Juvenile idiopathic arthritis

Summary

Juvenile idiopathic arthritis (MONDO:0011429) is a disease (an umbrella term covering 6 Mondo subtypes) with 75 cohort genes (125 GWAS associations across 14 studies) and 230 clinical trials. The dominant Reactome pathway is Interleukin-23 signaling (5 cohort genes). Top therapeutic interventions include methotrexate, tocilizumab, and tofacitinib.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 125
• ClinVar variants: 1
• Clinical trials: 230

Clinical features

Epidemiology

Prevalence records

8 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	7.8	Worldwide	Validated
Point prevalence	1-5 / 10 000	20.5	Worldwide	Validated
Annual incidence	1-9 / 100 000	1.5	Europe	Validated
Annual incidence	1-5 / 10 000	13	Czech Republic	Validated
Point prevalence	1-9 / 100 000	4.7	France	Validated
Point prevalence	6-9 / 10 000	74.6	Specific population	Validated
Point prevalence	1-9 / 100 000	8.9	United States	Not yet validated
Point prevalence	1-5 / 10 000	21	Czech Republic	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	juvenile idiopathic arthritis
Mondo ID	MONDO:0011429
EFO	EFO:0002609
MeSH	D001171
OMIM	604302
Orphanet	92
DOID	DOID:676
ICD-11	1322678686
NCIT	C114357
SNOMED CT	410502007
UMLS	C3495559
MedGen	760659
GARD	0018677
MedDRA	10059177
NORD	808
Is cancer (heuristic)	no

Also known as: acute juvenile rheumatoid arthritis · Arthritis, Juvenile Rheumatoid · JIA · Juvenile idiopathic arthritis · juvenile idiopathic arthritis · juvenile rheumatoid arthritis · monarticular juvenile rheumatoid arthritis · pauciarticular juvenile arthritis · pauciarticular onset juvenile chronic arthritis · rheumatoid arthritis, systemic juvenile, susceptibility to · systemic juvenile rheumatoid arthritis

Data availability: 1 ClinVar variant · 125 GWAS associations (14 studies) · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › juvenile idiopathic arthritis

Related subtypes (29): palindromic rheumatism, rheumatic pulmonary valve disease, lupus erythematosus, mixed connective tissue disease, Reye syndrome, Wissler syndrome, acroosteolysis dominant type, chondrocalcinosis 2, Gorham-Stout disease, rheumatoid arthritis, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, sweet syndrome, dermatomyositis, IL10-related early-onset inflammatory bowel disease, unexplained long-lasting fever/inflammatory syndrome, myalgia-eosinophilia syndrome associated with tryptophan, reactive arthritis, rheumatic fever, intermittent hydrarthrosis, fibroblastic rheumatism, interstitial granulomatous dermatitis with arthritis, scleroderma, idiopathic juvenile osteoporosis, polymyalgia rheumatica, autoinflammatory syndrome, progeria-associated arthropathy, LAMA5-related multisystemic syndrome, rheumatic disease of mitral valve, isolated sternocostoclavicular hyperostosis

Subtypes (6): polyarticular juvenile idiopathic arthritis, oligoarticular juvenile idiopathic arthritis, systemic-onset juvenile idiopathic arthritis, psoriasis-related juvenile idiopathic arthritis, enthesitis-related juvenile idiopathic arthritis, unspecified juvenile idiopathic arthritis

Genetics & variants

GWAS landscape

125 GWAS associations across 14 studies. Top hits map to 41 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs6679677	7e-30	PHTF1 - RSBN1	A	1.49
rs11889341	2e-19	STAT4	T	1.26
HLA-DRB1*08	1e-15		?	12.49
rs953387	3e-14	CXCR4 - HNRNPKP2	T	1.69
rs9960807	3e-14	LINC01882	G	1.28
rs4766578	2e-13	ATXN2	T	1.19
rs2481065	4e-13	ATP8B2	G	1.27
rs706778	1e-12	IL2RA	T	1.17
rs2614258	9e-12	AHI1	A	1.17
rs79815064	3e-11	CCR3	A	1.25
rs11580078	8e-11	IL23R, C1orf141	G
rs7725052	8e-11	RNU1-150P - TTC33	C
rs10822050	8e-11	LINC02929 - ALDH7A1P4	C
rs17885785	8e-11	INS-IGF2, IGF2, IGF2-AS	T
rs72743477	8e-11	SMAD3	G
rs117372389	8e-11	NKD1	T
rs2066363	8e-11	ADGRL2	C
rs7660520	8e-11	TENM3 - DCTD	A
rs7100025	8e-11	LINC00993	G
rs36001488	8e-11	ATG16L1	C
rs4625	8e-11	BSN-DT, DAG1	G
rs1332099	9e-11	NKX2-3 - SLC25A28	T
rs7731626	1e-10	ANKRD55	A
rs2395148	2e-10	TSBP1, TSBP1-AS1	?	5.37
rs755374	2e-10	IL12B-AS1	T
rs17466626	3e-10	LRRK2	G
rs6434390	1e-09	INPP1 - MFSD6	G	1.13
rs11741255	2e-09	IRF1, CARINH	A
rs12430303	2e-09	LINC02341	C	1.14
rs7647909	2e-09	FOXP1	G	1.17

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90502824	Fan J	2024	4,550	18,446	Revealing Novel Genomic Insights and Therapeutic Targets for Juvenile Idiopathic Arthritis through Omics.
GCST90010715	Lopez-Isac E	2020	3,305	9,196	Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms.
GCST90239777	Li J	2022	1,245	9,250	Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes through Integrative Genetic Analysis.
GCST001417	Thompson SD	2012	814	0	Genome-wide association analysis of juvenile idiopathic arthritis identifies a new susceptibility locus at chromosomal region 3q13.
GCST006128	Haasnoot AJW	2018	522	0	An amino acid motif in HLA-DRβ1 distinguishes patients with uveitis in juvenile idiopathic arthritis.
GCST003424	Finkel TH	2016	388	2,500	Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility.
GCST000309	Hinks A	2009	279	0	Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome-wide association analysis.
GCST012103	Nikopensius T	2021	263	6,956	Association analysis of juvenile idiopathic arthritis genetic susceptibility factors in Estonian patients.
GCST90018873	Sakaue S	2021	216	409,001	A cross-population atlas of genetic associations for 220 human phenotypes.
GCST006127	Haasnoot AJW	2018	192	0	An amino acid motif in HLA-DRβ1 distinguishes patients with uveitis in juvenile idiopathic arthritis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	30
intergenic_variant	12
3_prime_UTR_variant	2
regulatory_region_variant	2
unknown	1
non_coding_transcript_exon_variant	1
5_prime_UTR_variant	1
missense_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs6679677	1	113761186	C>A,T	0.05	intergenic_variant	PHTF1 - RSBN1	7e-30	Tier 4: intronic/intergenic
rs11889341	2	191079016	C>T	0.05	intron_variant	STAT4	2e-19	Tier 4: intronic/intergenic
HLA-DRB1*08							1e-15	Tier 4: intronic/intergenic
rs953387	2	136149600	A>C,G,T	0.26	intron_variant	CXCR4 - HNRNPKP2	3e-14	Tier 4: intronic/intergenic
rs9960807	18	12770852	A>G	0.05	intron_variant	LINC01882	3e-14	Tier 4: intronic/intergenic
rs4766578	12	111466567	T>A	0.05	intron_variant	ATXN2	2e-13	Tier 4: intronic/intergenic
rs2481065	1	154339435	G>A,C	0.05	intron_variant	ATP8B2	4e-13	Tier 4: intronic/intergenic
rs706778	10	6056986	C>G,T	0.05	intron_variant	IL2RA	1e-12	Tier 4: intronic/intergenic
rs2614258	6	135356064	A>C,G,T	0.05	intron_variant	AHI1	9e-12	Tier 4: intronic/intergenic
rs79815064	3	46236086	A>G	0.05	intron_variant	CCR3	3e-11	Tier 4: intronic/intergenic
rs11580078	1	67203951	C>A,G,T	0.43	intron_variant	IL23R, C1orf141	8e-11	Tier 4: intronic/intergenic
rs7725052	5	40487168	C>T	0.43	intron_variant	RNU1-150P - TTC33	8e-11	Tier 4: intronic/intergenic
rs10822050	10	62679011	T>C,G	0.39	intergenic_variant	LINC02929 - ALDH7A1P4	8e-11	Tier 4: intronic/intergenic
rs17885785	11	2146620	C>T	0.2	intron_variant	INS-IGF2, IGF2, IGF2-AS	8e-11	Tier 4: intronic/intergenic
rs72743477	15	67171953	A>C,G,T	0.21	intron_variant	SMAD3	8e-11	Tier 4: intronic/intergenic
rs117372389	16	50634166	G>T	0.02	3_prime_UTR_variant	NKD1	8e-11	Tier 2: splice/UTR
rs2066363	1	81771892	C>A,T	0.34	intron_variant	ADGRL2	8e-11	Tier 4: intronic/intergenic
rs7660520	4	182824168	G>A,C	0.26	intergenic_variant	TENM3 - DCTD	8e-11	Tier 4: intronic/intergenic
rs7100025	10	37303610	G>A	0.34	intron_variant	LINC00993	8e-11	Tier 4: intronic/intergenic
rs36001488	2	233276621	C>G,T	0.48	intron_variant	ATG16L1	8e-11	Tier 4: intronic/intergenic
rs4625	3	49534707	A>G	0.31	3_prime_UTR_variant	BSN-DT, DAG1	8e-11	Tier 2: splice/UTR
rs1332099	10	99538694	T>A,C,G	0.46	intergenic_variant	NKX2-3 - SLC25A28	9e-11	Tier 4: intronic/intergenic
rs7731626	5	56148856	G>A,C	0.39	intron_variant	ANKRD55	1e-10	Tier 4: intronic/intergenic
rs2395148	6	32353777	G>T	0.05	intron_variant	TSBP1, TSBP1-AS1	2e-10	Tier 4: intronic/intergenic
rs755374	5	159402286	C>A,G,T	0.32	intergenic_variant	IL12B-AS1	2e-10	Tier 4: intronic/intergenic
rs17466626	12	40366829	A>G	0.02	intron_variant	LRRK2	3e-10	Tier 4: intronic/intergenic
rs6434390	2	190398036	G>A,C,T	0.05	intergenic_variant	INPP1 - MFSD6	1e-09	Tier 4: intronic/intergenic
rs11741255	5	132475490	G>A	0.42	intron_variant	IRF1, CARINH	2e-09	Tier 4: intronic/intergenic
rs12430303	13	42457891	T>C	0.05	intergenic_variant	LINC02341	2e-09	Tier 4: intronic/intergenic
rs7647909	3	71151006	G>T	0.05	intron_variant	FOXP1	2e-09	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2140106	NM_170601.5(SIAE):c.1301A>C (p.Lys434Thr)	SIAE	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 63 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 3

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

Gene	HGNC	Evidence routes
STAT4	STAT4	GWAS, Orphanet
CFTR	CFTR	GWAS, Orphanet
ANKRD55	ANKRD55	GWAS, Orphanet

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
MIF	Limited	Autosomal dominant	juvenile idiopathic arthritis	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MIF	Orphanet:586	Cystic fibrosis
MIF	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
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
TGIF1	Orphanet:220386	Semilobar holoprosencephaly
TGIF1	Orphanet:280195	Septopreoptic holoprosencephaly
TGIF1	Orphanet:280200	Microform holoprosencephaly
TGIF1	Orphanet:93924	Lobar holoprosencephaly
TGIF1	Orphanet:93925	Alobar holoprosencephaly
TGIF1	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
TNFSF11	Orphanet:667	Autosomal recessive malignant osteopetrosis
TNFSF15	Orphanet:186	Primary biliary cholangitis
CD40LG	Orphanet:101088	X-linked hyper-IgM syndrome
JMJD1C	Orphanet:567	22q11.2 deletion syndrome
JMJD1C	Orphanet:91352	Germinoma of the central nervous system
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
ACTA2	Orphanet:2573	Moyamoya disease
ACTA2	Orphanet:404463	Multisystemic smooth muscle dysfunction syndrome
ACTA2	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection
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
TIMMDC1	Orphanet:2609	Isolated complex I deficiency
CACNA1I	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
CCR1	Orphanet:117	Behçet disease
CARD9	Orphanet:457088	Predisposition to invasive fungal disease due to CARD9 deficiency
ZMIZ1	Orphanet:528084	Non-specific syndromic intellectual disability
ZNF365	Orphanet:2073	Narcolepsy type 1
ZNF365	Orphanet:83465	Narcolepsy type 2
LRRK2	Orphanet:2828	Young-onset Parkinson disease
LRRK2	Orphanet:411602	Hereditary late-onset Parkinson disease
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis
IL23R	Orphanet:117	Behçet disease
AHI1	Orphanet:220493	Joubert syndrome with ocular defect
AHI1	Orphanet:475	Isolated Joubert syndrome
AHI1	Orphanet:791	Retinitis pigmentosa
CRB1	Orphanet:251295	Pigmented paravenous retinochoroidal atrophy

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	73
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MIF	HGNC:7097	ENSG00000240972	P14174	Macrophage migration inhibitory factor	gencc
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
SUOX	HGNC:11460	ENSG00000139531	P51687	Sulfite oxidase, mitochondrial	gwas
SYNGR1	HGNC:11498	ENSG00000100321	O43759	Synaptogyrin-1	gwas
TGIF1	HGNC:11776	ENSG00000177426	Q15583	Homeobox protein TGIF1	gwas
TNFRSF6B	HGNC:11921	ENSG00000243509	O95407	Tumor necrosis factor receptor superfamily member 6B	gwas
TNFSF11	HGNC:11926	ENSG00000120659	O14788	Tumor necrosis factor ligand superfamily member 11	gwas
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
TNFSF18	HGNC:11932	ENSG00000120337	Q9UNG2	Tumor necrosis factor ligand superfamily member 18	gwas
CD40LG	HGNC:11935	ENSG00000102245	P29965	CD40 ligand	gwas
TNFSF8	HGNC:11938	ENSG00000106952	P32971	Tumor necrosis factor ligand superfamily member 8	gwas
JMJD1C	HGNC:12313	ENSG00000171988	Q15652	Jumonji domain-containing protein 1C	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
ACTA2	HGNC:130	ENSG00000107796	P62736	Actin, aortic smooth muscle	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
TIMMDC1	HGNC:1321	ENSG00000113845	Q9NPL8	Complex I assembly factor TIMMDC1, mitochondrial	gwas
ATP8B2	HGNC:13534	ENSG00000143515	P98198	Phospholipid-transporting ATPase ID	gwas
CACNA1I	HGNC:1396	ENSG00000100346	Q9P0X4	Voltage-dependent T-type calcium channel subunit alpha-1I	gwas
CSMD1	HGNC:14026	ENSG00000183117	Q96PZ7	CUB and sushi domain-containing protein 1	gwas
NUAK1	HGNC:14311	ENSG00000074590	O60285	NUAK family SNF1-like kinase 1	gwas
C1QTNF6	HGNC:14343	ENSG00000133466	Q9BXI9	Complement C1q tumor necrosis factor-related protein 6	gwas
SNX16	HGNC:14980	ENSG00000104497	P57768	Sorting nexin-16	gwas
CTTNBP2	HGNC:15679	ENSG00000077063	Q8WZ74	Cortactin-binding protein 2	gwas
CCR1	HGNC:1602	ENSG00000163823	P32246	C-C chemokine receptor type 1	gwas
CCR3	HGNC:1604	ENSG00000183625	P51677	C-C chemokine receptor type 3	gwas
CARD9	HGNC:16391	ENSG00000187796	Q9H257	Caspase recruitment domain-containing protein 9	gwas
ZMIZ1	HGNC:16493	ENSG00000108175	Q9ULJ6	Zinc finger MIZ domain-containing protein 1	gwas
FNBP1	HGNC:17069	ENSG00000187239	Q96RU3	Formin-binding protein 1	gwas
ANKRD30A	HGNC:17234	ENSG00000148513	Q9BXX3	Ankyrin repeat domain-containing protein 30A	gwas
APOBEC3B	HGNC:17352	ENSG00000179750	Q9UH17	DNA dC->dU-editing enzyme APOBEC-3B	gwas
APOBEC3C	HGNC:17353	ENSG00000244509	Q9NRW3	DNA dC->dU-editing enzyme APOBEC-3C	gwas
CHST11	HGNC:17422	ENSG00000171310	Q9NPF2	Carbohydrate sulfotransferase 11	gwas
CDH6	HGNC:1765	ENSG00000113361	P55285	Cadherin-6	gwas
SBK1	HGNC:17699	ENSG00000188322	Q52WX2	Serine/threonine-protein kinase SBK1	gwas
SIAE	HGNC:18187	ENSG00000110013	Q9HAT2	Sialate O-acetylesterase	clinvar
ZNF365	HGNC:18194	ENSG00000138311	Q70YC4	Talanin	gwas
FICD	HGNC:18416	ENSG00000198855	Q9BVA6	Protein adenylyltransferase FICD	gwas
ADGRL2	HGNC:18582	ENSG00000117114	O95490	Adhesion G protein-coupled receptor L2	gwas
LRRK2	HGNC:18618	ENSG00000188906	Q5S007	Leucine-rich repeat serine/threonine-protein kinase 2	gwas
STAB2	HGNC:18629	ENSG00000136011	Q8WWQ8	Stabilin-2	gwas
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	gwas
IL23R	HGNC:19100	ENSG00000162594	Q5VWK5	Interleukin-23 receptor	gwas
ANGPTL5	HGNC:19705	ENSG00000187151	Q86XS5	Angiopoietin-related protein 5	gwas
LSM8	HGNC:20471	ENSG00000128534	O95777	U6 snRNA-associated Sm-like protein LSm8	gwas
CMKLR1	HGNC:2121	ENSG00000174600	Q99788	Chemerin-like receptor 1	gwas
ATG16L1	HGNC:21498	ENSG00000085978	Q676U5	Autophagy-related protein 16-1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MIF	Macrophage migration inhibitory factor	Pro-inflammatory cytokine involved in the innate immune response to bacterial pathogens.
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.
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…
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.
SYNGR1	Synaptogyrin-1	May play a role in regulated exocytosis.
TGIF1	Homeobox protein TGIF1	Binds to a retinoid X receptor (RXR) responsive element from the cellular retinol-binding protein II promoter (CRBPII-RXRE).
TNFRSF6B	Tumor necrosis factor receptor superfamily member 6B	Decoy receptor that can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL.
TNFSF11	Tumor necrosis factor ligand superfamily member 11	Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
TNFSF18	Tumor necrosis factor ligand superfamily member 18	Cytokine that binds to TNFRSF18/AITR/GITR.
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.
JMJD1C	Jumonji domain-containing protein 1C	Demethylates lysine in proteins, such as STAT3 or MDC1.
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.
ACTA2	Actin, aortic smooth muscle	Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
IKZF3	Zinc finger protein Aiolos	Transcription factor that plays an important role in the regulation of lymphocyte differentiation.
TIMMDC1	Complex I assembly factor TIMMDC1, mitochondrial	Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
ATP8B2	Phospholipid-transporting ATPase ID	Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane.
CACNA1I	Voltage-dependent T-type calcium channel subunit alpha-1I	Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene exp…
CSMD1	CUB and sushi domain-containing protein 1	Potential suppressor of squamous cell carcinomas.
NUAK1	NUAK family SNF1-like kinase 1	Serine/threonine-protein kinase involved in various processes such as cell adhesion, regulation of cell ploidy and senescence, cell proliferation and tumor progression.
SNX16	Sorting nexin-16	May be involved in several stages of intracellular trafficking.
CTTNBP2	Cortactin-binding protein 2	Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, and thus controls dendritic spinogenesis and dendritic spine maintenance.
CCR1	C-C chemokine receptor type 1	Chemokine receptor that plays a crucial role in regulating immune cell migration, inflammation, and immune responses.
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.
CARD9	Caspase recruitment domain-containing protein 9	Adapter protein that plays a key role in innate immune response against fungi by forming signaling complexes downstream of C-type lectin receptors.
ZMIZ1	Zinc finger MIZ domain-containing protein 1	Acts as a transcriptional coactivator.
FNBP1	Formin-binding protein 1	May act as a link between RND2 signaling and regulation of the actin cytoskeleton.
APOBEC3B	DNA dC->dU-editing enzyme APOBEC-3B	DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms.
APOBEC3C	DNA dC->dU-editing enzyme APOBEC-3C	DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms.
CHST11	Carbohydrate sulfotransferase 11	Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin.
CDH6	Cadherin-6	Cadherins are calcium-dependent cell adhesion proteins.
SBK1	Serine/threonine-protein kinase SBK1	May be involved in signal-transduction pathways related to the control of brain development.
SIAE	Sialate O-acetylesterase	Catalyzes the removal of O-acetyl ester groups from position 9 of the free diacetylated sialate N-acetyl-9-O-acetylneuraminate (Neu5,9Ac2) in the cytosol and of the diacetylated sialate residues of sialylglycoconjugates in the lysosomes.
ZNF365	Talanin	May play a role in uric acid excretion.
FICD	Protein adenylyltransferase FICD	Protein that can both mediate the addition of adenosine 5’-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context.
ADGRL2	Adhesion G protein-coupled receptor L2	Orphan adhesion G-protein coupled receptor (aGPCR), which mediates synapse specificity.
LRRK2	Leucine-rich repeat serine/threonine-protein kinase 2	Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking.
STAB2	Stabilin-2	Phosphatidylserine receptor that enhances the engulfment of apoptotic cells.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.
IL23R	Interleukin-23 receptor	Associates with IL12RB1 to form the interleukin-23 receptor.
LSM8	U6 snRNA-associated Sm-like protein LSm8	Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
CMKLR1	Chemerin-like receptor 1	Receptor for the chemoattractant adipokine chemerin/RARRES2 and for the omega-3 fatty acid derived molecule resolvin E1.
ATG16L1	Autophagy-related protein 16-1	Plays an essential role in both canonical and non-canonical autophagy: interacts with ATG12-ATG5 to mediate the lipidation to ATG8 family proteins (MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAPL1, GABARAPL2 and GABARAP).
AHI1	Jouberin	Involved in vesicle trafficking and required for ciliogenesis, formation of primary non-motile cilium, and recruitment of RAB8A to the basal body of primary cilium.
CORO1C	Coronin-1C	Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1.
CRB1	Protein crumbs homolog 1	Plays a role in photoreceptor morphogenesis in the retina.

Protein-family classification

Druggable: 25 · Difficult: 18 · Unknown: 32 · Druggable fraction: 0.33

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
Scaffold/PPI	10	2.3×	0.120
Complement	1	3.6×	0.525
Transporter	2	2.1×	0.525
GPCR	5	1.6×	0.525
Kinase	4	1.5×	0.525
Enzyme (other)	8	1.3×	0.525
Ion channel	1	1.5×	0.676
Antibody/Immunoglobulin	3	1.2×	0.676
Transcription factor	8	0.9×	0.858
Protease	1	0.5×	0.963
Other/Unknown	32	0.8×	0.992

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MIF	Enzyme (other)	yes	5.3.2.1	Macrophage_inhib_fac, Tautomerase/MIF_sf, Macrophage_inhib_fac_CS
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
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
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
SYNGR1	Other/Unknown	no		Marvel, Synaptogyrin
TGIF1	Transcription factor	no		HD, KN_HD, Homeodomain-like_sf
TNFRSF6B	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFRSF6B_N, TNFRSF_decoy_receptor
TNFSF11	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_ligand_10/11
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNFSF18	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNFSF18
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
JMJD1C	Enzyme (other)	yes	1.14.11.65	JmjC_dom, LSDs-like, KDM3A/B_DUF7030
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
ACTA2	Other/Unknown	no		Actin, Actin_CS, Actin/actin-like_CS
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
TIMMDC1	Other/Unknown	no		TIMMDC1
ATP8B2	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
CACNA1I	Ion channel	yes		VDCCAlpha1, VDCC_T_a1, Ion_trans_dom
CSMD1	Complement	yes		Sushi_SCR_CCP_dom, CUB_dom, Sperma_CUB_dom_sf
NUAK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
C1QTNF6	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom
SNX16	Other/Unknown	no		PX_dom, PX_dom_sf, SNX16_PX
CTTNBP2	Scaffold/PPI	no		Ankyrin_rpt, Cortactin-binding_p2_N, Ankyrin_rpt-contain_sf
CCR1	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR1
CCR3	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR3
CARD9	Other/Unknown	no		CARD, DEATH-like_dom_sf, CARD_CARD9
ZMIZ1	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, ZMIZ1_N
FNBP1	Scaffold/PPI	no		FCH_dom, SH3_domain, HR1_rho-bd
ANKRD30A	Scaffold/PPI	no		Ankyrin_rpt, Ankyrin_rpt-contain_sf, CC144C-like_CC_dom
APOBEC3B	Enzyme (other)	yes	3.5.4.38	CMP_dCMP_dom, APOBEC/CMP_deaminase_Zn-bd, Cytidine_deaminase-like
APOBEC3C	Enzyme (other)	yes	3.5.4.38	CMP_dCMP_dom, APOBEC/CMP_deaminase_Zn-bd, Cytidine_deaminase-like
CHST11	Enzyme (other)	yes	2.8.2.5	Sulfotransferase, Carb_sulfotrans_8-10
CDH6	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin-like_sf
SBK1	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
SIAE	Enzyme (other)	yes	3.1.1.53	SASA, SGNH_hydro_sf, SIAE
ZNF365	Transcription factor	no		GenomicStab_NeuMorph_Reg, FBX41/ZN365_Znf-C2H2
FICD	Other/Unknown	no		Fido, TPR-like_helical_dom_sf, TPR_rpt
ADGRL2	GPCR	yes		GPS, GPCR_2_secretin-like, Lectin_gal-bd_dom
LRRK2	Kinase	yes		Prot_kinase_dom, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
STAB2	Other/Unknown	no		Link_dom, EGF, FAS1_domain
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
IL23R	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
ANGPTL5	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS
LSM8	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm8
CMKLR1	GPCR	yes		GPCR_Rhodpsn, Formyl_rcpt-rel, CML1
ATG16L1	Scaffold/PPI	no		WD40_rpt, Autophagy-rel_prot_16_dom, WD40/YVTN_repeat-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

66 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	8
lymph node	7
right hemisphere of cerebellum	6
male germ line stem cell (sensu Vertebrata) in testis	6
monocyte	6
buccal mucosa cell	5
middle temporal gyrus	5
leukocyte	5
calcaneal tendon	5
Brodmann (1909) area 23	5
cortical plate	5
stromal cell of endometrium	4
tibia	4
mononuclear cell	4
secondary oocyte	4
adenohypophysis	3
olfactory bulb	3
mucosa of stomach	3
sperm	3
right lobe of liver	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MIF	147	ubiquitous	marker	pituitary gland, adenohypophysis, cortex of kidney
RUNX3	220	broad	marker	granulocyte, buccal mucosa cell, lymph node
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
ZFP36L1	289	ubiquitous	marker	mucosa of paranasal sinus, endocervix, mucosa of stomach
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
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
TGIF1	267	ubiquitous	marker	stromal cell of endometrium, gall bladder, ventricular zone
TNFRSF6B	127	broad	yes	olfactory segment of nasal mucosa, spleen, subcutaneous adipose tissue
TNFSF11	98	tissue_specific	marker	primordial germ cell in gonad, tibia, lymph node
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
CD40LG	124	tissue_specific	marker	granulocyte, lymph node, blood
TNFSF8	179	broad	marker	monocyte, leukocyte, mononuclear cell
JMJD1C	291	ubiquitous	marker	calcaneal tendon, right hemisphere of cerebellum, cerebellar hemisphere
EIPR1	249	ubiquitous	marker	prefrontal cortex, adenohypophysis, nucleus accumbens
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
ACTA2	289	ubiquitous	marker	cauda epididymis, blood vessel layer, saphenous vein
IKZF3	155	broad	marker	granulocyte, lymph node, epithelium of nasopharynx
TIMMDC1	259	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
ATP8B2	250	ubiquitous	marker	mucosa of stomach, right coronary artery, stromal cell of endometrium
CACNA1I	145		yes	Brodmann (1909) area 23, primary visual cortex, middle temporal gyrus
CSMD1	179	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, primary visual cortex
NUAK1	287	ubiquitous	marker	Brodmann (1909) area 23, middle temporal gyrus, hair follicle
C1QTNF6	170	ubiquitous	marker	decidua, right uterine tube, stromal cell of endometrium
SNX16	257	ubiquitous	yes	sperm, male germ cell, secondary oocyte
CTTNBP2	230	broad	marker	cortical plate, corpus callosum, embryo
CCR1	244	broad	marker	monocyte, mononuclear cell, leukocyte
CCR3	100	tissue_specific	yes	secondary oocyte, blood, oocyte
CARD9	172	broad	marker	monocyte, mononuclear cell, leukocyte

Protein interactions among cohort

Intra-cohort edges: 35.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
LRRK2	7,628
POLR3B	5,712
TYK2	3,932
ATG16L1	3,843
CARD9	3,636
SUOX	3,449
TNFSF11	3,410
ATXN2	3,360
PSMG1	3,355

Intra-cohort edges

A	B	Sources
ACTA2	MYL12B	intact
ADCY7	CXCR4	intact
ADCY8	CFTR	intact
ADGRL2	ATG16L1	intact
ADGRL2	CFTR	intact
ANGPTL5	CEP126	string_interaction
ANGPTL5	TNFSF15	string_interaction
ANO4	SPIC	string_interaction
APOBEC3B	APOBEC3C	string_interaction
ATG16L1	TNFSF15	string_interaction
ATP8B2	CXCR4	intact
ATXN2	ATXN2L	intact
ATXN2L	CFTR	intact
CCR1	CCR3	string_interaction
CD40LG	TNFSF8	string_interaction
CEP126	TNFSF11	intact
CFTR	CORO1C	intact
CFTR	CTTNBP2	string_interaction
CFTR	DAG1	intact
CFTR	MIF	intact
CFTR	MYL12B	intact
CFTR	SYNGR1	intact
CTTNBP2	REEP3	string_interaction
CXCR4	TNFSF18	biogrid_interaction
DAG1	TNFSF8	biogrid_interaction, intact
IKZF3	RUNX3	string_interaction
IL23R	STAT4	string_interaction
IL23R	TYK2	string_interaction
JMJD1C	REEP3	string_interaction
PSMG1	TNFRSF6B	string_interaction
STAT4	TYK2	string_interaction
TNFRSF6B	TNFSF15	biogrid_interaction, intact, string_interaction
TNFRSF6B	TNFSF8	string_interaction
TNFSF15	TNFSF18	string_interaction
TNFSF15	TNFSF8	string_interaction

Structural data

PDB: 46 · AlphaFold-only: 29 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MIF	P14174	118
CFTR	P13569	58
TYK2	P29597	52
LRRK2	Q5S007	44
CXCR4	P61073	33
POLR3B	Q9NW08	29
LSM8	O95777	20
ATG16L1	Q676U5	16
FICD	Q9BVA6	15
ERAP2	Q6P179	14
APOBEC3B	Q9UH17	13
PSMG1	O95456	13
TNFRSF6B	O95407	8
CD40LG	P29965	8
CARD9	Q9H257	8
DAG1	Q14118	8
TNFSF15	O95150	7
TNFSF18	Q9UNG2	7
CMKLR1	Q99788	5
CACNA1I	Q9P0X4	4
IL23R	Q5VWK5	4
ANKS1B	Q7Z6G8	4
TGIF1	Q15583	3
JMJD1C	Q15652	3
CCR1	P32246	3
ZFP36L1	Q07352	2
TNFSF11	O14788	2
SNX16	P57768	2
APOBEC3C	Q9NRW3	2
RUNX3	Q13761	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACTA2	P62736	95.43
SIAE	Q9HAT2	92.26
CHST11	Q9NPF2	89.39
EIPR1	Q53HC9	89.26
STAT4	Q14765	86.87
CYTL1	Q9NRR1	85.86
MYL12B	O14950	83.78
ATP8B2	P98198	82.24
ANGPTL5	Q86XS5	81.80
TNFSF8	P32971	80.07
ANO4	Q32M45	79.27
SBK1	Q52WX2	77.87
C1QTNF6	Q9BXI9	77.42
ADCY7	P51828	77.32
ABTB3	A6QL63	73.18
TIMMDC1	Q9NPL8	72.08
ADCY8	P40145	71.82
RALYL	Q86SE5	71.18
FAM169BP	Q8N8A8	70.84
SPIC	Q8N5J4	67.85
REEP3	Q6NUK4	64.74
ANKRD55	Q3KP44	63.43
NUAK1	O60285	62.48
ELFN2	Q5R3F8	61.79
CTTNBP2	Q8WZ74	58.83
ATXN2L	Q8WWM7	49.52
CEP126	Q9P2H0	49.44
IKZF3	Q9UKT9	48.06
ZNF365	Q70YC4	30.21

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 385. Enrichment computed across 110 evidence-associated genes (75 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 75 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	84.6×	5e-07	STAT4, TYK2, IL23R, IL12B, JAK2
Interleukin-12 signaling	5	27.2×	1e-04	STAT4, TYK2, IL12B, JAK2, MIF
TNFs bind their physiological receptors	5	26.2×	1e-04	TNFRSF6B, TNFSF11, TNFSF15, TNFSF18, TNFSF8
Interleukin-35 Signalling	3	38.1×	0.006	STAT4, TYK2, JAK2
GABA receptor activation	4	16.9×	0.007	ADCY7, ADCY8, GABRB3, GABRG3
Interleukin-10 signaling	4	12.4×	0.019	TYK2, CCR1, IL10, IL12B
RUNX3 regulates BCL2L11 (BIM) transcription	2	60.9×	0.023	RUNX3, SMAD3
Interleukin-12 family signaling	3	19.0×	0.024	STAT4, JAK2, MIF
Interleukin-20 family signaling	3	16.9×	0.028	STAT4, TYK2, JAK2
Interleukin receptor SHC signaling	3	16.3×	0.028	IL2RA, IL5, JAK2
Interleukin-4 and Interleukin-13 signaling	5	6.9×	0.028	TYK2, IL23R, IL10, IL12B, JAK2
RUNX3 regulates CDKN1A transcription	2	43.5×	0.028	RUNX3, SMAD3
mRNA Editing: C to U Conversion	2	33.8×	0.038	APOBEC3B, APOBEC3C
mRNA Editing	2	33.8×	0.038	APOBEC3B, APOBEC3C
Formation of the Editosome	2	33.8×	0.038	APOBEC3B, APOBEC3C
MAPK1 (ERK2) activation	2	30.4×	0.039	TYK2, JAK2
Adenylate cyclase activating pathway	2	30.4×	0.039	ADCY7, ADCY8
Interleukin-21 signaling	2	30.4×	0.039	STAT4, IL21
MAPK3 (ERK1) activation	2	27.7×	0.039	TYK2, JAK2
Interleukin-27 signaling	2	27.7×	0.039	TYK2, JAK2
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	3	12.0×	0.039	STAT4, IL10, MIF
FCGR3A-mediated IL10 synthesis	3	11.7×	0.039	ADCY7, ADCY8, IL10
Interleukin-6 signaling	2	25.4×	0.045	TYK2, JAK2
Smooth Muscle Contraction	3	10.6×	0.045	ACTA2, CACNA1I, MYL12B
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	2	23.4×	0.049	RUNX3, STAT4
Adenylate cyclase inhibitory pathway	2	20.3×	0.063	ADCY7, ADCY8
Formation of definitive endoderm	2	19.0×	0.069	CXCR4, SMAD3
PKA activation in glucagon signalling	2	17.9×	0.069	ADCY7, ADCY8
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	2	17.9×	0.069	TNFSF11, CD40LG
PKA activation	2	16.9×	0.069	ADCY7, ADCY8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 101 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	17	7.9×	4e-08	TNFSF11, TNFSF15, TNFSF8, TYK2, CCR1, CCR3, CMKLR1, CXCR4 (+9 more)
positive regulation of interleukin-17 production	7	41.7×	1e-07	TYK2, CARD9, IL23R, NOD2, IL12B, IL21, JAK2
positive regulation of T-helper 17 type immune response	5	69.5×	2e-06	TYK2, CARD9, IL23R, IL12B, JAK2
positive regulation of T cell proliferation	7	18.0×	3e-05	CD40LG, TYK2, IL23R, VTCN1, IL12B, IL21, JAK2
interleukin-12-mediated signaling pathway	4	74.2×	3e-05	STAT4, TYK2, IL12B, JAK2
positive regulation of cytosolic calcium ion concentration	9	10.4×	4e-05	CCR1, CCR3, CMKLR1, ADCY8, CXCR4, GPR35, JAK2, PRKG1 (+1 more)
positive regulation of type II interferon production	7	15.6×	5e-05	TYK2, IL23R, IL12B, IL18R1, IL21, JAK2, PTPN22
positive regulation of natural killer cell proliferation	4	55.6×	8e-05	TYK2, IL23R, IL12B, JAK2
positive regulation of osteoclast differentiation	5	28.8×	9e-05	TNFSF11, CCR1, IL23R, CORO1C, IL12B
positive regulation of cytokine production	6	16.1×	2e-04	CARD9, IL10, IL21, INS, MIF, PTGER4
interleukin-23-mediated signaling pathway	3	83.4×	4e-04	TYK2, IL23R, JAK2
positive regulation of NK T cell proliferation	3	83.4×	4e-04	TYK2, IL12B, JAK2
positive regulation of memory T cell differentiation	3	55.6×	0.001	IL23R, HLA-DRB1, IL12B
cell surface receptor signaling pathway via JAK-STAT	5	14.4×	0.002	STAT4, TYK2, IL23R, IL12B, JAK2
JNK cascade	5	13.5×	0.003	TNFSF11, CARD9, LRRK2, SMAD3, PTGER4
positive regulation of tumor necrosis factor production	6	9.1×	0.004	CARD9, LRRK2, NOD2, IL12B, JAK2, MIF
inflammatory response	11	4.1×	0.005	CD40LG, CCR1, CCR3, IL23R, CMKLR1, CXCR4, IL18R1, IL2RA (+3 more)
positive regulation of receptor signaling pathway via JAK-STAT	4	17.1×	0.005	TYK2, IL10, IL5, JAK2
regulation of T cell proliferation	3	31.3×	0.006	TNFSF18, TNFSF8, RAC2
positive regulation of interleukin-10 production	4	15.9×	0.006	CD40LG, NOD2, IL12B, IL21
positive regulation of granulocyte macrophage colony-stimulating factor production	3	29.4×	0.006	CARD9, IL23R, IL12B
obsolete positive regulation of NF-kappaB transcription factor activity	5	10.2×	0.006	TNFSF18, CD40LG, CARD9, NOD2, IL18R1
cytokine-mediated signaling pathway	6	7.8×	0.006	STAT4, TNFSF11, TYK2, CCR1, IL23R, JAK2
positive regulation of ERK1 and ERK2 cascade	7	5.9×	0.009	TNFSF11, ACTA2, CCR1, CARD9, NOD2, MIF, PTPN22
calcium-mediated signaling	5	9.1×	0.010	TNFSF11, CCR1, CCR3, LRRK2, CXCR4
negative regulation of T cell proliferation	4	13.1×	0.010	VTCN1, HLA-DRB1, IL10, IL2RA
T-helper cell differentiation	2	66.7×	0.013	IL12B, PTGER4
positive regulation of NK T cell activation	2	66.7×	0.013	IL23R, IL12B
positive regulation of tyrosine phosphorylation of STAT protein	3	21.8×	0.013	TNFSF18, IL21, JAK2
developmental growth	3	21.8×	0.013	ZMIZ1, CHST11, SMAD3

Therapeutics

Drugs indicated for this disease

19 approved, 11 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Abatacept	Approved (phase 4)
Adalimumab	Approved (phase 4)
Canakinumab	Approved (phase 4)
Celecoxib	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Etanercept	Approved (phase 4)
Etodolac	Approved (phase 4)
Hydrocortisone	Approved (phase 4)
Ibuprofen	Approved (phase 4)
Meloxicam	Approved (phase 4)
Methotrexate	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Naproxen	Approved (phase 4)
Oxaprozin	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Sulfasalazine	Approved (phase 4)
Tocilizumab	Approved (phase 4)
Baricitinib	Phase 3 (in late-stage trials)
Calcium	Phase 3 (in late-stage trials)
Certolizumab Pegol	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Golimumab	Phase 3 (in late-stage trials)
Guselkumab	Phase 3 (in late-stage trials)
Infliximab	Phase 3 (in late-stage trials)
Somatropin	Phase 3 (in late-stage trials)
Tofacitinib	Phase 3 (in late-stage trials)
Upadacitinib	Phase 3 (in late-stage trials)
Ustekinumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Anakinra, Calcium Carbonate, Givinostat, Rilonacept, Sarilumab, Ubidecarenone.

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 10 · Phased (≥1): 14 · Undrugged: 61

Druggability breadth: 53 of 110 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
MIF	METARAMINOL
TYK2	FEDRATINIB
IKZF3	POMALIDOMIDE
CACNA1I	NIMODIPINE
NUAK1	FEDRATINIB
CCR1	ABAMETAPIR
SBK1	AFATINIB
LRRK2	PONATINIB
CFTR	IVACAFTOR
CXCR4	PLERIXAFOR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
LRRK2	42	4
NUAK1	22	4
SBK1	14	4
CFTR	14	4
MIF	10	4
CCR1	8	4
CACNA1I	7	4
IKZF3	5	4
CXCR4	5	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
METARAMINOL	4	MIF
IBUDILAST	4	MIF
HEXACHLOROPHENE	4	MIF
HISTAMINE	4	MIF
FEDRATINIB	4	LRRK2, NUAK1, 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, NUAK1, TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	LRRK2, NUAK1, SBK1, TYK2
SUNITINIB	4	LRRK2, NUAK1, SBK1, TYK2
DASATINIB	4	SBK1, TYK2
ERLOTINIB	4	LRRK2, SBK1, TYK2
CRIZOTINIB	4	SBK1, TYK2
MIDOSTAURIN	4	LRRK2, NUAK1, TYK2
IMATINIB	4	TYK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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
CXCR4	560	Binding:386, Functional:174
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
NUAK1	342	Binding:342
CCR1	243	Binding:176, Functional:67
MIF	205	Binding:202, Functional:3
CCR3	175	Binding:107, Functional:68
IKZF3	101	Binding:100, Functional:1
SBK1	97	Binding:97
CMKLR1	58	Binding:37, Functional:21
CACNA1I	56	Binding:44, Functional:9, ADMET:3
ERAP2	46	Binding:40, ADMET:4, Functional:2
ADCY8	31	Binding:28, Functional:2, ADMET:1
TNFSF11	30	Binding:30
STAT4	20	Binding:20
ADCY7	16	Binding:14, Functional:2
IL23R	13	Binding:13
CD40LG	8	Binding:8
APOBEC3C	7	Binding:7
ATXN2	5	Binding:3, Functional:2
PSMG1	5	Binding:5
DAG1	4	Binding:4
JMJD1C	2	Binding:2
LSM8	2	Binding:2
APOBEC3B	1	Binding:1
SIAE	1	Binding:1
CORO1C	1	Binding:1
MYL12B	1	Binding:1
ATXN2L	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MIF	5.3.2.1, 5.3.3.12	phenylpyruvate tautomerase, L-dopachrome isomerase
SUOX	1.8.3.1	sulfite oxidase
JMJD1C	1.14.11.65	[histone H3]-dimethyl-L-lysine9 demethylase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
ATP8B2	7.6.2.1	P-type phospholipid transporter
APOBEC3B	3.5.4.38	single-stranded DNA cytosine deaminase
APOBEC3C	3.5.4.38	single-stranded DNA cytosine deaminase
CHST11	2.8.2.5	chondroitin 4-sulfotransferase
SIAE	3.1.1.53	sialate O-acetylesterase
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase
ADCY7	4.6.1.1	adenylate cyclase
ERAP2	3.4.11.1, 3.4.11.6	leucyl aminopeptidase, aminopeptidase B

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
MIF	205
TYK2	1,083
IKZF3	101
NUAK1	342
CCR1	243
CCR3	175
LRRK2	809
CFTR	520
CXCR4	560

Pharmacogenomics

Cohort genes with a PharmGKB record: 75; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

26 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)
METARAMINOL	4	MIF
IBUDILAST	4	MIF
HEXACHLOROPHENE	4	MIF
HISTAMINE	4	MIF
FEDRATINIB	4	LRRK2, NUAK1, SBK1, TYK2
RUXOLITINIB	4	LRRK2, SBK1, 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, NUAK1, TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	TYK2
NINTEDANIB	4	LRRK2, NUAK1, SBK1, TYK2
SUNITINIB	4	LRRK2, NUAK1, SBK1, TYK2
DASATINIB	4	SBK1, TYK2
ERLOTINIB	4	LRRK2, SBK1, TYK2
CRIZOTINIB	4	SBK1, TYK2
MIDOSTAURIN	4	LRRK2, NUAK1, TYK2
IMATINIB	4	TYK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	MIF, TYK2, IKZF3, CACNA1I, NUAK1, CCR1, SBK1, LRRK2, CFTR, CXCR4
B	Phased (≥1) drug, not yet approved	4	CCR3, CMKLR1, ADCY8, ERAP2
C	Druggable family + PDB, no drug	10	SUOX, JMJD1C, CSMD1, APOBEC3B, APOBEC3C, ADGRL2, IL23R, MFSD6, DAG1, VTCN1
D	Druggable family + AlphaFold only, no drug	3	CHST11, SIAE, ADCY7
E	Difficult family or no structure, no drug	48	RUNX3, ATXN2, ZFP36L1, STAT4, SYNGR1, TGIF1, TNFRSF6B, TNFSF11, TNFSF15, TNFSF18 (+38 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT4	20	TYK2
RUNX3	0	—
ATXN2	5	—
ZFP36L1	0	—
SUOX	0	—
SYNGR1	0	—
TGIF1	0	—
TNFRSF6B	0	—
TNFSF11	30	—
TNFSF15	0	—
TNFSF18	0	—
CD40LG	8	—
TNFSF8	0	—
JMJD1C	2	—
EIPR1	0	—
ACTA2	0	—
TIMMDC1	0	—
ATP8B2	0	—
CSMD1	0	—
C1QTNF6	0	—
SNX16	0	—
CTTNBP2	0	—
CARD9	0	—
ZMIZ1	0	—
FNBP1	0	—
ANKRD30A	0	—
APOBEC3B	1	—
APOBEC3C	7	—
CHST11	0	—
CDH6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 230.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	142
PHASE3	32
PHASE4	23
PHASE2	12
PHASE1	12
PHASE2/PHASE3	4
PHASE1/PHASE2	3
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05879419	PHASE4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT06618937	PHASE4	NOT_YET_RECRUITING	Toward Personalized Medicine to Guide Drug Withdrawal in Children with Juvenile Idiopathic Arthritis in Clinical Remission
NCT06653634	PHASE4	RECRUITING	Optimizing Treatment for Patients With Juvenile Idiopathic Arthritis in Sustained Remission: The MOVE-JIA Trial
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT00443430	PHASE4	COMPLETED	Trial of Early Aggressive Drug Therapy in Juvenile Idiopathic Arthritis
NCT00637780	PHASE4	TERMINATED	Study To Determine The Pharmacokinetics Of Sulfasalazine In Children With Juvenile Idiopathic Arthritis
NCT00731965	PHASE4	COMPLETED	Safety and Efficacy of Measles, Mumps, Rubella Vaccination in Juvenile Idiopathic Arthritis
NCT00792233	PHASE4	COMPLETED	Determining Predictors of Safe Discontinuation of Anti-TNF Treatment in JIA
NCT00807846	PHASE4	COMPLETED	A Study To Evaluate The Effects Of Celecoxib (Celebrex®) Or Naproxen On Blood Pressure In Pediatric Subjects
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01287715	PHASE4	UNKNOWN	Withdrawal of Etanercept After Successful Treatment of Juvenile Idiopathic Arthritis
NCT01544114	PHASE4	COMPLETED	A Safety Study of VIMOVO in Adolescents With Juvenile Idiopathic Arthritis (JIA)
NCT01563185	PHASE4	COMPLETED	Open-label Safety and Pharmacokinetic Study of DUEXIS® (Ibuprofen and Famotidine) Tablets in Juvenile Idiopathic Arthritis
NCT01734382	PHASE4	COMPLETED	A Study of Decreased Dose Frequency in Participants With Systemic Juvenile Arthritis Who Experience Laboratory Abnormalities During Treatment With RoActemra/Actemra (Tocilizumab)
NCT02024334	PHASE4	UNKNOWN	Efficacy Study of Leflunomide to Treat Juvenile Idiopathic Arthritis
NCT02196480	PHASE4	COMPLETED	23-valent Polysaccharide Pneumococcal Vaccine in Juvenile Idiopathic Arthritis Patients Under Anti-TNF Therapy
NCT03069638	PHASE4	COMPLETED	Intranasal Dexmedetomidine Sedation During Intra-articular Joint Injections in Pediatric Population
NCT03301883	PHASE4	COMPLETED	A Study of Tocilizumab in Chinese Participants With Systemic Juvenile Idiopathic Arthritis (sJIA)
NCT03816397	PHASE4	COMPLETED	Adalimumab in JIA-associated Uveitis Stopping Trial
NCT04614311	PHASE4	COMPLETED	Strategies Towards Personalised Treatment in Juvenile Idiopathic Arthritis (JIA).
NCT04687930	PHASE4	COMPLETED	Genicular Nerve Block in Juvenile Idiopathic Arthritis
NCT07428551	PHASE4	COMPLETED	Comparative Study of Leflunomide Plus Methotrexate Versus Methotrexate Monotherapy in Refractory Polyarticular Juvenile Idiopathic Arthritis Patients
NCT03773965	PHASE3	RECRUITING	A Study of Baricitinib in Participants From 1 Year to Less Than 18 Years Old With Juvenile Idiopathic Arthritis
NCT05609630	PHASE3	RECRUITING	Study of Oral Upadacitinib and Subcutaneous/Intravenous Tocilizumab to Evaluate Change in Disease Activity, Adverse Events and How Drug Moves Through the Body of Pediatric and Adolescent Participants With Active Systemic Juvenile Idiopathic Arthritis.
NCT07386587	PHASE3	ENROLLING_BY_INVITATION	Methotrexate Alone vs Methotrexate + Etanercept for Minimal/Low Disease Activity in Juvenile Idiopathic Arthritis
NCT07553182	PHASE3	RECRUITING	OLE Study With Filgotinib in JIA
NCT00012506	PHASE3	UNKNOWN	The Safety and Efficacy of a Tumor Necrosis Factor Receptor Fusion Protein on Uveitis Associated With Juvenile Rheumatoid Arthritis
NCT00034853	PHASE3	COMPLETED	Meloxicam [Mobic] in Juvenile Rheumatoid Arthritis (JRA)
NCT00078806	PHASE3	TERMINATED	Safety and Efficacy Study of Etanercept (Enbrel®) In Children With Systemic Onset Juvenile Rheumatoid Arthritis
NCT00095173	PHASE3	COMPLETED	BMS-188667 in Children and Adolescents With Juvenile Rheumatoid Arthritis
NCT00279747	PHASE3	COMPLETED	A One Year Double-blind Trial to Investigate the Efficacy and Safety of Meloxicam Oral Suspension in Juvenile Rheumatoid Arthritis (JRA/JIA)
NCT00420251	PHASE3	COMPLETED	Efficacy and Safety of Growth Hormone Treatment in Juvenile Idiopathic Arthritis
NCT00511329	PHASE2/PHASE3	TERMINATED	Growth Hormone in Children With Juvenile Rheumatoid Arthritis (JRA) and With Crohn’s Disease
NCT00570934	PHASE3	COMPLETED	Supplementation With Vitamin D, Calcium or Both on Calcium Absorption and Bone Mineral Content in Children With JRA
NCT00642460	PHASE3	COMPLETED	A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)
NCT00652925	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Celecoxib Suspension Compared to Naproxen Suspension in Patients With JRA
NCT00690573	PHASE3	COMPLETED	Safety, Efficacy, and Pharmacokinetics of Adalimumab in Japanese Children With Juvenile Rheumatoid Arthritis
NCT00775437	PHASE3	COMPLETED	Active Juvenile Idiopathic Arthritis (JIA) Compassionate Use
NCT00988221	PHASE3	COMPLETED	A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
METHOTREXATE	4	10
TOCILIZUMAB	4	5
TOFACITINIB	4	5
ABATACEPT	4	4
NAPROXEN	4	4
ENTECAVIR ANHYDROUS	4	3
BARICITINIB	4	2
ETANERCEPT	4	2
FILGOTINIB	4	2
MELOXICAM	4	2
SARILUMAB	4	2
UPADACITINIB	4	2
ADALIMUMAB	4	1
CALCIUM	4	1
CALCIUM CARBONATE	4	1
CANAKINUMAB	4	1
CELECOXIB	4	1
ELASOMERAN	4	1
FILGRASTIM	4	1
GIVINOSTAT	4	1
HYDROXYUREA	4	1
IBUPROFEN	4	1
LEFLUNOMIDE	4	1
RILONACEPT	4	1
SOMATROPIN	4	1
SULFASALAZINE	4	1
TOZINAMERAN	4	1
TRIAMCINOLONE HEXACETONIDE	4	1
GAMOLENIC ACID	3	1
UBIDECARENONE	3	1