Atopic eczema

Summary

Atopic eczema (MONDO:0004980) is a disease with 75 cohort genes (796 GWAS associations across 49 studies) and 1,494 clinical trials. The dominant Reactome pathway is Interleukin-18 signaling (4 cohort genes). Top therapeutic interventions include dupilumab, tacrolimus anhydrous, and lebrikizumab.

At a glance

• Cohort genes: 75
• GWAS associations: 796
• ClinVar variants: 5
• Clinical trials: 1,494

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atopic eczema
Mondo ID	MONDO:0004980
EFO	EFO:0000274
MeSH	D003876
OMIM	603165
DOID	DOID:3310
ICD-10-CM	L20
ICD-11	215767047
NCIT	C3001
SNOMED CT	200775004, 24079001
UMLS	C0011615
MedGen	41502
Is cancer (heuristic)	no

Also known as: AD · allergic form of dermatitis · ATOD · atopic dermatitis · atopic eczema · dermatitis, atopic · eczema · eczema, atopic · eczematous dermatitis

Data availability: 5 ClinVar variants · 796 GWAS associations (49 studies) · 1 HPO phenotype · 6 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › dermatitis › atopic eczema

Related subtypes (32): spongiotic dermatitis, psoriasis, contact dermatitis, urticaria, acneiform dermatitis, acrodermatitis, folliculitis, granuloma annulare, granulomatous dermatitis, lichen planus, neurodermatitis, neurotic excoriation, parapsoriasis, pityriasis rosea, seborrheic dermatitis, acanthosis nigricans, dermatosis papulosa nigra, lichen sclerosus et atrophicus, vitiligo, acne, porphyria cutanea tarda, dermatomyositis, acute generalized exanthematous pustulosis, hydroa vacciniforme, autoimmune bullous skin disease, cutaneous vasculitis, skin infection, intertrigo, lipodermatosclerosis, exfoliative dermatitis, radiodermatitis, food dermatitis

Subtypes (3): allergic cutaneous vasculitis, allergic contact dermatitis, allergic urticaria

Genetics & variants

GWAS landscape

796 GWAS associations across 49 studies. Top hits map to 29 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12123821	1e-228	CCDST	T	1.27
rs61816766	1e-228	CCDST	C	1.41
rs61815704	6e-212	IVL - LINC01527	G	1.36
rs72702900	4e-163	LCE1D - LCE1C	A	1.23
rs149199808	3e-134	SNX27	T	1.24
rs7936323	2e-133	EMSY - LINC02757	A	1.07
rs20541	1e-129	IL13, TH2LCRR	G	0.92
rs6062486	5e-109	RTEL1-TNFRSF6B, RTEL1	A	1.07
rs12251307	5e-107	RPL32P23 - RBM17	T	1.1
rs10791824	1e-105	OVOL1	G	1.07
rs2272128	2e-100	IL18RAP	A	0.93
rs10214273	3e-99	IL7R - CAPSL	G	0.93
rs2041733	4e-95	CLEC16A	C	0.94
rs71625130	2e-89	SNX27	A	1.17
rs146527530	2e-88	GABPB2	G	1.25
rs28520436	5e-81	PRR5L	T	1.18
rs558269137	5e-72	CCDST, FLG	?	0.69
rs2227491	1e-71	IL22	C	1.05
rs45599938	1e-62	IL2 - IL21	A	1.05
rs629326	5e-61	TAGAP-AS1, TAGAP	T	0.95
chr1:152313385	5e-59		A	0.29
rs7110818	2e-58	EMSY - LINC02757	?	0.12
rs7542147	5e-56	RUNX3 - MIR4425	C	1.05
rs10822037	4e-55	LINC02929	C	1.05
rs10836538	6e-55	PRR5L	T	0.95
rs7127307	6e-52	LINC02098 - ETS1	C	0.96
rs28383330	2e-51	HLA-DQA1	G	0.94
rs1295686	2e-51	TH2LCRR, IL13	?	0.12
rs4821569	5e-50	CSF2RB	G	1.04
rs2967677	8e-49	NFILZ	T	1.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90473917	UK Biobank Whole-Genome Sequencing Consortium	2025	70,720	387,720	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90667885	UK Biobank Whole-Genome Sequencing Consortium	2025	70,720	387,720	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90244787	Budu-Aggrey A	2023	60,653	804,329	European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.
GCST90244788	Budu-Aggrey A	2023	60,653	804,329	European and multi-ancestry genome-wide association meta-analysis of atopic dermatitis highlights importance of systemic immune regulation.
GCST90503108	Oliva M	2025	42,963	408,472	Integration of GWAS, QTLs and keratinocyte functional assays reveals molecular mechanisms of atopic dermatitis.
GCST90503109	Oliva M	2025	42,963	408,472	Integration of GWAS, QTLs and keratinocyte functional assays reveals molecular mechanisms of atopic dermatitis.
GCST90297795	Pasanen A	2024	35,156	846,868	Identifying atopic dermatitis risk loci in 1,094,060 individuals with sub analysis of disease severity and onset.
GCST90244002	Chen Y	2022	33,262	804,234	Genome-wide integration of genetic and genomic studies of atopic dermatitis: Insights into genetic architecture and pathogenesis.
GCST011476	Patrick MT	2021	30,937	1,566,815	Associations between COVID-19 and skin conditions identified through epidemiology and genomic studies.
GCST90027161	Sliz E	2021	22,474	774,187	Uniting biobank resources reveals novel genetic pathways modulating susceptibility for atopic dermatitis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	38
low_freq (0.01-0.05)	10
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	15
missense_variant	3
unknown	2
frameshift_variant	1
3_prime_UTR_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12123821	1	152206676	C>T	0.05	intron_variant	CCDST	1e-228	Tier 4: intronic/intergenic
rs61816766	1	152347096	T>C	0.03	intron_variant	CCDST	1e-228	Tier 4: intronic/intergenic
rs61815704	1	152921415	C>G,T	0.02	intergenic_variant	IVL - LINC01527	6e-212	Tier 4: intronic/intergenic
rs72702900	1	152799487	T>A	0.04	intergenic_variant	LCE1D - LCE1C	4e-163	Tier 4: intronic/intergenic
rs149199808	1	151653920	C>A,T	0.03	intron_variant	SNX27	3e-134	Tier 4: intronic/intergenic
rs7936323	11	76582714	G>A	0.46	intergenic_variant	EMSY - LINC02757	2e-133	Tier 4: intronic/intergenic
rs20541	5	132660272	A>C,G,T	0.22	missense_variant	IL13, TH2LCRR	1e-129	Tier 1: coding
rs6062486	20	63671186	G>A,T	0.31	intron_variant	RTEL1-TNFRSF6B, RTEL1	5e-109	Tier 4: intronic/intergenic
rs12251307	10	6081532	C>G,T	0.12	intergenic_variant	RPL32P23 - RBM17	5e-107	Tier 4: intronic/intergenic
rs10791824	11	65791795	A>C,G,T	0.42	intron_variant	OVOL1	1e-105	Tier 4: intronic/intergenic
rs2272128	2	102423469	G>A,C,T	0.23	intron_variant	IL18RAP	2e-100	Tier 4: intronic/intergenic
rs10214273	5	35883884	T>A,G	0.27	intergenic_variant	IL7R - CAPSL	3e-99	Tier 4: intronic/intergenic
rs2041733	16	11135732	T>C,G	0.46	intron_variant	CLEC16A	4e-95	Tier 4: intronic/intergenic
rs71625130	1	151652618	G>A	0.04	intron_variant	SNX27	2e-89	Tier 4: intronic/intergenic
rs146527530	1	151086720	T>A,G	0.02	intron_variant	GABPB2	2e-88	Tier 4: intronic/intergenic
rs28520436	11	36406897	C>T	0.03	intron_variant	PRR5L	5e-81	Tier 4: intronic/intergenic
rs558269137	1	152312601	CACTG>C	0.05	frameshift_variant	CCDST, FLG	5e-72	Tier 1: coding
rs2227491	12	68252741	T>A,C,G	0.39	intron_variant	IL22	1e-71	Tier 4: intronic/intergenic
rs45599938	4	122465565	G>A,C	0.35	intergenic_variant	IL2 - IL21	1e-62	Tier 4: intronic/intergenic
rs629326	6	159075681	G>T	0.39	intron_variant	TAGAP-AS1, TAGAP	5e-61	Tier 4: intronic/intergenic
chr1:152313385							5e-59	Tier 4: intronic/intergenic
rs7110818	11	76581531	C>T	0.05	intergenic_variant	EMSY - LINC02757	2e-58	Tier 4: intronic/intergenic
rs7542147	1	24968127	T>A,C	0.49	intergenic_variant	RUNX3 - MIR4425	5e-56	Tier 4: intronic/intergenic
rs10822037	10	62616798	T>C	0.39	intron_variant	LINC02929	4e-55	Tier 4: intronic/intergenic
rs10836538	11	36343703	G>T	0.34	intron_variant	PRR5L	6e-55	Tier 4: intronic/intergenic
rs7127307	11	128317488	T>C	0.49	intron_variant	LINC02098 - ETS1	6e-52	Tier 4: intronic/intergenic
rs28383330	6	32632563	A>G	0.13	intergenic_variant	HLA-DQA1	2e-51	Tier 4: intronic/intergenic
rs1295686	5	132660151	T>A,C,G	0.05	intron_variant	TH2LCRR, IL13	2e-51	Tier 4: intronic/intergenic
rs4821569	22	36920831	A>C,G	0.47	intron_variant	CSF2RB	5e-50	Tier 4: intronic/intergenic
rs2967677	19	8679457	C>T	0.15	3_prime_UTR_variant	NFILZ	8e-49	Tier 2: splice/UTR

ClinVar germline variants

5 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
16319	NM_002016.2(FLG):c.1501C>T (p.Arg501Ter)	CCDST	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
373928	NM_000525.4(KCNJ11):c.185C>G (p.Thr62Arg)	KCNJ11	Likely pathogenic	no assertion criteria provided
734446	NM_001199138.2(NLRC4):c.1651A>T (p.Ile551Phe)	NLRC4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
523566	NM_173483.4(CYP4F22):c.1211T>C (p.Leu404Pro)	CYP4F22	Uncertain significance	criteria provided, single submitter
523567	NM_173483.4(CYP4F22):c.1544G>T (p.Arg515Leu)	CYP4F22	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 71 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
CCDST	CCDST	GWAS

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
STAT3	Orphanet:2314	Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency
STAT3	Orphanet:438159	STAT3-related early-onset multisystem autoimmune disease
STAT3	Orphanet:512017	Chronic lymphoproliferative disorder of natural killer cells
STAT3	Orphanet:520	Acute promyelocytic leukemia
STAT3	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
STAT3	Orphanet:86872	T-cell large granular lymphocyte leukemia
STAT3	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
TGM3	Orphanet:1410	Uncombable hair syndrome
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux
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
RTEL1	Orphanet:1775	Dyskeratosis congenita
RTEL1	Orphanet:2032	Idiopathic pulmonary fibrosis
RTEL1	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
CHST8	Orphanet:263548	Peeling skin syndrome type A
CARD11	Orphanet:300324	Persistent polyclonal B-cell lymphocytosis
CARD11	Orphanet:357237	Combined immunodeficiency due to CARD11 deficiency
CARD11	Orphanet:464336	BENTA disease
CARD11	Orphanet:619972	CADINS disease
EFHC1	Orphanet:1941	Juvenile absence epilepsy
EFHC1	Orphanet:307	Juvenile myoclonic epilepsy
NLRC4	Orphanet:436166	Periodic fever-infantile enterocolitis-autoinflammatory syndrome
NLRC4	Orphanet:576349	NLRC4-related familial cold autoinflammatory syndrome
MFN2	Orphanet:2398	Multiple symmetric lipomatosis
MFN2	Orphanet:64751	Hereditary motor and sensory neuropathy type 5
MFN2	Orphanet:90118	Severe early-onset axonal neuropathy due to MFN2 deficiency
MFN2	Orphanet:90120	Hereditary motor and sensory neuropathy type 6
MFN2	Orphanet:99947	Autosomal dominant Charcot-Marie-Tooth disease type 2A2
TNIP1	Orphanet:536	Systemic lupus erythematosus
PPP2R3C	Orphanet:171709	Male infertility due to globozoospermia
PPP2R3C	Orphanet:1770	XY type gonadal dysgenesis-associated anomalies syndrome
ZNF365	Orphanet:2073	Narcolepsy type 1
ZNF365	Orphanet:83465	Narcolepsy type 2
CYP24A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
CYP4F22	Orphanet:313	Lamellar ichthyosis
BLTP1	Orphanet:610569	KIAA1109-related early lethal congenital brain malformations-arthrogryposis syndrome
ACTL9	Orphanet:276234	Non-syndromic male infertility due to sperm motility disorder
TBL1XR1	Orphanet:487825	Pierpont syndrome
TBL1XR1	Orphanet:520	Acute promyelocytic leukemia
EGR2	Orphanet:101084	Charcot-Marie-Tooth disease type 1D
EGR2	Orphanet:64748	Dejerine-Sottas syndrome
EGR2	Orphanet:99951	Charcot-Marie-Tooth disease type 4E
ETS1	Orphanet:536	Systemic lupus erythematosus

Cohort genes → proteins

75 cohort genes, 69 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	72
gwas_and_clinvar	1
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CCDST	HGNC:55988	ENSG00000236427		cervical cancer associated DHX9 suppressive transcript	gwas,clinvar
SLC9A4	HGNC:11077	ENSG00000180251	Q6AI14	Sodium/hydrogen exchanger 4	gwas
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	gwas
SPRR1B	HGNC:11260	ENSG00000169469	P22528	Cornifin-B	gwas
SPRR3	HGNC:11268	ENSG00000163209	Q9UBC9	Small proline-rich protein 3	gwas
STAT3	HGNC:11364	ENSG00000168610	P40763	Signal transducer and activator of transcription 3	gwas
TGM3	HGNC:11779	ENSG00000125780	Q08188	Protein-glutamine gamma-glutamyltransferase E	gwas
TNFRSF6B	HGNC:11921	ENSG00000243509	O95407	Tumor necrosis factor receptor superfamily member 6B	gwas
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	gwas
CRNN	HGNC:1230	ENSG00000143536	Q9UBG3	Cornulin	gwas
VAX2	HGNC:12661	ENSG00000116035	Q9UIW0	Ventral anterior homeobox 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
DEXI	HGNC:13267	ENSG00000182108	O95424	Dexamethasone-induced protein	gwas
SLC6A15	HGNC:13621	ENSG00000072041	Q9H2J7	Sodium-dependent neutral amino acid transporter B(0)AT2	gwas
DMRTA1	HGNC:13826	ENSG00000176399	Q5VZB9	Doublesex- and mab-3-related transcription factor A1	gwas
DDX39B	HGNC:13917	ENSG00000198563	Q13838	Spliceosome RNA helicase DDX39B	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
GPSM3	HGNC:13945	ENSG00000213654	Q9Y4H4	G-protein-signaling modulator 3	gwas
MRPS21	HGNC:14046	ENSG00000266472	P82921	Small ribosomal subunit protein bS21m	gwas
XIRP2	HGNC:14303	ENSG00000163092	A4UGR9	Xin actin-binding repeat-containing protein 2	gwas
OR2W5	HGNC:15424	ENSG00000203664	A6NFC9	Putative olfactory receptor 2W5	gwas
PAQR8	HGNC:15708	ENSG00000170915	Q8TEZ7	Membrane progestin receptor beta	gwas
RTEL1	HGNC:15888	ENSG00000258366	Q9NZ71	Regulator of telomere elongation helicase 1	gwas
CHST8	HGNC:15993	ENSG00000124302	Q9H2A9	Carbohydrate sulfotransferase 8	gwas
CARD11	HGNC:16393	ENSG00000198286	Q9BXL7	Caspase recruitment domain-containing protein 11	gwas
EFHC1	HGNC:16406	ENSG00000096093	Q5JVL4	EF-hand domain-containing protein 1	gwas
NLRC4	HGNC:16412	ENSG00000091106	Q9NPP4	NLR family CARD domain-containing protein 4	clinvar
LCE5A	HGNC:16614	ENSG00000186207	Q5TCM9	Late cornified envelope protein 5A	gwas
TRAM2	HGNC:16855	ENSG00000065308	Q15035	Translocating chain-associated membrane protein 2	gwas
MFN2	HGNC:16877	ENSG00000116688	O95140	Mitofusin-2	gwas
TNIP1	HGNC:16903	ENSG00000145901	Q15025	TNFAIP3-interacting protein 1	gwas
RNF111	HGNC:17384	ENSG00000157450	Q6ZNA4	E3 ubiquitin-protein ligase Arkadia	gwas
PPP2R3C	HGNC:17485	ENSG00000092020	Q969Q6	Serine/threonine-protein phosphatase 2A regulatory subunit B’’ subunit gamma	gwas
CD207	HGNC:17935	ENSG00000116031	Q9UJ71	C-type lectin domain family 4 member K	gwas
EMSY	HGNC:18071	ENSG00000158636	Q7Z589	BRCA2-interacting transcriptional repressor EMSY	gwas
ZNF365	HGNC:18194	ENSG00000138311	Q70YC4	Talanin	gwas
NLRP10	HGNC:21464	ENSG00000182261	Q86W26	NACHT, LRR and PYD domains-containing protein 10	gwas
ATF6B	HGNC:2349	ENSG00000213676	Q99941	Cyclic AMP-dependent transcription factor ATF-6 beta	gwas
ADO	HGNC:23506	ENSG00000181915	Q96SZ5	2-aminoethanethiol dioxygenase	gwas
R3HCC1L	HGNC:23512	ENSG00000166024	Q7Z5L2	Coiled-coil domain-containing protein R3HCC1L	gwas
RASIP1	HGNC:24716	ENSG00000105538	Q5U651	Ras-interacting protein 1	gwas
AP5B1	HGNC:25104	ENSG00000254470	Q2VPB7	AP-5 complex subunit beta-1	gwas
CIART	HGNC:25200	ENSG00000159208	Q8N365	Circadian-associated transcriptional repressor	gwas
TMTC2	HGNC:25440	ENSG00000179104	Q8N394	Protein O-mannosyl-transferase TMTC2	gwas
PRR5L	HGNC:25878	ENSG00000135362	Q6MZQ0	Proline-rich protein 5-like	gwas
CYP24A1	HGNC:2602	ENSG00000019186	Q07973	1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial	gwas
PUS10	HGNC:26505	ENSG00000162927	Q3MIT2	tRNA pseudouridine synthase Pus10	gwas
CYP4F22	HGNC:26820	ENSG00000171954	Q6NT55	Ultra-long-chain fatty acid omega-hydroxylase	clinvar
BLTP1	HGNC:26953	ENSG00000138688	Q2LD37	Bridge-like lipid transfer protein family member 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC9A4	Sodium/hydrogen exchanger 4	Electroneutral antiporter that exchanges sodium for protons or ammonium ions at the basolateral membrane of epithelia to regulate cell volume and intracellular pH upon hypertonic conditions.
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SPRR1B	Cornifin-B	Cross-linked envelope protein of keratinocytes.
SPRR3	Small proline-rich protein 3	Cross-linked envelope protein of keratinocytes.
STAT3	Signal transducer and activator of transcription 3	Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
TGM3	Protein-glutamine gamma-glutamyltransferase E	Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins.
TNFRSF6B	Tumor necrosis factor receptor superfamily member 6B	Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
CRNN	Cornulin	Promotes cell proliferation, G1/S cell cycle progression and induces expression of the cell cycle regulator CCND1.
VAX2	Ventral anterior homeobox 2	Transcription factor that may function in dorsoventral specification of the forebrain.
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.
SLC6A15	Sodium-dependent neutral amino acid transporter B(0)AT2	Functions as a sodium-dependent neutral amino acid transporter.
DDX39B	Spliceosome RNA helicase DDX39B	Involved in nuclear export of spliced and unspliced mRNA.
GPSM3	G-protein-signaling modulator 3	Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins.
XIRP2	Xin actin-binding repeat-containing protein 2	Protects actin filaments from depolymerization.
OR2W5	Putative olfactory receptor 2W5	Odorant receptor.
PAQR8	Membrane progestin receptor beta	Plasma membrane progesterone (P4) receptor coupled to G proteins.
RTEL1	Regulator of telomere elongation helicase 1	A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability.
CHST8	Carbohydrate sulfotransferase 8	Catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans.
CARD11	Caspase recruitment domain-containing protein 11	Adapter protein that plays a key role in adaptive immune response by transducing the activation of NF-kappa-B downstream of T-cell receptor (TCR) and B-cell receptor (BCR) engagement.
EFHC1	EF-hand domain-containing protein 1	Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
NLRC4	NLR family CARD domain-containing protein 4	Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis.
LCE5A	Late cornified envelope protein 5A	Precursors of the cornified envelope of the stratum corneum.
TRAM2	Translocating chain-associated membrane protein 2	Necessary for collagen type I synthesis.
MFN2	Mitofusin-2	Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion.
TNIP1	TNFAIP3-interacting protein 1	Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG.
RNF111	E3 ubiquitin-protein ligase Arkadia	E3 ubiquitin-protein ligase.
PPP2R3C	Serine/threonine-protein phosphatase 2A regulatory subunit B’’ subunit gamma	May regulate MCM3AP phosphorylation through phosphatase recruitment.
CD207	C-type lectin domain family 4 member K	Calcium-dependent lectin displaying mannose-binding specificity.
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.
ZNF365	Talanin	May play a role in uric acid excretion.
NLRP10	NACHT, LRR and PYD domains-containing protein 10	Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID.
ATF6B	Cyclic AMP-dependent transcription factor ATF-6 beta	Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 beta), which is embedded in the endoplasmic reticulum membrane.
ADO	2-aminoethanethiol dioxygenase	Plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate.
RASIP1	Ras-interacting protein 1	Required for the proper formation of vascular structures that develop via both vasculogenesis and angiogenesis.
AP5B1	AP-5 complex subunit beta-1	As part of AP-5, a probable fifth adaptor protein complex it may be involved in endosomal transport.
CIART	Circadian-associated transcriptional repressor	Transcriptional repressor which forms a negative regulatory component of the circadian clock and acts independently of the circadian transcriptional repressors: CRY1, CRY2 and BHLHE41.
TMTC2	Protein O-mannosyl-transferase TMTC2	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
PRR5L	Proline-rich protein 5-like	Associates with the mTORC2 complex that regulates cellular processes including survival and organization of the cytoskeleton.
CYP24A1	1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial	A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis.
PUS10	tRNA pseudouridine synthase Pus10	Protein with different functions depending on its subcellular location: involved in miRNA processing in the nucleus and acts as a tRNA pseudouridylate synthase in the cytoplasm.
CYP4F22	Ultra-long-chain fatty acid omega-hydroxylase	A cytochrome P450 monooxygenase involved in epidermal ceramide biosynthesis.
BLTP1	Bridge-like lipid transfer protein family member 1	Bridge-like lipid transfer protein that functions as molecular bridges between endoplasmic reticulum and the membranes targeted for lipid delivery.
ACTL9	Actin-like protein 9	Testis-specic protein that plays an important role in fusion of proacrosomal vesicles and perinuclear theca formation.
CLEC16A	Protein CLEC16A	Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.
ZNF652	Zinc finger protein 652	DNA-binding transcription repressor that acts together with CBFA2T2 to repress expression of target genes, such as TCF12.
LCE3A	Late cornified envelope protein 3A	A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense.
LCE3E	Late cornified envelope protein 3E	Precursors of the cornified envelope of the stratum corneum.
LCE1E	Late cornified envelope protein 1E	Precursors of the cornified envelope of the stratum corneum.

Protein-family classification

Druggable: 10 · Difficult: 13 · Unknown: 52 · Druggable fraction: 0.13

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	52	1.2×	0.092
Transcription factor	11	1.2×	0.937
Antibody/Immunoglobulin	2	0.8×	0.937
Enzyme (other)	4	0.6×	0.937
GPCR	2	0.6×	0.937
Protease	1	0.5×	0.937
Scaffold/PPI	2	0.5×	0.937
Kinase	1	0.4×	0.937

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CCDST	Other/Unknown	no
SLC9A4	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SPRR1B	Other/Unknown	no
SPRR3	Other/Unknown	no
STAT3	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TGM3	Antibody/Immunoglobulin	yes	2.3.2.13	Transglutaminase_N, Transglutaminase-like, Transglutaminase_C
TNFRSF6B	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
CRNN	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, S100_Ca-bd_sub
VAX2	Transcription factor	no		HTH_motif, HD, Homeodomain-like_sf
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
ADAMTS10	Protease	yes		TSP1_rpt, Peptidase_M12B, Peptidase_M12B_N
DEXI	Other/Unknown	no		Dexamethasone-induced
SLC6A15	Other/Unknown	no		Na/ntran_symport, Neutral_aa_SLC6, SNS_sf
DMRTA1	Other/Unknown	no		DM_DNA-bd, DMA, UBA-like_sf
DDX39B	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd
TSBP1	Other/Unknown	no		TSBP1
GPSM3	Other/Unknown	no		GoLoco_motif, TPR-like_helical_dom_sf, GPSM3
MRPS21	Other/Unknown	no		Ribosomal_bS21, Ribosomal_bS21_sf
XIRP2	Other/Unknown	no		Actin-binding_Xin_repeat, XIRP1/XIRP2
OR2W5	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
PAQR8	Other/Unknown	no		AdipoR/HlyIII-related
RTEL1	Other/Unknown	no		Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
CHST8	Other/Unknown	no		Sulfotransferase, Carb_sulfotrans_8-10
CARD11	Scaffold/PPI	no		CARD, DEATH-like_dom_sf, P-loop_NTPase
EFHC1	Other/Unknown	no		EF_hand_dom, DM10_dom, EF-hand-dom_pair
NLRC4	Transcription factor	no		CARD, NACHT_NTPase, DEATH-like_dom_sf
LCE5A	Other/Unknown	no		LCE
TRAM2	Other/Unknown	no		TLC-dom, Translocation_assoc_membrane
MFN2	Other/Unknown	no		Fzo/mitofusin_HR2, Mitofusin_fam, P-loop_NTPase
TNIP1	Other/Unknown	no
RNF111	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RING/FYVE/PHD, RNF111_N
PPP2R3C	Other/Unknown	no		EF-hand-dom_pair, EF_Hand_1_Ca_BS, PPP2R3C
CD207	Other/Unknown	no		C-type_lectin-like, C-type_lectin-like/link_sf, CTDL_fold
EMSY	Other/Unknown	no		ENT_dom, EMSY, ENT_dom-like_sf
ZNF365	Transcription factor	no		GenomicStab_NeuMorph_Reg, FBX41/ZN365_Znf-C2H2
NLRP10	Other/Unknown	no		DAPIN, NACHT_NTPase, DEATH-like_dom_sf
ATF6B	Transcription factor	no		bZIP, bZIP_sf, ATF_bZIP_TF
ADO	Enzyme (other)	yes	1.13.11.19	RmlC_Cupin_sf, PCO/ADO, RmlC-like_jellyroll
R3HCC1L	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, R3HC1/R3HCL
RASIP1	Other/Unknown	no		RA_dom, Dilute_dom, SMAD_FHA_dom_sf
AP5B1	Other/Unknown	no		AP5B1, AP5B1_N, AP5B1_middle
CIART	Other/Unknown	no		Ciart
TMTC2	Other/Unknown	no		TPR-like_helical_dom_sf, TMTC_DUF1736, TPR_rpt
PRR5L	Other/Unknown	no		Bit61/PRR5
CYP24A1	Enzyme (other)	yes	1.14.14.24	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
PUS10	Enzyme (other)	yes	5.4.99.25	PsdUridine_synth_cat_dom_sf, Pus10-like, Pus10-like_C
CYP4F22	Enzyme (other)	yes	1.14.14.177	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
BLTP1	Other/Unknown	no		BLTP1, BLTP1_N, BLTP1_M

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	1
moderate (6-20)	0
broad (>20)	74
unknown	0

Top tissues across cohort

Tissue	Cohort genes
lower esophagus mucosa	9
male germ line stem cell (sensu Vertebrata) in testis	9
granulocyte	9
skin of leg	6
primordial germ cell in gonad	6
ventricular zone	5
left testis	5
blood	5
monocyte	5
skin of abdomen	5
secondary oocyte	5
apex of heart	4
cerebellar hemisphere	4
right testis	4
zone of skin	4
calcaneal tendon	4
cortical plate	3
spleen	3
sural nerve	3
leukocyte	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDST	111	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, lower esophagus mucosa, quadriceps femoris
SLC9A4	67	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, stomach, body of stomach
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
SPRR1B	175	broad	marker	amniotic fluid, gingiva, cervix squamous epithelium
SPRR3	174	broad	marker	lower esophagus mucosa, oral cavity, pharyngeal mucosa
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung
TGM3	120	tissue_specific	marker	lower esophagus mucosa, esophagus mucosa, skin of leg
TNFRSF6B	127	broad	yes	olfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNXB	134	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland
CRNN	157	tissue_specific	marker	lower esophagus mucosa, tongue squamous epithelium, pharyngeal mucosa
VAX2	150	ubiquitous	marker	primordial germ cell in gonad, cerebellar hemisphere, cerebellar cortex
IKZF3	155	broad	marker	granulocyte, lymph node, epithelium of nasopharynx
ADAMTS10	254	ubiquitous	yes	descending thoracic aorta, right coronary artery, kidney epithelium
DEXI	282	ubiquitous	yes	apex of heart, hindlimb stylopod muscle, left adrenal gland cortex
SLC6A15	204	ubiquitous	marker	cortical plate, pigmented layer of retina, retina
DMRTA1	131	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, right lobe of liver, islet of Langerhans
DDX39B	263	ubiquitous	marker	granulocyte, adenohypophysis, ventricular zone
TSBP1	58	tissue_specific	yes	left testis, testis, right testis
GPSM3	133	ubiquitous	marker	granulocyte, blood, spleen
MRPS21	255	ubiquitous	marker	cardiac muscle of right atrium, left ventricle myocardium, lateral nuclear group of thalamus
XIRP2	150	tissue_specific	marker	deltoid, biceps brachii, quadriceps femoris
OR2W5	0		yes	granulocyte, sural nerve, ganglionic eminence
PAQR8	235	tissue_specific	marker	inferior vagus X ganglion, globus pallidus, medial globus pallidus
RTEL1	134	ubiquitous	yes	sural nerve, right hemisphere of cerebellum, cerebellar hemisphere
CHST8	167	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, pituitary gland, adenohypophysis
CARD11	188	broad	marker	granulocyte, lymph node, spleen
EFHC1	272	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
NLRC4	166	broad	marker	monocyte, leukocyte, blood
LCE5A	81	tissue_specific	yes	skin of leg, zone of skin, skin of abdomen
TRAM2	250	ubiquitous	marker	oocyte, secondary oocyte, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 28.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
SMARCA4	8,138
FGFR1	5,693
DDX39B	5,600
TBL1XR1	4,066
MFN2	3,853
ETS1	3,729
CARD11	3,587
TNIP1	3,304
IKZF3	3,285

Intra-cohort edges

A	B	Sources
ACTL9	EMSY	string_interaction
ACTL9	PRR5L	string_interaction
ADO	EGR2	string_interaction
ATF6B	TNXB	string_interaction
CAPSL	CLEC16A	string_interaction
CCDC80	LRRC32	string_interaction
CCDC80	TRAM2	string_interaction
CLEC16A	DEXI	string_interaction
CLEC16A	ZBTB10	string_interaction
CRCT1	CRNN	string_interaction
CRCT1	SPRR3	string_interaction
CRNN	SPRR3	string_interaction
CRNN	TGM3	string_interaction
DEXI	ZBTB10	string_interaction
EFHC1	IKZF3	biogrid_interaction, intact
EFHC1	PAQR8	string_interaction
EFHC1	PRR5L	intact
EMSY	LRRC32	string_interaction
FDX2	ZGLP1	string_interaction
LCE1E	LCE3E	string_interaction
LCE1E	LCE5A	biogrid_interaction
LCE3E	LCE5A	string_interaction
LCE5A	SPRR1B	string_interaction
LRRC32	STAT3	biogrid_interaction
NLRC4	NLRP10	string_interaction
NLRP10	TNIP1	string_interaction
SPRR3	TGM3	string_interaction
TNXB	TSBP1	string_interaction

Structural data

PDB: 30 · AlphaFold-only: 39 · No structure: 6

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR1	P11362	83
MRPS21	P82921	71
SMARCA4	P51532	31
CD207	Q9UJ71	22
ETS1	P14921	21
DDX39B	Q13838	17
TGM3	Q08188	11
ADO	Q96SZ5	9
TNFRSF6B	O95407	8
TNIP1	Q15025	8
GLB1	P16278	8
GRM4	Q14833	8
STAT3	P40763	6
NLRC4	Q9NPP4	6
LRRC32	Q14392	6
FDX2	Q6P4F2	5
RNF111	Q6ZNA4	4
TNXB	P22105	3
RTEL1	Q9NZ71	3
MFN2	O95140	3
EMSY	Q7Z589	3
CARD11	Q9BXL7	2
EFHC1	Q5JVL4	2
RASIP1	Q5U651	2
AP5B1	Q2VPB7	2
ZBTB10	Q96DT7	2
XIRP2	A4UGR9	1
NLRP10	Q86W26	1
PUS10	Q3MIT2	1
TBL1XR1	Q9BZK7	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP4F22	Q6NT55	93.59
PAQR8	Q8TEZ7	93.25
CAPSL	Q8WWF8	91.88
TMTC2	Q8N394	90.57
PPP2R3C	Q969Q6	90.08
CYP24A1	Q07973	89.03
ACTL9	Q8TC94	87.56
TRAM2	Q15035	85.96
SLC6A15	Q9H2J7	80.15
CHST8	Q9H2A9	79.90
ADAMTS10	Q9H324	73.88
CLEC16A	Q2KHT3	72.17
GPSM3	Q9Y4H4	71.77
VAX2	Q9UIW0	70.91
SPRR1B	P22528	70.02
DEXI	O95424	69.88
PRR5L	Q6MZQ0	68.40
SLC9A4	Q6AI14	66.73
ZGLP1	P0C6A0	62.89
CCDC80	Q76M96	62.51
OR2W5	A6NFC9	60.12
LCE3E	Q5T5B0	59.34
LCE3A	Q5TA76	57.44
DMRTA1	Q5VZB9	57.14
ZNF652	Q9Y2D9	56.60
ATF6B	Q99941	55.31
CIART	Q8N365	55.07
LCE1E	Q5T753	53.42
CRCT1	Q9UGL9	53.29
LCE5A	Q5TCM9	53.12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 388. Enrichment computed across 105 evidence-associated genes (64 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 64 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-18 signaling	4	89.2×	2e-05	IL13, IL18R1, IL18RAP, IL4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	13.7×	9e-04	SMARCA4, TBL1XR1, ETS1, IL13, IL4, RAD50
Formation of the cornified envelope	6	8.2×	0.011	SPRR1B, SPRR3, LCE5A, LCE3A, LCE3E, LCE1E
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	2	35.7×	0.069	IL2, IL2RA
Interleukin-21 signaling	2	35.7×	0.069	STAT3, IL21
Endosomal/Vacuolar pathway	2	32.4×	0.069	HLA-B, HLA-C
Interleukin-6 signaling	2	29.7×	0.069	STAT3, IL6R
Interleukin-2 signaling	2	29.7×	0.069	IL2, IL2RA
Interleukin-7 signaling	3	14.9×	0.069	SMARCA4, STAT3, IL7R
Interferon gamma signaling	4	7.8×	0.069	HLA-B, HLA-C, HLA-DQA1, HLA-DRB1
Keratinization	6	5.2×	0.069	SPRR1B, SPRR3, LCE5A, LCE3A, LCE3E, LCE1E
Interleukin-15 signaling	2	23.8×	0.100	STAT3, IL15RA
Interleukin-4 and Interleukin-13 signaling	4	6.4×	0.102	STAT3, IL13, IL4, IL6R
Translocation of ZAP-70 to Immunological synapse	2	19.8×	0.124	HLA-DQA1, HLA-DRB1
Defective CYP4F22 causes ARCI5	1	178.4×	0.128	CYP4F22
Defective CYP24A1 causes HCAI	1	178.4×	0.128	CYP24A1
MGMT-mediated DNA damage reversal	1	178.4×	0.128	MGMT
Phosphorylation of CD3 and TCR zeta chains	2	17.0×	0.129	HLA-DQA1, HLA-DRB1
Co-inhibition by PD-1	2	16.2×	0.129	HLA-DQA1, HLA-DRB1
Interleukin-37 signaling	2	16.2×	0.129	STAT3, IL18R1
Signaling by FGFR1 amplification mutants	1	89.2×	0.143	FGFR1
MPS IV - Morquio syndrome B (Keratin metabolism)	1	89.2×	0.143	GLB1
Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome	1	89.2×	0.143	KCNJ11
Defective ABCC8 can cause hypo- and hyper-glycemias	1	89.2×	0.143	KCNJ11
The IPAF inflammasome	1	89.2×	0.143	NLRC4
MPS IV - Morquio syndrome B (CS/DS degradation)	1	89.2×	0.143	GLB1
DAP12 interactions	2	14.9×	0.143	HLA-B, HLA-C
Interleukin receptor SHC signaling	2	12.8×	0.143	IL2, IL2RA
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	2	12.3×	0.143	RTEL1, RAD50
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	2	12.3×	0.143	HLA-B, HLA-C

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 93 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	17	8.6×	7e-09	CD207, ETS1, HLA-B, HLA-C, HLA-DQA1, HLA-DRB1, IL13, IL18R1 (+9 more)
positive regulation of inflammatory response	9	14.1×	5e-06	STAT3, GPSM3, NLRC4, TNIP1, NLRP10, ETS1, IL1RL1, IL2 (+1 more)
keratinization	7	17.6×	3e-05	SPRR1B, SPRR3, TGM3, LCE5A, LCE3A, LCE3E, LCE1E
interleukin-2-mediated signaling pathway	3	68.0×	0.001	STAT3, IL2, IL2RA
positive regulation of B cell proliferation	5	18.5×	0.001	CARD11, IL13, IL2, IL21, IL4
adaptive immune response	8	7.2×	0.002	NLRP10, HLA-B, HLA-C, HLA-DQA1, IL18R1, IL18RAP, IL2, MICB
regulation of CD4-positive, alpha-beta T cell proliferation	2	181.2×	0.003	IL2, IL2RA
detection of bacterium	3	45.3×	0.003	NLRC4, HLA-B, HLA-DRB1
regulation of T cell homeostatic proliferation	2	120.8×	0.006	IL2, IL2RA
positive regulation of interleukin-10 production	4	17.3×	0.006	STAT3, IL13, IL21, IL4
obsolete positive regulation of NF-kappaB transcription factor activity	5	11.1×	0.006	CRNN, CARD11, NLRC4, IL18R1, IL18RAP
negative regulation of complement-dependent cytotoxicity	2	72.5×	0.018	IL13, IL4
positive regulation of tissue remodeling	2	60.4×	0.023	IL2, IL21
interleukin-18-mediated signaling pathway	2	60.4×	0.023	IL18R1, IL18RAP
positive regulation of natural killer cell mediated cytotoxicity	3	18.1×	0.027	HLA-C, IL18RAP, IL21
cell surface receptor signaling pathway via STAT	3	18.1×	0.027	STAT3, IL2, IL6R
gamma-delta T cell activation	2	45.3×	0.032	MICA, MICB
positive regulation of T cell mediated cytotoxicity	3	16.5×	0.032	HLA-B, HLA-C, HLA-DRB1
inflammatory response	9	3.6×	0.032	STAT3, NLRC4, TNIP1, NLRP10, IL13, IL18R1, IL18RAP, IL1RL1 (+1 more)
positive regulation of immunoglobulin production	3	15.5×	0.034	IL13, IL2, IL21
activated T cell proliferation	2	40.3×	0.037	IL2, IL2RA
positive regulation of T cell differentiation	3	14.7×	0.037	SMARCA4, IL2RA, IL4
positive regulation of natural killer cell differentiation	2	36.2×	0.040	IL15RA, IL21
interleukin-15-mediated signaling pathway	2	36.2×	0.040	STAT3, IL15RA
response to heat	3	13.6×	0.040	CRNN, MICA, MICB
outer ear morphogenesis	2	33.0×	0.042	FGFR1, PRKRA
positive regulation of isotype switching to IgG isotypes	2	33.0×	0.042	IL2, IL4
T-helper 17 cell lineage commitment	2	33.0×	0.042	STAT3, IL6R
peptide cross-linking	2	30.2×	0.048	SPRR1B, TGM3
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	2	27.9×	0.050	HLA-B, HLA-C

Therapeutics

Drugs indicated for this disease

16 approved, 22 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Abrocitinib	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Crisaborole	Approved (phase 4)
Desonide	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Dupilumab	Approved (phase 4)
Fluocinolone Acetonide	Approved (phase 4)
Fluticasone Propionate	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Hydrocortisone Butyrate	Approved (phase 4)
Lebrikizumab	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Pimecrolimus	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Tralokinumab	Approved (phase 4)
Amlitelimab	Phase 3 (in late-stage trials)
Baricitinib	Phase 3 (in late-stage trials)
Bergapten	Phase 3 (in late-stage trials)
Betamethasone Valerate	Phase 3 (in late-stage trials)
Cimetidine	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Difamilast	Phase 3 (in late-stage trials)
Enbucrilate	Phase 3 (in late-stage trials)
Maltodextrin	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Nemolizumab	Phase 3 (in late-stage trials)
PAC-14028	Phase 3 (in late-stage trials)
Paraffin	Phase 3 (in late-stage trials)
Rocatinlimab	Phase 3 (in late-stage trials)
Roflumilast	Phase 3 (in late-stage trials)
Ruxolitinib	Phase 3 (in late-stage trials)
Stapokibart	Phase 3 (in late-stage trials)
Tacrolimus Anhydrous	Phase 3 (in late-stage trials)
Tapinarof	Phase 3 (in late-stage trials)
Tradipitant	Phase 3 (in late-stage trials)
Upadacitinib	Phase 3 (in late-stage trials)
Urea	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Apremilast, Astegolimab, Benralizumab, Bermekimab, Betamethasone, Brepocitinib, Calcipotriene, Cholecalciferol, Delgocitinib, Etrasimod, Fevipiprant, Fexofenadine, Fluocinonide, Halobetasol Propionate, Hydrocortisone Acetate, Indigo, Itepekimab, Ivermectin, Lactulose, Ligelizumab, Lirentelimab, Mapracorat, Melatonin, Mometasone Furoate, Mufemilast, Nalmefene, Oatmeal, Colloidal, Omiganan, Rilzabrutinib, Rosiptor, Secukinumab, Sertaconazole, Tezepelumab, Timapiprant, Tozorakimab, Triamcinolone, Triamcinolone Acetonide, Ustekinumab.

Drug target analysis

Approved (phase 4): 6 · Phase ≥3: 7 · Phased (≥1): 9 · Undrugged: 66

Druggability breadth: 36 of 105 evidence-associated genes (34%) 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
STAT3	MOMELOTINIB
IKZF3	POMALIDOMIDE
SLC6A15	LORATADINE
CYP24A1	KETOCONAZOLE
FGFR1	PONATINIB
GLB1	MIGALASTAT

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR1	93	4
STAT3	18	4
IKZF3	5	4
CYP24A1	4	4
GRM4	3	3
SMARCA4	2	2
TGM3	1	2
SLC6A15	1	4
GLB1	1	4
CCDST	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOMELOTINIB	4	STAT3
NITAZOXANIDE	4	STAT3
NICLOSAMIDE	4	FGFR1, STAT3
DIGOXIN	4	STAT3
BARICITINIB	4	STAT3
DIGITOXIN	4	STAT3
DEUCRAVACITINIB	4	STAT3
POMALIDOMIDE	4	IKZF3
LENALIDOMIDE	4	IKZF3
THALIDOMIDE	4	IKZF3
LORATADINE	4	SLC6A15
KETOCONAZOLE	4	CYP24A1
CALCITRIOL	4	CYP24A1
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

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

Symbol	Assays	Type breakdown
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
GRM4	252	Functional:161, Binding:91
SMARCA4	230	Binding:207, ADMET:12, Functional:11
GLB1	124	Binding:123, ADMET:1
IKZF3	101	Binding:100, Functional:1
CYP24A1	35	Binding:28, ADMET:7
TGM3	15	Binding:15
NLRC4	13	Binding:13
CD207	6	Binding:6
SLC6A15	5	Binding:5
MFN2	3	Binding:3
ZBTB10	3	Binding:3
TBL1XR1	2	Binding:2
SPRR3	1	Binding:1
DDX39B	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TGM3	2.3.2.13	protein-glutamine gamma-glutamyltransferase
RNF111	2.3.2.27	RING-type E3 ubiquitin transferase
ADO	1.13.11.19	cysteamine dioxygenase
CYP24A1	1.14.14.24, 1.14.15.16	vitamin D 25-hydroxylase, vitamin D3 24-hydroxylase
PUS10	5.4.99.25, 5.4.99.B22, 5.4.99.B25	tRNA pseudouridine55 synthase, ,
CYP4F22	1.14.14.177	ultra-long-chain fatty acid omega-hydroxylase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
SMARCA4	230
STAT3	1,319
IKZF3	101
FGFR1	1,465
GLB1	124
GRM4	252

Pharmacogenomics

Cohort genes with a PharmGKB record: 70; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 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)
MOMELOTINIB	4	STAT3
NITAZOXANIDE	4	STAT3
NICLOSAMIDE	4	FGFR1, STAT3
DIGOXIN	4	STAT3
DIGITOXIN	4	STAT3
DEUCRAVACITINIB	4	STAT3
POMALIDOMIDE	4	IKZF3
LENALIDOMIDE	4	IKZF3
THALIDOMIDE	4	IKZF3
LORATADINE	4	SLC6A15
KETOCONAZOLE	4	CYP24A1
CALCITRIOL	4	CYP24A1
PONATINIB	4	FGFR1
PEMIGATINIB	4	FGFR1
NINTEDANIB	4	FGFR1
FEDRATINIB	4	FGFR1
TIVOZANIB	4	FGFR1
LENVATINIB	4	FGFR1
AXITINIB	4	FGFR1
SORAFENIB	4	FGFR1
INFIGRATINIB PHOSPHATE	4	FGFR1
INFIGRATINIB	4	FGFR1
REGORAFENIB	4	FGFR1
ENTRECTINIB	4	FGFR1
CABOZANTINIB	4	FGFR1
CAPIVASERTIB	4	FGFR1
VANDETANIB	4	FGFR1
NINTEDANIB ESYLATE	4	FGFR1
BRIGATINIB	4	FGFR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	6	STAT3, IKZF3, SLC6A15, CYP24A1, FGFR1, GLB1
B	Phased (≥1) drug, not yet approved	3	SMARCA4, TGM3, GRM4
C	Druggable family + PDB, no drug	3	TNXB, ADO, PUS10
D	Druggable family + AlphaFold only, no drug	3	ADAMTS10, OR2W5, CYP4F22
E	Difficult family or no structure, no drug	60	CCDST, SLC9A4, SPRR1B, SPRR3, TNFRSF6B, CRNN, VAX2, DEXI, DMRTA1, DDX39B (+50 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CRNN	0	TGM3
CCDST	0	—
SLC9A4	0	—
SPRR1B	0	—
SPRR3	1	—
TNFRSF6B	0	—
TNXB	0	—
VAX2	0	—
ADAMTS10	0	—
DEXI	0	—
DMRTA1	0	—
DDX39B	1	—
TSBP1	0	—
GPSM3	0	—
MRPS21	0	—
XIRP2	0	—
OR2W5	0	—
PAQR8	0	—
RTEL1	0	—
CHST8	0	—
CARD11	0	—
EFHC1	0	—
NLRC4	13	—
LCE5A	0	—
TRAM2	0	—
MFN2	3	—
TNIP1	0	—
RNF111	0	—
PPP2R3C	0	—
CD207	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,494.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	325
PHASE3	215
Not specified	190
PHASE1	166
PHASE4	129
PHASE1/PHASE2	48
EARLY_PHASE1	14
PHASE2/PHASE3	13

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05042258	PHASE4	RECRUITING	Using Dupilumab to Improve Circadian Function, Sleep and Pruritus in Children With Moderate/Severe Atopic Dermatitis
NCT05268107	PHASE4	RECRUITING	Ethnic Differences in Mechanisms of Action of Dupilumab
NCT05285839	PHASE4	RECRUITING	Dupixent and Narrowband UVB for Atopic Dermatitis
NCT05566262	PHASE4	ACTIVE_NOT_RECRUITING	Bodewell Products for the Treatment of Atopic Dermatitis
NCT05642208	PHASE4	ACTIVE_NOT_RECRUITING	Dupilumab Step-down Strategy to Maintain Remission in Adult and Adolescents Patients With Atopic Dermatitis
NCT05758532	PHASE4	RECRUITING	Non-specific Effects of a Modified Measles Vaccination Schedule to Prevent Allergy and Unrelated Infection in Children
NCT05858619	PHASE4	RECRUITING	Molecular Signatures of Cutaneous Dupilumab Response
NCT05983068	PHASE4	ACTIVE_NOT_RECRUITING	A Study of Long-term Effect of Dupilumab on Skin Barrier Function in Pediatric Participants With Atopic Dermatitis
NCT06004986	PHASE4	RECRUITING	DUPIlumab Dose REDUCtion in Patients With Controlled Atopic Eczema
NCT06116526	PHASE4	RECRUITING	Dupilumab De-escalation in Pediatric Atopic Dermatitis
NCT06397781	PHASE4	NOT_YET_RECRUITING	Effect of S. Aureus Skin Decolonization on Disease Severity in Atopic Dermatitis Patients
NCT06465732	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Dupilumab in Combination With Tofacitinib in Moderate to Severe Adult AD Patients
NCT06906497	PHASE4	RECRUITING	Lebrikizumab in Moderate-to-severe Atopic Dermatitis
NCT07006792	PHASE4	ACTIVE_NOT_RECRUITING	A Study to See How Well Lebrikizumab Works in Adults and Adolescents With Moderate Atopic Dermatitis (Eczema) and High Itch Burden
NCT07352566	PHASE4	NOT_YET_RECRUITING	Utilization of a Microdevice for Psoriasis and Atopic Dermatitis
NCT07367932	PHASE4	NOT_YET_RECRUITING	Comparative Study of Crisaborole vs. Tacrolimus in Atopic Dermatitis
NCT07437534	PHASE4	NOT_YET_RECRUITING	Comparative Evaluation of the Safety and Effectiveness of Crisaborole Ointment (2%) Versus Tacrolimus Ointment (0.1%) for the Topical Treatment of Atopic Dermatitis
NCT07438509	PHASE4	NOT_YET_RECRUITING	Efficacy of Crisaborole 2% Cream Versus Placebo in Mild to Moderate Atopic Eczema
NCT07447063	PHASE4	NOT_YET_RECRUITING	The Impact of Dietary Salt on the Severity of Eczema
NCT07487831	PHASE4	NOT_YET_RECRUITING	The Impact of Salt Intake on Sodium in the Skin and Inflammatory Skin Disease
NCT07560618	PHASE4	NOT_YET_RECRUITING	Obtaining Descriptive Classifications of Pruritus and Assessing Change in Pruritus Over Time in Atopic Dermatitis Patients Using Topical Roflumilast Cream.
NCT00106496	PHASE4	COMPLETED	A Multi-Center Study of Short and Long-term Use of Protopic Ointment in Patients With Atopic Dermatitis
NCT00117377	PHASE4	COMPLETED	Effects of Pimecrolimus Cream 1% on the Molecular and Cellular Profile of Adult Male Patients With Atopic Dermatitis
NCT00119158	PHASE4	COMPLETED	Combination Therapy for Atopic Dermatitis
NCT00120302	PHASE4	COMPLETED	Quality of Life Study in Adults With Facial Eczema
NCT00121316	PHASE4	COMPLETED	Safety and Efficacy of Pimecrolimus Cream 1% in Mild to Moderate Head and Neck Atopic Dermatitis (AD) Patients
NCT00121381	PHASE4	COMPLETED	Pimecrolimus Cream 1% Plus Topical Corticosteroid in Patients (2-17 Years of Age) With Severe Atopic Dermatitis
NCT00124709	PHASE4	TERMINATED	Safety and Efficacy of Pimecrolimus Cream 1% in Atopic Disease Modification
NCT00130364	PHASE4	COMPLETED	Efficacy and Safety of Pimecrolimus Cream 1% in Patients (2 to 11 Years Old) With Mild to Moderate Facial Atopic Dermatitis
NCT00139581	PHASE4	COMPLETED	Comparison of Pimecrolimus Cream 1% Twice-Daily to Once-Daily Dosing in the Management of Atopic Dermatitis in Pediatric Subjects
NCT00150059	PHASE4	COMPLETED	Efficacy and Safety of Pimecrolimus Cream 1% in Patients ≥ 3 Months of Age With Mild or Moderate Atopic Dermatitis
NCT00179959	PHASE4	COMPLETED	The Impact of Treating Staphylococcus Aureus Infection and Colonization on the Clinical Severity of Atopic Dermatitis
NCT00180141	PHASE4	COMPLETED	Elidel-Study: Elidel in Patients With Atopic Dermatitis
NCT00185510	PHASE4	COMPLETED	Efficacy and Safety Study of Advantan for Maintenance Treatment of Atopic Dermatitis
NCT00236106	PHASE4	COMPLETED	Short Term Growth in Children With Atopic Dermatitis
NCT00367016	PHASE4	COMPLETED	Immunologic Basis of Anti-IgE Therapy (Study II: On Patients With Asthma)
NCT00367393	PHASE4	COMPLETED	Reconstitution With Pimecrolimus Cream 1% of Steroid-damaged Skin in Adults With Atopic Dermatitis
NCT00368719	PHASE4	WITHDRAWN	Evaluation to Assess the Long Term Safety of Tacrolimus Ointment for Atopic Dermatitis
NCT00445081	PHASE4	COMPLETED	Prednisolone vs. Ciclosporine in Severe Atopic Eczema
NCT00460083	PHASE4	COMPLETED	Epiceram Versus Elidel for Treatment of Mild to Moderate Atopic Dermatitis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
DUPILUMAB	4	39
TACROLIMUS ANHYDROUS	4	36
LEBRIKIZUMAB	4	22
PIMECROLIMUS	4	22
CRISABOROLE	4	17
ABROCITINIB	4	16
TRALOKINUMAB	4	16
UPADACITINIB	4	15
BARICITINIB	4	9
MONTELUKAST	4	9
RUXOLITINIB	4	8
TOFACITINIB	4	8
CHOLECALCIFEROL	4	7
TAPINAROF	4	7
FEXOFENADINE	4	6
NEMOLIZUMAB	4	6
TRIAMCINOLONE	4	6
MOMETASONE FUROATE	4	5
APREMILAST	4	4
CYCLOSPORINE	4	4
UREA	4	4
ALITRETINOIN	4	3
CLOBETASOL PROPIONATE	4	3
FLUOCINONIDE	4	3
HYDROCORTISONE	4	3
OMALIZUMAB	4	3
TEZEPELUMAB	4	3
USTEKINUMAB	4	3
ALEFACEPT	4	2
BENRALIZUMAB	4	2