Allergic rhinitis

Summary

Allergic rhinitis (MONDO:0011786) is a disease with 75 cohort genes (357 GWAS associations across 37 studies) and 764 clinical trials. The dominant Reactome pathway is Interleukin-4 and Interleukin-13 signaling (7 cohort genes). Top therapeutic interventions include azelastine, fexofenadine, and cetirizine.

At a glance

• Cohort genes: 75
• GWAS associations: 357
• Clinical trials: 764

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	allergic rhinitis
Mondo ID	MONDO:0011786
EFO	EFO:0005854
DOID	DOID:4481
ICD-11	1711769234
NCIT	C79532
SNOMED CT	61582004
UMLS	C2607914
MedGen	382012
Is cancer (heuristic)	no

Also known as: allergic form of rhinitis · allergic rhinitis · atopic rhinitis · non-seasonal allergic rhinitis · Perenial allergic rhinitis · perennial allergic rhinitis · seasonal allergic rhinitis

Data availability: 357 GWAS associations (37 studies) · 1 HPO phenotype · 1 cell line.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › allergic respiratory disease › allergic rhinitis

Related subtypes (3): allergic asthma, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis

Subtypes (3): seasonal allergic rhinitis, vasomotor rhinitis, perennial allergic rhinitis

Genetics & variants

GWAS landscape

357 GWAS associations across 37 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs72823641	1e-78	IL18R1, IL1RL1	T	1.16
rs7936312	1e-77	EMSY - LINC02757	T	1.11
rs5743604	1e-72	TLR1	A	1.15
rs28407950	7e-70	HLA-DQA1 - HLA-DQB1	C	1.12
rs28690449	2e-64	TLR10 - TLR1	C	1.12
rs1438673	7e-62	WDR36 - RPS3AP21	C	1.09
rs34290285	6e-58	D2HGDH	G	1.11
rs7728912	5e-52	SLC25A46 - BCLAF1P1	C	1.13
rs6881270	1e-48	IL7R	C	1.1
rs12935657	6e-45	CLEC16A	G	1.09
rs62404084	1e-43	HLA-DQA1	C	1.11
rs112401631	1e-43	CCR7 - SMARCE1	A	1.34
rs144829310	2e-37	GTF3AP1 - IL33	T	1.1
rs72743461	5e-37	SMAD3	A	1.08
rs13020553	2e-33	IL18R1, IL1RL1	G	1.08
rs61839660	1e-32	IL2RA	T	1.12
rs7717955	4e-32	IL7R	C	1.06
rs55646091	5e-32	EMSY - LINC02757	A	1.17
rs11236797	5e-32	EMSY - LINC02757	A	1.14
rs1775553	1e-31	LINC02676 - LINC00709	C	1.07
rs34004019	1e-30	HLA-DQA1 - HLA-DQB1	A	1.12
rs950881	2e-30	IL1RL1, IL18R1	G	1.14
rs17454584	2e-30	ADAD1 - IL2	G	1.08
rs3024971	5e-30	STAT6	T	1.11
rs45599938	1e-29	IL2 - IL21	A	1.07
rs891058	3e-29	LINC00299	G	1.07
rs5743618	4e-27	TLR1	C	1.11
rs66819621	2e-25	TLR1	A	1.18
rs117710327	3e-25	SLC7A10 - CEBPA	C	1.13
rs7744020	4e-25	HLA-DQA1 - HLA-DQB1	A	1.13

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST009716	Johansson A	2019	106,772	239,773	Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.
GCST90476021	Verma A	2024	92,310	311,377	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST009717	Johansson A	2019	84,034	239,773	Genome-wide association analysis of 350 000 Caucasians from the UK Biobank identifies novel loci for asthma, hay fever and eczema.
GCST006409	Waage J	2018	59,762	152,358	Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.
GCST90478107	Verma A	2024	30,185	77,322	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480240	Verma A	2024	30,185	77,322	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90038664	Donertas HM	2021	27,415	457,183	Common genetic associations between age-related diseases.
GCST90077815	Backman JD	2021	27,391	304,363	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90081801	Backman JD	2021	27,391	304,363	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90077816	Backman JD	2021	21,078	307,974	Exome sequencing and analysis of 454,787 UK Biobank participants.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	46
low_freq (0.01-0.05)	4
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	21
intergenic_variant	19
regulatory_region_variant	4
3_prime_UTR_variant	2
non_coding_transcript_exon_variant	2
missense_variant	1
TF_binding_site_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs72823641	2	102319699	T>A,C	0.137	intron_variant	IL18R1, IL1RL1	1e-78	Tier 4: intronic/intergenic
rs7936312	11	76582682	G>C,T	0.477	intergenic_variant	EMSY - LINC02757	1e-77	Tier 4: intronic/intergenic
rs5743604	4	38799664	A>G	0.199	intron_variant	TLR1	1e-72	Tier 4: intronic/intergenic
rs28407950	6	32658571	C>G,T	0.244	intergenic_variant	HLA-DQA1 - HLA-DQB1	7e-70	Tier 4: intronic/intergenic
rs28690449	4	38787511	C>A,G,T	0.201	intergenic_variant	TLR10 - TLR1	2e-64	Tier 4: intronic/intergenic
rs1438673	5	111131801	C>A,G,T	0.483	intergenic_variant	WDR36 - RPS3AP21	7e-62	Tier 4: intronic/intergenic
rs34290285	2	241759225	G>A	0.255	intron_variant	D2HGDH	6e-58	Tier 4: intronic/intergenic
rs7728912	5	110812772	T>A,C,G	0.146	intergenic_variant	SLC25A46 - BCLAF1P1	5e-52	Tier 4: intronic/intergenic
rs6881270	5	35878993	C>T	0.275	3_prime_UTR_variant	IL7R	1e-48	Tier 2: splice/UTR
rs12935657	16	11125184	G>A,T	0.244	intron_variant	CLEC16A	6e-45	Tier 4: intronic/intergenic
rs62404084	6	32635544	C>T	0.193	intergenic_variant	HLA-DQA1	1e-43	Tier 4: intronic/intergenic
rs112401631	17	40608272	T>A	0.019	regulatory_region_variant	CCR7 - SMARCE1	1e-43	Tier 3: regulatory
rs144829310	9	6208030	G>T	0.162	intergenic_variant	GTF3AP1 - IL33	2e-37	Tier 4: intronic/intergenic
rs72743461	15	67149412	C>A,T	0.237	intron_variant	SMAD3	5e-37	Tier 4: intronic/intergenic
rs13020553	2	102315366	C>G,T	0.388	intron_variant	IL18R1, IL1RL1	2e-33	Tier 4: intronic/intergenic
rs61839660	10	6052734	C>T	0.099	intron_variant	IL2RA	1e-32	Tier 4: intronic/intergenic
rs7717955	5	35862739	C>T	0.267	intron_variant	IL7R	4e-32	Tier 4: intronic/intergenic
rs55646091	11	76588387	G>A	0.048	regulatory_region_variant	EMSY - LINC02757	5e-32	Tier 3: regulatory
rs11236797	11	76588605	C>A	0.451	regulatory_region_variant	EMSY - LINC02757	5e-32	Tier 3: regulatory
rs1775553	10	9012362	C>T	0.423	intron_variant	LINC02676 - LINC00709	1e-31	Tier 4: intronic/intergenic
rs34004019	6	32658626	A>G	0.267	intergenic_variant	HLA-DQA1 - HLA-DQB1	1e-30	Tier 4: intronic/intergenic
rs950881	2	102316052	G>A,C,T	0.147	intron_variant	IL1RL1, IL18R1	2e-30	Tier 4: intronic/intergenic
rs17454584	4	122432277	A>G	0.218	intergenic_variant	ADAD1 - IL2	2e-30	Tier 4: intronic/intergenic
rs3024971	12	57099944	T>G	0.107	intron_variant	STAT6	5e-30	Tier 4: intronic/intergenic
rs45599938	4	122465565	G>A,C	0.334	intergenic_variant	IL2 - IL21	1e-29	Tier 4: intronic/intergenic
rs891058	2	8302417	G>A	0.295	regulatory_region_variant	LINC00299	3e-29	Tier 3: regulatory
rs5743618	4	38797027	C>A,G	0.272	missense_variant	TLR1	4e-27	Tier 1: coding
rs66819621	4	38817782	A>G,T	0.157	intergenic_variant	TLR1	2e-25	Tier 4: intronic/intergenic
rs117710327	19	33235672	C>A	0.062	TF_binding_site_variant	SLC7A10 - CEBPA	3e-25	Tier 3: regulatory
rs7744020	6	32658353	G>A	0.307	intergenic_variant	HLA-DQA1 - HLA-DQB1	4e-25	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 42 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BCL6	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL6	Orphanet:545	Follicular lymphoma
BCL6	Orphanet:98838	Primary mediastinal large B-cell lymphoma
BCL6	Orphanet:98839	Intravascular large B-cell lymphoma
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
SMARCE1	Orphanet:1465	Coffin-Siris syndrome
SMARCE1	Orphanet:2495	Meningioma
SMARCE1	Orphanet:263662	Familial multiple meningioma
STAT6	Orphanet:2126	Solitary fibrous tumor
TNFSF11	Orphanet:667	Autosomal recessive malignant osteopetrosis
PRDM16	Orphanet:154	Familial isolated dilated cardiomyopathy
PRDM16	Orphanet:1606	1p36 deletion syndrome
PRDM16	Orphanet:54260	Left ventricular noncompaction
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
BSND	Orphanet:89938	Bartter syndrome type 4
BSND	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CD247	Orphanet:169160	T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
CD247	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
CD247	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
SLC45A1	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
CEBPA	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
CEBPA	Orphanet:319465	Inherited acute myeloid leukemia
CEBPA	Orphanet:319480	Acute myeloid leukemia with CEBPA somatic mutations
SLC35D1	Orphanet:3144	Schneckenbecken dysplasia
FAM20C	Orphanet:1832	Osteosclerotic bone dysplasia
FTO	Orphanet:210144	Lethal polymalformative syndrome, Boissel type
CELF2	Orphanet:442835	Non-specific early-onset epileptic encephalopathy
AAGAB	Orphanet:79501	Punctate palmoplantar keratoderma type 1
DAW1	Orphanet:244	Primary ciliary dyskinesia
MTRFR	Orphanet:254930	Combined oxidative phosphorylation defect type 7
MTRFR	Orphanet:320375	Autosomal recessive spastic paraplegia type 55
DDX6	Orphanet:528084	Non-specific syndromic intellectual disability
RMI2	Orphanet:508512	Intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome
D2HGDH	Orphanet:79315	D-2-hydroxyglutaric aciduria
JAZF1	Orphanet:213711	Endometrial stromal sarcoma
JAZF1	Orphanet:536	Systemic lupus erythematosus
ABCA1	Orphanet:31150	Tangier disease
ABCA1	Orphanet:425	Apolipoprotein A-I deficiency
SH2B3	Orphanet:3318	Essential thrombocythemia
SH2B3	Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BCL6	HGNC:1001	ENSG00000113916	P41182	B-cell lymphoma 6 protein	gwas
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
ST8SIA2	HGNC:10870	ENSG00000140557	Q92186	Alpha-2,8-sialyltransferase 8B	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
STAT6	HGNC:11368	ENSG00000166888	P42226	Signal transducer and activator of transcription 6	gwas
SULT1A1	HGNC:11453	ENSG00000196502	P50225	Sulfotransferase 1A1	gwas
SULT1A2	HGNC:11454	ENSG00000197165	P50226	Sulfotransferase 1A2	gwas
TAX1BP1	HGNC:11575	ENSG00000106052	Q86VP1	Tax1-binding protein 1	gwas
TLR1	HGNC:11847	ENSG00000174125	Q15399	Toll-like receptor 1	gwas
TNFSF11	HGNC:11926	ENSG00000120659	O14788	Tumor necrosis factor ligand superfamily member 11	gwas
TPD52	HGNC:12005	ENSG00000076554	P55327	Tumor protein D52	gwas
ZNF217	HGNC:13009	ENSG00000171940	O75362	Zinc finger protein 217	gwas
PRDM16	HGNC:14000	ENSG00000142611	Q9HAZ2	Histone-lysine N-methyltransferase PRDM16	gwas
CDK2AP1	HGNC:14002	ENSG00000111328	O14519	Cyclin-dependent kinase 2-associated protein 1	gwas
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
CAMK4	HGNC:1464	ENSG00000152495	Q16566	Calcium/calmodulin-dependent protein kinase type IV	gwas
CBLN1	HGNC:1543	ENSG00000102924	P23435	Cerebellin-1	gwas
TLR10	HGNC:15634	ENSG00000174123	Q9BXR5	Toll-like receptor 10	gwas
IL33	HGNC:16028	ENSG00000137033	O95760	Interleukin-33	gwas
CCR7	HGNC:1608	ENSG00000126353	P32248	C-C chemokine receptor type 7	gwas
BSND	HGNC:16512	ENSG00000162399	Q8WZ55	Barttin	gwas
FERD3L	HGNC:16660	ENSG00000146618	Q96RJ6	Fer3-like protein	gwas
ACTR1A	HGNC:167	ENSG00000138107	P61163	Alpha-centractin	gwas
CD247	HGNC:1677	ENSG00000198821	P20963	T-cell surface glycoprotein CD3 zeta chain	gwas
DLGAP5	HGNC:16864	ENSG00000126787	Q15398	Disks large-associated protein 5	gwas
GJA10	HGNC:16995	ENSG00000135355	Q969M2	Gap junction alpha-10 protein	gwas
MOB4	HGNC:17261	ENSG00000115540	Q9Y3A3	MOB-like protein phocein	gwas
NEGR1	HGNC:17302	ENSG00000172260	Q7Z3B1	Neuronal growth regulator 1	gwas
SLC45A1	HGNC:17939	ENSG00000162426	Q9Y2W3	Proton-associated sugar transporter A	gwas
EMSY	HGNC:18071	ENSG00000158636	Q7Z589	BRCA2-interacting transcriptional repressor EMSY	gwas
RBFOX1	HGNC:18222	ENSG00000078328	Q9NWB1	RNA binding protein fox-1 homolog 1	gwas
CEBPA	HGNC:1833	ENSG00000245848	P49715	CCAAT/enhancer-binding protein alpha	gwas
TTC6	HGNC:19739	ENSG00000139865	Q86TZ1	Tetratricopeptide repeat protein 6	gwas
RNF144A	HGNC:20457	ENSG00000151692	P50876	E3 ubiquitin-protein ligase RNF144A	gwas
ZPBP2	HGNC:20678	ENSG00000186075	Q6X784	Zona pellucida-binding protein 2	gwas
SLC35D1	HGNC:20800	ENSG00000116704	Q9NTN3	Nucleotide sugar transporter SLC35D1	gwas
SYCP2L	HGNC:21537	ENSG00000153157	Q5T4T6	Synaptonemal complex protein 2-like	gwas
FAM20C	HGNC:22140	ENSG00000177706	Q8IXL6	Extracellular serine/threonine protein kinase FAM20C	gwas
OBP2B	HGNC:23381	ENSG00000171102	Q9NPH6	Odorant-binding protein 2b	gwas
AKR1E2	HGNC:23437	ENSG00000165568	Q96JD6	1,5-anhydro-D-fructose reductase	gwas
GSDMB	HGNC:23690	ENSG00000073605	Q8TAX9	Gasdermin-B	gwas
CHRDL2	HGNC:24168	ENSG00000054938	Q6WN34	Chordin-like protein 2	gwas
FTO	HGNC:24678	ENSG00000140718	Q9C0B1	Alpha-ketoglutarate-dependent dioxygenase FTO	gwas
TPRG1	HGNC:24759	ENSG00000188001	Q6ZUI0	Tumor protein p63-regulated gene 1 protein	gwas
SVIP	HGNC:25238	ENSG00000198168	Q8NHG7	Small VCP/p97-interacting protein	gwas
CELF2	HGNC:2550	ENSG00000048740	O95319	CUGBP Elav-like family member 2	gwas
AAGAB	HGNC:25662	ENSG00000103591	Q6PD74	Alpha- and gamma-adaptin-binding protein p34	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BCL6	B-cell lymphoma 6 protein	Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.
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.
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).
ST8SIA2	Alpha-2,8-sialyltransferase 8B	Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan acceptor through alpha-2,8-linkages.
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).
STAT6	Signal transducer and activator of transcription 6	Carries out a dual function: signal transduction and activation of transcription.
SULT1A1	Sulfotransferase 1A1	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of a wide variety of acceptor molecules bearing a hydroxyl or an amine group.
SULT1A2	Sulfotransferase 1A2	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of catecholamines, phenolic drugs and neurotransmitters.
TAX1BP1	Tax1-binding protein 1	Ubiquitin-binding adapter that participates in inflammatory, antiviral and innate immune processes as well as selective autophagy regulation.
TLR1	Toll-like receptor 1	Participates in the innate immune response to microbial agents.
TNFSF11	Tumor necrosis factor ligand superfamily member 11	Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK.
ZNF217	Zinc finger protein 217	Binds to the promoters of target genes and functions as repressor.
PRDM16	Histone-lysine N-methyltransferase PRDM16	Transcription regulator that acts both as a histone methyltransferase or chromatin adapter, depending on the context.
CDK2AP1	Cyclin-dependent kinase 2-associated protein 1	Inhibitor of cyclin-dependent kinase CDK2.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
CAMK4	Calcium/calmodulin-dependent protein kinase type IV	Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK4 signaling cascade and regulates, mainly by phosphorylation, the activity of several transcription activators, such as CREB1, MEF2D, JUN and RORA…
CBLN1	Cerebellin-1	Required for synapse integrity and synaptic plasticity.
TLR10	Toll-like receptor 10	Participates in the innate immune response to microbial agents.
IL33	Interleukin-33	Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
CCR7	C-C chemokine receptor type 7	Receptor for the MIP-3-beta chemokine.
BSND	Barttin	Regulatory subunit of anion-selective CLCNKA:BSND and CLCNKB:BSND heteromeric channels involved in basolateral chloride conductance along the nephron to achieve urine concentration and maintain systemic acid-base homeostasis, and in the st…
FERD3L	Fer3-like protein	Transcription factor that binds to the E-box and functions as inhibitor of transcription.
ACTR1A	Alpha-centractin	Part of the ACTR1A/ACTB filament around which the dynactin complex is built.
CD247	T-cell surface glycoprotein CD3 zeta chain	Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.
DLGAP5	Disks large-associated protein 5	Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells.
GJA10	Gap junction alpha-10 protein	One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
MOB4	MOB-like protein phocein	Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.
NEGR1	Neuronal growth regulator 1	May be involved in cell-adhesion.
SLC45A1	Proton-associated sugar transporter A	Proton-associated glucose transporter in the brain.
EMSY	BRCA2-interacting transcriptional repressor EMSY	Regulator which is able to repress transcription, possibly via its interaction with a multiprotein chromatin remodeling complex that modifies the chromatin.
RBFOX1	RNA binding protein fox-1 homolog 1	RNA-binding protein that regulates alternative splicing events by binding to 5’-UGCAUGU-3’ elements.
CEBPA	CCAAT/enhancer-binding protein alpha	Transcription factor that coordinates proliferation arrest and the differentiation of myeloid progenitors, adipocytes, hepatocytes, and cells of the lung and the placenta.
RNF144A	E3 ubiquitin-protein ligase RNF144A	E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
ZPBP2	Zona pellucida-binding protein 2	Is implicated in sperm-oocyte interaction during fertilization.
SLC35D1	Nucleotide sugar transporter SLC35D1	Antiporter that transports nucleotide sugars across the endoplasmic reticulum (ER) membrane in exchange for either their cognate nucleoside monophosphate or another nucleotide sugar.
SYCP2L	Synaptonemal complex protein 2-like	Oocyte-specific protein that localizes to centromeres at the dictyate stage and regulates the survival of primordial oocytes.
FAM20C	Extracellular serine/threonine protein kinase FAM20C	Golgi serine/threonine protein kinase that phosphorylates secretory pathway proteins within Ser-x-Glu/pSer motifs and plays a key role in biomineralization of bones and teeth.
OBP2B	Odorant-binding protein 2b	Probably binds and transports small hydrophobic volatile molecules.
AKR1E2	1,5-anhydro-D-fructose reductase	Catalyzes the NADPH-dependent reduction of 1,5-anhydro-D-fructose (AF) to 1,5-anhydro-D-glucitol.
GSDMB	Gasdermin-B	Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death.
CHRDL2	Chordin-like protein 2	May inhibit BMPs activity by blocking their interaction with their receptors.
FTO	Alpha-ketoglutarate-dependent dioxygenase FTO	RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis.
SVIP	Small VCP/p97-interacting protein	Negative regulator of the ER-associated degradation pathway (ERAD) of misfolded proteins.
CELF2	CUGBP Elav-like family member 2	RNA-binding protein implicated in the regulation of several post-transcriptional events.
AAGAB	Alpha- and gamma-adaptin-binding protein p34	May be involved in endocytic recycling of growth factor receptors such as EGFR.
SLC68A1	Solute carrier family 68 member 1	May act as a cation symporter.
DAW1	Dynein assembly factor with WD repeat domains 1	Required for axonemal dynein assembly and ciliary motility in ciliated organs, including Kupffer’s vesicle, during embryogenesis.
ZNF776	Zinc finger protein 776	May be involved in transcriptional regulation.

Protein-family classification

Druggable: 23 · Difficult: 14 · Unknown: 38 · Druggable fraction: 0.31

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
Transporter	5	5.2×	0.031
Nuclear receptor	1	5.2×	0.650
Kinase	5	1.9×	0.650
Phosphatase	1	1.1×	0.875
Transcription factor	10	1.1×	0.875
Enzyme (other)	6	1.0×	0.875
Scaffold/PPI	4	0.9×	0.875
Other/Unknown	38	0.9×	0.875
Antibody/Immunoglobulin	2	0.8×	0.875
GPCR	2	0.6×	0.875
Protease	1	0.5×	0.875

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BCL6	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
RORA	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
ST8SIA2	Enzyme (other)	yes	2.4.99.8	Glyco_trans_29, Sialyl_trans, GT29-like_sf
SLC7A10	Transporter	yes		AA/rel_permease1, AminoAcid_Transporter
SMARCE1	Other/Unknown	no		HMG_box_dom, HMG_box_dom_sf
STAT6	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
SULT1A1	Enzyme (other)	yes	2.8.2.1	Sulfotransferase_dom, P-loop_NTPase
SULT1A2	Enzyme (other)	yes	2.8.2.1	Sulfotransferase_dom, P-loop_NTPase
TAX1BP1	Other/Unknown	no		CALCOCO1-like, SKICH, CALCOCO1/2_Zn_UBZ1
TLR1	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TNFSF11	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_ligand_10/11
TPD52	Other/Unknown	no		TPD52
ZNF217	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Krueppel_C2H2-ZF
PRDM16	Transcription factor	no	2.1.1.367	SET_dom, Znf_C2H2_type, Znf_C2H2_sf
CDK2AP1	Other/Unknown	no		DOC_1/2
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
CAMK4	Kinase	yes	2.7.11.17	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CBLN1	Other/Unknown	no		C1q_dom, Tumour_necrosis_fac-like_dom, Cerebellin_Synaptic_Org
TLR10	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
IL33	Other/Unknown	no		IL-33, IL33_C
CCR7	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR7
BSND	Other/Unknown	no		Barttin
FERD3L	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, E-box_TF_Regulators
ACTR1A	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
CD247	Other/Unknown	no		Phos_immunorcpt_sig_ITAM, CD3_zeta/IgE_Fc_rcpt_gamma, T-cell_CD3_zeta
DLGAP5	Other/Unknown	no		SAPAP
GJA10	Other/Unknown	no		Connexin, Connexin_N, Connexin_CS
MOB4	Kinase	yes		MOB_kinase_act_fam, MOB_kinase_act_sf
NEGR1	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
SLC45A1	Transporter	yes		MFS, MFS_trans_sf
EMSY	Other/Unknown	no		ENT_dom, EMSY, ENT_dom-like_sf
RBFOX1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBFOX1-3
CEBPA	Other/Unknown	no		bZIP, C/EBP_chordates, C/EBP
TTC6	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, Ycf3
RNF144A	Transcription factor	no	2.3.2.31	Znf_RING, IBR_dom, Znf_RING/FYVE/PHD
ZPBP2	Antibody/Immunoglobulin	yes		Ig-like_dom, Sp38-bd, Ig-like_fold
SLC35D1	Transporter	yes		Sugar_P_trans_dom, TPT_transporter
SYCP2L	Other/Unknown	no		SYCP2-like, SYCP2_SLD, SYCP2_ARLD
FAM20C	Other/Unknown	no		FAM20_C, FAM20
OBP2B	Other/Unknown	no		Lipocln_cytosolic_FA-bd_dom, Lipocalin, von_Ebner_gland
AKR1E2	Other/Unknown	no		Aldo/ket_reductase_CS, AKR, NADP_OxRdtase_dom
GSDMB	Other/Unknown	no		Gasdermin, Gasdermin_pore, Gasdermin_PUB
CHRDL2	Other/Unknown	no		VWF_dom, CHRDL_1/2_C, CHRDL1/2
FTO	Enzyme (other)	yes	1.14.11.53	FTO_C, FTO_cat_dom, FTO
TPRG1	Phosphatase	yes		Inositol_phosphatase, hSac2, TPRG1-like
SVIP	Other/Unknown	no		SVIP, SVIP_metazoa
CELF2	Other/Unknown	no		RRM_dom, Hud_Sxl_RNA, Nucleotide-bd_a/b_plait_sf
AAGAB	Other/Unknown	no		Alpha/Gamma-adaptin-bd_p34

Expression context

Cohort genes with no expression data: 0.

68 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
cortical plate	8
ganglionic eminence	7
calcaneal tendon	7
secondary oocyte	7
ventricular zone	6
left testis	6
right testis	6
bronchial epithelial cell	5
sperm	5
granulocyte	4
lymph node	4
mucosa of transverse colon	4
right lobe of liver	4
oocyte	4
primordial germ cell in gonad	4
sural nerve	4
cerebellar cortex	4
cerebellar hemisphere	4
ileal mucosa	4
male germ line stem cell (sensu Vertebrata) in testis	4

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BCL6	300	ubiquitous	marker	gastrocnemius, mucosa of stomach, blood
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
ST8SIA2	98	broad	marker	cortical plate, ganglionic eminence, ventricular zone
SLC7A10	138	broad	yes	omental fat pad, peritoneum, adipose tissue of abdominal region
SMARCE1	197	ubiquitous	marker	calcaneal tendon, embryo, ganglionic eminence
STAT6	292	ubiquitous	marker	granulocyte, right ovary, left ovary
SULT1A1	177	ubiquitous	marker	mucosa of transverse colon, right lobe of liver, right adrenal gland cortex
SULT1A2	128	broad	marker	duodenum, mucosa of transverse colon, right lobe of liver
TAX1BP1	301	ubiquitous	marker	secondary oocyte, oocyte, bronchial epithelial cell
TLR1	218	broad	marker	monocyte, mononuclear cell, leukocyte
TNFSF11	98	tissue_specific	marker	primordial germ cell in gonad, tibia, lymph node
TPD52	291	ubiquitous	marker	jejunal mucosa, lateral nuclear group of thalamus, secondary oocyte
ZNF217	258	ubiquitous	marker	endometrium epithelium, germinal epithelium of ovary, palpebral conjunctiva
PRDM16	202	broad	marker	sural nerve, pigmented layer of retina, ascending aorta
CDK2AP1	304	ubiquitous	marker	parotid gland, tibia, spinal cord
BACH2	237	ubiquitous	marker	cortical plate, sural nerve, epithelium of nasopharynx
CAMK4	205	ubiquitous	marker	cerebellar vermis, cerebellar cortex, cerebellar hemisphere
CBLN1	164	broad	yes	cerebellar cortex, cerebellar hemisphere, cerebellum
TLR10	166	tissue_specific	marker	lymph node, ileal mucosa, ileum
IL33	239	broad	marker	calcaneal tendon, right coronary artery, olfactory segment of nasal mucosa
CCR7	169	broad	marker	vermiform appendix, lymph node, blood
BSND	22	tissue_specific	marker	kidney epithelium, adult mammalian kidney, metanephros cortex
FERD3L	33	tissue_specific	yes	sural nerve, cortical plate, bone marrow cell
ACTR1A	291	ubiquitous	marker	cortical plate, ganglionic eminence, lower esophagus muscularis layer
CD247	179	broad	marker	granulocyte, thymus, blood
DLGAP5	186	ubiquitous	marker	secondary oocyte, ventricular zone, oocyte
GJA10	7		marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, sural nerve
MOB4	292	ubiquitous	marker	adrenal tissue, skeletal muscle tissue of biceps brachii, heart right ventricle

Protein interactions among cohort

Intra-cohort edges: 21.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DDX6	5,922
CEBPA	5,784
BCL6	3,984
ABCA1	3,551
TNFSF11	3,410
ATXN2	3,360
STAT6	3,345
WDR36	3,290
CAMK4	3,127
TAX1BP1	3,089

Intra-cohort edges

A	B	Sources
ADAD1	CAPSL	string_interaction
ADAD1	SH2B3	string_interaction
AKR1E2	ZNF776	string_interaction
ATXN2	DDX6	intact, string_interaction
ATXN2	RBFOX1	string_interaction
ATXN2	SH2B3	string_interaction
BACH2	CLEC16A	string_interaction
BACH2	SH2B3	string_interaction
BCL6	CXCR5	string_interaction
CAPSL	CLEC16A	string_interaction
CAPSL	DLGAP5	biogrid_interaction, intact
CCR7	CD247	intact
CCR7	CXCR5	string_interaction
CLEC16A	SH2B3	string_interaction
DYRK4	ZNF776	string_interaction
EMSY	WDR36	string_interaction
FERD3L	ZNF776	string_interaction
FTO	NEGR1	string_interaction
GSDMB	ZPBP2	string_interaction
SULT1A1	SULT1A2	biogrid_interaction, intact
TLR1	TLR10	intact, string_interaction

Structural data

PDB: 45 · AlphaFold-only: 30 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL6	P41182	246
DCAF1	Q9Y4B6	46
CD247	P20963	38
FTO	Q9C0B1	28
RTF1	Q92541	18
RBKS	Q9H477	14
SULT1A1	P50225	11
GSDMB	Q8TAX9	11
TAX1BP1	Q86VP1	10
DDX6	P26196	9
SMARCE1	Q969G3	8
STAT6	P42226	7
CCR7	P32248	7
CELF2	O95319	7
ABCA1	O95477	7
TLR1	Q15399	6
RMI2	Q96E14	6
D2HGDH	Q8N465	6
IL33	O95760	5
SIK3	Q9Y2K2	5
SLC7A10	Q9NS82	4
ZNF217	O75362	4
CBLN1	P23435	4
DLGAP5	Q15398	4
RBFOX1	Q9NWB1	4
RORA	P35398	3
EMSY	Q7Z589	3
AAGAB	Q6PD74	3
WDR36	Q8NI36	3
TNFSF11	O14788	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AKR1E2	Q96JD6	93.51
TTC6	Q86TZ1	91.96
CAPSL	Q8WWF8	91.88
OBP2B	Q9NPH6	87.33
ZPBP2	Q6X784	86.81
ST8SIA2	Q92186	85.70
SLC68A1	Q14CX5	82.45
SLC35D1	Q9NTN3	80.98
CXCR5	P32302	80.85
DYRK4	Q9NR20	78.50
SPPL3	Q8TCT6	78.39
ADAD1	Q96M93	78.19
NKAIN3	Q8N8D7	77.17
TPRG1	Q6ZUI0	73.90
CLEC16A	Q2KHT3	72.17
SVIP	Q8NHG7	71.90
FERD3L	Q96RJ6	71.10
JAZF1	Q86VZ6	70.25
LRRIQ3	A6PVS8	70.18
TPD52	P55327	69.11
CHRDL2	Q6WN34	68.31
SYCP2L	Q5T4T6	66.45
SLC45A1	Q9Y2W3	66.26
ZNF776	Q68DI1	65.93
SH2B3	Q9UQQ2	63.45
MIER1	Q8N108	62.88
GJA10	Q969M2	58.72
BSND	Q8WZ55	53.80
SPHKAP	Q2M3C7	47.68
LINC00299	Q6ZSB3	33.74

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 572. Enrichment computed across 127 evidence-associated genes (82 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 82 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-4 and Interleukin-13 signaling	7	8.8×	0.008	BCL6, RORA, STAT6, GATA3, ALOX15, IL13, MYC
Defective ABCA1 causes TGD	2	139.3×	0.015	ABCA1, APOA1
Interleukin-33 signaling	2	92.8×	0.029	IL33, IL1RL1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	5	8.9×	0.034	STAT6, GATA3, IL13, NFATC2, RAD50
HDL assembly	2	34.8×	0.109	ABCA1, APOA1
Interleukin-18 signaling	2	34.8×	0.109	IL13, IL18R1
Regulation of NFE2L2 gene expression	2	34.8×	0.109	MYC, NFKB1
FCERI mediated Ca+2 mobilization	3	13.1×	0.109	FCER1G, IGKV5-2, NFATC2
Signaling by Interleukins	6	4.7×	0.110	BCL6, RORA, STAT6, ALOX15, SMAD3, MYC
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	2	27.9×	0.126	IL2, NFATC2
Endosomal/Vacuolar pathway	2	25.3×	0.138	HLA-B, HLA-C
FCGR activation	2	21.4×	0.138	CD247, IGKV5-2
Scavenging of heme from plasma	2	21.4×	0.138	IGKV5-2, APOA1
Passive transport by Aquaporins	2	21.4×	0.138	AQP2, AQP5
Phase II - Conjugation of compounds	3	10.2×	0.138	SULT1A1, SULT1A2, SLC35D1
Interferon gamma signaling	4	6.1×	0.138	HLA-B, HLA-C, HLA-DQA1, HLA-DQB1
Cytokine Signaling in Immune system	7	3.5×	0.138	BCL6, RORA, STAT6, SH2B3, ALOX15, SMAD3, MYC
Plasma lipoprotein assembly	2	17.4×	0.182	ABCA1, APOA1
Defective SLC35D1 causes SCHBCKD	1	139.3×	0.207	SLC35D1
Translocation of ZAP-70 to Immunological synapse	2	15.5×	0.207	CD247, HLA-DQA1
Role of LAT2/NTAL/LAB on calcium mobilization	2	14.7×	0.209	FCER1G, IGKV5-2
Signaling by TGF-beta Receptor Complex	3	7.3×	0.209	ITGB8, SMAD3, MYC
Phosphorylation of CD3 and TCR zeta chains	2	13.3×	0.219	CD247, HLA-DQA1
Binding and Uptake of Ligands by Scavenger Receptors	2	13.3×	0.219	IGKV5-2, APOA1
Cytosolic sulfonation of small molecules	2	12.7×	0.219	SULT1A1, SULT1A2
Co-inhibition by PD-1	2	12.7×	0.219	CD247, HLA-DQA1
Interleukin-37 signaling	2	12.7×	0.219	IL18R1, SMAD3
Immune System	13	2.1×	0.219	BCL6, RORA, STAT6, TAX1BP1, ACTR1A, SVIP, SH2B3, ALOX15 (+5 more)
Biosynthesis of DPAn-6 SPMs	1	69.6×	0.229	ALOX15
Biosynthesis of DPAn-3-derived protectins and resolvins	1	69.6×	0.229	ALOX15

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 113 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	16	6.7×	2e-06	CXCR5, TLR1, TNFSF11, TLR10, CCR7, HLA-B, HLA-C, HLA-DQA1 (+8 more)
macrophage differentiation	5	20.7×	0.002	IL33, CEBPA, FOSL2, GATA3, IL1RL1
positive regulation of macrophage activation	4	29.8×	0.002	IL33, CEBPA, IL13, IL1RL1
adaptive immune response	9	6.7×	0.002	CAMK4, CD247, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1, IGKV5-2, IL18R1 (+1 more)
positive regulation of B cell proliferation	5	15.2×	0.003	BCL6, IL13, IL2, IL21, NFATC2
negative regulation of inflammatory response	7	8.5×	0.003	RORA, GATA3, IL13, APOA1, IL2, SMAD3, NFKB1
mammary gland epithelial cell proliferation	3	40.7×	0.007	STAT6, TNFSF11, ID2
regulation of Cdc42 protein signal transduction	3	37.3×	0.007	CCR7, ABCA1, APOA1
positive regulation of interleukin-5 production	3	37.3×	0.007	IL33, GATA3, IL1RL1
negative regulation of transcription by RNA polymerase II	18	2.8×	0.007	BCL6, STAT6, TNFSF11, ZNF217, PRDM16, BACH2, IL33, CEBPA (+10 more)
positive regulation of immunoglobulin production	4	17.0×	0.009	IL33, IL13, IL2, IL21
isotype switching to IgE isotypes	2	99.4×	0.012	BCL6, STAT6
positive regulation of gene expression	11	3.8×	0.014	TNFSF11, IL33, CEBPA, LRRC32, ID2, IL13, IL7R, ITGB8 (+3 more)
inflammatory response	11	3.7×	0.016	BCL6, TLR1, CAMK4, TLR10, CCR7, GATA3, ALOX15, IL13 (+3 more)
immune system development	2	74.6×	0.019	GATA3, SMAD3
negative regulation of T-helper 1 type immune response	2	59.6×	0.030	IL33, IL1RL1
positive regulation of tissue remodeling	2	49.7×	0.038	IL2, IL21
lipoprotein biosynthetic process	2	49.7×	0.038	ABCA1, APOA1
negative regulation of response to cytokine stimulus	2	49.7×	0.038	SH2B3, APOA1
positive regulation of cholesterol efflux	3	16.6×	0.042	ABCA1, APOA1, NFKB1
T cell receptor signaling pathway	5	6.7×	0.047	CD247, SPPL3, FOSL2, GATA3, HLA-DQB1
negative regulation of immunoglobulin production	2	37.3×	0.049	IL33, ZPBP2
interleukin-33-mediated signaling pathway	2	37.3×	0.049	IL33, IL1RL1
positive regulation of interleukin-4 production	3	14.9×	0.049	IL33, FCER1G, GATA3
antigen processing and presentation of exogenous peptide antigen via MHC class II	3	14.4×	0.049	FCER1G, HLA-DQA1, HLA-DQB1
cartilage development	4	8.9×	0.049	CHRDL2, GATA3, ITGB8, NFATC2
positive regulation of inflammatory response	5	6.4×	0.049	IL33, CEBPA, IL1RL1, IL2, IL21
Fc-gamma receptor signaling pathway	2	33.1×	0.055	CD247, FCER1G
type 2 immune response	2	33.1×	0.055	BCL6, IL33
T-helper 2 cell differentiation	2	33.1×	0.055	BCL6, GATA3

Therapeutics

Drugs indicated for this disease

15 approved, 13 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Beclomethasone Dipropionate	Approved (phase 4)
Budesonide	Approved (phase 4)
Ciclesonide	Approved (phase 4)
Desloratadine	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Epinephrine	Approved (phase 4)
Fluticasone Furoate	Approved (phase 4)
Fluticasone Propionate	Approved (phase 4)
Loratadine	Approved (phase 4)
Mometasone Furoate	Approved (phase 4)
Montelukast	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Pseudoephedrine	Approved (phase 4)
Triamcinolone Acetonide	Approved (phase 4)
Azelastine	Phase 3 (in late-stage trials)
Betamethasone	Phase 3 (in late-stage trials)
Cetirizine	Phase 3 (in late-stage trials)
Epinastine	Phase 3 (in late-stage trials)
Freneslerbart	Phase 3 (in late-stage trials)
Levocetirizine	Phase 3 (in late-stage trials)
Mevonlerbart	Phase 3 (in late-stage trials)
Mometasone	Phase 3 (in late-stage trials)
Olopatadine	Phase 3 (in late-stage trials)
Omalizumab	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Stapokibart	Phase 3 (in late-stage trials)
Triamcinolone	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Borneol, Dupilumab, Fevipiprant, Ginger, Histamine, Oxymetazoline, Timapiprant.

Drug target analysis

Approved (phase 4): 7 · Phase ≥3: 8 · Phased (≥1): 11 · Undrugged: 64

Druggability breadth: 55 of 127 evidence-associated genes (43%) 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
STAT6	THIORIDAZINE HYDROCHLORIDE
SULT1A1	ESTRADIOL
CAMK4	RUXOLITINIB
FTO	FLUORESCEIN
SIK3	MOMELOTINIB
DYRK4	ABEMACICLIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SIK3	25	4
FTO	18	4
CAMK4	14	4
STAT6	11	4
DYRK4	7	4
SULT1A1	3	4
CCR7	3	3
BCL6	2	2
RORA	2	4
DDX6	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRETINOIN	4	RORA
THIORIDAZINE HYDROCHLORIDE	4	STAT6
DOXORUBICIN HYDROCHLORIDE	4	STAT6
AMSACRINE	4	STAT6
ADENOSINE	4	STAT6
AMANTADINE	4	STAT6
BISACODYL	4	STAT6
ESTRADIOL	4	SULT1A1
ETHINYL ESTRADIOL	4	SULT1A1
RUXOLITINIB	4	CAMK4, SIK3
DABRAFENIB	4	CAMK4, SIK3
CERITINIB	4	CAMK4
GILTERITINIB	4	CAMK4
NINTEDANIB	4	CAMK4
SUNITINIB	4	CAMK4
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
MOMELOTINIB	4	SIK3
FEDRATINIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
ABEMACICLIB	4	DYRK4
QUERCETIN	3	FTO, STAT6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
CAMK4	342	Binding:342
BCL6	209	Binding:202, Functional:7
SIK3	173	Binding:173
FTO	153	Binding:153
RORA	115	Binding:111, Functional:3, Unclassified:1
DYRK4	94	Binding:93, Functional:1
STAT6	81	Binding:77, Functional:4
TLR1	59	Binding:59
CCR7	46	Binding:33, Functional:13
CXCR5	33	Binding:21, Functional:12
TNFSF11	30	Binding:30
SULT1A1	19	ADMET:15, Binding:4
DCAF1	18	Binding:18
SMARCE1	7	Binding:7
RTF1	7	Binding:7
ATXN2	5	Binding:3, Functional:2
DDX6	4	Binding:4
BACH2	3	Binding:3
PRDM16	2	Binding:2
FAM20C	2	Binding:2
ABCA1	2	Binding:2
MIER1	2	Binding:2
SULT1A2	1	ADMET:1
CDK2AP1	1	Binding:1
IL33	1	Binding:1
CELF2	1	Binding:1
WDR36	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ST8SIA2	2.4.99.8	alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
SULT1A1	2.8.2.1, 2.8.2.2	aryl sulfotransferase, alcohol sulfotransferase
SULT1A2	2.8.2.1, 2.8.2.2, 2.8.2.9	aryl sulfotransferase, alcohol sulfotransferase, tyrosine-ester sulfotransferase
PRDM16	2.1.1.367, 2.1.1.370	[histone H3]-lysine9 N-methyltransferase, [histone H3]-lysine4 N-dimethyltransferase
CAMK4	2.7.11.17	Ca2+/calmodulin-dependent protein kinase
RNF144A	2.3.2.31	RBR-type E3 ubiquitin transferase
FTO	1.14.11.53	mRNA N6-methyladenine demethylase
DDX6	3.6.4.13	RNA helicase
D2HGDH	1.1.99.39	D-2-hydroxyglutarate dehydrogenase
RBKS	2.7.1.15	ribokinase
DYRK4	2.7.12.1	dual-specificity kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCL6	209
RORA	115
CAMK4	342
FTO	153
SIK3	173

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
THIORIDAZINE HYDROCHLORIDE	4	STAT6
DOXORUBICIN HYDROCHLORIDE	4	STAT6
AMSACRINE	4	STAT6
ADENOSINE	4	STAT6
AMANTADINE	4	STAT6
BISACODYL	4	STAT6
ESTRADIOL	4	SULT1A1
ETHINYL ESTRADIOL	4	SULT1A1
RUXOLITINIB	4	CAMK4, SIK3
DABRAFENIB	4	CAMK4, SIK3
CERITINIB	4	CAMK4
GILTERITINIB	4	CAMK4
NINTEDANIB	4	CAMK4
SUNITINIB	4	CAMK4
FLUORESCEIN	4	FTO
DEMECLOCYCLINE	4	FTO
ROXADUSTAT	4	FTO
MECLOFENAMIC ACID	4	FTO
AMILORIDE	4	FTO
TACRINE	4	FTO
ENTACAPONE	4	FTO
MOMELOTINIB	4	SIK3
FEDRATINIB	4	SIK3
VANDETANIB	4	SIK3
BOSUTINIB	4	SIK3
DASATINIB	4	SIK3
MIDOSTAURIN	4	SIK3
ABEMACICLIB	4	DYRK4
QUERCETIN	3	FTO, STAT6

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	7	RORA, STAT6, SULT1A1, CAMK4, FTO, SIK3, DYRK4
B	Phased (≥1) drug, not yet approved	4	BCL6, CCR7, DDX6, RTF1
C	Druggable family + PDB, no drug	7	SLC7A10, SULT1A2, MOB4, NEGR1, D2HGDH, ABCA1, RBKS
D	Druggable family + AlphaFold only, no drug	8	CXCR5, ST8SIA2, SLC45A1, ZPBP2, SLC35D1, TPRG1, SLC68A1, SPPL3
E	Difficult family or no structure, no drug	49	ATXN2, SMARCE1, TAX1BP1, TLR1, TNFSF11, TPD52, ZNF217, PRDM16, CDK2AP1, BACH2 (+39 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ATXN2	5	—
CXCR5	33	—
ST8SIA2	0	—
SLC7A10	0	—
SMARCE1	7	—
SULT1A2	1	—
TAX1BP1	0	—
TLR1	59	—
TNFSF11	30	—
TPD52	0	—
ZNF217	0	—
PRDM16	2	—
CDK2AP1	1	—
BACH2	3	—
CBLN1	0	—
TLR10	0	—
IL33	1	—
BSND	0	—
FERD3L	0	—
ACTR1A	0	—
CD247	0	—
DLGAP5	0	—
GJA10	0	—
MOB4	0	—
NEGR1	0	—
SLC45A1	0	—
EMSY	0	—
RBFOX1	0	—
CEBPA	0	—
TTC6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 764.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	262
PHASE3	170
PHASE4	124
PHASE2	121
PHASE1	54
PHASE1/PHASE2	20
PHASE2/PHASE3	9
EARLY_PHASE1	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04815187	PHASE4	ACTIVE_NOT_RECRUITING	Repurposed Use of Allergic Rhinitis and Allergic Asthma Drug to Reduce Vertigo and Hearing Loss in Meniere’s Disease
NCT06785662	PHASE4	NOT_YET_RECRUITING	Budesonide Irrigation in Allergic Rhinitis
NCT07294326	PHASE4	NOT_YET_RECRUITING	A Prospective, Randomized, Controlled Study Comparing the Efficacy of Intranasal Corticosteroids (INCS) Combined With Intranasal Antihistamines (INAH) and INCS Combined With Oral Antihistamines (OAH) in the Treatment of Moderate to Severe Allergic Rhinitis Symptoms
NCT07415278	PHASE4	ACTIVE_NOT_RECRUITING	INTRANASAL FLUTICASONE VERSUS FLUTICASONE-AZELASTINE COMBINATION
NCT07532993	PHASE4	NOT_YET_RECRUITING	Comparison of Antihistamine and Antileukotriene Add-On Therapy to Intranasal Corticosteroid in Allergic Rhinitis
NCT00157937	PHASE4	COMPLETED	A Study to Compare Effectiveness of Montelukast Sodium With Comparator in Mild to Moderate Persistent Asthmatics (0476-329)
NCT00160537	PHASE4	COMPLETED	POPULAR (Preference Of Patient Using Levocetirizine in Allergic Rhinitis)
NCT00223587	PHASE4	TERMINATED	Seasonal Allergic Rhinitis and Driving Ability
NCT00250263	PHASE4	COMPLETED	A Trial of Immunological Outcomes of Sublingual Immunotherapy for House Dust Mite (D. Pteronyssinus) Allergy
NCT00355771	PHASE4	COMPLETED	Levocetirizine 5 mg: Reduction of Symptoms, Airway Resistance and Sleep Impairment in Persistent Allergic Rhinitis
NCT00358527	PHASE4	COMPLETED	Mometasone Furoate on Sleep Disturbances in Subjects With Seasonal Allergic Rhinitis (Study P04608) (COMPLETED)
NCT00359216	PHASE4	COMPLETED	The Effects of Mometasone Furoate Nasal Spray in Subjects With Sleep-disordered Breathing (SDB) Associated With Perennial Allergic Rhinitis (Study P04726)
NCT00361439	PHASE4	TERMINATED	Treatment of Olfactory Dysfunction in Seasonal Allergic Rhinitis
NCT00367016	PHASE4	COMPLETED	Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)
NCT00380705	PHASE4	COMPLETED	Quality of Life in Asthma and Rhinitis Allergic With Singulair (0476-365)
NCT00439712	PHASE4	COMPLETED	Levocetirizine in the Treatment of Nasal Obstruction Due to Perennial Allergic Rhinitis
NCT00442559	PHASE4	COMPLETED	Montelukast in Mild Asthmatic Children With Allergic Rhinitis (0476-367)
NCT00458835	PHASE4	COMPLETED	Comparison Between Systemic Exposure to Ciclesonide Nasal Spray, Ciclesonide HFA Nasal Aerosol and Orally Inhaled Ciclesonide (BY9010/M1-422)
NCT00460538	PHASE4	COMPLETED	Efficacy and Safety of Lectranal® in Treatment of Seasonal Allergic Rhinitis Symptoms
NCT00473915	PHASE4	COMPLETED	Intranasal Steroids and the Nasal Ocular Response
NCT00487032	PHASE4	COMPLETED	Differential Adrenoreceptor Mediated Tachyphylaxis and Upregulation
NCT00488176	PHASE4	UNKNOWN	Comparison of the Effect of Montelukast and Cetirizine on Allergic Inflammation in Children With Allergic Rhinitis
NCT00491374	PHASE4	TERMINATED	Study of Nasonex® in Improving Sleep Disturbances Related to Perennial Allergic Rhinitis (Study P04909)(TERMINATED)
NCT00491504	PHASE4	COMPLETED	This Study Contains an Active Drug Treatment Group With Mometasone Furoate Nasal Spray and a Placebo (Dummy) Treatment Group for Seasonal Allergic Rhinitis (SAR). (Study P05073)(COMPLETED)
NCT00559546	PHASE4	COMPLETED	Montelukast as a Controller of Atopic Syndrome
NCT00561717	PHASE4	COMPLETED	A Randomized, Placebo Controlled Study to Determine the Efficacy and Speed of a Nasal Spray in Allergen Induced Seasonal Allergic Rhinitis
NCT00584987	PHASE4	COMPLETED	Intranasal Steroids and Oxymetazoline in Allergic Rhinitis
NCT00590772	PHASE4	COMPLETED	The Role of Montelukast in Rhinitis and Sleep
NCT00621959	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Impact on Health-related Quality of Life of Levocetirizine in Adults With Seasonal Allergic Rhinitis
NCT00636870	PHASE4	COMPLETED	Fexofenadine (Allegra®) in Healthy Adults Who Have Been Identified as Slow Metabolizers for Desloratadine
NCT00637455	PHASE4	COMPLETED	Single Center, Randomized, Double-Blind,Crossover Study Comparing Effects Of Single-Dose Fexofenadine HCl 180 mg, Cetirizine 10 mg, and Placebo on Cognitive Performance in Naval Flight Personnel
NCT00637585	PHASE4	COMPLETED	Fexofenadine HCl 180 mg, Desloratadine 5 mg and Placebo in Suppression of Wheal and Flare Induced by Histamine
NCT00637611	PHASE4	COMPLETED	Single-Center, Double-Blind, Randomized , Parallel Study Comparing Onset of Action, Efficacy & Safety of a Single-Dose of Fexofenadine HCl 180 mg vs Montelukast Na 10 mg & Placebo in Treating Seasonal Allergic Rhinitis Subjects in an Allergen Exposure Unit
NCT00638118	PHASE4	COMPLETED	Fexofenadine HCl 180 mg, Montelukast Sodium 10 mg and Placebo in Suppression of Wheal and Flare Induced by Seasonal Allergen
NCT00641212	PHASE4	COMPLETED	Children, Perennial Allergic Rhinitis (PAR), l-t Growth
NCT00653224	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Impact on Health-related Quality of Life of Levocetirizine in Adults With Seasonal Allergic Rhinitis
NCT00679250	PHASE4	COMPLETED	To Evaluate Adenosine Monophosphate and Allergen Challenge in Allergic Rhinitis
NCT00691665	PHASE4	COMPLETED	Comparison of Olopatadine 0.6% and Fluticasone Proprionate 50mcg Nasal Sprays in a Two Week Seasonal Allergic Rhinitis Trial
NCT00698594	PHASE4	COMPLETED	Comparison of Effectiveness and Safety of Sublingual Immunotherapy in Children With Allergic Rhinitis
NCT00730912	PHASE4	COMPLETED	Post Approval Pharmacokinetic Study of Loratadine in Japanese Pediatric and Adult Patients (Study P05539)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
AZELASTINE	4	74
FEXOFENADINE	4	43
CETIRIZINE	4	27
MONTELUKAST	4	24
DESLORATADINE	4	22
LEVOCETIRIZINE	4	22
OXYMETAZOLINE	4	21
LORATADINE	4	17
OLOPATADINE	4	12
FLUTICASONE PROPIONATE	4	11
BILASTINE	4	10
MOMETASONE FUROATE	4	10
CICLESONIDE	4	9
BEPOTASTINE	4	8
OMALIZUMAB	4	8
PSEUDOEPHEDRINE	4	8
BECLOMETHASONE DIPROPIONATE	4	6
DEXCHLORPHENIRAMINE	4	6
FLUTICASONE FUROATE	4	6
HISTAMINE	4	6
DIPHENHYDRAMINE	4	3
BETAMETHASONE	4	2
BUDESONIDE	4	2
PHENYLEPHRINE	4	2
CHOLECALCIFEROL	4	1
EPHEDRINE	4	1
EPINASTINE	4	1
ESKETAMINE	4	1
IDELALISIB	4	1
METHACHOLINE	4	1