Childhood onset asthma

Summary

Childhood onset asthma (MONDO:0005405) is a disease with 75 cohort genes (502 GWAS associations across 28 studies) and 62 clinical trials. The dominant Reactome pathway is Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells) (8 cohort genes). Top therapeutic interventions include beclomethasone dipropionate and ipratropium bromide.

At a glance

• Cohort genes: 75
• GWAS associations: 502
• Clinical trials: 62

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	childhood onset asthma
Mondo ID	MONDO:0005405
DOID	DOID:0080815
SNOMED CT	233678006
UMLS	C0264408
MedGen	538550
Is cancer (heuristic)	no

Also known as: asthma of childhood · childhood asthma · paediatric asthma · pediatric asthma

Data availability: 502 GWAS associations (28 studies).

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › bronchial disorder › asthma › childhood onset asthma

Related subtypes (7): cough variant asthma, intrinsic asthma, status asthmaticus, allergic asthma, occupational asthma, chronic asthma, acute asthma

Genetics & variants

GWAS landscape

502 GWAS associations across 28 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs4795399	1e-257	GSDMB	?	1.29
rs72823641	2e-136	IL18R1, IL1RL1	?	1.3
rs11651596	2e-124	ZPBP2 - GSDMB	?
rs7848215	5e-115	GTF3AP1 - IL33	?	1.21
rs9901146	8e-99	ZPBP2 - GSDMB	G	1.18
rs1837253	7e-94	BCLAF1P1 - TSLP	?	1.19
rs11236797	1e-93	EMSY - LINC02757	?	1.16
rs5743618	3e-74	TLR1	?	1.17
rs55646091	6e-74	EMSY - LINC02757	?	1.36
rs61816761	4e-73	FLG, CCDST	?
rs1861245	2e-69	IL18R1, IL1RL1	?	1.15
rs34290285	4e-69	D2HGDH	?	1.17
rs6594499	4e-66	WDR36 - RPS3AP21	?	1.13
rs17843580	3e-64	HLA-DQA1 - HLA-DQB1	G	0.16
rs72743461	6e-63	SMAD3	?	1.15
rs340934	3e-62	RANBP6 - GTF3AP1	?	1.17
rs28407950	1e-59	HLA-DQA1 - HLA-DQB1	C	1.35
rs928412	3e-59	GTF3AP1 - IL33	?
rs78545931	9e-59	CFAP144P2 - IL1RL1	?	1.4
rs12123821	4e-55	CCDST	?
rs117097909	2e-51	GSDMB	?	1.29
rs12935657	1e-49	CLEC16A	?	1.13
rs2299012	1e-49	RAD50	?	1.14
rs61894547	6e-44	EMSY	?
rs9860547	4e-42	LPP	?	1.1
rs992969	7e-42	GTF3AP1 - IL33	A	1.25
rs1612986	8e-41	LINC02676 - LINC00709	?	1.13
rs12413578	9e-41	LINC02676 - LINC00709	?	1.18
rs928413	2e-40	GTF3AP1 - IL33	G	1.19
rs62408233	3e-38	BACH2	?	1.1

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90018895	Sakaue S	2021	27,712	411,131	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST90081472	Backman JD	2021	16,952	26,201	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081473	Backman JD	2021	16,952	280,473	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085458	Backman JD	2021	16,952	26,201	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90085459	Backman JD	2021	16,952	280,473	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90428823	Yu X	2024	13,962	317,337	Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.
GCST007800	Ferreira MAR	2019	13,962	300,671	Genetic Architectures of Childhood- and Adult-Onset Asthma Are Partly Distinct.
GCST009841	Zhu Z	2019	13,435	393,186	Shared Genetic and Experimental Links between Obesity-Related Traits and Asthma Subtypes in UK Biobank.
GCST008917	Zhu Z	2019	9,676	347,481	Shared Genetics of Asthma and Mental Health Disorders: A Large-Scale Genome-Wide Cross-Trait Analysis.
GCST007995	Pividori M	2019	9,433	318,237	Shared and distinct genetic risk factors for childhood-onset and adult-onset asthma: genome-wide and transcriptome-wide studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	5
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	50
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	24
intergenic_variant	18
regulatory_region_variant	4
missense_variant	1
stop_gained	1
5_prime_UTR_variant	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs4795399	17	39905186	T>A,C	0.05	intron_variant	GSDMB	1e-257	Tier 4: intronic/intergenic
rs72823641	2	102319699	T>A,C	0.05	intron_variant	IL18R1, IL1RL1	2e-136	Tier 4: intronic/intergenic
rs11651596	17	39899863	T>C	0.05	intergenic_variant	ZPBP2 - GSDMB	2e-124	Tier 4: intronic/intergenic
rs7848215	9	6213468	C>A,G,T	0.05	intergenic_variant	GTF3AP1 - IL33	5e-115	Tier 4: intronic/intergenic
rs9901146	17	39887090	G>A	0.49	intergenic_variant	ZPBP2 - GSDMB	8e-99	Tier 4: intronic/intergenic
rs1837253	5	111066174	T>C	0.05	intron_variant	BCLAF1P1 - TSLP	7e-94	Tier 4: intronic/intergenic
rs11236797	11	76588605	C>A	0.05	regulatory_region_variant	EMSY - LINC02757	1e-93	Tier 3: regulatory
rs5743618	4	38797027	C>A,G	0.05	missense_variant	TLR1	3e-74	Tier 1: coding
rs55646091	11	76588387	G>A	0.05	regulatory_region_variant	EMSY - LINC02757	6e-74	Tier 3: regulatory
rs61816761	1	152313385	G>A,C,T	0.05	stop_gained	FLG, CCDST	4e-73	Tier 1: coding
rs1861245	2	102350446	C>T	0.05	intron_variant	IL18R1, IL1RL1	2e-69	Tier 4: intronic/intergenic
rs34290285	2	241759225	G>A	0.05	intron_variant	D2HGDH	4e-69	Tier 4: intronic/intergenic
rs6594499	5	111134439	C>A	0.05	regulatory_region_variant	WDR36 - RPS3AP21	4e-66	Tier 3: regulatory
rs17843580	6	32647774	A>G	0.05	intergenic_variant	HLA-DQA1 - HLA-DQB1	3e-64	Tier 4: intronic/intergenic
rs72743461	15	67149412	C>A,T	0.05	intron_variant	SMAD3	6e-63	Tier 4: intronic/intergenic
rs340934	9	6081804	G>A,C,T	0.05	intergenic_variant	RANBP6 - GTF3AP1	3e-62	Tier 4: intronic/intergenic
rs28407950	6	32658571	C>G,T	0.244	intergenic_variant	HLA-DQA1 - HLA-DQB1	1e-59	Tier 4: intronic/intergenic
rs928412	9	6213148	A>C,G,T	0.05	intergenic_variant	GTF3AP1 - IL33	3e-59	Tier 4: intronic/intergenic
rs78545931	2	102265892	A>G	0.05	intron_variant	CFAP144P2 - IL1RL1	9e-59	Tier 4: intronic/intergenic
rs12123821	1	152206676	C>T	0.05	intron_variant	CCDST	4e-55	Tier 4: intronic/intergenic
rs117097909	17	39908718	G>A	0.05	intron_variant	GSDMB	2e-51	Tier 4: intronic/intergenic
rs12935657	16	11125184	G>A,T	0.05	intron_variant	CLEC16A	1e-49	Tier 4: intronic/intergenic
rs2299012	5	132581248	A>C,T	0.05	intron_variant	RAD50	1e-49	Tier 4: intronic/intergenic
rs61894547	11	76537586	C>G,T	0.05	intron_variant	EMSY	6e-44	Tier 4: intronic/intergenic
rs9860547	3	188411191	G>A,T	0.05	intron_variant	LPP	4e-42	Tier 4: intronic/intergenic
rs992969	9	6209697	A>C,G,T	0.252	intergenic_variant	GTF3AP1 - IL33	7e-42	Tier 4: intronic/intergenic
rs1612986	10	9022753	T>C	0.05	intergenic_variant	LINC02676 - LINC00709	8e-41	Tier 4: intronic/intergenic
rs12413578	10	9007290	C>G,T	0.05	intron_variant	LINC02676 - LINC00709	9e-41	Tier 4: intronic/intergenic
rs928413	9	6213387	G>A,C,T	0.25	intergenic_variant	GTF3AP1 - IL33	2e-40	Tier 4: intronic/intergenic
rs62408233	6	90266890	G>A	0.05	intron_variant	BACH2	3e-38	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
TNFRSF11A	TNFRSF11A	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
RORC	Orphanet:477857	Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
SEMA3E	Orphanet:138	CHARGE syndrome
SLC18A3	Orphanet:98914	Presynaptic congenital myasthenic syndromes
SLC18A3	Orphanet:994	Fetal akinesia deformation sequence
SLC22A5	Orphanet:158	Systemic primary carnitine deficiency
SMARCE1	Orphanet:1465	Coffin-Siris syndrome
SMARCE1	Orphanet:2495	Meningioma
SMARCE1	Orphanet:263662	Familial multiple meningioma
STAT5B	Orphanet:220465	Laron syndrome with immunodeficiency
STAT5B	Orphanet:520	Acute promyelocytic leukemia
STAT6	Orphanet:2126	Solitary fibrous tumor
STK11	Orphanet:2869	Peutz-Jeghers syndrome
SUOX	Orphanet:99731	Isolated sulfite oxidase deficiency
HNF1A	Orphanet:319303	Chromophobe renal cell carcinoma
HNF1A	Orphanet:324575	Hyperinsulinism due to HNF1A deficiency
HNF1A	Orphanet:404511	Clear cell papillary renal cell carcinoma
HNF1A	Orphanet:552	MODY
TNFRSF11A	Orphanet:1782	Dysosteosclerosis
TNFRSF11A	Orphanet:178389	Osteopetrosis-hypogammaglobulinemia syndrome
TNFRSF11A	Orphanet:2801	Juvenile Paget disease
TNFRSF11A	Orphanet:391490	Adult-onset myasthenia gravis
TNFRSF11A	Orphanet:85195	Familial expansile osteolysis
TNFSF11	Orphanet:667	Autosomal recessive malignant osteopetrosis
TNFSF15	Orphanet:186	Primary biliary cholangitis
TNFSF4	Orphanet:2073	Narcolepsy type 1
TNFSF4	Orphanet:536	Systemic lupus erythematosus
FASLG	Orphanet:3261	Autoimmune lymphoproliferative syndrome
TRAF3	Orphanet:1930	Herpes simplex virus encephalitis
TRIO	Orphanet:476126	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
XPR1	Orphanet:1980	Bilateral striopallidodentate calcinosis
IKZF3	Orphanet:67038	B-cell chronic lymphocytic leukemia
IKZF3	Orphanet:699590	Immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency
IKZF3	Orphanet:699593	Combined immunodeficiency-lymphopenia-cancer predisposing syndrome due to AIOLOS deficiency
ADAMTS10	Orphanet:3449	Weill-Marchesani syndrome
SERPINB7	Orphanet:140966	Palmoplantar keratoderma, Nagashima type
ABHD16A	Orphanet:631085	Autosomal recessive spastic paraplegia type 86
SLC44A4	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome

Cohort genes → proteins

75 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TRIM39	HGNC:10065	ENSG00000204599	Q9HCM9	E3 ubiquitin-protein ligase TRIM39	gwas
SNORD48	HGNC:10188	ENSG00000201823		small nucleolar RNA, C/D box 48	gwas
SNORD52	HGNC:10202	ENSG00000201754		small nucleolar RNA, C/D box 52	gwas
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
RORC	HGNC:10260	ENSG00000143365	P51449	Nuclear receptor ROR-gamma	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
CCL20	HGNC:10619	ENSG00000115009	P78556	C-C motif chemokine 20	gwas
SEMA3E	HGNC:10727	ENSG00000170381	O15041	Semaphorin-3E	gwas
SLC18A3	HGNC:10936	ENSG00000187714	Q16572	Vesicular acetylcholine transporter	gwas
SLC22A5	HGNC:10969	ENSG00000197375	O76082	Organic cation/carnitine transporter 2	gwas
BRAP	HGNC:1099	ENSG00000089234	Q7Z569	BRCA1-associated protein	gwas
SLC7A10	HGNC:11058	ENSG00000130876	Q9NS82	Asc-type amino acid transporter 1	gwas
SMARCE1	HGNC:11109	ENSG00000073584	Q969G3	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	gwas
BTF3P11	HGNC:1126	ENSG00000118903		basic transcription factor 3 pseudogene 11	gwas
STAT5A	HGNC:11366	ENSG00000126561	P42229	Signal transducer and activator of transcription 5A	gwas
STAT5B	HGNC:11367	ENSG00000173757	P51692	Signal transducer and activator of transcription 5B	gwas
STAT6	HGNC:11368	ENSG00000166888	P42226	Signal transducer and activator of transcription 6	gwas
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	gwas
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gwas
TAX1BP1	HGNC:11575	ENSG00000106052	Q86VP1	Tax1-binding protein 1	gwas
TBX21	HGNC:11599	ENSG00000073861	Q9UL17	T-box transcription factor TBX21	gwas
HNF1A	HGNC:11621	ENSG00000135100	P20823	Hepatocyte nuclear factor 1-alpha	gwas
TCF19	HGNC:11629	ENSG00000137310	Q9Y242	Transcription factor 19	gwas
TCP11	HGNC:11658	ENSG00000124678	Q8WWU5	T-complex protein 11 homolog	gwas
TLE4	HGNC:11840	ENSG00000106829	Q04727	Transducin-like enhancer protein 4	gwas
TLR1	HGNC:11847	ENSG00000174125	Q15399	Toll-like receptor 1	gwas
TSPAN8	HGNC:11855	ENSG00000127324	P19075	Tetraspanin-8	gwas
TM9SF2	HGNC:11865	ENSG00000125304	Q99805	Transmembrane 9 superfamily member 2	gwas
TMSB4X	HGNC:11881	ENSG00000205542	P62328	Thymosin beta-4	gwas
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	gwas
TNFRSF11A	HGNC:11908	ENSG00000141655	Q9Y6Q6	Tumor necrosis factor receptor superfamily member 11A	gwas
TNFSF11	HGNC:11926	ENSG00000120659	O14788	Tumor necrosis factor ligand superfamily member 11	gwas
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
TNFSF18	HGNC:11932	ENSG00000120337	Q9UNG2	Tumor necrosis factor ligand superfamily member 18	gwas
TNFSF4	HGNC:11934	ENSG00000117586	P23510	Tumor necrosis factor ligand superfamily member 4	gwas
FASLG	HGNC:11936	ENSG00000117560	P48023	Tumor necrosis factor ligand superfamily member 6	gwas
TPD52	HGNC:12005	ENSG00000076554	P55327	Tumor protein D52	gwas
TRAF3	HGNC:12033	ENSG00000131323	Q13114	TNF receptor-associated factor 3	gwas
CRNN	HGNC:1230	ENSG00000143536	Q9UBG3	Cornulin	gwas
TRIO	HGNC:12303	ENSG00000038382	O75962	Triple functional domain protein	gwas
VARS1	HGNC:12651	ENSG00000204394	P26640	Valine–tRNA ligase	gwas
WNT11	HGNC:12776	ENSG00000085741	O96014	Protein Wnt-11	gwas
XPR1	HGNC:12827	ENSG00000143324	Q9UBH6	Solute carrier family 53 member 1	gwas
TRIM26	HGNC:12962	ENSG00000234127	Q12899	Tripartite motif-containing protein 26	gwas
ZNF217	HGNC:13009	ENSG00000171940	O75362	Zinc finger protein 217	gwas
TSHZ2	HGNC:13010	ENSG00000182463	Q9NRE2	Teashirt homolog 2	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
ADAMTS10	HGNC:13201	ENSG00000142303	Q9H324	A disintegrin and metalloproteinase with thrombospondin motifs 10	gwas
GSDMA	HGNC:13311	ENSG00000167914	Q96QA5	Gasdermin-A	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRIM39	E3 ubiquitin-protein ligase TRIM39	E3 ubiquitin-protein ligase.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RORC	Nuclear receptor ROR-gamma	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
CXCR5	C-X-C chemokine receptor type 5	Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
CCL20	C-C motif chemokine 20	Acts as a ligand for C-C chemokine receptor CCR6.
SEMA3E	Semaphorin-3E	Plays an important role in signaling via the cell surface receptor PLXND1.
SLC18A3	Vesicular acetylcholine transporter	Electrogenic antiporter that exchanges one cholinergic neurotransmitter, acetylcholine or choline, with two intravesicular protons across the membrane of synaptic vesicles.
SLC22A5	Organic cation/carnitine transporter 2	Sodium-ion dependent, high affinity carnitine transporter.
BRAP	BRCA1-associated protein	Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein.
SLC7A10	Asc-type amino acid transporter 1	Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane.
SMARCE1	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1	Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
STAT5A	Signal transducer and activator of transcription 5A	Carries out a dual function: signal transduction and activation of transcription.
STAT5B	Signal transducer and activator of transcription 5B	Carries out a dual function: signal transduction and activation of transcription.
STAT6	Signal transducer and activator of transcription 6	Carries out a dual function: signal transduction and activation of transcription.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
SUOX	Sulfite oxidase, mitochondrial	Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
TAX1BP1	Tax1-binding protein 1	Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation.
TBX21	T-box transcription factor TBX21	Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs.
HNF1A	Hepatocyte nuclear factor 1-alpha	Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver.
TCF19	Transcription factor 19	Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition.
TCP11	T-complex protein 11 homolog	Plays a role in the process of sperm capacitation and acrosome reactions.
TLE4	Transducin-like enhancer protein 4	Transcriptional corepressor that binds to a number of transcription factors.
TLR1	Toll-like receptor 1	Participates in the innate immune response to microbial agents.
TSPAN8	Tetraspanin-8	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.
TM9SF2	Transmembrane 9 superfamily member 2	In the intracellular compartments, may function as a channel or small molecule transporter.
TMSB4X	Thymosin beta-4	Plays an important role in the organization of the cytoskeleton.
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
TNFRSF11A	Tumor necrosis factor receptor superfamily member 11A	Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis.
TNFSF11	Tumor necrosis factor ligand superfamily member 11	Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
TNFSF18	Tumor necrosis factor ligand superfamily member 18	Cytokine that binds to TNFRSF18/AITR/GITR.
TNFSF4	Tumor necrosis factor ligand superfamily member 4	Cytokine that binds to TNFRSF4.
FASLG	Tumor necrosis factor ligand superfamily member 6	Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells.
TRAF3	TNF receptor-associated factor 3	Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in…
CRNN	Cornulin	Promotes cell proliferation, G1/S cell cycle progression and induces expression of the cell cycle regulator CCND1.
TRIO	Triple functional domain protein	Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases.
VARS1	Valine–tRNA ligase	Catalyzes the attachment of valine to tRNA(Val).
WNT11	Protein Wnt-11	Ligand for members of the frizzled family of seven transmembrane receptors.
XPR1	Solute carrier family 53 member 1	Inorganic ion transporter that mediates phosphate ion export across the plasma membrane.
TRIM26	Tripartite motif-containing protein 26	E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs).
ZNF217	Zinc finger protein 217	Binds to the promoters of target genes and functions as repressor.
TSHZ2	Teashirt homolog 2	Probable transcriptional regulator involved in developmental processes.
IKZF3	Zinc finger protein Aiolos	Transcription factor that plays an important role in the regulation of lymphocyte differentiation.
ADAMTS10	A disintegrin and metalloproteinase with thrombospondin motifs 10	Metalloprotease that participate in microfibrils assembly.
GSDMA	Gasdermin-A	This form constitutes the precursor of the pore-forming protein and acts as a sensor of infection: upon infection by S.pyogenes, specifically cleaved by S.pyogenes effector protein SpeB in epithelial cells, releasing the N-terminal moiety…
SLC6A15	Sodium-dependent neutral amino acid transporter B(0)AT2	Functions as a sodium-dependent neutral amino acid transporter.
SCUBE3	Signal peptide, CUB and EGF-like domain-containing protein 3	Is a positive regulator of the BMP signaling pathway, required for proper chondrogenesis, osteogenesis and skeletal development.
NEUROD4	Neurogenic differentiation factor 4	Probably acts as a transcriptional activator.
SERPINB7	Serpin B7	Might function as an inhibitor of Lys-specific proteases.

Protein-family classification

Druggable: 13 · Difficult: 18 · Unknown: 44 · Druggable fraction: 0.17

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	2	10.3×	0.162
Transcription factor	15	1.6×	0.168
Transporter	3	3.1×	0.241
Other/Unknown	44	1.1×	0.883
Antibody/Immunoglobulin	2	0.8×	0.989
Kinase	2	0.7×	0.989
Scaffold/PPI	3	0.7×	0.989
Protease	1	0.5×	0.989
Enzyme (other)	2	0.3×	0.989
GPCR	1	0.3×	0.989

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TRIM39	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
SNORD48	Other/Unknown	no
SNORD52	Other/Unknown	no
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RORC	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
CCL20	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Chemokine_CC_DCCL
SEMA3E	Antibody/Immunoglobulin	yes		Semap_dom, Ig-like_dom, Immunoglobulin_dom
SLC18A3	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC22A5	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
BRAP	Transcription factor	no		Znf_UBP, Znf_RING, BRAP2/ETP1_RRM
SLC7A10	Transporter	yes		AA/rel_permease1, AminoAcid_Transporter
SMARCE1	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf
BTF3P11	Other/Unknown	no
STAT5A	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT5B	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT6	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SUOX	Enzyme (other)	yes	1.8.3.1	OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
TAX1BP1	Other/Unknown	no		CALCOCO1-like, SKICH, CALCOCO1/2_Zn_UBZ1
TBX21	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
HNF1A	Transcription factor	no		HD, HNF1b_C, HNF1a_C
TCF19	Transcription factor	no		FHA_dom, Znf_PHD, SMAD_FHA_dom_sf
TCP11	Other/Unknown	no		Tcp11
TLE4	Scaffold/PPI	no		WD40_rpt, Groucho/TLE_N, Groucho_enhance
TLR1	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TSPAN8	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
TM9SF2	Other/Unknown	no		EMP70
TMSB4X	Other/Unknown	no		Beta-thymosin, Beta-thymosin_sf
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
TNFRSF11A	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_11, TNFR_11A
TNFSF11	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_ligand_10/11
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF18	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNFSF18
TNFSF4	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
FASLG	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TPD52	Other/Unknown	no		TPD52
TRAF3	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom
CRNN	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, S100_Ca-bd_sub
TRIO	Kinase	yes		DH_dom, Prot_kinase_dom, CRAL-TRIO_dom
VARS1	Enzyme (other)	yes	6.1.1.9	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Valyl-tRNA_ligase
WNT11	Other/Unknown	no		Wnt, Wnt_CS, Wnt_C
XPR1	Other/Unknown	no		SPX_dom, EXS_C
TRIM26	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
ZNF217	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Krueppel_C2H2-ZF
TSHZ2	Transcription factor	no		HD, Znf_C2H2_type, Teashirt_fam
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
ADAMTS10	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
GSDMA	Other/Unknown	no		Gasdermin, Gasdermin_pore, Gasdermin_PUB

Expression context

Cohort genes with no expression data: 0.

56 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)	1
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	11
left testis	10
right testis	8
monocyte	8
leukocyte	7
primordial germ cell in gonad	6
male germ line stem cell (sensu Vertebrata) in testis	6
lymph node	5
cortical plate	5
testis	5
blood	5
ventricular zone	5
liver	4
sural nerve	4
cartilage tissue	4
right lobe of liver	4
jejunal mucosa	4
skin of leg	4
zone of skin	4
epithelium of nasopharynx	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRIM39	134	ubiquitous	yes	granulocyte, primordial germ cell in gonad, left testis
SNORD48	74	tissue_specific	yes	sural nerve, vermiform appendix, liver
SNORD52	8	tissue_specific	yes	sural nerve, Brodmann (1909) area 9, liver
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
RORC	209	broad	marker	gastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
CCL20	202	broad	marker	epithelium of nasopharynx, cartilage tissue, gall bladder
SEMA3E	197	broad	marker	cortical plate, calcaneal tendon, blood vessel layer
SLC18A3	60	tissue_specific	yes	primordial germ cell in gonad, endometrium epithelium, putamen
SLC22A5	235	ubiquitous	marker	gastrocnemius, mucosa of transverse colon, muscle of leg
BRAP	286	ubiquitous	marker	left testis, right testis, testis
SLC7A10	138	broad	yes	omental fat pad, peritoneum, adipose tissue of abdominal region
SMARCE1	197	ubiquitous	marker	calcaneal tendon, embryo, ganglionic eminence
BTF3P11	76		yes	male germ line stem cell (sensu Vertebrata) in testis, endometrium epithelium, Brodmann (1909) area 10
STAT5A	190	ubiquitous	marker	granulocyte, monocyte, leukocyte
STAT5B	295	ubiquitous	marker	blood, body of uterus, left uterine tube
STAT6	292	ubiquitous	marker	granulocyte, right ovary, left ovary
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
SUOX	267	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex
TAX1BP1	301	ubiquitous	marker	secondary oocyte, oocyte, bronchial epithelial cell
TBX21	149	broad	marker	granulocyte, blood, male germ line stem cell (sensu Vertebrata) in testis
HNF1A	81	tissue_specific	yes	right lobe of liver, mucosa of transverse colon, liver
TCF19	133	ubiquitous	yes	primordial germ cell in gonad, ventricular zone, lymph node
TCP11	156	tissue_specific	marker	sperm, male germ cell, left testis
TLE4	288	ubiquitous	marker	cranial nerve II, left testis, right testis
TLR1	218	broad	marker	monocyte, mononuclear cell, leukocyte
TSPAN8	262	broad	marker	colonic mucosa, mucosa of sigmoid colon, jejunal mucosa
TM9SF2	295	ubiquitous	marker	mucosa of sigmoid colon, bronchial epithelial cell, colonic mucosa
TMSB4X	137	ubiquitous	marker	monocyte, leukocyte, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 45.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNF	11,116
VARS1	5,848
DDX39B	5,600
STK11	5,146
FASLG	4,373
STAT5A	4,153
STAT5B	3,986
TRAF3	3,493
SUOX	3,449
TNFSF11	3,410

Intra-cohort edges

A	B	Sources
ABHD16A	DDX39B	string_interaction
ABHD16A	GPANK1	string_interaction
ABHD16A	LY6G5B	string_interaction
ABHD16A	LY6G5C	string_interaction
ABHD16A	PRRC2A	string_interaction
APOM	GPANK1	string_interaction
BACH2	TSHZ2	intact
BAG6	PRRC2A	string_interaction
C6orf15	CCHCR1	string_interaction
C6orf15	TCF19	string_interaction
CCHCR1	TCF19	string_interaction
DMRTA1	STAT5B	biogrid_interaction, intact
FASLG	TNF	string_interaction
GPANK1	LY6G5B	string_interaction
GPANK1	LY6G5C	string_interaction
GPANK1	LY6G6C	string_interaction
GPANK1	PRRC2A	string_interaction
LY6G5B	LY6G5C	string_interaction
LY6G5B	LY6G6C	string_interaction
LY6G5B	LY6G6F	string_interaction
LY6G5B	MPIG6B	string_interaction
LY6G5C	LY6G6C	string_interaction
LY6G5C	LY6G6F	string_interaction
LY6G5C	VWA7	string_interaction
LY6G6C	LY6G6F	string_interaction
LY6G6C	MPIG6B	string_interaction
LY6G6C	SAPCD1	string_interaction
LY6G6C	VWA7	string_interaction
LY6G6F	MPIG6B	string_interaction
LY6G6F	SAPCD1	string_interaction
LY6G6F	VWA7	string_interaction
RORC	TBX21	string_interaction
SAPCD1	VWA7	string_interaction
SCUBE3	TCP11	string_interaction
SMARCE1	TSHZ2	string_interaction
STAT5A	STAT5B	intact
STAT5B	SUOX	intact
STAT6	TBX21	string_interaction
TLR1	TNF	string_interaction
TNF	TNFRSF11A	string_interaction
TNFRSF11A	TNFSF11	intact, string_interaction
TNFRSF11A	TRAF3	biogrid_interaction
TNFSF15	TNFSF18	string_interaction
TNFSF18	TNFSF4	string_interaction
VARS1	VWA7	string_interaction

Structural data

PDB: 36 · AlphaFold-only: 35 · No structure: 4

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RORC	P51449	161
TNF	P01375	52
XPR1	Q9UBH6	51
LSM2	Q9Y333	20
DDX39B	Q13838	17
SLC18A3	Q16572	11
TAX1BP1	Q86VP1	10
TRAF3	Q13114	10
BAG6	P46379	10
SMARCE1	Q969G3	8
STAT6	P42226	7
TNFSF15	O95150	7
TNFSF18	Q9UNG2	7
CCL20	P78556	6
HNF1A	P20823	6
TLR1	Q15399	6
STAT5A	P42229	5
SLC7A10	Q9NS82	4
STK11	Q15831	4
TRIO	O75962	4
ZNF217	O75362	4
DOCK9	Q9BZ29	4
TRIM39	Q9HCM9	3
RORA	P35398	3
SLC22A5	O76082	3
TMSB4X	P62328	3
FASLG	P48023	3
APOM	O95445	3
STAT5B	P51692	2
TNFSF11	O14788	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
WNT11	O96014	90.35
SERPINB7	O75635	89.91
ABHD16A	O95870	89.90
VARS1	P26640	88.12
TSPAN8	P19075	87.75
TM9SF2	Q99805	84.95
LY6G6C	O95867	84.90
SEMA3E	O15041	84.62
VWA7	Q9Y334	84.03
SLC44A4	Q53GD3	83.79
TRIM26	Q12899	83.49
CXCR5	P32302	80.85
GSDMA	Q96QA5	80.60
SLC6A15	Q9H2J7	80.15
LY6G5C	Q5SRR4	79.53
CCHCR1	Q8TD31	79.52
TCP11	Q8WWU5	78.50
SCUBE3	Q8IX30	77.61
LY6G6F	Q5SQ64	77.31
BRAP	Q7Z569	76.92
LY6G5B	Q8NDX9	76.66
SAPCD1	Q5SSQ6	75.98
ADAMTS10	Q9H324	73.88
GPANK1	O95872	71.48
TPD52	P55327	69.11
TLE4	Q04727	68.88
TCF19	Q9Y242	63.17
NEUROD4	Q9HD90	63.06
TBX21	Q9UL17	61.95
DMRTA1	Q5VZB9	57.14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 590. Enrichment computed across 250 evidence-associated genes (127 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 127 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	8	9.2×	0.001	STAT5A, STAT5B, STAT6, TBX21, TBL1XR1, ETS1, GATA3, IL13
TNFs bind their physiological receptors	5	15.5×	0.004	TNFSF11, TNFSF15, TNFSF18, TNFSF4, FASLG
Interleukin-4 and Interleukin-13 signaling	7	5.7×	0.046	RORA, RORC, STAT6, TNF, FASLG, GATA3, IL13
Interleukin-33 signaling	2	60.0×	0.054	IL33, IL1RL1
Negative regulators of DDX58/IFIH1 signaling	4	10.3×	0.056	TAX1BP1, TRAF3, CYLD, ATG5
TNFR2 non-canonical NF-kB pathway	5	7.1×	0.056	TNF, TNFRSF11A, TNFSF11, FASLG, TRAF3
Interferon gamma signaling	6	5.9×	0.056	TRIM26, HLA-B, HLA-C, HLA-DPA1, HLA-DQA1, HLA-DQB1
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	3	15.9×	0.060	TNFRSF11A, TNFSF11, TRAF3
Translocation of ZAP-70 to Immunological synapse	3	15.0×	0.064	CD247, HLA-DPA1, HLA-DQA1
Phosphorylation of CD3 and TCR zeta chains	3	12.8×	0.091	CD247, HLA-DPA1, HLA-DQA1
Co-inhibition by PD-1	3	12.3×	0.095	CD247, HLA-DPA1, HLA-DQA1
Erythropoietin activates STAT5	2	25.7×	0.099	STAT5A, STAT5B
STAT5 Activation	2	25.7×	0.099	STAT5A, STAT5B
Loss of function of MECP2 in Rett syndrome	2	22.5×	0.099	CAMK4, TBL1XR1
Pervasive developmental disorders	2	22.5×	0.099	CAMK4, TBL1XR1
Interleukin-18 signaling	2	22.5×	0.099	IL13, IL18R1
Disorders of Developmental Biology	2	22.5×	0.099	CAMK4, TBL1XR1
Disorders of Nervous System Development	2	22.5×	0.099	CAMK4, TBL1XR1
Attenuation phase	3	9.6×	0.099	HSPA1A, HSPA1B, HSPA1L
RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	3	9.6×	0.099	RORA, RORC, TBL1XR1
Regulation of TNFR1 signaling	4	7.0×	0.099	TAX1BP1, TNF, OTULIN, CYLD
Signaling by Interleukins	7	3.5×	0.099	RORA, RORC, CCL20, STAT5A, STAT5B, STAT6, ANXA2
Cytokine Signaling in Immune system	9	2.9×	0.099	RORA, RORC, CCL20, STAT5A, STAT5B, STAT6, FASLG, SH2B3 (+1 more)
Immune System	19	1.9×	0.099	RORA, RORC, CCL20, STAT5A, STAT5B, STAT6, TAX1BP1, FASLG (+11 more)
Interleukin-9 signaling	2	20.0×	0.099	STAT5A, STAT5B
FGFR1 mutant receptor activation	2	18.0×	0.099	STAT5A, STAT5B
Interleukin-21 signaling	2	18.0×	0.099	STAT5A, STAT5B
Signaling by KIT in disease	2	18.0×	0.099	STAT5A, STAT5B
FLT3 signaling in disease	2	18.0×	0.099	STAT5A, STAT5B
STAT5 activation downstream of FLT3 ITD mutants	2	18.0×	0.099	STAT5A, STAT5B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 201 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	22	5.2×	5e-07	CXCR5, CCL20, TLR1, TNF, TNFSF11, TNFSF15, TNFSF4, LST1 (+14 more)
positive regulation of inflammatory response	11	8.0×	1e-04	STAT5A, STAT5B, TNF, TNFSF18, TNFSF4, IL33, TLR6, CEBPA (+3 more)
positive regulation of interleukin-6 production	10	8.3×	2e-04	TLR1, TNF, TNFSF4, IL33, TLR6, TSLP, AIF1, FCER1G (+2 more)
regulation of steroid metabolic process	4	47.9×	3e-04	RORA, RORC, STAT5A, STAT5B
Peyer’s patch development	4	41.9×	4e-04	RORC, STAT5A, STAT5B, ID2
positive regulation of macrophage activation	5	21.0×	8e-04	IL33, TLR6, CEBPA, IL13, IL1RL1
positive regulation of extrinsic apoptotic signaling pathway	6	13.6×	0.001	TNF, TNFSF11, TNFSF15, FASLG, TLR6, CYLD
positive regulation of interleukin-5 production	4	27.9×	0.002	IL33, TSLP, GATA3, IL1RL1
microglial cell activation	5	15.5×	0.002	TLR1, TNF, TLR6, AIF1, IL13
positive regulation of chemokine production	6	11.2×	0.002	TNF, TNFSF4, IL33, TSLP, AIF1, IL1RL1
positive regulation of interleukin-13 production	4	22.4×	0.003	TNFSF4, IL33, TSLP, GATA3
tumor necrosis factor-mediated signaling pathway	6	9.9×	0.003	TMSB4X, TNF, TNFRSF11A, TNFSF11, TNFSF18, TRAF3
adaptive immune response	11	4.6×	0.003	TNFRSF11A, TNFSF18, CAMK4, CD247, HLA-B, HLA-C, HLA-DPA1, HLA-DQA1 (+3 more)
inflammatory response	17	3.2×	0.003	CCL20, TLR1, TNF, TNFSF4, CAMK4, TLR10, CCR7, TLR6 (+9 more)
negative regulation of transcription by RNA polymerase II	27	2.4×	0.003	RORC, STAT6, TBX21, TLE4, TNF, TNFSF11, TNFSF4, FASLG (+19 more)
positive regulation of erythrocyte differentiation	5	12.7×	0.004	STAT5B, ETS1, HSPA1A, HSPA1B, ID2
positive regulation of type 2 immune response	3	35.9×	0.005	TNFSF4, IL33, NOD2
negative regulation of T-helper 17 cell lineage commitment	3	35.9×	0.005	STAT5A, TBX21, TNFSF18
obsolete positive regulation of NF-kappaB transcription factor activity	7	7.2×	0.005	TNF, TNFSF18, CRNN, HSPA1A, HSPA1B, NOD2, IL18R1
positive regulation of T-helper 1 cell cytokine production	3	31.4×	0.007	TBX21, IL18R1, IL1R1
positive regulation of fever generation by positive regulation of prostaglandin secretion	2	83.8×	0.009	TNFRSF11A, TNFSF11
regulation of epithelial cell differentiation	3	27.9×	0.009	STAT5A, STAT5B, GATA3
positive regulation of interleukin-10 production	5	10.0×	0.009	TNFSF4, TSLP, FCER1G, NOD2, IL13
positive regulation of non-canonical NF-kappaB signal transduction	6	7.6×	0.009	TNF, TNFRSF11A, TNFSF11, TRIM26, NOD2, IL18R1
mammary gland epithelial cell proliferation	3	22.9×	0.015	STAT6, TNFSF11, ID2
growth hormone receptor signaling pathway via JAK-STAT	3	22.9×	0.015	STAT5A, STAT5B, STAT6
osteoclast differentiation	5	8.6×	0.016	TNF, TNFRSF11A, TNFSF11, SBNO2, FCER1G
immune response-activating cell surface receptor signaling pathway	2	55.9×	0.017	BAG6, NCR3
negative regulation of mast cell apoptotic process	2	55.9×	0.017	STAT5A, FCER1G
regulation of lymphocyte differentiation	2	55.9×	0.017	IKZF3, NDFIP1

Therapeutics

Drug target analysis

Approved (phase 4): 9 · Phase ≥3: 10 · Phased (≥1): 10 · Undrugged: 65

Druggability breadth: 75 of 250 evidence-associated genes (30%) 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
RORA	TRETINOIN
RORC	DIGOXIN
STAT5A	MOMELOTINIB
STAT6	THIORIDAZINE HYDROCHLORIDE
STK11	FEDRATINIB
TNF	PREDNISOLONE
IKZF3	POMALIDOMIDE
SLC6A15	LORATADINE
ABHD16A	ORLISTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STK11	17	4
TNF	12	4
STAT6	11	4
RORC	9	4
IKZF3	5	4
STAT5A	4	4
RORA	2	4
STAT5B	1	3
SLC6A15	1	4
ABHD16A	1	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRETINOIN	4	RORA, RORC
DIGOXIN	4	RORC
ALITRETINOIN	4	RORC
MOMELOTINIB	4	STAT5A
THIORIDAZINE HYDROCHLORIDE	4	STAT6
DOXORUBICIN HYDROCHLORIDE	4	STAT6
AMSACRINE	4	STAT6
ADENOSINE	4	STAT6
AMANTADINE	4	STAT6
BISACODYL	4	STAT6
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IKZF3, TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	IKZF3, TNF
THALIDOMIDE	4	IKZF3
LORATADINE	4	SLC6A15
ORLISTAT	4	ABHD16A
SURAMIN HEXASODIUM	3	STAT5A, STAT5B
LESTAURTINIB	3	STAT5A, STK11
QUERCETIN	3	STAT6
TIAPRIDE	3	STAT6
DINACICLIB	3	STK11
DOVITINIB	3	STK11
RUBOXISTAURIN	3	STK11

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 3.

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

Symbol	Assays	Type breakdown
RORC	758	Binding:707, Functional:50, Unclassified:1
STK11	244	Binding:244
STAT5A	199	Binding:199
TNF	193	Binding:162, Functional:31
RORA	115	Binding:111, Functional:3, Unclassified:1
IKZF3	101	Binding:100, Functional:1
SLC22A5	97	Functional:79, ADMET:18
STAT6	81	Binding:77, Functional:4
TLR1	59	Binding:59
STAT5B	55	Binding:55
CXCR5	33	Binding:21, Functional:12
TNFSF11	30	Binding:30
SLC18A3	17	Binding:17
ABHD16A	13	Binding:13
SMARCE1	7	Binding:7
VARS1	7	Binding:7
ATXN2	5	Binding:3, Functional:2
SLC6A15	5	Binding:5
BACH2	3	Binding:3
BRAP	2	Binding:2
FASLG	2	Binding:2
TRIO	2	Binding:2
HNF1A	1	Binding:1
TM9SF2	1	Binding:1
TMSB4X	1	Binding:1
DDX39B	1	Binding:1
PRRC2A	1	Binding:1
BAG6	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
STK11	2.7.11.1	non-specific serine/threonine protein kinase
SUOX	1.8.3.1	sulfite oxidase
VARS1	6.1.1.9	valine-tRNA ligase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RORA	115
RORC	758
STAT5A	199
STK11	244
TNF	193
IKZF3	101

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; 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)
TRETINOIN	4	RORA, RORC
DIGOXIN	4	RORC
ALITRETINOIN	4	RORC
MOMELOTINIB	4	STAT5A
THIORIDAZINE HYDROCHLORIDE	4	STAT6
DOXORUBICIN HYDROCHLORIDE	4	STAT6
AMSACRINE	4	STAT6
ADENOSINE	4	STAT6
AMANTADINE	4	STAT6
BISACODYL	4	STAT6
FEDRATINIB	4	STK11
PACRITINIB	4	STK11
NINTEDANIB	4	STK11
SUNITINIB	4	STK11
MIDOSTAURIN	4	STK11
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IKZF3, TNF
PENTOXIFYLLINE	4	TNF
MESALAMINE	4	TNF
LENALIDOMIDE	4	IKZF3, TNF
THALIDOMIDE	4	IKZF3
LORATADINE	4	SLC6A15
ORLISTAT	4	ABHD16A
SURAMIN HEXASODIUM	3	STAT5A, STAT5B
LESTAURTINIB	3	STAT5A, STK11
QUERCETIN	3	STAT6
TIAPRIDE	3	STAT6
DINACICLIB	3	STK11
DOVITINIB	3	STK11
RUBOXISTAURIN	3	STK11

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	9	RORA, RORC, STAT5A, STAT6, STK11, TNF, IKZF3, SLC6A15, ABHD16A
B	Phased (≥1) drug, not yet approved	1	STAT5B
C	Druggable family + PDB, no drug	5	SLC18A3, SLC22A5, SLC7A10, SUOX, TRIO
D	Druggable family + AlphaFold only, no drug	5	CXCR5, SEMA3E, VARS1, ADAMTS10, LY6G6F
E	Difficult family or no structure, no drug	55	TRIM39, SNORD48, SNORD52, ATXN2, CCL20, BRAP, SMARCE1, BTF3P11, TAX1BP1, TBX21 (+45 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRRC2A	1	ABHD16A
GPANK1	0	ABHD16A
LY6G5C	0	ABHD16A
TRIM39	0	—
SNORD48	0	—
SNORD52	0	—
ATXN2	5	—
CXCR5	33	—
CCL20	0	—
SEMA3E	0	—
SLC18A3	17	—
SLC22A5	97	—
BRAP	2	—
SLC7A10	0	—
SMARCE1	7	—
BTF3P11	0	—
SUOX	0	—
TAX1BP1	0	—
TBX21	0	—
HNF1A	1	—
TCF19	0	—
TCP11	0	—
TLE4	0	—
TLR1	59	—
TSPAN8	0	—
TM9SF2	1	—
TMSB4X	1	—
TNFRSF11A	0	—
TNFSF11	30	—
TNFSF15	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 62.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	56
EARLY_PHASE1	2
PHASE4	1
PHASE3	1
PHASE2/PHASE3	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01997463	PHASE4	COMPLETED	Supervised Asthma Medication in Schools (SAMS)
NCT06223828	PHASE2/PHASE3	RECRUITING	Azithromycin for Critical Asthma - Pediatrics
NCT01450774	PHASE3	COMPLETED	Comparison of Combination of Beclomethasone Dipropionate and Formoterol Fumarate Versus Single Components Assessed by Knemometry and Urinary Cortisol Measurements in Asthmatic Children
NCT01326182	PHASE2	COMPLETED	Intervention for Depressed Latina Mothers of Children With Asthma
NCT04250779	EARLY_PHASE1	UNKNOWN	Evaluating Efficacy of Smart Device in Assisting With Inhaler Technique and Adherence
NCT04617015	EARLY_PHASE1	COMPLETED	Defining and Treating Depression-related Asthma
NCT03842033	Not specified	ACTIVE_NOT_RECRUITING	Implementing a Guidelines-Based M-Health Intervention for High Risk Asthma Patients
NCT05105386	Not specified	NOT_YET_RECRUITING	The Impact of Synergies of Indoor Air Pollutants on Childhood Health and Wellbeing
NCT05608668	Not specified	RECRUITING	Inspiratory Pulmonary Rehabilitation for Children With Obesity and Asthma
NCT05945355	Not specified	RECRUITING	Mechanistic Study of Inspiratory Training in Childhood Asthma (MICA)
NCT05999032	Not specified	RECRUITING	The Puerto Rico Asthma Integrated Response Program (PR-AIR)
NCT06278662	Not specified	RECRUITING	Cohort Multiple Randomized Controlled Trial in Pediatric Asthma
NCT06321471	Not specified	ACTIVE_NOT_RECRUITING	AeviceMD for Pediatric Asthma Management
NCT06388460	Not specified	RECRUITING	Asthma Link Effectiveness Trial
NCT06535087	Not specified	RECRUITING	The Impact of Airway Allergic Diseases on Children’s and Parents’ Quality of Life
NCT06691971	Not specified	RECRUITING	AeviceMD for Detection of Wheeze in Pediatric and Adult Populations
NCT06902766	Not specified	RECRUITING	Towards Digital Management of Paediatric Asthma
NCT06903897	Not specified	RECRUITING	Social Needs Screening and Chronic Diseases Study (WE CARE)
NCT06974331	Not specified	NOT_YET_RECRUITING	Effect of Multimedia Protocol About Asthma Control
NCT07047430	Not specified	RECRUITING	The Airports, Air Quality, and Asthma (AAA) Study
NCT07261423	Not specified	RECRUITING	Pollution Intervention to Impact Kids Asthma Study
NCT07369817	Not specified	NOT_YET_RECRUITING	Optimization and Testing of ALRITE, a Clinical Decision Support Tool for Management of Respiratory Illnesses in Young Children in Primary Care Health Facilities in Uganda
NCT07381790	Not specified	RECRUITING	Modern Technologies in Lower Respiratory Tract Infections in Children
NCT07397676	Not specified	ACTIVE_NOT_RECRUITING	Quality of Life - Effects of a Physical Therapy Intervention to for Children and Adolescents With Asthma
NCT07453667	Not specified	NOT_YET_RECRUITING	Humidity Asthma Interventions for Low Socioeconomic Status Children
NCT07472283	Not specified	NOT_YET_RECRUITING	Design, Development and Evaluation of a Digital Health Assistant for Paediatric Asthma
NCT07500532	Not specified	RECRUITING	Evaluation of the Medentum Diagnostik Platform for Pediatric ENT Conditions and Asthma
NCT07582211	Not specified	NOT_YET_RECRUITING	Bilevel Positive Airway Pressure (BPAP) for Severe Asthma
NCT00204828	Not specified	COMPLETED	T Regulatory and Childhood Asthma
NCT00839046	Not specified	COMPLETED	A Community-based Participatory Research (CBPR) Intervention for Childhood Asthma Using Air Filters and Air Conditioners
NCT01451944	Not specified	WITHDRAWN	Effect of Home Health Case Management on Asthma Morbidity
NCT01472471	Not specified	COMPLETED	Urinary 8-isoprostane is Elevated in Acute Childhood Asthma
NCT01650844	Not specified	COMPLETED	School-Based Telemedicine Enhanced Asthma Management
NCT02068573	Not specified	COMPLETED	AsthmaVent - Effect of Mechanical Ventilation on Asthma Control in Children
NCT02205723	Not specified	WITHDRAWN	Smartphone-facilitated Asthma Control
NCT02341573	Not specified	COMPLETED	Experienced Chinese Herbal Formulas on Pediatric Asthma
NCT02404103	Not specified	COMPLETED	Flunisolide HFA in Children With Small Airway Disease
NCT02405962	Not specified	COMPLETED	Training Parents by Acceptance and Commitment Therapy for Managing Childhood Asthma Care
NCT02451709	Not specified	COMPLETED	STudy of Asthma Adherence Reminders
NCT02678949	Not specified	UNKNOWN	Changes in the Lung Clearance Index in Pediatric Patients With Asthma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BECLOMETHASONE DIPROPIONATE	4	1
IPRATROPIUM BROMIDE	4	1
CHEMBL1319520	0	1
CHEMBL4299381	0	1
CHEMBL1237108	0	1
CHEMBL1908368	0	1