Inherited susceptibility to asthma

disease
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Also known as asthma, nocturnal, susceptibility to

Summary

Inherited susceptibility to asthma (MONDO:0010940) is a disease (an umbrella term covering 9 Mondo subtypes) with 11 cohort genes. The dominant Reactome pathway is Interleukin-4 and Interleukin-13 signaling (5 cohort genes).

At a glance

  • Umbrella term: 9 Mondo subtypes
  • Cohort genes: 11
  • ClinVar variants: 13

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

FieldValue
Canonical nameinherited susceptibility to asthma
Mondo IDMONDO:0010940
OMIM600807
UMLSC1869116
MedGen358271
Is cancer (heuristic)no

Also known as: asthma, nocturnal, susceptibility to

Data availability: 13 ClinVar variants · 2 GenCC gene-disease records.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease susceptibility › inherited disease susceptibilityinherited susceptibility to asthma

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, 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, vitiligo-associated multiple autoimmune disease susceptibility 1, 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

Subtypes (9): asthma-related traits, susceptibility to, 1, asthma-related traits, susceptibility to, 2, asthma-related traits, susceptibility to, 3, asthma-related traits, susceptibility to, 4, asthma-related traits, susceptibility to, 5, asthma-related traits, susceptibility to, 6, asthma-related traits, susceptibility to, 7, asthma-related traits, susceptibility to, 8, asthma, aspirin-induced, susceptibility to

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:

4 uncertain significance, 3 risk factor, 2 conflicting classifications of pathogenicity, 2 benign; risk factor, 1 drug response, 1 established risk allele

ClinVarVariant (HGVS)GeneClassificationReview
8368NC_000017.11:g.34274816GAGAAG[9]CCL11risk factorno assertion criteria provided
5160NM_006895.3(HNMT):c.314C>T (p.Thr105Ile)HNMTBenign; risk factorno assertion criteria provided
14672NM_001354991.2(IL13):c.-93+487C>TIL13risk factorno assertion criteria provided
14673NM_002188.3(IL13):c.431A>G (p.Gln144Arg)IL13Benign; risk factorno assertion criteria provided
4528335NM_000963.4(PTGS2):c.-1290C>TPTGS2Established risk alleleno assertion criteria provided
4253NC_000005.10:g.147878599G>ASCGB3A2risk factorno assertion criteria provided
225964NC_000006.12:g.31575254G>ATNFdrug responsereviewed by expert panel
445774NM_006895.3(HNMT):c.475del (p.His159fs)HNMTConflicting classifications of pathogenicitycriteria provided, conflicting classifications
134553NM_004972.4(JAK2):c.2538G>C (p.Glu846Asp)INSL6Conflicting classifications of pathogenicitycriteria provided, conflicting classifications
2502178NM_006895.3(HNMT):c.137+2287G>AHNMTUncertain significancecriteria provided, single submitter
14055IL12B, 4237G-AIL12BUncertain significanceno assertion criteria provided
12253NM_003357.5(SCGB1A1):c.-38=SCGB1A1Uncertain significanceno assertion criteria provided
3892678NM_000594.4(TNF):c.248C>A (p.Thr83Asn)TNFUncertain significancecriteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · 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.

GeneClassificationInheritanceDiseaseRecords
ADRB2LimitedAutosomal dominantinherited susceptibility to asthma
MUC7LimitedAutosomal dominantinherited susceptibility to asthma

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
HNMTOrphanet:88616Autosomal recessive non-syndromic intellectual disability
IL12BOrphanet:319558Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
IL12BOrphanet:3287Takayasu arteritis

Cohort genes → proteins

11 cohort genes, 11 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence11

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
ADRB2HGNC:286ENSG00000169252P07550Beta-2 adrenergic receptorgencc
MUC7HGNC:7518ENSG00000171195Q8TAX7Mucin-7gencc
CCL11HGNC:10610ENSG00000172156P51671Eotaxinclinvar
TNFHGNC:11892ENSG00000232810P01375Tumor necrosis factorclinvar
SCGB1A1HGNC:12523ENSG00000149021P11684Uteroglobinclinvar
SCGB3A2HGNC:18391ENSG00000164265Q96PL1Secretoglobin family 3A member 2clinvar
HNMTHGNC:5028ENSG00000150540P50135Histamine N-methyltransferaseclinvar
IL12BHGNC:5970ENSG00000113302P29460Interleukin-12 subunit betaclinvar
IL13HGNC:5973ENSG00000169194P35225Interleukin-13clinvar
INSL6HGNC:6089ENSG00000120210Q9Y581Insulin-like peptide INSL6clinvar
PTGS2HGNC:9605ENSG00000073756P35354Prostaglandin G/H synthase 2clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
ADRB2Beta-2 adrenergic receptorG protein-coupled receptor for catecholamines that couples to both G(s) and G(i) proteins, activating bifurcated signaling pathways.
MUC7Mucin-7May function in a protective capacity by promoting the clearance of bacteria in the oral cavity and aiding in mastication, speech, and swallowing.
CCL11EotaxinChemokine that plays a central role in both allergic and non-allergic inflammatory reactions by inducing the migration of different leukocyte types including eosinophils, basophils, macrophages and dendritic cells.
TNFTumor necrosis factorCytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
SCGB1A1UteroglobinBinds phosphatidylcholine, phosphatidylinositol, polychlorinated biphenyls (PCB) and weakly progesterone, potent inhibitor of phospholipase A2.
SCGB3A2Secretoglobin family 3A member 2Secreted cytokine-like protein.
HNMTHistamine N-methyltransferaseInactivates histamine by N-methylation.
IL12BInterleukin-12 subunit betaCytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.
IL13Interleukin-13Cytokine that plays important roles in allergic inflammation and immune response to parasite infection.
INSL6Insulin-like peptide INSL6May have a role in sperm development and fertilization.
PTGS2Prostaglandin G/H synthase 2Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory respon…

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 7 · Druggable fraction: 0.36

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.

FamilyGenesFoldFDR
Antibody/Immunoglobulin12.6×0.419
Enzyme (other)22.2×0.419
GPCR12.2×0.419
Other/Unknown71.1×0.419

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
ADRB2GPCRyesGPCR_Rhodpsn, ADRB2_rcpt, ADR_fam
MUC7Other/UnknownnoMUC7
CCL11Other/UnknownnoChemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
TNFOther/UnknownnoTNF_alpha, TNF_dom, TNF
SCGB1A1Other/UnknownnoUteroglobin, Secretoglobin, Secretoglobin_sf
SCGB3A2Other/UnknownnoSecretoglobin_3A
HNMTEnzyme (other)yes2.1.1.8HHMT-like, SAM-dependent_MTases_sf
IL12BAntibody/ImmunoglobulinyesHematopoietin_rcpt_L_F3_CS, Ig_sub2, FN3_dom
IL13Other/UnknownnoIL-4/IL-13, 4_helix_cytokine-like_core, IL-4/IL-13_CS
INSL6Other/UnknownnoInsulin-like, Insulin-like_pep_6, Insulin_CS
PTGS2Enzyme (other)yes1.14.99.1EGF, Haem_peroxidase_sf, Haem_peroxidase_animal

Expression context

Cohort genes with no expression data: 0.

11 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)11
unknown0

Top tissues across cohort

TissueCohort genes
cartilage tissue2
granulocyte2
trachea2
male germ line stem cell (sensu Vertebrata) in testis2
right lung2
left testis2
right testis2
upper leg skin1
parotid gland1
saliva-secreting gland1
caecum1
cardia of stomach1
pylorus1
bone marrow1
bronchial epithelial cell1
epithelium of bronchus1
lower lobe of lung1
gall bladder1
monocyte1
mononuclear cell1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
ADRB2242ubiquitousmarkercartilage tissue, granulocyte, upper leg skin
MUC7155tissue_specificmarkertrachea, parotid gland, saliva-secreting gland
CCL11128broadmarkerpylorus, cardia of stomach, caecum
TNF119broadmarkergranulocyte, male germ line stem cell (sensu Vertebrata) in testis, bone marrow
SCGB1A1170tissue_specificmarkerbronchial epithelial cell, epithelium of bronchus, right lung
SCGB3A2154tissue_specificmarkertrachea, right lung, lower lobe of lung
HNMT289ubiquitousmarkergall bladder, monocyte, mononuclear cell
IL12B33tissue_specificmarkerprimordial germ cell in gonad, decidua, hair follicle
IL13128tissue_specificmarkerleft testis, right testis, testis
INSL6152tissue_specificmarkermale germ line stem cell (sensu Vertebrata) in testis, left testis, right testis
PTGS2249ubiquitousmarkerseminal vesicle, cartilage tissue, mucosa of urinary bladder

Protein interactions among cohort

Intra-cohort edges: 6.

Hub genes (top 10 by interactor count)

SymbolInteractor count
TNF11,116
PTGS25,663
ADRB23,598
IL133,427
SCGB1A11,197
HNMT1,166
MUC7973
IL12B804
SCGB3A2553
INSL6509

Intra-cohort edges

ABSources
HNMTSCGB3A2string_interaction
IL12BTNFstring_interaction
IL13TNFstring_interaction
MUC7SCGB3A2string_interaction
PTGS2TNFstring_interaction
SCGB1A1SCGB3A2string_interaction

Structural data

PDB: 8 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

SymbolUniProtPDB entries
ADRB2P07550145
TNFP0137552
IL12BP2946020
IL13P3522513
HNMTP501357
PTGS2P353547
CCL11P516714
SCGB1A1P116842

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
SCGB3A2Q96PL174.66
MUC7Q8TAX755.60
INSL6Q9Y58154.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 58. Enrichment computed across 11 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

PathwayCohort genesFoldFDRSample cohort genes
Interleukin-4 and Interleukin-13 signaling557.2×6e-07CCL11, TNF, IL12B, IL13, PTGS2
Interleukin-10 signaling377.7×2e-04TNF, IL12B, PTGS2
Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives1634.4×0.030PTGS2
Biosynthesis of EPA-derived SPMs1317.2×0.031PTGS2
Biosynthesis of DPAn-3 SPMs1317.2×0.031PTGS2
Synthesis of 15-eicosatetraenoic acid derivatives1211.5×0.031PTGS2
TNFR1-mediated ceramide production1211.5×0.031TNF
Biosynthesis of DHA-derived SPMs1211.5×0.031PTGS2
Metabolism of ingested SeMet, Sec, MeSec into H2Se1158.6×0.031HNMT
Interleukin-18 signaling1158.6×0.031IL13
Adrenoceptors1141.0×0.031ADRB2
Interleukin-23 signaling1141.0×0.031IL12B
Histidine catabolism1126.9×0.031HNMT
Class A/1 (Rhodopsin-like receptors)216.5×0.031CCL11, ADRB2
GPCR ligand binding214.3×0.031CCL11, ADRB2
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)197.6×0.037TNF
Synthesis of Prostaglandins (PG) and Thromboxanes (TX)184.6×0.038PTGS2
Defective GALNT3 causes HFTC179.3×0.038MUC7
Defective GALNT12 causes CRCS1179.3×0.038MUC7
Defective C1GALT1C1 causes TNPS174.6×0.039MUC7
Scavenging by Class A Receptors166.8×0.041SCGB3A2
Binding and Uptake of Ligands by Scavenger Receptors160.4×0.043SCGB3A2
Termination of O-glycan biosynthesis155.2×0.045MUC7
TNFR1-induced proapoptotic signaling148.8×0.045TNF
Dectin-2 family147.0×0.045MUC7
TNF signaling147.0×0.045TNF
Interleukin-12 signaling145.3×0.045IL12B
Signaling by GPCR28.9×0.045CCL11, ADRB2
Amine ligand-binding receptors138.5×0.050ADRB2
TNFR1-induced NF-kappa-B signaling pathway137.3×0.050TNF

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO termCohort genesFoldFDRSample cohort genes
positive regulation of fever generation2936.2×5e-04TNF, PTGS2
response to nematode2416.1×0.002IL13, PTGS2
response to selenium ion2312.1×0.002IL13, PTGS2
microglial cell activation2138.7×0.006TNF, IL13
negative regulation of neurogenesis2138.7×0.006CCL11, TNF
positive regulation of osteoclast differentiation2129.1×0.006TNF, IL12B
histamine catabolic process11872.4×0.006HNMT
positive regulation of translational initiation by iron11872.4×0.006TNF
negative regulation of branching involved in lung morphogenesis11872.4×0.006TNF
positive regulation of mini excitatory postsynaptic potential11872.4×0.006ADRB2
cellular response to non-ionic osmotic stress11872.4×0.006PTGS2
negative regulation of bile acid secretion11872.4×0.006TNF
response to Gram-negative bacterium11872.4×0.006TNF
positive regulation of interleukin-33 production11872.4×0.006TNF
negative regulation of lung ciliated cell differentiation11872.4×0.006IL13
positive regulation of lung goblet cell differentiation11872.4×0.006IL13
response to 3,3’,5-triiodo-L-thyronine11872.4×0.006TNF
positive regulation of pancreatic stellate cell proliferation11872.4×0.006IL13
positive regulation of immunoglobulin production2107.0×0.006TNF, IL13
positive regulation of nitric oxide biosynthetic process2101.2×0.006TNF, PTGS2
brown fat cell differentiation296.0×0.006ADRB2, PTGS2
positive regulation of interleukin-10 production289.2×0.006IL12B, IL13
cellular response to amyloid-beta287.1×0.006TNF, ADRB2
T cell proliferation285.1×0.006SCGB1A1, IL12B
embryo implantation278.0×0.006SCGB1A1, PTGS2
positive regulation of smooth muscle cell proliferation273.4×0.006TNF, IL13
response to glucocorticoid272.0×0.006TNF, SCGB1A1
cell surface receptor signaling pathway via JAK-STAT264.6×0.006TNF, IL12B
positive regulation of cell adhesion260.4×0.006TNF, IL12B
positive regulation of non-canonical NF-kappaB signal transduction256.7×0.006TNF, IL12B

Therapeutics

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 8

Druggability breadth: 7 of 11 evidence-associated genes (64%) 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.

SymbolExample approved molecule
ADRB2LABETALOL HYDROCHLORIDE
TNFPREDNISOLONE
PTGS2CELECOXIB

Top cohort targets by molecule count

SymbolMoleculesMax phase
PTGS21924
ADRB21664
TNF124
MUC700
CCL1100
SCGB1A100
SCGB3A200
HNMT00
IL12B00
IL1300

Drugs targeting cohort genes (top 30)

MoleculeMax phaseTargets in cohort
LABETALOL HYDROCHLORIDE4ADRB2
PHENYLEPHRINE4ADRB2
NOREPINEPHRINE4ADRB2, PTGS2
PROPRANOLOL HYDROCHLORIDE4ADRB2
SOTALOL HYDROCHLORIDE4ADRB2
PROPRANOLOL4ADRB2
ISOPROTERENOL4ADRB2
SOTALOL4ADRB2
PRACTOLOL4ADRB2
LEVOSALBUTAMOL4ADRB2
CANDESARTAN CILEXETIL4ADRB2, PTGS2
CLOTRIMAZOLE4ADRB2, PTGS2
SALMETEROL XINAFOATE4ADRB2
INDACATEROL4ADRB2
ARIPIPRAZOLE4ADRB2
AMOXAPINE4ADRB2
DESLORATADINE4ADRB2
VILANTEROL4ADRB2, PTGS2
TIOCONAZOLE4ADRB2
DIHYDROERGOTAMINE MESYLATE4ADRB2
DIPIVEFRIN HYDROCHLORIDE4ADRB2
ISOETHARINE MESYLATE4ADRB2
ISOETHARINE4ADRB2, PTGS2
LEVOBUNOLOL4ADRB2
RIBOFLAVIN 5’-PHOSPHATE4ADRB2, PTGS2
FORMOTEROL4ADRB2
EPINEPHRINE BITARTRATE4ADRB2
SALMETEROL4ADRB2
MIFEPRISTONE4ADRB2
METOPROLOL4ADRB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

SymbolAssaysType breakdown
PTGS21,548Binding:1478, Functional:35, ADMET:34, Toxicity:1
ADRB21,026Binding:596, Functional:423, ADMET:7
TNF193Binding:162, Functional:31
HNMT9Binding:7, ADMET:2
CCL111Binding:1

Cohort enzymes (BRENDA EC)

SymbolEC numbersNames
HNMT2.1.1.8histamine N-methyltransferase
PTGS21.14.99.1prostaglandin-endoperoxide synthase

Cohort genes with high screening signal

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

SymbolChEMBL assays
ADRB21,026
TNF193
PTGS21,548

Pharmacogenomics

Cohort genes with a PharmGKB record: 11; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

SymbolCPIC guidelines
ADRB21

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.

CompoundMax phaseCohort target (bioactivity)
LABETALOL HYDROCHLORIDE4ADRB2
PHENYLEPHRINE4ADRB2
NOREPINEPHRINE4ADRB2, PTGS2
PROPRANOLOL HYDROCHLORIDE4ADRB2
SOTALOL HYDROCHLORIDE4ADRB2
PROPRANOLOL4ADRB2
ISOPROTERENOL4ADRB2
SOTALOL4ADRB2
PRACTOLOL4ADRB2
LEVOSALBUTAMOL4ADRB2
CANDESARTAN CILEXETIL4ADRB2, PTGS2
CLOTRIMAZOLE4ADRB2, PTGS2
SALMETEROL XINAFOATE4ADRB2
INDACATEROL4ADRB2
ARIPIPRAZOLE4ADRB2
AMOXAPINE4ADRB2
DESLORATADINE4ADRB2
VILANTEROL4ADRB2, PTGS2
TIOCONAZOLE4ADRB2
DIHYDROERGOTAMINE MESYLATE4ADRB2
DIPIVEFRIN HYDROCHLORIDE4ADRB2
ISOETHARINE MESYLATE4ADRB2
ISOETHARINE4ADRB2, PTGS2
LEVOBUNOLOL4ADRB2
RIBOFLAVIN 5’-PHOSPHATE4ADRB2, PTGS2
FORMOTEROL4ADRB2
EPINEPHRINE BITARTRATE4ADRB2
SALMETEROL4ADRB2
MIFEPRISTONE4ADRB2
METOPROLOL4ADRB2

Druggability pyramid

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

TierDefinitionGenesSymbols
AApproved (phase 4 drug)3ADRB2, TNF, PTGS2
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug2HNMT, IL12B
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug6MUC7, CCL11, SCGB1A1, SCGB3A2, IL13, INSL6

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
MUC70
CCL111
SCGB1A10
SCGB3A20
HNMT9
IL12B0
IL130
INSL60

Clinical trials & evidence

Clinical trials

Clinical trials: 0.