Ulcerative colitis

Summary

Ulcerative colitis (MONDO:0005101) is a disease with 75 cohort genes (1,323 GWAS associations across 97 studies) and 1,312 clinical trials. The dominant Reactome pathway is Interleukin-20 family signaling (7 cohort genes). Top therapeutic interventions include mesalamine, vedolizumab, and tofacitinib.

At a glance

• Cohort genes: 75
• GWAS associations: 1,323
• Clinical trials: 1,312

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ulcerative colitis
Mondo ID	MONDO:0005101
EFO	EFO:0000729
MeSH	D003093
Orphanet	771
DOID	DOID:8577
ICD-10-CM	K51
ICD-11	784669405
NCIT	C2952
SNOMED CT	64766004
UMLS	C0009324
MedGen	3532
Is cancer (heuristic)	no

Also known as: colitis ulcerative · left-sided ulcerative colitis · ulcerative colitis · ulcerative colitis (disease)

Data availability: 1,323 GWAS associations (97 studies) · 1 GenCC gene-disease record · 1 HPO phenotype · 18 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › intestinal disorder › gastroenteritis › colitis › ulcerative colitis

Related subtypes (8): ischemic colitis, microscopic colitis, chemical colitis, diversion colitis, ileocolitis, indeterminate colitis, infectious colitis, proctocolitis

Subtypes (2): distal colitis, pancolitis

Genetics & variants

GWAS landscape

1,323 GWAS associations across 97 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs5743293	1e-320	NOD2, CYLD-AS1	?
rs9271511	1e-158	HLA-DRB1 - HLA-DQA1	?	0.35
rs80174646	1e-143	IL23R	?
rs6927022	5e-133	HLA-DQA1	A	1.44
rs7517847	1e-98	IL23R, C1orf141	?
rs76901167	2e-94	HLA-DRB1 - HLA-DQA1	?
rs2066845	6e-94	NOD2	?
rs117506082	4e-88	HCG27 - HLA-C	G	3.39
rs113653754	1e-86	HLA-DQA1 - HLA-DQB1	C	1.36
rs9271209	2e-85	HLA-DRB1 - HLA-DQA1	?
rs6426833	3e-76	RNF186-AS1 - OTUD3	A	1.26
rs1992661	1e-74	RNU1-150P - TTC33	?
rs9271366	2e-70	HLA-DRB1 - HLA-DQA1	C	4.44
rs9263739	4e-67	CCHCR1	T	2.73
rs35300242	5e-67	ATG16L1	?
rs748670681	6e-61	TNRC18	?	0.79
rs9268853	1e-55	HLA-DRB9	T	1.4
rs17622378	2e-55	IRF1, CARINH	?
rs3197999	7e-55	MST1	?
rs9977672	5e-54	LINC02940 - RPL23AP12	?
rs469758	6e-54	ERAP1	?
rs2836878	7e-53	LINC02940 - RPL23AP12	G	1.25
rs115378818	7e-53	TSBP1, TSBP1-AS1	C	0.92
rs4672505	2e-52	RN7SL51P - RN7SL18P	?
rs10748781	6e-51	LINC01475	?
rs11581607	8e-49	IL23R	?	0.45
rs10995271	3e-48	LINC02929 - ALDH7A1P4	?
rs2357623	4e-48	NKD1 - SNX20	?
rs6017342	5e-46	LINC01620	?	0.18
rs3024495	2e-45	IL10	?	0.23

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST005837	Huang H	2017	20,155	34,257	Fine-mapping inflammatory bowel disease loci to single-variant resolution.
GCST001728	Jostins L	2012	12,924	21,442	Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
GCST005321	Broce I	2018	12,577	23,475	Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies.
GCST004133	de Lange KM	2017	12,366	33,609	Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease.
GCST005537	Ellinghaus D	2016	8,726	34,213	Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.
GCST008658	Luo Y	2017	7,760	16,065	Exploring the genetic architecture of inflammatory bowel disease by whole-genome sequencing identifies association at ADCY7.
GCST002548	Julia A	2014	7,483	21,211	A genome-wide association study identifies a novel locus at 6q22.1 associated with ulcerative colitis.
GCST90016625	Peyrot WJ	2021	6,968	8,875	Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.
GCST003045	Liu JZ	2015	6,968	20,464	Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.
GCST000964	Anderson CA	2011	6,687	19,718	Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	5
Tier 2: splice/UTR	0
Tier 3: regulatory	4
Tier 4: intronic/intergenic	41

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	4

Functional consequences

Consequence	Count
intron_variant	22
intergenic_variant	18
missense_variant	3
regulatory_region_variant	3
frameshift_variant	1
TF_binding_site_variant	1
non_coding_transcript_exon_variant	1
stop_gained	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs5743293	16	50729868			frameshift_variant	NOD2, CYLD-AS1	1e-320	Tier 1: coding
rs9271511	6	32621706	G>A	0.05	intron_variant	HLA-DRB1 - HLA-DQA1	1e-158	Tier 4: intronic/intergenic
rs80174646	1	67242472	G>T	0.05	intron_variant	IL23R	1e-143	Tier 4: intronic/intergenic
rs6927022	6	32644620	A>G,T	0.465	intergenic_variant	HLA-DQA1	5e-133	Tier 4: intronic/intergenic
rs7517847	1	67215986	T>A,C,G	0.05	intron_variant	IL23R, C1orf141	1e-98	Tier 4: intronic/intergenic
rs76901167	6	32608701			intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-94	Tier 4: intronic/intergenic
rs2066845	16	50722629	G>C,T		missense_variant	NOD2	6e-94	Tier 1: coding
rs117506082	6	31245448	A>G	0.05	intergenic_variant	HCG27 - HLA-C	4e-88	Tier 4: intronic/intergenic
rs113653754	6	32658495		0.27	intergenic_variant	HLA-DQA1 - HLA-DQB1	1e-86	Tier 4: intronic/intergenic
rs9271209	6	32611258	G>A,C,T	0.05	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-85	Tier 4: intronic/intergenic
rs6426833	1	19845367	G>A,C,T	0.46	TF_binding_site_variant	RNF186-AS1 - OTUD3	3e-76	Tier 3: regulatory
rs1992661	5	40414887	G>A	0.05	intron_variant	RNU1-150P - TTC33	1e-74	Tier 4: intronic/intergenic
rs9271366	6	32619077	G>A,C,T	0.21	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-70	Tier 4: intronic/intergenic
rs9263739	6	31143579	C>T	0.15	intron_variant	CCHCR1	4e-67	Tier 4: intronic/intergenic
rs35300242	2	233260144	G>A,C	0.05	intron_variant	ATG16L1	5e-67	Tier 4: intronic/intergenic
rs748670681	7	5397122	C>T		intron_variant	TNRC18	6e-61	Tier 4: intronic/intergenic
rs9268853	6	32461866	T>A,C	0.34	intron_variant	HLA-DRB9	1e-55	Tier 4: intronic/intergenic
rs17622378	5	132442760	A>G	0.05	intron_variant	IRF1, CARINH	2e-55	Tier 4: intronic/intergenic
rs3197999	3	49684099	G>A,C,T	0.05	missense_variant	MST1	7e-55	Tier 1: coding
rs9977672	21	39091357	G>A	0.05	intergenic_variant	LINC02940 - RPL23AP12	5e-54	Tier 4: intronic/intergenic
rs469758	5	96786011	C>T	0.05	intron_variant	ERAP1	6e-54	Tier 4: intronic/intergenic
rs2836878	21	39093608	G>A	0.27	intergenic_variant	LINC02940 - RPL23AP12	7e-53	Tier 4: intronic/intergenic
rs115378818	6	32333650	C>T	0.011	intron_variant	TSBP1, TSBP1-AS1	7e-53	Tier 4: intronic/intergenic
rs4672505	2	62333197	A>C,G,T	0.05	intron_variant	RN7SL51P - RN7SL18P	2e-52	Tier 4: intronic/intergenic
rs10748781	10	99523573	C>A,G	0.05	non_coding_transcript_exon_variant	LINC01475	6e-51	Tier 4: intronic/intergenic
rs11581607	1	67242007	G>A	0.05	intron_variant	IL23R	8e-49	Tier 4: intronic/intergenic
rs10995271	10	62678726	G>A,C	0.05	intergenic_variant	LINC02929 - ALDH7A1P4	3e-48	Tier 4: intronic/intergenic
rs2357623	16	50660100	A>G,T	0.05	intergenic_variant	NKD1 - SNX20	4e-48	Tier 4: intronic/intergenic
rs6017342	20	44436388	A>C,G,T	0.05	intergenic_variant	LINC01620	5e-46	Tier 4: intronic/intergenic
rs3024495	1	206769068	C>A,G,T	0.05	intron_variant	IL10	2e-45	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · Orphanet: 60 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SCGN	Moderate	Autosomal recessive	ulcerative colitis

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCGN	Orphanet:714481	SCGN-related severe early-onset hereditary ulcerative colitis
RORC	Orphanet:477857	Mendelian susceptibility to mycobacterial diseases due to complete RORgamma receptor deficiency
CFB	Orphanet:544472	Atypical hemolytic uremic syndrome with complement gene abnormality
SKIC2	Orphanet:84064	Trichohepatoenteric syndrome
SLC11A1	Orphanet:3389	Tuberculosis
SLC11A1	Orphanet:586	Cystic fibrosis
SLC22A5	Orphanet:158	Systemic primary carnitine deficiency
SLC34A1	Orphanet:157215	Hereditary hypophosphatemic rickets with hypercalciuria
SLC34A1	Orphanet:244305	Dominant hypophosphatemia with nephrolithiasis or osteoporosis
SLC34A1	Orphanet:300547	Autosomal recessive infantile hypercalcemia
SLC34A1	Orphanet:3337	Primary Fanconi renotubular syndrome
SLC9A3	Orphanet:103908	Congenital sodium diarrhea
SLC9A3	Orphanet:586	Cystic fibrosis
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
STAT5B	Orphanet:220465	Laron syndrome with immunodeficiency
STAT5B	Orphanet:520	Acute promyelocytic leukemia
STK11	Orphanet:2869	Peutz-Jeghers syndrome
BTNL2	Orphanet:797	Sarcoidosis
SUOX	Orphanet:99731	Isolated sulfite oxidase deficiency
TCAP	Orphanet:154	Familial isolated dilated cardiomyopathy
TCAP	Orphanet:34514	Telethonin-related limb-girdle muscular dystrophy R7
MYRF	Orphanet:647811	Cardiac-urogenital syndrome
TLR4	Orphanet:117	Behçet disease
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TNFRSF1A	Orphanet:32960	Tumor necrosis factor receptor 1 associated periodic syndrome
TNFRSF1A	Orphanet:329967	Intermittent hydrarthrosis
CD40	Orphanet:101090	Hyper-IgM syndrome type 3
TNFRSF9	Orphanet:664726	EBV-induced lymphoproliferative disease due to CD137 deficiency
TNFSF15	Orphanet:186	Primary biliary cholangitis
CD40LG	Orphanet:101088	X-linked hyper-IgM syndrome
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux
TREX1	Orphanet:247691	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations
TREX1	Orphanet:481662	Familial Chilblain lupus
TREX1	Orphanet:51	Aicardi-Goutières syndrome
TREX1	Orphanet:536	Systemic lupus erythematosus
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
C2	Orphanet:169147	Immunodeficiency due to a classical component pathway complement deficiency
UBE2L3	Orphanet:536	Systemic lupus erythematosus
ACTA2	Orphanet:2573	Moyamoya disease
ACTA2	Orphanet:404463	Multisystemic smooth muscle dysfunction syndrome

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	74
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCGN	HGNC:16941	ENSG00000079689	O76038	Secretagogin	gencc
RNF5	HGNC:10068	ENSG00000204308	Q99942	E3 ubiquitin-protein ligase RNF5	gwas
RORC	HGNC:10260	ENSG00000143365	P51449	Nuclear receptor ROR-gamma	gwas
RPL3	HGNC:10332	ENSG00000100316	P39023	Large ribosomal subunit protein uL3	gwas
CFB	HGNC:1037	ENSG00000243649	P00751	Complement factor B	gwas
RPS6KB1	HGNC:10436	ENSG00000108443	P23443	Ribosomal protein S6 kinase beta-1	gwas
SCNN1D	HGNC:10601	ENSG00000162572	P51172	Epithelial sodium channel subunit delta	gwas
CCL20	HGNC:10619	ENSG00000115009	P78556	C-C motif chemokine 20	gwas
CCL21	HGNC:10620	ENSG00000137077	O00585	C-C motif chemokine 21	gwas
ENTR1	HGNC:10667	ENSG00000165689	Q96C92	Endosome-associated-trafficking regulator 1	gwas
SDF2L1	HGNC:10676	ENSG00000128228	Q9HCN8	Stromal cell-derived factor 2-like protein 1	gwas
SKIC2	HGNC:10898	ENSG00000204351	Q15477	Superkiller complex protein 2	gwas
SLC11A1	HGNC:10907	ENSG00000018280	P49279	Natural resistance-associated macrophage protein 1	gwas
SLC22A4	HGNC:10968	ENSG00000197208	Q9H015	Solute carrier family 22 member 4	gwas
SLC22A5	HGNC:10969	ENSG00000197375	O76082	Organic cation/carnitine transporter 2	gwas
SLC34A1	HGNC:11019	ENSG00000131183	Q06495	Sodium-dependent phosphate transport protein 2A	gwas
BRD2	HGNC:1103	ENSG00000204256	P25440	Bromodomain-containing protein 2	gwas
SLC6A7	HGNC:11054	ENSG00000011083	Q99884	Sodium-dependent proline transporter	gwas
SLC9A3	HGNC:11073	ENSG00000066230	P48764	Sodium/hydrogen exchanger 3	gwas
SNAPC4	HGNC:11137	ENSG00000165684	Q5SXM2	snRNA-activating protein complex subunit 4	gwas
BSN	HGNC:1117	ENSG00000164061	Q9UPA5	Protein bassoon	gwas
STAT3	HGNC:11364	ENSG00000168610	P40763	Signal transducer and activator of transcription 3	gwas
STAT5A	HGNC:11366	ENSG00000126561	P42229	Signal transducer and activator of transcription 5A	gwas
STAT5B	HGNC:11367	ENSG00000173757	P51692	Signal transducer and activator of transcription 5B	gwas
STK11	HGNC:11389	ENSG00000118046	Q15831	Serine/threonine-protein kinase STK11	gwas
WHR1	HGNC:11398	ENSG00000204344	P49842	Winged helix repair factor 1	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gwas
SYNGR1	HGNC:11498	ENSG00000100321	O43759	Synaptogyrin-1	gwas
TCAP	HGNC:11610	ENSG00000173991	O15273	Telethonin	gwas
TCF19	HGNC:11629	ENSG00000137310	Q9Y242	Transcription factor 19	gwas
TCTA	HGNC:11692	ENSG00000145022	P57738	T-cell leukemia translocation-altered gene protein	gwas
SERINC3	HGNC:11699	ENSG00000132824	Q13530	Serine incorporator 3	gwas
MYRF	HGNC:1181	ENSG00000124920	Q9Y2G1	Myelin regulatory factor	gwas
TLR4	HGNC:11850	ENSG00000136869	O00206	Toll-like receptor 4	gwas
TNF	HGNC:11892	ENSG00000232810	P01375	Tumor necrosis factor	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
TNFRSF1A	HGNC:11916	ENSG00000067182	P19438	Tumor necrosis factor receptor superfamily member 1A	gwas
CD40	HGNC:11919	ENSG00000101017	P25942	Tumor necrosis factor receptor superfamily member 5	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
CD40LG	HGNC:11935	ENSG00000102245	P29965	CD40 ligand	gwas
TNFSF8	HGNC:11938	ENSG00000106952	P32971	Tumor necrosis factor ligand superfamily member 8	gwas
TNP2	HGNC:11952	ENSG00000178279	Q05952	Nuclear transition protein 2	gwas
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	gwas
TOM1	HGNC:11982	ENSG00000100284	O60784	Target of Myb1 membrane trafficking protein	gwas
TREX1	HGNC:12269	ENSG00000213689	Q9NSU2	Three-prime repair exonuclease 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF5	E3 ubiquitin-protein ligase RNF5	Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins.
RORC	Nuclear receptor ROR-gamma	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RPL3	Large ribosomal subunit protein uL3	Component of the large ribosomal subunit.
CFB	Complement factor B	Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the…
RPS6KB1	Ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
SCNN1D	Epithelial sodium channel subunit delta	Potential alternative pore-forming subunit of the epithelial sodium channel (ENaC), capable of replacing the alpha/SCNN1A subunit, creating a more active channel with distinct properties.
CCL20	C-C motif chemokine 20	Acts as a ligand for C-C chemokine receptor CCR6.
CCL21	C-C motif chemokine 21	Inhibits hemopoiesis and stimulates chemotaxis.
ENTR1	Endosome-associated-trafficking regulator 1	Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis.
SKIC2	Superkiller complex protein 2	Helicase component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways.
SLC11A1	Natural resistance-associated macrophage protein 1	Macrophage-specific antiporter that fluxes metal ions in either direction against a proton gradient.
SLC22A4	Solute carrier family 22 member 4	Transporter that mediates the transport of endogenous and microbial zwitterions and organic cations.
SLC22A5	Organic cation/carnitine transporter 2	Sodium-ion dependent, high affinity carnitine transporter.
SLC34A1	Sodium-dependent phosphate transport protein 2A	Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane.
BRD2	Bromodomain-containing protein 2	Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at ‘Lys-5’ and ‘Lys-12’ (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures.
SLC6A7	Sodium-dependent proline transporter	Brain specific sodium (and chloride)-dependent proline transporter.
SLC9A3	Sodium/hydrogen exchanger 3	Plasma membrane Na(+)/H(+) antiporter.
SNAPC4	snRNA-activating protein complex subunit 4	Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes.
BSN	Protein bassoon	Scaffold protein of the presynaptic cytomatrix at the active zone (CAZ) which is the place in the synapse where neurotransmitter is released.
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.
STAT5A	Signal transducer and activator of transcription 5A	Carries out a dual function: signal transduction and activation of transcription.
STAT5B	Signal transducer and activator of transcription 5B	Carries out a dual function: signal transduction and activation of transcription.
STK11	Serine/threonine-protein kinase STK11	Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage…
WHR1	Winged helix repair factor 1	DNA-binding protein which is required for efficient transcription-coupled nucleotide excision repair (TC-NER).
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
SUOX	Sulfite oxidase, mitochondrial	Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
SYNGR1	Synaptogyrin-1	May play a role in regulated exocytosis.
TCAP	Telethonin	Muscle assembly regulating factor.
TCF19	Transcription factor 19	Potential transcription factor that may play a role in the regulation of genes involved in cell cycle G1/S transition.
TCTA	T-cell leukemia translocation-altered gene protein	May be required for cellular fusion during osteoclastogenesis.
SERINC3	Serine incorporator 3	Restriction factor required to restrict infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early step of viral infection.
MYRF	Myelin regulatory factor	Constitutes a precursor of the transcription factor.
TLR4	Toll-like receptor 4	Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways.
TNF	Tumor necrosis factor	Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR.
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…
TNFRSF1A	Tumor necrosis factor receptor superfamily member 1A	Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.
CD40	Tumor necrosis factor receptor superfamily member 5	Receptor for TNFSF5/CD40LG.
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.
CD40LG	CD40 ligand	Cytokine that acts as a ligand to CD40/TNFRSF5.
TNFSF8	Tumor necrosis factor ligand superfamily member 8	Cytokine that binds to TNFRSF8/CD30.
TNP2	Nuclear transition protein 2	Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
TOM1	Target of Myb1 membrane trafficking protein	Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways.
TREX1	Three-prime repair exonuclease 1	Major cellular 3’-to-5’ DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3’ termini.
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.

Protein-family classification

Druggable: 20 · Difficult: 12 · Unknown: 43 · Druggable fraction: 0.27

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
Protease	5	2.4×	0.596
Nuclear receptor	1	5.2×	0.690
Complement	1	3.6×	0.690
Transporter	2	2.1×	0.690
Kinase	3	1.1×	0.803
Transcription factor	10	1.1×	0.803
Other/Unknown	43	1.0×	0.803
Phosphatase	1	1.1×	0.817
Enzyme (other)	5	0.8×	0.836
Antibody/Immunoglobulin	2	0.8×	0.836
Scaffold/PPI	2	0.5×	0.936

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCGN	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
RNF5	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
RORC	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RPL3	Other/Unknown	no		Ribosomal_uL3, Transl_B-barrel_sf, Ribosomal_uL3_CS
CFB	Protease	yes	3.4.21.47	Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
RPS6KB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
SCNN1D	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
CCL20	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Chemokine_CC_DCCL
CCL21	Other/Unknown	no		Chemokine_IL8-like_dom, Chemokine_CC_DCCL, Interleukin_8-like_sf
ENTR1	Other/Unknown	no		ENTR1
SDF2L1	Other/Unknown	no		MIR_motif, MIR_dom_sf
SKIC2	Other/Unknown	no		Helicase_C-like, DEAD/DEAH_box_helicase_dom, Ski2/MTR4_C
SLC11A1	Other/Unknown	no		NRAMP_fam
SLC22A4	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC22A5	Transporter	yes		Orgcat_transp/SVOP, MFS_sugar_transport-like, Sugar_transporter_CS
SLC34A1	Other/Unknown	no		Na/Pi_transpt
BRD2	Other/Unknown	no		Bromodomain, Bromodomain_CS, NET_dom
SLC6A7	Other/Unknown	no		Na/ntran_symport, SNS_sf
SLC9A3	Other/Unknown	no		NaH_exchanger, Cation/H_exchanger_TM, Na/H_exchanger_3/5
SNAPC4	Transcription factor	no		SANT/Myb, Homeodomain-like_sf, SANT_dom
BSN	Transcription factor	no		Znf_piccolo, Znf_FYVE_PHD, Znf_RING/FYVE/PHD
STAT3	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT5A	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT5B	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STK11	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
WHR1	Other/Unknown	no		STK19-like
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
SUOX	Enzyme (other)	yes	1.8.3.1	OxRdtase_Mopterin-bd_dom, Cyt_B5-like_heme/steroid-bd, MoCF_OxRdtse_dimer
SYNGR1	Other/Unknown	no		Marvel, Synaptogyrin
TCAP	Other/Unknown	no		Telethonin, Titin-like_dom_sf
TCF19	Transcription factor	no		FHA_dom, Znf_PHD, SMAD_FHA_dom_sf
TCTA	Other/Unknown	no		TCTA
SERINC3	Other/Unknown	no		TDE1/TMS
MYRF	Transcription factor	no		p53-like_TF_DNA-bd_sf, NDT80_DNA-bd_dom, MYRF_C2
TLR4	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TNF	Other/Unknown	no		TNF_alpha, TNF_dom, TNF
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TNFRSF14	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_14, TNFRSF14/UL144_N
TNFRSF1A	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
CD40	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_5, TNFRSF5_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
CD40LG	Other/Unknown	no		CD40L, TNF_dom, Tumour_necrosis_fac-like_dom
TNFSF8	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
TNP2	Other/Unknown	no		TP2
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TOM1	Other/Unknown	no		VHS_dom, GAT_dom, ENTH_VHS
TREX1	Enzyme (other)	yes	3.1.11.2	RNaseH-like_sf, Ribonucl_H, RNaseH_sf

Expression context

Cohort genes with no expression data: 0.

62 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)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	11
right lobe of liver	9
lymph node	7
left testis	6
adenohypophysis	6
gall bladder	5
right testis	5
adult mammalian kidney	4
gastrocnemius	4
hindlimb stylopod muscle	4
male germ line stem cell (sensu Vertebrata) in testis	4
liver	4
endothelial cell	4
right hemisphere of cerebellum	4
cartilage tissue	4
mucosa of transverse colon	4
right uterine tube	4
leukocyte	4
right adrenal gland	4
spleen	4

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCGN	153	tissue_specific	marker	islet of Langerhans, type B pancreatic cell, pancreas
RNF5	134	ubiquitous	marker	ganglionic eminence, adult mammalian kidney, cortical plate
RORC	209	broad	marker	gastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, hindlimb stylopod muscle
RPL3	307	ubiquitous	marker	left ovary, right ovary, type B pancreatic cell
CFB	134	broad	marker	right lobe of liver, liver, gall bladder
RPS6KB1	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, calcaneal tendon
SCNN1D	161	ubiquitous	yes	right hemisphere of cerebellum, right testis, left testis
CCL20	202	broad	marker	epithelium of nasopharynx, cartilage tissue, gall bladder
CCL21	206	tissue_specific	marker	lymph node, right lobe of thyroid gland, vermiform appendix
ENTR1	278	ubiquitous	marker	left testis, right testis, right lobe of liver
SDF2L1	199	ubiquitous	marker	mucosa of transverse colon, adenohypophysis, right lobe of liver
SKIC2	134	ubiquitous	yes	right lobe of liver, pituitary gland, adenohypophysis
SLC11A1	204	broad	marker	right lung, upper lobe of left lung, granulocyte
SLC22A4	201	ubiquitous	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
SLC22A5	235	ubiquitous	marker	gastrocnemius, mucosa of transverse colon, muscle of leg
SLC34A1	52	tissue_specific	marker	nephron tubule, adult mammalian kidney, kidney epithelium
BRD2	134	ubiquitous	marker	ventricular zone, granulocyte, ganglionic eminence
SLC6A7	105	tissue_specific	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
SLC9A3	164	tissue_specific	yes	mucosa of transverse colon, sural nerve, metanephros cortex
SNAPC4	249	ubiquitous	yes	sural nerve, endothelial cell, right uterine tube
BSN	156	broad	marker	frontal pole, paraflocculus, middle temporal gyrus
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung
STAT5A	190	ubiquitous	marker	granulocyte, monocyte, leukocyte
STAT5B	295	ubiquitous	marker	blood, body of uterus, left uterine tube
STK11	238	ubiquitous	marker	left testis, right testis, hindlimb stylopod muscle
WHR1	134	ubiquitous	marker	left adrenal gland, left adrenal gland cortex, right adrenal gland
BTNL2	106		yes	sural nerve, ventricular zone, primordial germ cell in gonad
SUOX	267	ubiquitous	marker	right lobe of liver, right adrenal gland, right adrenal gland cortex
SYNGR1	298	ubiquitous	marker	Brodmann (1909) area 10, right hemisphere of cerebellum, cerebellar hemisphere
TCAP	213	tissue_specific	marker	apex of heart, hindlimb stylopod muscle, skeletal muscle tissue of rectus abdominis

Protein interactions among cohort

Intra-cohort edges: 46.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TNF	11,116
STAT3	10,108
RPL3	6,978
TLR4	6,974
VARS1	5,848
RPS6KB1	5,474
STK11	5,146
TNFRSF1A	4,523
STAT5A	4,153
UQCRC1	4,109

Intra-cohort edges

A	B	Sources
ACTA2	TREX1	biogrid_interaction
BTNL2	SLC11A1	string_interaction
C2	SKIC2	string_interaction
C2	WHR1	string_interaction
CD40	CD40LG	biogrid_interaction, intact, string_interaction
CD40	SCGN	intact
CD40	TNF	string_interaction
CD40	TNFRSF9	string_interaction
CD40	TNFSF8	string_interaction
CD40	TRAF3IP2	biogrid_interaction
CD40LG	TNFSF8	string_interaction
RORC	USP4	biogrid_interaction
SDF2L1	TNFRSF6B	intact
SKIC2	WHR1	string_interaction
SLC11A1	SLC34A1	string_interaction
SLC22A4	SLC22A5	intact
SLC34A1	SLC9A3	string_interaction
STAT3	STAT5A	string_interaction
STAT3	STAT5B	biogrid_interaction, string_interaction
STAT3	TYK2	string_interaction
STAT5A	STAT5B	intact
STAT5A	TYK2	string_interaction
STAT5B	SUOX	intact
STAT5B	TYK2	string_interaction
STK11	WDR6	biogrid_interaction, intact, string_interaction
TNF	TNFRSF14	string_interaction
TNF	TNFRSF1A	biogrid_interaction, intact, string_interaction
TNF	TNFRSF6B	string_interaction
TNF	TNFSF8	string_interaction
TNFAIP3	TNFRSF1A	biogrid_interaction
TNFAIP3	TRAF3IP2	string_interaction
TNFRSF14	TNFRSF6B	string_interaction
TNFRSF14	TNFSF15	string_interaction
TNFRSF14	TNFSF18	string_interaction
TNFRSF14	TNFSF8	string_interaction
TNFRSF1A	TNFRSF6B	string_interaction
TNFRSF1A	TNFSF15	string_interaction
TNFRSF1A	TNFSF8	string_interaction
TNFRSF6B	TNFSF15	biogrid_interaction, intact, string_interaction
TNFRSF6B	TNFSF8	string_interaction
TNFRSF9	TNFSF18	string_interaction
TNFRSF9	TNFSF8	string_interaction
TNFSF15	TNFSF18	string_interaction
TNFSF15	TNFSF8	string_interaction
TNXB	WHR1	string_interaction
UBA7	UBE2L3	biogrid_interaction

Structural data

PDB: 53 · AlphaFold-only: 22 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL3	P39023	193
BRD2	P25440	174
RORC	P51449	161
TNF	P01375	52
TYK2	P29597	52
CFB	P00751	26
RPS6KB1	P23443	22
UBE2L3	P68036	21
SNAPC4	Q5SXM2	18
TNFAIP3	P21580	17
TLR4	O00206	15
CD40	P25942	14
TNFRSF9	Q07011	14
C2	P06681	14
TNFRSF1A	P19438	13
TREX1	Q9NSU2	12
C4A	P0C0L4	12
SKIC2	Q15477	11
PLA2G2E	Q9NZK7	9
TNFRSF14	Q92956	8
TNFRSF6B	O95407	8
CD40LG	P29965	8
SLC6A7	Q99884	7
TNFSF15	O95150	7
TNFSF18	Q9UNG2	7
CCL20	P78556	6
STAT3	P40763	6
TOM1	O60784	6
UBA7	P41226	6
CCL21	O00585	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GLYAT	Q6IB77	95.71
ACTA2	P62736	95.43
FAXDC2	Q96IV6	92.28
VAMP3	Q15836	91.56
SDF2L1	Q9HCN8	89.30
EIPR1	Q53HC9	89.26
WNT2	P09544	88.89
VARS1	P26640	88.12
BTNL2	Q9UIR0	85.97
WDR6	Q9NNW5	85.72
SLC22A4	Q9H015	85.07
SIRAL2	Q9NWS6	83.77
GSDMA	Q96QA5	80.60
TNFSF8	P32971	80.07
SLC34A1	Q06495	72.24
RNF5	Q99942	68.71
TCTA	P57738	66.03
ENTR1	Q96C92	65.28
TCF19	Q9Y242	63.17
TNP2	Q05952	59.17
IKZF3	Q9UKT9	48.06
BSN	Q9UPA5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 660. Enrichment computed across 250 evidence-associated genes (165 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 165 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-20 family signaling	7	17.9×	5e-05	STAT3, STAT5A, STAT5B, TYK2, IL22, IL26, IFNLR1
TNFs bind their physiological receptors	7	16.7×	5e-05	TNFRSF14, TNFRSF1A, TNFRSF6B, TNFRSF9, TNFSF15, TNFSF18, TNFSF8
Interleukin-10 signaling	8	11.3×	1e-04	CCL20, STAT3, TNF, TNFRSF1A, TYK2, CCR1, CCR2, CCR5
FGFR1 mutant receptor activation	4	27.7×	0.001	STAT3, STAT5A, STAT5B, CEP43
Chemokine receptors bind chemokines	7	7.9×	0.003	CCL20, CCL21, CCR1, CCR2, CCR3, CCR5, CCRL2
Signaling by cytosolic FGFR1 fusion mutants	4	15.4×	0.012	STAT3, STAT5A, STAT5B, CEP43
Activation of C3 and C5	3	23.1×	0.014	CFB, C2, C4A
Interleukin-9 signaling	3	23.1×	0.014	STAT3, STAT5A, STAT5B
Interleukin-23 signaling	3	23.1×	0.014	STAT3, TYK2, IL23R
Signaling by CSF3 (G-CSF)	4	13.8×	0.014	STAT3, STAT5A, STAT5B, TYK2
Immune System	27	2.1×	0.014	RORC, CCL20, STAT3, STAT5A, STAT5B, BTNL2, SYNGR1, CD40LG (+19 more)
Interleukin-21 signaling	3	20.8×	0.017	STAT3, STAT5A, STAT5B
Signaling by KIT in disease	3	20.8×	0.017	STAT3, STAT5A, STAT5B
Signaling by Leptin	3	18.9×	0.020	STAT3, STAT5A, STAT5B
TNFR1-induced proapoptotic signaling	4	10.7×	0.020	TNF, TNFAIP3, TNFRSF1A, USP4
Inactivation of CSF3 (G-CSF) signaling	4	10.7×	0.020	STAT3, STAT5A, STAT5B, TYK2
Signaling by FGFR in disease	4	10.2×	0.022	STAT3, STAT5A, STAT5B, CEP43
Notch-HLH transcription pathway	4	9.9×	0.024	HDAC9, HDAC7, MAML2, HDAC11
Cytokine Signaling in Immune system	12	3.0×	0.026	RORC, CCL20, STAT3, STAT5A, STAT5B, CD40LG, CAMK2A, CCR1 (+4 more)
Regulation of TNFR1 signaling	5	6.8×	0.027	TNF, TNFAIP3, TNFRSF1A, UBE2L3, USP4
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	5.3×	0.028	STAT5A, STAT5B, HDAC9, HDAC7, MAML2, HDAC11
Signaling by Interleukins	9	3.5×	0.032	RORC, CCL20, STAT3, STAT5A, STAT5B, CCR1, CCR2, CCR5 (+1 more)
G alpha (i) signalling events	12	2.8×	0.032	CCL20, CCL21, GPSM3, CAMK2A, TAS1R3, CCR1, CCR2, CCR3 (+4 more)
Synthesis of IPs in the nucleus	2	34.6×	0.032	IP6K2, IP6K1
Interleukin-15 signaling	3	13.8×	0.032	STAT3, STAT5A, STAT5B
TNFR1-induced NF-kappa-B signaling pathway	4	8.1×	0.035	TNF, TNFAIP3, TNFRSF1A, USP4
Peptide ligand-binding receptors	8	3.6×	0.043	CCL20, CCL21, UTS2, CCR1, CCR2, CCR3, CCR5, CCRL2
SLC-mediated transmembrane transport	9	3.2×	0.046	SLC22A4, SLC22A5, SLC6A7, SLC9A3, SLC26A6, SLC16A10, SLC9A8, SLC35D1 (+1 more)
Interleukin-2 family signaling	3	11.5×	0.047	STAT3, STAT5A, STAT5B
Signaling by FGFR1 in disease	4	7.1×	0.051	STAT3, STAT5A, STAT5B, CEP43

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 224 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
cell surface receptor signaling pathway via JAK-STAT	10	13.0×	6e-06	STAT3, STAT5A, STAT5B, TNF, TNFRSF1A, CD40, TYK2, CCR2 (+2 more)
inflammatory response	24	4.0×	6e-06	CCL20, CCL21, SLC11A1, STAT3, TLR4, TNF, TNFAIP3, TNFRSF1A (+16 more)
positive regulation of inflammatory response	11	7.1×	2e-04	STAT3, STAT5A, STAT5B, TLR4, TNF, TNFRSF1A, TNFSF18, GPSM3 (+3 more)
Peyer’s patch development	4	37.6×	9e-04	RORC, STAT5A, STAT5B, ADA
positive regulation of cytokine production involved in inflammatory response	6	14.6×	1e-03	STAT3, TLR4, TNF, GPSM3, CARD9, CD6
calcium-mediated signaling	9	7.4×	0.001	CCL20, TNF, CCR1, CCR2, CCR3, CCR5, CCRL2, ADA (+1 more)
immune response	17	3.6×	0.002	CCL20, CCL21, TLR4, TNF, TNFRSF14, TNFSF15, TNFSF8, TYK2 (+9 more)
positive regulation of interleukin-2 production	6	12.5×	0.002	STAT5A, STAT5B, BTNL2, CCR2, CARD11, CD28
growth hormone receptor signaling pathway via JAK-STAT	4	27.4×	0.002	STAT3, STAT5A, STAT5B, TYK2
positive regulation of canonical NF-kappaB signal transduction	13	4.2×	0.002	CCL21, STAT3, TLR4, TNF, TNFRSF1A, CD40, TNFSF15, CD40LG (+5 more)
interleukin-23-mediated signaling pathway	3	37.6×	0.007	STAT3, TYK2, IL23R
dendritic cell chemotaxis	4	17.7×	0.008	CCL21, CCR1, CCR2, CCR5
positive regulation of type II interferon production	7	7.0×	0.008	SLC11A1, TLR4, TNF, TYK2, CCR2, CD226, IL23R
cytokine-mediated signaling pathway	9	5.2×	0.008	STAT3, STAT5A, STAT5B, TNFRSF1A, TYK2, CCR1, CCR2, IFNLR1 (+1 more)
regulation of steroid metabolic process	3	32.2×	0.009	RORC, STAT5A, STAT5B
obsolete positive regulation of NF-kappaB transcription factor activity	7	6.4×	0.012	TLR4, TNF, TNFSF18, CD40LG, CAMK2A, CARD9, CARD11
regulatory T cell differentiation	3	28.2×	0.012	RORC, ZBTB46, CD28
B cell activation	5	10.2×	0.012	CD40, HDAC9, SKAP2, ICOSLG, BANK1
response to bacterium	7	6.0×	0.014	RNF5, CFB, SLC11A1, C2, IKZF3, ERAP1, BANK1
MHC class II biosynthetic process	2	75.2×	0.014	SLC11A1, TLR4
CD4-positive, alpha-beta T cell proliferation	3	25.1×	0.014	CARD11, CD28, NDFIP1
positive regulation of T cell receptor signaling pathway	4	13.7×	0.014	CARD11, CD28, CD226, ADA
cell chemotaxis	7	5.8×	0.016	CCL20, CCL21, CCR1, CCR2, CCR3, CCR5, CCRL2
positive regulation of T cell proliferation	6	6.9×	0.016	BTNL2, CD40LG, TYK2, CD28, CD6, IL23R
positive regulation of T-helper 1 type immune response	3	22.6×	0.016	SLC11A1, CCR2, IL23R
CD40 signaling pathway	3	22.6×	0.016	CD40, CD40LG, TRAF3IP2
positive regulation of protein localization to nucleus	5	8.8×	0.016	STK11, TYK2, TRIM8, ORMDL3, PARK7
positive regulation of activated T cell proliferation	4	12.0×	0.019	STAT5A, STAT5B, ICOSLG, IL23R
T cell costimulation	5	8.4×	0.019	CCL21, TNFRSF14, CD40LG, CARD11, CD28
immune response-activating cell surface receptor signaling pathway	2	50.1×	0.025	BAG6, NCR3

Therapeutics

Drugs indicated for this disease

17 approved, 24 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Adalimumab	Approved (phase 4)
Betamethasone Acetate	Approved (phase 4)
Budesonide	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Golimumab	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Infliximab	Approved (phase 4)
Isopropyl Alcohol	Approved (phase 4)
Mesalamine	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Mirikizumab	Approved (phase 4)
Phytonadione	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Sulfasalazine	Approved (phase 4)
Ustekinumab	Approved (phase 4)
Vedolizumab	Approved (phase 4)
Abatacept	Phase 3 (in late-stage trials)
Allopurinol	Phase 3 (in late-stage trials)
Andrographolide	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Cobitolimod	Phase 3 (in late-stage trials)
Curcumin	Phase 3 (in late-stage trials)
Diosmin	Phase 3 (in late-stage trials)
Etrasimod	Phase 3 (in late-stage trials)
Etrolizumab	Phase 3 (in late-stage trials)
Filgotinib	Phase 3 (in late-stage trials)
Guselkumab	Phase 3 (in late-stage trials)
Obefazimod	Phase 3 (in late-stage trials)
Ontamalimab	Phase 3 (in late-stage trials)
Ozanimod	Phase 3 (in late-stage trials)
Risankizumab	Phase 3 (in late-stage trials)
Tacrolimus Anhydrous	Phase 3 (in late-stage trials)
Tetomilast	Phase 3 (in late-stage trials)
Thalidomide	Phase 3 (in late-stage trials)
Tofacitinib	Phase 3 (in late-stage trials)
Tulisokibart	Phase 3 (in late-stage trials)
Upadacitinib	Phase 3 (in late-stage trials)
Valganciclovir	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alicaforsen, Aminosalicylic Acid, Amoxicillin, Andecaliximab, Apremilast, Basiliximab, Bifidobacterium Spp., Brazikumab, Brepocitinib, Cannabidiol, Cannabinol, Ceftriaxone, Certolizumab Pegol, Daclizumab, Dupilumab, Empagliflozin, Hydroxocobalamin, INTERFERON BETA-1A, Itacitinib, Lactobacillus Acidophilus, Lutikizumab, Maltodextrin, Melatonin, Metformin, Methotrexate, Metronidazole, Mocravimod, Mongersen Sodium, Mufemilast, Naltrexone, Oxygen, Peficitinib, Phosphatidylcholine, Rebamipide, Ritlecitinib, Rituximab, Rosiglitazone, Rosuvastatin, Sitokiren, Sodium Chloride, Spesolimab, Telotristat, Terbinafine, Tralokinumab, Vancomycin, Vercirnon, Vidofludimus, Visilizumab, Zasocitinib.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 15 · Phased (≥1): 18 · Undrugged: 57

Druggability breadth: 103 of 250 evidence-associated genes (41%) 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
RORC	DIGOXIN
RPL3	GENTAMICIN SULFATE
CFB	IPTACOPAN
RPS6KB1	FEDRATINIB
SLC34A1	SODIUM PHOSPHATE, DIBASIC, ANHYDROUS
SLC9A3	TENAPANOR HYDROCHLORIDE
STAT3	MOMELOTINIB
STAT5A	MOMELOTINIB
STK11	FEDRATINIB
TLR4	METHOTREXATE
TNF	PREDNISOLONE
TYK2	FEDRATINIB
IKZF3	POMALIDOMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
RPS6KB1	39	4
STAT3	18	4
STK11	17	4
TNF	12	4
RORC	9	4
BRD2	9	3
TLR4	6	4
IKZF3	5	4
STAT5A	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DIGOXIN	4	RORC, STAT3
TRETINOIN	4	RORC
ALITRETINOIN	4	RORC
GENTAMICIN SULFATE	4	RPL3
IPTACOPAN	4	CFB
FEDRATINIB	4	RPS6KB1, STK11, TYK2
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1
BOSUTINIB	4	RPS6KB1, TYK2
NINTEDANIB	4	RPS6KB1, STK11, TYK2
SUNITINIB	4	RPS6KB1, STK11, TYK2
CRIZOTINIB	4	RPS6KB1, TYK2
MIDOSTAURIN	4	RPS6KB1, STK11, TYK2
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
TENAPANOR HYDROCHLORIDE	4	SLC9A3
TENAPANOR	4	SLC9A3
MOMELOTINIB	4	STAT3, STAT5A, TYK2
NITAZOXANIDE	4	STAT3
NICLOSAMIDE	4	STAT3
BARICITINIB	4	STAT3, TYK2
DIGITOXIN	4	STAT3
DEUCRAVACITINIB	4	STAT3, TYK2
PACRITINIB	4	STK11, TYK2
METHOTREXATE	4	TLR4
POLYMYXIN B	4	TLR4
CARVEDILOL	4	TLR4
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IKZF3, TNF
PENTOXIFYLLINE	4	TNF

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 9.

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

Symbol	Assays	Type breakdown
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
RORC	758	Binding:707, Functional:50, Unclassified:1
BRD2	681	Binding:655, Functional:19, ADMET:7
RPS6KB1	585	Binding:582, Functional:2, ADMET:1
TLR4	267	Binding:254, Functional:10, ADMET:3
STK11	244	Binding:244
STAT5A	199	Binding:199
TNF	193	Binding:162, Functional:31
IKZF3	101	Binding:100, Functional:1
SLC22A5	97	Functional:79, ADMET:18
RPL3	90	Binding:90
STAT5B	55	Binding:55
WHR1	36	Binding:36
CFB	33	Binding:33
SLC22A4	29	Functional:26, ADMET:3
TNFRSF1A	24	Binding:23, Functional:1
SLC9A3	20	Binding:18, Functional:2
PLA2G2E	19	Binding:19
USP19	13	Binding:13
USP4	13	Binding:13
TNFRSF9	11	Binding:11
CD40	10	Binding:10
SLC34A1	8	Binding:7, Functional:1
CD40LG	8	Binding:8
VARS1	7	Binding:7
SNAPC4	6	Binding:6
WDR6	6	Binding:6
C2	4	Binding:4
RNF5	2	Binding:2
SLC6A7	2	Binding:2
UBE2L3	2	Binding:2
WNT2	2	Binding:2
SLC11A1	1	Binding:1
TNFAIP3	1	Binding:1
UBASH3A	1	Binding:1
UBA7	1	Binding:1
UQCRC1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFB	3.4.21.47	alternative-complement-pathway C3/C5 convertase
RPS6KB1	2.7.11.1	non-specific serine/threonine protein kinase
STK11	2.7.11.1	non-specific serine/threonine protein kinase
SUOX	1.8.3.1	sulfite oxidase
TREX1	3.1.11.2	exodeoxyribonuclease III
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
UBE2L3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
VARS1	6.1.1.9	valine-tRNA ligase
GLYAT	2.3.1.13, 2.3.1.71	glycine N-acyltransferase, glycine N-benzoyltransferase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
RORC	758
RPS6KB1	585
BRD2	681
STAT3	1,319
STAT5A	199
STK11	244
TLR4	267
TNF	193
TYK2	1,083
IKZF3	101

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

28 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)
DIGOXIN	4	RORC, STAT3
TRETINOIN	4	RORC
ALITRETINOIN	4	RORC
GENTAMICIN SULFATE	4	RPL3
IPTACOPAN	4	CFB
FEDRATINIB	4	RPS6KB1, STK11, TYK2
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1
BOSUTINIB	4	RPS6KB1, TYK2
NINTEDANIB	4	RPS6KB1, STK11, TYK2
SUNITINIB	4	RPS6KB1, STK11, TYK2
CRIZOTINIB	4	RPS6KB1, TYK2
MIDOSTAURIN	4	RPS6KB1, STK11, TYK2
SODIUM PHOSPHATE, DIBASIC, ANHYDROUS	4	SLC34A1
POTASSIUM PHOSPHATE, MONOBASIC	4	SLC34A1
TENAPANOR HYDROCHLORIDE	4	SLC9A3
TENAPANOR	4	SLC9A3
MOMELOTINIB	4	STAT3, STAT5A, TYK2
NICLOSAMIDE	4	STAT3
BARICITINIB	4	STAT3, TYK2
DIGITOXIN	4	STAT3
PACRITINIB	4	STK11, TYK2
METHOTREXATE	4	TLR4
POLYMYXIN B	4	TLR4
CARVEDILOL	4	TLR4
PREDNISOLONE	4	TNF
POMALIDOMIDE	4	IKZF3, TNF
PENTOXIFYLLINE	4	TNF

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	13	RORC, RPL3, CFB, RPS6KB1, SLC34A1, SLC9A3, STAT3, STAT5A, STK11, TLR4 (+3 more)
B	Phased (≥1) drug, not yet approved	5	BRD2, SNAPC4, STAT5B, TNFRSF1A, PLA2G2E
C	Druggable family + PDB, no drug	11	SLC22A5, SUOX, TNXB, TREX1, UBASH3A, C2, UBE2L3, UQCRC1, USP19, USP4 (+1 more)
D	Druggable family + AlphaFold only, no drug	4	SLC22A4, BTNL2, VARS1, GLYAT
E	Difficult family or no structure, no drug	42	SCGN, RNF5, SCNN1D, CCL20, CCL21, ENTR1, SDF2L1, SKIC2, SLC11A1, SLC6A7 (+32 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TNFRSF6B	0	TNFRSF1A
WDR6	6	STK11
SCGN	0	—
RNF5	2	—
SCNN1D	0	—
CCL20	0	—
CCL21	0	—
ENTR1	0	—
SDF2L1	0	—
SKIC2	0	—
SLC11A1	1	—
SLC22A4	29	—
SLC22A5	97	—
SLC6A7	2	—
BSN	0	—
WHR1	36	—
BTNL2	0	—
SUOX	0	—
SYNGR1	0	—
TCAP	0	—
TCF19	0	—
TCTA	0	—
SERINC3	0	—
MYRF	0	—
TNFAIP3	1	—
TNFRSF14	0	—
CD40	10	—
TNFRSF9	11	—
TNFSF15	0	—
TNFSF18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,312.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	491
PHASE2	204
PHASE3	143
PHASE1	102
PHASE4	89
PHASE1/PHASE2	32
PHASE2/PHASE3	25
EARLY_PHASE1	14

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04183608	PHASE4	RECRUITING	A Trial COmparing staNdard of Care Versus Treat to Target With telemonitoRing and Patient Education in Patients With Ulcerative cOlitis Initiating Adalimumab
NCT04314375	PHASE4	RECRUITING	Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Extended-release Tablets in Pediatric Subjects Aged 5 to 17 Years With Active, Mild to Moderate Ulcerative Colitis
NCT04743518	PHASE4	RECRUITING	Impact of Anti-TNF, Vedolizumab and Tofacitinib on Aortic Stiffness, Carotid Intima-media Thickness and Cardiovascular Risk of Patients With Ulcerative Colitis
NCT04835506	PHASE4	ACTIVE_NOT_RECRUITING	Proactive Infliximab Optimization Using a Pharmacokinetic Dashboard Versus Standard of Care in Patients With Inflammatory Bowel Disease: The OPTIMIZE Trial
NCT04999228	PHASE4	RECRUITING	Top Down Versus Step up in Pediatric Ulcerative Colitis
NCT04999241	PHASE4	NOT_YET_RECRUITING	Combined Application of EEN in the Induction of Remission in PUC
NCT05313620	PHASE4	RECRUITING	Effect of Tofacitinib on Coagulation and Platelet Function, and Its Role in Thromboembolic Events
NCT05481619	PHASE4	RECRUITING	Study of the Effect of Vedolizumab on Intestinal Microecological Changes and Its Efficacy in the Treatment of Ulcerative Colitis
NCT05867329	PHASE4	RECRUITING	Feasibility Pilot Sequential Multiple Assignment Randomized Trial (SMART) for Acute Severe Ulcerative Colitis
NCT05976802	PHASE4	NOT_YET_RECRUITING	Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Budesonide Rectal Foam in Pediatric Patients Aged 5 to 17 Years With Active, Mild to Moderate Distal Ulcerative Colitis
NCT06095128	PHASE4	RECRUITING	A Study of Vedolizumab With Tofacitinib in Adults With Ulcerative Colitis (UC)
NCT06113913	PHASE4	RECRUITING	Subcutaneous Infliximab After A Previous Intravenous Dose Optimization
NCT06298461	PHASE4	RECRUITING	Bowel Preparation for Colonoscopy Among Individuals With Crohn’s and Ulcerative Colitis Disease.
NCT06581328	PHASE4	RECRUITING	A Study of Vedolizumab in Adults With Ulcerative Colitis or Crohn’s Disease in the Community Setting
NCT06609447	PHASE4	RECRUITING	The Efficacy and Safety of Combining Probiotic VSL#3 With Vedolizumab for the Treatment of Moderate Ulcerative Colitis
NCT06625450	PHASE4	NOT_YET_RECRUITING	TOFACITINIB vs TOFACITINIB WITH MESALAMINE IN ULCERATIVE COLITIS
NCT06788340	PHASE4	NOT_YET_RECRUITING	MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease
NCT06964113	PHASE4	RECRUITING	A Study of Filgotinib 200 mg in Korean Participants With Moderately to Severely Active Ulcerative Colitis Under Routine Clinical Practice
NCT07059130	PHASE4	NOT_YET_RECRUITING	Evaluating the Efficacy and Safety of Mirikizumab in Adults Over 60 With Moderate to Severe Crohn’s Disease and Ulcerative Colitis
NCT07235904	PHASE4	RECRUITING	Efficacy of Top-down Therapy With Mirikizumab Versus Standard of Care With Azathioprine in Patients With Newly Diagnosed Moderate-to-severe Ulcerative Colitis
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT07248644	PHASE4	NOT_YET_RECRUITING	Immunosuppressant Discontinuation in Elderly Patients With Ulcerative Colitis And Long-term Remission
NCT07258771	PHASE4	RECRUITING	Upadacitinib Combined With Corticosteroids vs Corticosteroid Monotherapy Induction for Inpatients and Outpatients With Acute Severe Ulcerative Colitis
NCT07303686	PHASE4	RECRUITING	De-escalation of Ustekinumab Therapy in Patients With Crohn’s Disease and Ulcerative Colitis
NCT07576452	PHASE4	NOT_YET_RECRUITING	FirST Lines of Biologics in pAtients With ulceRaTivE Colitis: a Randomised Controlled Trial
NCT00167882	PHASE4	COMPLETED	The Influence of 5-Aminosalicylates on Thiopurine Metabolite Levels
NCT00194818	PHASE4	COMPLETED	Asacol Dosing Study for Active Ulcerative Colitis
NCT00209287	PHASE4	TERMINATED	Study of Effects and of Modifications in Apoptosis Regulators Observed After Stopping 5-ASA Treatment in Patients With Inactive Ulcerative Colitis
NCT00219414	PHASE4	COMPLETED	Study for the Treatment of Ulcerative Colitis With Adacolumn (Companion to US Study 512-04-205)
NCT00446849	PHASE4	COMPLETED	Strategies in Maintenance for Patients Receiving Long-term Therapy (S.I.M.P.L.E.) With MMX (Multi-Matrix System) Mesalamine for Ulcerative Colitis (UC)
NCT00542152	PHASE4	COMPLETED	Study Comparing Cyclosporine With Infliximab in Steroid-refractory Severe Attacks of Ulcerative Colitis
NCT00652145	PHASE4	COMPLETED	Dose Escalation and Remission (DEAR)
NCT00702611	PHASE4	TERMINATED	Efficacy Study of Granulocytapheresis Plus Steroids vs Steroids Alone in Active Steroid Dependant Ulcerative Colitis
NCT00947674	PHASE4	TERMINATED	A Study of Leukocytapheresis (LCAP) in Patients With Ulcerative Colitis (UC)
NCT01078935	PHASE4	UNKNOWN	The Effect of Probiotics on the Rate of Recovery of Inflammatory Bowel Disease Exacerbation, Endothelial Function, and Markers of Inflammation
NCT01124149	PHASE4	COMPLETED	Ability to Maintain or Achieve Clinical and Endoscopic Remission With MMX Mesalamine Once Daily in Adults With Ulcerative Colitis
NCT01341808	PHASE4	COMPLETED	Immunogenicity of Hepatitis A Vaccine in Inflammatory Bowel Disease (IBD) Patients
NCT01346826	PHASE4	COMPLETED	Safety of Accelerated Infliximab Infusions in Patients With Inflammatory Bowel Disease (IBD)
NCT01408810	PHASE4	COMPLETED	Evaluation of Histologic and Endoscopic Remission Induced by Infliximab in Moderate to Severe Ulcerative Colitis
NCT01418131	PHASE4	COMPLETED	Rectal Tacrolimus in the Treatment of Resistant Ulcerative Proctitis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MESALAMINE	4	46
VEDOLIZUMAB	4	32
TOFACITINIB	4	16
MIRIKIZUMAB	4	12
INFLIXIMAB	4	11
ETRASIMOD	4	9
FILGOTINIB	4	9
GOLIMUMAB	4	7
BERBERINE	4	6
OZANIMOD	4	6
UPADACITINIB	4	6
AZATHIOPRINE	4	5
RISANKIZUMAB	4	5
AMINOSALICYLIC ACID	4	3
PICOSULFURIC ACID	4	3
ADALIMUMAB	4	2
BALSALAZIDE DISODIUM	4	2
BASILIXIMAB	4	2
CANNABIDIOL	4	2
CERTOLIZUMAB PEGOL	4	2
DEUCRAVACITINIB	4	2
METHYLPREDNISOLONE	4	2
NITAZOXANIDE	4	2
OXYGEN	4	2
USTEKINUMAB	4	2
ABATACEPT	4	1
APREMILAST	4	1
ASCORBIC ACID	4	1
ATORVASTATIN CALCIUM	4	1
BEZLOTOXUMAB	4	1