Celiac disease

disease

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Also known as celiac spruecoeliac spruegluten intolerancegluten-induced enteropathynon tropical sprue

Summary

Celiac disease (MONDO:0005130) is a disease with 75 cohort genes (289 GWAS associations across 42 studies) and 256 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (5 cohort genes). Top therapeutic interventions include prucalopride, guselkumab, and pancrelipase.

At a glance

Cohort genes: 75
GWAS associations: 289
Clinical trials: 256

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	celiac disease
Mondo ID	MONDO:0005130
EFO	EFO:0001060
MeSH	D002446
OMIM	212750
Orphanet	555
DOID	DOID:10608
ICD-10-CM	K90.0
ICD-11	2005943638
NCIT	C26714
SNOMED CT	396331005
UMLS	C0007570
MedGen	3291
Is cancer (heuristic)	no

Also known as: celiac disease · celiac sprue · coeliac sprue · gluten intolerance · gluten-induced enteropathy · non tropical sprue

Data availability: 289 GWAS associations (42 studies) · 1 cell line.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › autoimmune disorder of gastrointestinal tract › celiac disease

Subtypes (1): Lane Hamilton syndrome

Genetics & variants

GWAS landscape

289 GWAS associations across 42 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
rs72500564	2e-122	HLA-DPB1	T	0.78
rs13213957	4e-105	SLC17A1	C	0.84
rs72848256	3e-100	HLA-DQA1	G	0.91
chr6:32631434	7e-77		C	0.74
rs9275032	3e-68	HLA-DQB1 - MTCO3P1	C	0.67
rs6679677	1e-53	PHTF1 - RSBN1	?	1.41
rs2030519	5e-52	LPP	?	1.32
rs2187668	1e-50	HLA-DQA1	A	6.23
rs4988888	7e-47	HLA-DQB1	?	2.14
rs28732228	4e-44	HLA-DRA - HLA-DRB9	C	1.45
rs1464510	3e-40	LPP	A	1.29
rs13132308	2e-38	IL21-AS1	A	1.41
rs6913838	5e-33	HLA-DOA - HLA-DPA1	C	0.37
rs1359062	4e-30	RGS2-AS1	?	1.33
rs17264332	5e-30	LINC03004	G	1.29
rs760294	4e-29	ABHD16A	A	0.63
rs17753641	7e-29	IL12A-AS1	G	1.38
rs10947428	7e-29	ITPR3	C	0.37
rs17810546	4e-28	IL12A-AS1	G	1.36
rs13151961	2e-27	BLTP1	?	1.35
imm_3_161120372	3e-27		A	1.36
rs206764	1e-26	BRD2 - HLA-DOA	G	0.33
rs9276964	1e-24	BRD2 - HLA-DOA	G	0.39
rs2395269	1e-21	PSMB9, TAP1	G	0.46
rs424232	5e-21	NOTCH4 - TSBP1-AS1	C
rs3184504	5e-21	ATXN2, SH2B3	C	1.19
rs653178	7e-21	ATXN2	G	1.2
rs2097282	1e-20	UQCRC2P1 - CCR2	?	1.2
rs3190930	2e-20	PTPRK	T	1.21
rs2844470	5e-20	PRRC2A	T	0.68

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005321	Broce I	2018	12,577	23,475	Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.
GCST010064	Ricano-Ponce I	2019	12,567	14,013	Immunochip meta-analysis in European and Argentinian populations identifies two novel genetic loci associated with celiac disease.
GCST005523	Trynka G	2011	11,812	11,837	Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.
GCST009874	Marquez A	2018	11,489	22,308	Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.
GCST90558088	Shigesi N	2025	7,173	330,282	The phenotypic and genetic association between endometriosis and immunological diseases.
GCST005563	Liu JZ	2013	6,333	106,357	Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
GCST000612	Dubois PC	2010	4,533	10,750	Multiple common variants for celiac disease influencing immune gene expression.
GCST000955	Festen EA	2011	3,230	6,251	A meta-analysis of genome-wide association scans identifies IL18RAP, PTPN2, TAGAP, and PUS10 as shared risk loci for Crohn’s disease and celiac disease.
GCST90078832	Backman JD	2021	2,911	151,167	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90082818	Backman JD	2021	2,911	151,167	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	2
Tier 2: splice/UTR	2
Tier 3: regulatory	2
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	13
unknown	3
3_prime_UTR_variant	2
regulatory_region_variant	2
missense_variant	2
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs72500564	6	33087420	C>T	0.209	3_prime_UTR_variant	HLA-DPB1	2e-122	Tier 2: splice/UTR
rs13213957	6	25785998	T>C	0.099	intron_variant	SLC17A1	4e-105	Tier 4: intronic/intergenic
rs72848256	6	32633754	A>G,T	0.202	intergenic_variant	HLA-DQA1	3e-100	Tier 4: intronic/intergenic
chr6:32631434				0.226			7e-77	Tier 4: intronic/intergenic
rs9275032	6	32676062	T>A,C	0.235	intergenic_variant	HLA-DQB1 - MTCO3P1	3e-68	Tier 4: intronic/intergenic
rs6679677	1	113761186	C>A,T	0.05	intergenic_variant	PHTF1 - RSBN1	1e-53	Tier 4: intronic/intergenic
rs2030519	3	188402113	G>A	0.05	intron_variant	LPP	5e-52	Tier 4: intronic/intergenic
rs2187668	6	32638107	C>A,G,T	0.26	intron_variant	HLA-DQA1	1e-50	Tier 4: intronic/intergenic
rs4988888	6	32667420	T>C	0.05	intergenic_variant	HLA-DQB1	7e-47	Tier 4: intronic/intergenic
rs28732228	6	32459588	A>C	0.048	intron_variant	HLA-DRA - HLA-DRB9	4e-44	Tier 4: intronic/intergenic
rs1464510	3	188394766	C>A,G,T	0.49	intron_variant	LPP	3e-40	Tier 4: intronic/intergenic
rs13132308	4	122629959	A>G	0.166	intron_variant	IL21-AS1	2e-38	Tier 4: intronic/intergenic
rs6913838	6	33028518	T>C	0.402	regulatory_region_variant	HLA-DOA - HLA-DPA1	5e-33	Tier 3: regulatory
rs1359062	1	192572342	C>A,G,T	0.05	intron_variant	RGS2-AS1	4e-30	Tier 4: intronic/intergenic
rs17264332	6	137684378	A>G,T	0.211	intron_variant	LINC03004	5e-30	Tier 4: intronic/intergenic
rs760294	6	31689924	C>A	0.105	intron_variant	ABHD16A	4e-29	Tier 4: intronic/intergenic
rs17753641	3	159929885	A>G	0.05	intron_variant	IL12A-AS1	7e-29	Tier 4: intronic/intergenic
rs10947428	6	33679281	T>C	0.219	intron_variant	ITPR3	7e-29	Tier 4: intronic/intergenic
rs17810546	3	159947262	A>G	0.13	intron_variant	IL12A-AS1	4e-28	Tier 4: intronic/intergenic
rs13151961	4	122194347	A>C,G	0.14	intron_variant	BLTP1	2e-27	Tier 4: intronic/intergenic
imm_3_161120372				0.111			3e-27	Tier 4: intronic/intergenic
rs206764	6	32998583	A>C,G,T	0.317	intergenic_variant	BRD2 - HLA-DOA	1e-26	Tier 4: intronic/intergenic
rs9276964	6	32997190	A>G	0.227	intergenic_variant	BRD2 - HLA-DOA	1e-24	Tier 4: intronic/intergenic
rs2395269	6	32849997	T>A,G	0.135	intron_variant	PSMB9, TAP1	1e-21	Tier 4: intronic/intergenic
rs424232	6	32240547	C>A,G,T	0.05	intergenic_variant	NOTCH4 - TSBP1-AS1	5e-21	Tier 4: intronic/intergenic
rs3184504	12	111446804	T>A,C,G	0.488	missense_variant	ATXN2, SH2B3	5e-21	Tier 1: coding
rs653178	12	111569952	C>A,G,T	0.5	intron_variant	ATXN2	7e-21	Tier 4: intronic/intergenic
rs2097282	3	46336534	C>A,G,T	0.314	intergenic_variant	UQCRC2P1 - CCR2	1e-20	Tier 4: intronic/intergenic
rs3190930	6	127970054	C>G,T	0.05	3_prime_UTR_variant	PTPRK	2e-20	Tier 2: splice/UTR
rs2844470	6	31626404	A>T	0.065	intron_variant	PRRC2A	5e-20	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 56 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RUNX1	Orphanet:102724	Acute myeloid leukemia with t(8;21)(q22;q22) translocation
RUNX1	Orphanet:521	Chronic myeloid leukemia
RUNX1	Orphanet:71290	Familial platelet disorder with associated myeloid malignancy
RUNX1	Orphanet:98850	Aggressive systemic mastocytosis
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
STAT4	Orphanet:117	Behçet disease
STAT4	Orphanet:536	Systemic lupus erythematosus
STAT4	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
STAT4	Orphanet:93552	Pediatric systemic lupus erythematosus
SUOX	Orphanet:99731	Isolated sulfite oxidase deficiency
SYT2	Orphanet:98914	Presynaptic congenital myasthenic syndromes
TH	Orphanet:101150	Autosomal recessive dopa-responsive dystonia
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TNFRSF9	Orphanet:664726	EBV-induced lymphoproliferative disease due to CD137 deficiency
TNFSF15	Orphanet:186	Primary biliary cholangitis
TNFSF4	Orphanet:2073	Narcolepsy type 1
TNFSF4	Orphanet:536	Systemic lupus erythematosus
CD40LG	Orphanet:101088	X-linked hyper-IgM syndrome
FASLG	Orphanet:3261	Autoimmune lymphoproliferative syndrome
TNNI2	Orphanet:1146	Distal arthrogryposis type 1
TNNI2	Orphanet:1147	Sheldon-Hall syndrome
TNNT3	Orphanet:1146	Distal arthrogryposis type 1
TNNT3	Orphanet:1147	Sheldon-Hall syndrome
TREH	Orphanet:103909	Trehalase deficiency
TRPC3	Orphanet:458798	Spinocerebellar ataxia type 41
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
UBE2L3	Orphanet:536	Systemic lupus erythematosus
UBE4A	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
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
BACH2	Orphanet:714472	Inflammatory bowel disease-autoimmunity-sinopulmonary infections-lymphadenopathy syndrome
MMEL1	Orphanet:186	Primary biliary cholangitis
TLR7	Orphanet:536	Systemic lupus erythematosus
TLR8	Orphanet:675628	TLR8-related inflammation-severe neutropenia-bone marrow failure-lymphoproliferation syndrome
ZNF335	Orphanet:329228	Microcephalic primordial dwarfism due to ZNF335 deficiency
CCR1	Orphanet:117	Behçet disease
PARK7	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:90020	Parkinson-dementia complex of Guam
CARD9	Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
CD28	Orphanet:2584	Classic mycosis fungoides
CD28	Orphanet:3162	Sézary syndrome
CD247	Orphanet:169160	T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
CD247	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MRPL23	HGNC:10322	ENSG00000214026	Q16540	Large ribosomal subunit protein uL23m	gwas
RUNX1	HGNC:10471	ENSG00000159216	Q01196	Runt-related transcription factor 1	gwas
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
CCL21	HGNC:10620	ENSG00000137077	O00585	C-C motif chemokine 21	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
SLC9A4	HGNC:11077	ENSG00000180251	Q6AI14	Sodium/hydrogen exchanger 4	gwas
STAC	HGNC:11353	ENSG00000144681	Q99469	SH3 and cysteine-rich domain-containing protein	gwas
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gwas
SYT2	HGNC:11510	ENSG00000143858	Q8N9I0	Synaptotagmin-2	gwas
TH	HGNC:11782	ENSG00000180176	P07101	Tyrosine 3-monooxygenase	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
TNFRSF14	HGNC:11912	ENSG00000157873	Q92956	Tumor necrosis factor receptor superfamily member 14	gwas
TNFRSF6B	HGNC:11921	ENSG00000243509	O95407	Tumor necrosis factor receptor superfamily member 6B	gwas
TNFRSF9	HGNC:11924	ENSG00000049249	Q07011	Tumor necrosis factor receptor superfamily member 9	gwas
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
TNFSF18	HGNC:11932	ENSG00000120337	Q9UNG2	Tumor necrosis factor ligand superfamily member 18	gwas
TNFSF4	HGNC:11934	ENSG00000117586	P23510	Tumor necrosis factor ligand superfamily member 4	gwas
CD40LG	HGNC:11935	ENSG00000102245	P29965	CD40 ligand	gwas
FASLG	HGNC:11936	ENSG00000117560	P48023	Tumor necrosis factor ligand superfamily member 6	gwas
TNNI2	HGNC:11946	ENSG00000130598	P48788	Troponin I, fast skeletal muscle	gwas
TNNT3	HGNC:11950	ENSG00000130595	P45378	Troponin T, fast skeletal muscle	gwas
TPTE	HGNC:12023	ENSG00000274391	P56180	Putative tyrosine-protein phosphatase TPTE	gwas
TREH	HGNC:12266	ENSG00000118094	O43280	Trehalase	gwas
TRPC3	HGNC:12335	ENSG00000138741	Q13507	Short transient receptor potential channel 3	gwas
EIPR1	HGNC:12383	ENSG00000032389	Q53HC9	EARP and GARP complex-interacting protein 1	gwas
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gwas
UBASH3A	HGNC:12462	ENSG00000160185	P57075	Ubiquitin-associated and SH3 domain-containing protein A	gwas
UBE2E3	HGNC:12479	ENSG00000170035	Q969T4	Ubiquitin-conjugating enzyme E2 E3	gwas
UBE2L3	HGNC:12488	ENSG00000185651	P68036	Ubiquitin-conjugating enzyme E2 L3	gwas
UBE4A	HGNC:12499	ENSG00000110344	Q14139	Ubiquitin conjugation factor E4 A	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
SMIM29	HGNC:1340	ENSG00000186577	Q86T20	Small integral membrane protein 29	gwas
TMEM187	HGNC:13705	ENSG00000177854	Q14656	Transmembrane protein 187	gwas
IGF2-AS	HGNC:14062	ENSG00000099869	Q6U949	Putative insulin-like growth factor 2 antisense gene protein	gwas
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
CNOT6	HGNC:14099	ENSG00000113300	Q9ULM6	CCR4-NOT transcription complex subunit 6	gwas
STK32B	HGNC:14217	ENSG00000152953	Q9NY57	Serine/threonine-protein kinase 32B	gwas
MMEL1	HGNC:14668	ENSG00000142606	Q495T6	Membrane metallo-endopeptidase-like 1	gwas
SNX6	HGNC:14970	ENSG00000129515	Q9UNH7	Sorting nexin-6	gwas
CCT8L2	HGNC:15553	ENSG00000198445	Q96SF2	T-complex protein 1 subunit theta-like 2	gwas
TLR7	HGNC:15631	ENSG00000196664	Q9NYK1	Toll-like receptor 7	gwas
TLR8	HGNC:15632	ENSG00000101916	Q9NR97	Toll-like receptor 8	gwas
TAGAP	HGNC:15669	ENSG00000164691	Q8N103	T-cell activation Rho GTPase-activating protein	gwas
SCHIP1	HGNC:15678	ENSG00000151967	P0DPB3	Schwannomin-interacting protein 1	gwas
BAGE2	HGNC:15723	ENSG00000187172	Q86Y30	B melanoma antigen 2	gwas
ZNF335	HGNC:15807	ENSG00000198026	Q9H4Z2	Zinc finger protein 335	gwas
NAV1	HGNC:15989	ENSG00000134369	Q8NEY1	Neuron navigator 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RUNX1	Runt-related transcription factor 1	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
RUNX3	Runt-related transcription factor 3	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
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).
CCL21	C-C motif chemokine 21	Inhibits hemopoiesis and stimulates chemotaxis.
ZFP36L1	mRNA decay activator protein ZFP36L1	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
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.
STAC	SH3 and cysteine-rich domain-containing protein	Promotes expression of the ion channel CACNA1H at the cell membrane, and thereby contributes to the regulation of channel activity.
STAT4	Signal transducer and activator of transcription 4	Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
SUOX	Sulfite oxidase, mitochondrial	Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
SYT2	Synaptotagmin-2	Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties.
TH	Tyrosine 3-monooxygenase	Catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-Dopa), the rate-limiting step in the biosynthesis of catecholamines, dopamine, noradrenaline, and adrenaline.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TNFRSF14	Tumor necrosis factor receptor superfamily member 14	Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signal…
TNFRSF6B	Tumor necrosis factor receptor superfamily member 6B	Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNFRSF9	Tumor necrosis factor receptor superfamily member 9	Receptor for TNFSF9/4-1BBL.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
TNFSF18	Tumor necrosis factor ligand superfamily member 18	Cytokine that binds to TNFRSF18/AITR/GITR.
TNFSF4	Tumor necrosis factor ligand superfamily member 4	Cytokine that binds to TNFRSF4.
CD40LG	CD40 ligand	Cytokine that acts as a ligand to CD40/TNFRSF5.
FASLG	Tumor necrosis factor ligand superfamily member 6	Cytokine that binds to TNFRSF6/FAS, a receptor that transduces the apoptotic signal into cells.
TNNI2	Troponin I, fast skeletal muscle	Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TNNT3	Troponin T, fast skeletal muscle	Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
TPTE	Putative tyrosine-protein phosphatase TPTE	Could be involved in signal transduction.
TREH	Trehalase	Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose.
TRPC3	Short transient receptor potential channel 3	Forms a receptor-activated non-selective calcium permeant cation channel.
EIPR1	EARP and GARP complex-interacting protein 1	Acts as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network.
TYK2	Non-receptor tyrosine-protein kinase TYK2	Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.
UBASH3A	Ubiquitin-associated and SH3 domain-containing protein A	Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases.
UBE2E3	Ubiquitin-conjugating enzyme E2 E3	Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins.
UBE2L3	Ubiquitin-conjugating enzyme E2 L3	Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases.
UBE4A	Ubiquitin conjugation factor E4 A	Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases.
IKZF3	Zinc finger protein Aiolos	Transcription factor that plays an important role in the regulation of lymphocyte differentiation.
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
CNOT6	CCR4-NOT transcription complex subunit 6	Poly(A) nuclease with 3’-5’ RNase activity.
MMEL1	Membrane metallo-endopeptidase-like 1	Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development.
SNX6	Sorting nexin-6	Involved in several stages of intracellular trafficking.
CCT8L2	T-complex protein 1 subunit theta-like 2	Possible molecular chaperone; assists the folding of proteins upon ATP hydrolysis.
TLR7	Toll-like receptor 7	Endosomal receptor that plays a key role in innate and adaptive immunity.
TLR8	Toll-like receptor 8	Endosomal receptor that plays a key role in innate and adaptive immunity.
TAGAP	T-cell activation Rho GTPase-activating protein	May function as a GTPase-activating protein and may play important roles during T-cell activation.
BAGE2	B melanoma antigen 2	Unknown.
ZNF335	Zinc finger protein 335	Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters.
NAV1	Neuron navigator 1	May be involved in neuronal migration.
CCR1	C-C chemokine receptor type 1	Chemokine receptor that plays a crucial role in regulating immune cell migration, inflammation, and immune responses.
CCR2	C-C chemokine receptor type 2	Key functional receptor for CCL2 but can also bind CCL7, and CCL12.
CCR3	C-C chemokine receptor type 3	G protein-coupled receptor (GPCR) that plays a key role in the immune system by regulating the migration and activation of white blood cells in response to chemokines.
CCR5	C-C chemokine receptor type 5	Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level.
CCR9	C-C chemokine receptor type 9	Receptor for chemokine SCYA25/TECK.
CCRL2	C-C chemokine receptor-like 2	Receptor for CCL19 and chemerin/RARRES2.

Protein-family classification

Druggable: 26 · Difficult: 19 · Unknown: 30 · Druggable fraction: 0.35

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
GPCR	8	2.5×	0.128
Ion channel	2	3.0×	0.450
Phosphatase	2	2.2×	0.450
Scaffold/PPI	7	1.6×	0.450
Transcription factor	12	1.3×	0.450
Kinase	4	1.5×	0.476
Antibody/Immunoglobulin	3	1.2×	0.681
Enzyme (other)	6	1.0×	0.754
Protease	1	0.5×	0.972
Other/Unknown	30	0.7×	0.998

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MRPL23	Other/Unknown	no		Nucleotide-bd_a/b_plait_sf, Ribosomal_uL23/eL15/eS24_sf, Ribosomal_uL23-like
RUNX1	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
RUNX3	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
CCL21	Other/Unknown	no		Chemokine_IL8-like_dom, Chemokine_CC_DCCL, Interleukin_8-like_sf
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
SLC9A4	Other/Unknown	no		NHE-2/4, NaH_exchanger, Cation/H_exchanger_TM
STAC	Scaffold/PPI	no		SH3_domain, PKC_DAG/PE, STAC1_SH3
STAT4	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
SUOX	Enzyme (other)	yes	1.8.3.1	OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
SYT2	Other/Unknown	no		C2_dom, Synaptotagmin, C2_domain_sf
TH	Enzyme (other)	yes	1.14.16.2	ArAA_hydroxylase, Tyr_3_mOase, ArAA_hydroxylase_Fe/CU_BS
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TNFRSF14	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_14, TNFRSF14/UL144_N
TNFRSF6B	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNFRSF9	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, Growth_fac_rcpt_cys_sf, TNFR_9
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF18	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNFSF18
TNFSF4	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
CD40LG	Other/Unknown	no		CD40L, TNF_dom, Tumour_necrosis_fac-like_dom
FASLG	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNNI2	Other/Unknown	no		Troponin, Troponin_sf, Troponin_I
TNNT3	Other/Unknown	no		Troponin, TNNT, Troponin_sf
TPTE	Ion channel	yes		Tyr_Pase_dom, Ion_trans_dom, Tensin_C2-dom
TREH	Enzyme (other)	yes	3.2.1.28	Glyco_hydro_37, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_sf
TRPC3	Ion channel	yes		Ankyrin_rpt, TRPC_channel, TRPC3_channel
EIPR1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
UBASH3A	Phosphatase	yes		SH3_domain, UBA-like_sf, His_Pase_superF_clade-1
UBE2E3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
UBE2L3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
UBE4A	Transcription factor	no	2.3.2.27	Ubox_domain, Znf_RING/FYVE/PHD, Ub_conjug_fac_E4_core
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
SMIM29	Other/Unknown	no		SMIM29
TMEM187	Other/Unknown	no		TMEM187
IGF2-AS	Other/Unknown	no
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
CNOT6	Phosphatase	yes		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, Endo/exonuclease/phosphatase
STK32B	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
MMEL1	Protease	yes	3.4.24.B14	Peptidase_M13, Peptidase_M13_N, Peptidase_M13_C
SNX6	Scaffold/PPI	no		PX_dom, SNX5/SNX6/SNX32, Vps5_C
CCT8L2	Other/Unknown	no		Cpn60/GroEL/TCP-1, TCP-1, GroEL-like_apical_dom_sf
TLR7	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TLR8	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TAGAP	Other/Unknown	no		RhoGAP_dom, Rho_GTPase_activation_prot, ARHGAP20-like_RhoGAP
SCHIP1	Other/Unknown	no		SCHIP_1_C, SCHIP_1
BAGE2	Other/Unknown	no		BAGE-like
ZNF335	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Zinc_finger/UBP_domain
NAV1	Other/Unknown	no		AAA+_ATPase, P-loop_NTPase, Nav/unc-53

Expression context

Cohort genes with no expression data: 0.

64 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)	2
broad (>20)	73
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	11
lymph node	9
male germ line stem cell (sensu Vertebrata) in testis	9
buccal mucosa cell	7
monocyte	7
blood	7
mononuclear cell	6
oocyte	6
secondary oocyte	6
leukocyte	6
olfactory segment of nasal mucosa	3
mucosa of paranasal sinus	3
olfactory bulb	3
spleen	3
vermiform appendix	3
middle temporal gyrus	3
cartilage tissue	3
duodenum	3
jejunal mucosa	3
primordial germ cell in gonad	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MRPL23	134	ubiquitous	marker	olfactory segment of nasal mucosa, apex of heart, right uterine tube
RUNX1	253	ubiquitous	marker	olfactory segment of nasal mucosa, epithelium of bronchus, mucosa of paranasal sinus
RUNX3	220	broad	marker	granulocyte, buccal mucosa cell, lymph node
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
CCL21	206	tissue_specific	marker	lymph node, right lobe of thyroid gland, vermiform appendix
ZFP36L1	289	ubiquitous	marker	mucosa of paranasal sinus, endocervix, mucosa of stomach
SLC9A4	67	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, stomach, body of stomach
STAC	191	ubiquitous	marker	dorsal root ganglion, periodontal ligament, trigeminal ganglion
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
SUOX	267	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex
SYT2	165	tissue_specific	yes	olfactory bulb, pons, type B pancreatic cell
TH	147	tissue_specific	marker	substantia nigra pars reticulata, substantia nigra pars compacta, male germ line stem cell (sensu Vertebrata) in testis
TNFAIP3	274	ubiquitous	marker	vena cava, mucosa of paranasal sinus, vermiform appendix
TNFRSF14	134	ubiquitous	marker	granulocyte, spleen, right uterine tube
TNFRSF6B	127	broad	yes	olfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNFRSF9	133	broad	marker	buccal mucosa cell, lymph node, cartilage tissue
TNFSF15	149	broad	marker	cartilage tissue, jejunal mucosa, duodenum
TNFSF18	98	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, gall bladder, stromal cell of endometrium
TNFSF4	181	broad	marker	primordial germ cell in gonad, monocyte, mononuclear cell
CD40LG	124	tissue_specific	marker	granulocyte, lymph node, blood
FASLG	118	tissue_specific	marker	granulocyte, blood, lymph node
TNNI2	134	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, gastrocnemius
TNNT3	135	broad	marker	hindlimb stylopod muscle, skeletal muscle tissue, gastrocnemius
TPTE	26	ubiquitous	marker	right testis, left testis, testis
TREH	162	tissue_specific	marker	jejunal mucosa, duodenum, small intestine
TRPC3	163	broad	marker	buccal mucosa cell, secondary oocyte, oocyte
EIPR1	249	ubiquitous	marker	prefrontal cortex, adenohypophysis, nucleus accumbens
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
UBASH3A	133	broad	marker	granulocyte, blood, lymph node

Protein interactions among cohort

Intra-cohort edges: 50.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LRRK2	7,628
PARK7	5,722
RUNX1	4,994
FASLG	4,373
TLR7	4,103
TYK2	3,932
TNFAIP3	3,716
CD80	3,664
CARD9	3,636
TLR8	3,532

Intra-cohort edges

A	B	Sources
BACH2	TAGAP	string_interaction
BACH2	UBASH3A	string_interaction
CCL21	CCR5	string_interaction
CCL21	CCR9	string_interaction
CCL21	CCRL2	string_interaction
CCL21	CXCR5	string_interaction
CCR1	CCR3	string_interaction
CCR1	CCR5	string_interaction
CCR1	CCR9	string_interaction
CCR2	CCR5	string_interaction
CCR2	CCRL2	string_interaction
CCR3	CCR5	string_interaction
CCR5	CCR9	string_interaction
CD247	CD28	string_interaction
CD247	TNFRSF9	string_interaction
CD247	UBASH3A	biogrid_interaction
CD28	CD40LG	string_interaction
CD28	CD80	biogrid_interaction, intact, string_interaction
CD28	ICOSLG	intact, string_interaction
CD28	TNFRSF9	string_interaction
CD28	TNFSF18	string_interaction
CD28	TNFSF4	string_interaction
CD40LG	CD80	string_interaction
CD40LG	ICOSLG	string_interaction
CD40LG	TNFSF4	string_interaction
CD80	NAV1	biogrid_interaction
CD80	TNFRSF9	string_interaction
CNOT6	ZFP36L1	biogrid_interaction
FASLG	FNBP1	biogrid_interaction, intact
FASLG	TNFRSF6B	biogrid_interaction, intact, string_interaction
ICOSLG	TNFRSF9	string_interaction
ICOSLG	TNFSF18	string_interaction
ICOSLG	TNFSF4	string_interaction
IKZF3	RUNX1	string_interaction
IKZF3	RUNX3	string_interaction
LRRK2	PARK7	string_interaction
OLIG3	TNFAIP3	string_interaction
OLIG3	TNFRSF14	string_interaction
RUNX1	RUNX3	string_interaction
STAT4	TYK2	string_interaction
TLR7	TLR8	intact, string_interaction
TNFRSF14	TNFRSF6B	string_interaction
TNFRSF14	TNFSF15	string_interaction
TNFRSF14	TNFSF18	string_interaction
TNFRSF6B	TNFSF15	biogrid_interaction, intact, string_interaction
TNFRSF9	TNFSF18	string_interaction
TNFRSF9	TNFSF4	string_interaction
TNFSF15	TNFSF18	string_interaction
TNFSF18	TNFSF4	string_interaction
TNNI2	TNNT3	biogrid_interaction, string_interaction

Structural data

PDB: 49 · AlphaFold-only: 25 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PARK7	Q99497	88
MRPL23	Q16540	86
TYK2	P29597	52
LRRK2	Q5S007	44
TLR8	Q9NR97	39
CD247	P20963	38
CCR5	P51681	26
UBE2L3	P68036	21
TRPC3	Q13507	19
ELMO1	Q92556	18
TNFAIP3	P21580	17
TNFRSF9	Q07011	14
CD28	P10747	10
TNFRSF14	Q92956	8
TNFRSF6B	O95407	8
CD40LG	P29965	8
CARD9	Q9H257	8
TH	P07101	7
TNFSF15	O95150	7
TNFSF18	Q9UNG2	7
CCR2	P41597	7
CD80	P33681	6
RUNX1	Q01196	5
CCL21	O00585	5
FASLG	P48023	3
CCR1	P32246	3
YPEL5	P62699	3
ZFP36L1	Q07352	2
STAC	Q99469	2
TNNI2	P48788	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TREH	O43280	92.80
TMEM187	Q14656	92.12
MMEL1	Q495T6	90.34
EIPR1	Q53HC9	89.26
SNX6	Q9UNH7	89.14
STAT4	Q14765	86.87
STK32B	Q9NY57	86.38
CCT8L2	Q96SF2	84.62
TPTE	P56180	82.16
CXCR5	P32302	80.85
TNNT3	P45378	77.99
CCRL2	O00421	77.93
SBK1	Q52WX2	77.87
NKAIN2	Q5VXU1	76.15
SMIM29	Q86T20	71.70
SLC9A4	Q6AI14	66.73
OLIG3	Q7RTU3	63.67
SCHIP1	P0DPB3	61.13
IGF2-AS	Q6U949	57.72
TAGAP	Q8N103	57.36
ZNF335	Q9H4Z2	52.13
NAV1	Q8NEY1	50.18
IKZF3	Q9UKT9	48.06
BAGE2	Q86Y30	42.45
ZNF365	Q70YC4	30.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 555. Enrichment computed across 195 evidence-associated genes (125 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 125 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-23 signaling	5	50.8×	6e-06	STAT4, TYK2, IL23R, IL12B, JAK2
TNFs bind their physiological receptors	7	22.1×	6e-06	TNFRSF14, TNFRSF6B, TNFRSF9, TNFSF15, TNFSF18, TNFSF4, FASLG
Interleukin-10 signaling	8	14.9×	9e-06	TYK2, CCR1, CCR2, CCR5, CD80, IL10, IL12A, IL12B
Chemokine receptors bind chemokines	8	12.0×	4e-05	CXCR5, CCL21, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2
Cytokine Signaling in Immune system	15	4.9×	4e-05	STAT4, CD40LG, FASLG, CCR1, CCR2, CCR5, CD80, SOCS1 (+7 more)
RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs)	4	36.5×	2e-04	RUNX1, CTLA4, IL2, IL2RA
Phosphorylation of CD3 and TCR zeta chains	5	21.8×	2e-04	CD247, CSK, HLA-DQA1, PTPN22, PTPRC
Interleukin-4 and Interleukin-13 signaling	9	7.4×	2e-04	FASLG, TYK2, IL23R, SOCS1, IL10, IL12A, IL12B, IRF4 (+1 more)
Signaling by Interleukins	11	5.7×	2e-04	STAT4, CCR1, CCR2, CCR5, CD80, SOCS1, IRAK1, IRF4 (+3 more)
Interleukin-35 Signalling	4	30.4×	4e-04	STAT4, TYK2, IL12A, JAK2
Interleukin-12 signaling	5	16.3×	6e-04	STAT4, TYK2, IL12A, IL12B, JAK2
NOD1/2 Signaling Pathway	5	12.7×	0.002	TNFAIP3, CARD9, NOD2, IRAK1, MAP3K7
Immune System	22	2.3×	0.009	STAT4, CD40LG, FASLG, CCR1, CCR2, CCR5, CARD9, CD28 (+14 more)
Interleukin receptor SHC signaling	4	13.1×	0.009	IL2, IL2RA, IL5, JAK2
Class A/1 (Rhodopsin-like receptors)	8	4.8×	0.010	CCL21, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2, GPR35
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	7	5.4×	0.011	CD28, CD80, ICOS, IL1RL1, INS, IRAK1, RAC2
RUNX3 regulates RUNX1-mediated transcription	2	60.9×	0.011	RUNX1, RUNX3
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	3	21.1×	0.011	RUNX1, RUNX3, STAT4
Regulation of IFNG signaling	3	19.6×	0.012	SOCS1, JAK2, PTPN2
Signal Transduction	25	2.0×	0.012	RUNX1, RUNX3, CCL21, TAGAP, CCR1, CCR2, CCR3, CCR5 (+17 more)
Interferon gamma signaling	6	6.0×	0.013	SOCS1, HLA-DQA1, HLA-DQB1, IRF4, JAK2, CIITA
Translocation of ZAP-70 to Immunological synapse	3	15.2×	0.023	CD247, HLA-DQA1, PTPN22
Negative regulation of the PI3K/AKT network	4	8.9×	0.024	CD28, CD80, INS, IRAK1
Transcriptional regulation by RUNX3	4	8.7×	0.026	RUNX1, RUNX3, ITGA4, SMAD3
RUNX3 regulates BCL2L11 (BIM) transcription	2	36.5×	0.026	RUNX3, SMAD3
Signaling by CSF3 (G-CSF)	3	13.7×	0.027	TYK2, SOCS1, JAK2
Peptide ligand-binding receptors	7	4.2×	0.031	CCL21, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2
RUNX3 Regulates Immune Response and Cell Migration	2	30.4×	0.031	RUNX3, ITGA4
Co-inhibition by PD-1	3	12.5×	0.031	CD247, CSK, HLA-DQA1
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	3	12.5×	0.031	NOD2, IRAK1, MAP3K7

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 169 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	34	9.5×	2e-20	CXCR5, CCL21, TNFRSF14, TNFSF15, TNFSF4, TYK2, CCR1, CCR2 (+26 more)
positive regulation of type II interferon production	13	17.3×	4e-10	TNFSF4, TYK2, TLR7, TLR8, CCR2, IL23R, IL12A, IL12B (+5 more)
positive regulation of interleukin-17 production	9	32.0×	2e-09	TYK2, CARD9, IL23R, NOD2, IL12B, IL2, IL21, JAK2 (+1 more)
inflammatory response	23	5.1×	5e-08	CCL21, TNFAIP3, TNFSF4, CD40LG, TLR7, TLR8, CCR1, CCR2 (+15 more)
adaptive immune response	16	8.0×	5e-08	TNFRSF14, TNFSF18, CD247, ICOSLG, THEMIS, CSK, CTLA4, CTSH (+8 more)
positive regulation of T-helper 17 type immune response	6	49.9×	2e-07	TYK2, CARD9, IL23R, IL12B, JAK2, PRKCQ
positive regulation of T cell proliferation	10	15.3×	2e-07	TNFSF4, CD40LG, TYK2, CD28, CD80, IL23R, IL12B, IL21 (+2 more)
positive regulation of interleukin-2 production	8	22.2×	4e-07	RUNX1, CCR2, CD28, CD80, IRF4, MAP3K7, PRKCQ, PTPRC
positive regulation of interleukin-10 production	8	19.0×	1e-06	TNFSF4, CD40LG, CD28, INAVA, NOD2, IL12B, IL21, IRF4
interleukin-12-mediated signaling pathway	5	55.4×	2e-06	STAT4, TYK2, IL12A, IL12B, JAK2
positive regulation of canonical NF-kappaB signal transduction	15	6.5×	2e-06	CCL21, TNFSF15, CD40LG, FASLG, TLR7, TLR8, CARD9, INAVA (+7 more)
T cell costimulation	8	17.7×	2e-06	CCL21, TNFRSF14, CD40LG, CD28, CD80, CSK, EFNB2, ICOS
cell chemotaxis	10	11.0×	3e-06	CXCR5, CCL21, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2 (+2 more)
positive regulation of inflammatory response	11	9.5×	3e-06	TNFSF18, TNFSF4, TLR7, CCR1, CCR2, ETS1, IL12B, IL1RL1 (+3 more)
positive regulation of activated T cell proliferation	6	23.9×	1e-05	ICOSLG, IL23R, IGF2, IL12B, IL2, IL2RA
T cell receptor signaling pathway	10	9.0×	2e-05	CD28, CD247, ICOSLG, THEMIS, CSK, CTLA4, HLA-DQB1, MAP3K7 (+2 more)
positive regulation of cytosolic calcium ion concentration	11	7.6×	2e-05	CXCR5, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2, GPR35 (+3 more)
cellular defense response	7	13.2×	8e-05	CCR2, CCR3, CCR5, CCR9, IL1RL2, LSP1, NCF2
positive regulation of immunoglobulin production	6	17.1×	9e-05	TNFSF4, IL10, IL2, IL21, IL5, PTPRC
obsolete positive regulation of NF-kappaB transcription factor activity	8	9.7×	1e-04	TNFSF18, CD40LG, CARD9, NOD2, IL18R1, IL18RAP, IRAK1, PRKCQ
cell surface receptor signaling pathway via JAK-STAT	7	12.0×	1e-04	STAT4, TYK2, CCR2, IL23R, SOCS1, IL12B, JAK2
positive regulation of cytokine production	7	11.3×	2e-04	TNFSF4, CARD9, CD28, IL10, IL21, INS, PTGER4
JNK cascade	7	11.3×	2e-04	TLR7, CARD9, LRRK2, IRAK1, SMAD3, MAP3K7, PTGER4
calcium-mediated signaling	8	8.7×	2e-04	CXCR5, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2, LRRK2
response to muramyl dipeptide	4	33.2×	2e-04	TNFAIP3, CARD9, INAVA, NOD2
positive regulation of natural killer cell proliferation	4	33.2×	2e-04	TYK2, IL23R, IL12B, JAK2
T follicular helper cell differentiation	4	33.2×	2e-04	ICOSLG, ICOS, IL21, ASCL2
canonical NF-kappaB signal transduction	6	13.0×	3e-04	TLR7, TLR8, NOD2, IRAK1, MAP3K7, REL
negative regulation of T cell receptor signaling pathway	6	13.0×	3e-04	UBASH3A, CD80, CSK, CTLA4, PTPN2, PTPN22
positive regulation of interleukin-6 production	8	7.9×	4e-04	TNFSF4, TLR7, TLR8, CARD9, INAVA, NOD2, IL1RL2, POU2AF1

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Phytonadione	Approved (phase 4)

5 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Larazotide	Phase 3
Prednisolone	Phase 2
Ritlecitinib	Phase 2
Vedolizumab	Phase 2
Vercirnon	Phase 2

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 11 · Phased (≥1): 17 · Undrugged: 58

Druggability breadth: 94 of 195 evidence-associated genes (48%) 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
RUNX1	APOMORPHINE HYDROCHLORIDE
TYK2	FEDRATINIB
IKZF3	POMALIDOMIDE
STK32B	NERATINIB
TLR7	IMIQUIMOD
CCR1	ABAMETAPIR
CCR2	CISPLATIN
CCR5	TERFENADINE
SBK1	AFATINIB
LRRK2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
LRRK2	42	4
CCR2	17	4
CCR5	15	4
SBK1	14	4
TLR7	9	4
TLR8	8	2
CCR1	8	4
IKZF3	5	4
STK32B	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
APOMORPHINE HYDROCHLORIDE	4	RUNX1
FEDRATINIB	4	LRRK2, SBK1, TYK2
RUXOLITINIB	4	LRRK2, SBK1, TYK2
TOFACITINIB	4	LRRK2, TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	LRRK2, TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	LRRK2, TYK2
BOSUTINIB	4	LRRK2, TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	LRRK2, SBK1, TYK2
SUNITINIB	4	LRRK2, SBK1, TYK2
DASATINIB	4	SBK1, TYK2
ERLOTINIB	4	LRRK2, SBK1, TYK2
CRIZOTINIB	4	SBK1, TYK2
MIDOSTAURIN	4	LRRK2, TYK2
IMATINIB	4	TYK2
POMALIDOMIDE	4	IKZF3
LENALIDOMIDE	4	IKZF3
THALIDOMIDE	4	IKZF3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

Symbol	Assays	Type breakdown
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
LRRK2	809	Binding:799, ADMET:7, Functional:3
CCR2	426	Binding:277, Functional:149
CCR5	409	Binding:243, Functional:166
TLR8	395	Binding:378, Functional:16, ADMET:1
TLR7	356	Binding:321, Functional:35
CCR1	243	Binding:176, Functional:67
CCR3	175	Binding:107, Functional:68
STK32B	118	Binding:118
IKZF3	101	Binding:100, Functional:1
SBK1	97	Binding:97
PARK7	62	Binding:62
TRPC3	45	Binding:45
CXCR5	33	Binding:21, Functional:12
CCR9	30	Binding:17, Functional:13
RUNX1	20	Binding:17, Functional:3
STAT4	20	Binding:20
TNFRSF9	11	Binding:11
TH	8	Binding:8
CD40LG	8	Binding:8
CCRL2	6	Binding:5, Functional:1
ELMO1	6	Binding:6
ICOSLG	6	Binding:6
ATXN2	5	Binding:3, Functional:2
TREH	4	Binding:4
BACH2	3	Binding:3
CNOT6	3	Binding:3
FASLG	2	Binding:2
UBE2L3	2	Binding:2
MMEL1	2	Binding:2
TNFAIP3	1	Binding:1
UBASH3A	1	Binding:1
UBE4A	1	Binding:1
CD28	1	Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SUOX	1.8.3.1	sulfite oxidase
TH	1.14.16.2	tyrosine 3-monooxygenase
TREH	3.2.1.28	alpha,alpha-trehalase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
UBE2E3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
UBE2L3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
UBE4A	2.3.2.27, 2.3.2.B12	RING-type E3 ubiquitin transferase,
MMEL1	3.4.24.B14
PARK7	3.5.1.124, 4.2.1.130	protein deglycase, D-lactate dehydratase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TYK2	1,083
IKZF3	101
STK32B	118
TLR7	356
TLR8	395
CCR1	243
CCR2	426
CCR3	175
CCR5	409
LRRK2	809

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)
APOMORPHINE HYDROCHLORIDE	4	RUNX1
FEDRATINIB	4	LRRK2, SBK1, TYK2
RUXOLITINIB	4	LRRK2, SBK1, TYK2
TOFACITINIB	4	LRRK2, TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	LRRK2, TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	TYK2
TOFACITINIB CITRATE	4	LRRK2, TYK2
BOSUTINIB	4	LRRK2, TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	LRRK2, SBK1, TYK2
SUNITINIB	4	LRRK2, SBK1, TYK2
DASATINIB	4	SBK1, TYK2
ERLOTINIB	4	LRRK2, SBK1, TYK2
CRIZOTINIB	4	SBK1, TYK2
MIDOSTAURIN	4	LRRK2, TYK2
IMATINIB	4	TYK2
POMALIDOMIDE	4	IKZF3
LENALIDOMIDE	4	IKZF3
THALIDOMIDE	4	IKZF3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	RUNX1, TYK2, IKZF3, STK32B, TLR7, CCR1, CCR2, CCR5, SBK1, LRRK2
B	Phased (≥1) drug, not yet approved	7	TREH, TRPC3, TLR8, CCR3, CCR9, ELMO1, PARK7
C	Druggable family + PDB, no drug	10	SUOX, TH, UBASH3A, UBE2E3, UBE2L3, CNOT6, CD28, CD80, ICOSLG, ADGRL2
D	Druggable family + AlphaFold only, no drug	4	CXCR5, TPTE, MMEL1, CCRL2
E	Difficult family or no structure, no drug	44	MRPL23, RUNX3, ATXN2, CCL21, ZFP36L1, SLC9A4, STAC, STAT4, SYT2, TNFAIP3 (+34 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT4	20	TYK2
MRPL23	0	—
RUNX3	0	—
ATXN2	5	—
CXCR5	33	—
CCL21	0	—
ZFP36L1	0	—
SLC9A4	0	—
STAC	0	—
SUOX	0	—
SYT2	0	—
TH	8	—
TNFAIP3	1	—
TNFRSF14	0	—
TNFRSF6B	0	—
TNFRSF9	11	—
TNFSF15	0	—
TNFSF18	0	—
TNFSF4	0	—
CD40LG	8	—
FASLG	2	—
TNNI2	0	—
TNNT3	0	—
TPTE	0	—
EIPR1	0	—
UBASH3A	1	—
UBE2E3	0	—
UBE2L3	2	—
UBE4A	1	—
SMIM29	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 256.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	180
PHASE2	33
PHASE1	20
PHASE4	7
PHASE1/PHASE2	7
EARLY_PHASE1	5
PHASE2/PHASE3	3
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02475369	PHASE4	TERMINATED	Pancreatic Enzyme Supplementation for Celiac Disease
NCT02806206	PHASE4	UNKNOWN	Prucalopride Prior to Small Bowel Capsule Endoscopy
NCT03351972	PHASE4	COMPLETED	Differences in Preparation for Small Bowel Capsule Endoscopy
NCT03866538	PHASE4	TERMINATED	Budesonide in Patients With Immune Mediated Enteropathies
NCT04160767	PHASE4	UNKNOWN	Celiac Disease and Vitamin Status: Evaluation of the Effect of Supplementation With a Probiotic (VIVOMIXX®) in a Cohoort of Celiac Patients
NCT04788797	PHASE4	COMPLETED	AN-PEP on Gluten Exposure in Celiacs
NCT05114278	PHASE4	UNKNOWN	Effect of Intravenous Iron Supplementation on Celiac Disease Remission (IRONCEL)
NCT01045837	PHASE2/PHASE3	COMPLETED	Effect of Addition of Short Course of Prednisolone to Gluten Free Diet in Naive Celiac Disease Patients
NCT01100099	PHASE2/PHASE3	COMPLETED	HLA-DQ2-gliadin Tetramer for Diagnosis of Celiac Disease
NCT01338324	PHASE2/PHASE3	COMPLETED	Protocol for Correlating Enteropathic Severity and Small Intestinal CYP3A4 Activity in Patients With Celiac Disease
NCT03569007	PHASE3	TERMINATED	Study to Evaluate the Efficacy and Safety of Larazotide Acetate for the Relief of CeD Symptoms
NCT06557772	PHASE2	ACTIVE_NOT_RECRUITING	A Phase 2a/b Study of the Efficacy and Safety of Subcutaneous Amlitelimab in Adults With Nonresponsive Celiac Disease
NCT06807463	PHASE2	ACTIVE_NOT_RECRUITING	A Trial to Assess the Efficacy and Safety of TEV-53408 in Adults With Celiac Disease
NCT06982963	PHASE2	RECRUITING	Randomized, Double Blind, Placebo-controlled Phase 2 Study in Adults With Celiac Disease
NCT07239336	PHASE2	RECRUITING	Study of DONQ52 in Active Celiac Disease
NCT07298343	PHASE2	RECRUITING	Evaluating the Efficacy and Tolerability of ZED1227 in Subjects With Non-responsive Celiac Disease
NCT00362856	PHASE2	COMPLETED	Safety and Tolerability Study of Larazotide Acetate in Celiac Disease Subjects
NCT00492960	PHASE2	COMPLETED	Study to Assess the Efficacy of Larazotide Acetate for the Treatment of Celiac Disease
NCT00540657	PHASE2	COMPLETED	A Phase II Study of CCX282-B in Patients With Celiac Disease
NCT00620451	PHASE2	COMPLETED	Randomized, Double-Blind, Placebo-Controlled Study of Larazotide Acetate in Subjects With Active Celiac Disease
NCT00671138	PHASE2	COMPLETED	Inoculating Celiac Disease Patients With the Human Hookworm Necator Americanus: Evaluating Immunity and Gluten-sensitivity
NCT00810654	PHASE1/PHASE2	COMPLETED	Effect of Aspergillus Niger Prolyl Endoprotease (AN-PEP) Enzyme on the Effects of Gluten Ingestion in Patients With Coeliac Disease
NCT00889473	PHASE2	COMPLETED	Study of the Efficacy of Larazotide Acetate to Treat Celiac Disease
NCT00959114	PHASE2	COMPLETED	Safety and Efficacy of ALV003 for the Treatment of Celiac Disease
NCT00962182	PHASE1/PHASE2	COMPLETED	Study of Enzyme Supplements to Treat Celiac Disease
NCT01255696	PHASE2	COMPLETED	Safety and Efficacy of Varying Methods of ALV003 Administration for the Treatment of Celiac Disease
NCT01396213	PHASE2	COMPLETED	A Double-blind Placebo-controlled Study to Evaluate Larazotide Acetate for the Treatment of Celiac Disease
NCT01661933	PHASE1/PHASE2	COMPLETED	Desensitising Celiac Disease Patients With the Human Hookworm
NCT01917630	PHASE2	UNKNOWN	Evaluation of the Efficacy and Safety of ALV003 in Symptomatic in Celiac Disease Patients
NCT01990885	PHASE1/PHASE2	COMPLETED	Safety and Systemic Exposure Study of BL-7010 in Well-Controlled Celiac Patients.
NCT02220166	PHASE2	COMPLETED	Safety of Prolonged Administration of Triticum Monococcum in Celiac Disease
NCT02244047	PHASE1/PHASE2	COMPLETED	Cytokine Profile in Children With Celiac Disease
NCT02472119	PHASE2	UNKNOWN	Wheat Flour Treatment With Microbial Transglutaminase and Lysine Ethyl Ester: New Frontiers in Celiac Disease Treatment.
NCT02637141	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of AMG 714 in Adult Patients With Celiac Disease
NCT02929316	PHASE2	TERMINATED	Vedolizumab Induction May Prevent Celiac Enteritis
NCT03271138	PHASE2	COMPLETED	Bifidobacterium Infantis NLS Super Strain for Celiac Disease Patients on a Gluten-free Diet With Persistent Gastrointestinal Symptoms
NCT03585478	PHASE2	COMPLETED	Latiglutenase as a Treatment for Celiac Disease
NCT03644069	PHASE2	UNKNOWN	A Study of the Safety, Efficacy and Tolerability of Nexvax-2 in Patients With Celiac Disease (CeD)
NCT03707730	PHASE2	COMPLETED	A Randomized, Double-Blind, Placebo Controlled, Crossover Trial to Evaluate Safety and Efficacy of AGY in Celiac Disease
NCT03738475	PHASE2	COMPLETED	Study of the Safety, Pharmacodynamics, Efficacy, and PK of TIMP-GLIA in Subjects With Celiac Disease

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PRUCALOPRIDE	4	2
GUSELKUMAB	4	1
PANCRELIPASE	4	1
PREDNISOLONE	4	1
RITLECITINIB	4	1
TERIFLUNOMIDE	4	1
TRYPTOPHAN	4	1
VEDOLIZUMAB	4	1
LARAZOTIDE	3	7
AMLITELIMAB	3	1
BIFIDOBACTERIUM SPP.	3	1
LATIGLUTENASE	2	7
ORDESEKIMAB	2	1
PETESICATIB	2	1
ZAMAGLUTENASE	2	1
ZED-1227	2	1
PROLYL ENDOPEPTIDASE	-1	1

Cohort genes: MRPL23, RUNX1, RUNX3, ATXN2, CXCR5, CCL21, ZFP36L1, SLC9A4, STAC, STAT4, SUOX, SYT2, TH, TNFAIP3, TNFRSF14, TNFRSF6B, TNFRSF9, TNFSF15, TNFSF18, TNFSF4, CD40LG, FASLG, TNNI2, TNNT3, TPTE, TREH, TRPC3, EIPR1, TYK2, UBASH3A, UBE2E3, UBE2L3, UBE4A, IKZF3, SMIM29, TMEM187, IGF2-AS, BACH2, CNOT6, STK32B, MMEL1, SNX6, CCT8L2, TLR7, TLR8, TAGAP, SCHIP1, ZNF335, NAV1, CCR1, CCR2, CCR3, CCR5, CCR9, CCRL2, DOK5, ELMO1, PARK7, CARD9, NKAIN2, ZMIZ1, CD28, CD247, CD80, FNBP1, ICOSLG, ANKRD30A, SBK1, OLIG3, ZNF365, YPEL5, EMX2OS, ADGRL2, LRRK2
Drugs: Prucalopride, Guselkumab, Pancrelipase, Prednisolone, Ritlecitinib, Teriflunomide, Tryptophan, Vedolizumab, Larazotide, Amlitelimab, Bifidobacterium Spp.