB	4	ITK
IBRUTINIB	4	ITK
BOSUTINIB	4	ITK
ACALABRUTINIB	4	ITK
ZANUBRUTINIB	4	ITK
RITLECITINIB	4	ITK
NINTEDANIB	4	ITK
SUNITINIB	4	ITK
DASATINIB	4	ITK
QUIZARTINIB	4	ITK
CRIZOTINIB	4	ITK
CANERTINIB	3	ITK
EVOBRUTINIB	3	ITK
REMIBRUTINIB	3	ITK
DOVITINIB	3	ITK
LESTAURTINIB	3	ITK
FORETINIB	2	ITK
TANDUTINIB	2	ITK
SU-014813	2	ITK
REBASTINIB	2	ITK
CENISERTIB	2	ITK
ILORASERTIB	2	ITK
OSI-632	2	ITK
SPEBRUTINIB	2	ITK
BMS-986142	2	ITK
BMS-919373	2	ITK
ATUZABRUTINIB	2	ITK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ITK	563	Binding:547, Functional:10, ADMET:6
NLRP1	2	Functional:1, Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ITK	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ITK	563

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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)
PERHEXILINE MALEATE	4	NLRP1
DITHIAZANINE IODIDE	4	NLRP1
FEDRATINIB	4	ITK
AXITINIB	4	ITK
IBRUTINIB	4	ITK
BOSUTINIB	4	ITK
ACALABRUTINIB	4	ITK
ZANUBRUTINIB	4	ITK
RITLECITINIB	4	ITK
NINTEDANIB	4	ITK
SUNITINIB	4	ITK
DASATINIB	4	ITK
QUIZARTINIB	4	ITK
CRIZOTINIB	4	ITK
CANERTINIB	3	ITK
EVOBRUTINIB	3	ITK
REMIBRUTINIB	3	ITK
DOVITINIB	3	ITK
LESTAURTINIB	3	ITK
FORETINIB	2	ITK
TANDUTINIB	2	ITK
SU-014813	2	ITK
REBASTINIB	2	ITK
CENISERTIB	2	ITK
ILORASERTIB	2	ITK
OSI-632	2	ITK
SPEBRUTINIB	2	ITK
BMS-986142	2	ITK
BMS-919373	2	ITK
ATUZABRUTINIB	2	ITK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	2	NLRP1, ITK
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: 0.