Sarcoidosis

Summary

Sarcoidosis (MONDO:0019338) is a disease (an umbrella term covering 8 Mondo subtypes) with 72 cohort genes (284 GWAS associations across 41 studies) and 193 clinical trials. The dominant Reactome pathway is Interferon gamma signaling (11 cohort genes). Top therapeutic interventions include corticotropin, cravacitinib, and bosentan.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 72
• GWAS associations: 284
• Phenotypes (HPO): 77
• Clinical trials: 193

Clinical features

Epidemiology

Prevalence records

34 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000		Worldwide	Validated
Point prevalence	1-5 / 10 000	20	Europe	Validated
Annual incidence	1-9 / 100 000	3.3	Croatia	Validated
Annual incidence	1-9 / 100 000	5	United Kingdom	Validated
Annual incidence	1-9 / 100 000	4.5	Spain	Validated
Annual incidence	1-9 / 100 000	4.68	Denmark	Validated
Annual incidence	1-9 / 100 000	7	Switzerland	Validated
Annual incidence	1-9 / 100 000	1.07	Greece	Validated
Annual incidence	1-9 / 100 000	3.84	Iceland	Validated
Annual incidence	1-9 / 100 000	4	Czech Republic	Validated
Annual incidence	1-9 / 100 000	5.35	Australia	Validated
Annual incidence	1-9 / 100 000	1.01	Japan	Validated
Annual incidence	1-9 / 1 000 000	0.125	Korea, Republic of	Validated
Annual incidence	1-9 / 1 000 000	0.56	Singapore	Validated
Annual incidence	1-9 / 100 000	4.9	France	Validated
Annual incidence	1-5 / 10 000	11.5	Sweden	Validated
Annual incidence	1-5 / 10 000	14.4	Norway	Validated
Annual incidence	1-9 / 100 000	2.3	Guadeloupe	Validated
Annual incidence	1-9 / 1 000 000	0.4	Uruguay	Validated
Point prevalence	6-9 / 10 000	60	United States	Validated

Signs & symptoms

Clinical features (HPO)

77 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000554	Uveitis	Frequent (30-79%)
HP:0001386	Joint swelling	Frequent (30-79%)
HP:0001410	Decreased liver function	Frequent (30-79%)
HP:0001824	Weight loss	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001882	Leukopenia	Frequent (30-79%)
HP:0001945	Fever	Frequent (30-79%)
HP:0002088	Abnormal lung morphology	Frequent (30-79%)
HP:0002094	Dyspnea	Frequent (30-79%)
HP:0002103	Abnormality of the pleura	Frequent (30-79%)
HP:0002202	Pleural effusion	Frequent (30-79%)
HP:0003011	Abnormality of the musculature	Frequent (30-79%)
HP:0011121	Abnormal skin morphology	Frequent (30-79%)
HP:0012219	Erythema nodosum	Frequent (30-79%)
HP:0012378	Fatigue	Frequent (30-79%)
HP:0012735	Cough	Frequent (30-79%)
HP:0100749	Chest pain	Frequent (30-79%)
HP:0100828	Increased T cell count	Frequent (30-79%)
HP:0200036	Skin nodule	Frequent (30-79%)
HP:0000518	Cataract	Occasional (5-29%)
HP:0000618	Blindness	Occasional (5-29%)
HP:0000620	Dacryocystitis	Occasional (5-29%)
HP:0000787	Nephrolithiasis	Occasional (5-29%)
HP:0000873	Diabetes insipidus	Occasional (5-29%)
HP:0000953	Hyperpigmentation of the skin	Occasional (5-29%)
HP:0001010	Hypopigmentation of the skin	Occasional (5-29%)
HP:0001097	Keratoconjunctivitis sicca	Occasional (5-29%)
HP:0001369	Arthritis	Occasional (5-29%)
HP:0001399	Hepatic failure	Occasional (5-29%)
HP:0001409	Portal hypertension	Occasional (5-29%)
HP:0001482	Subcutaneous nodule	Occasional (5-29%)
HP:0001596	Alopecia	Occasional (5-29%)
HP:0001903	Anemia	Occasional (5-29%)
HP:0001970	Tubulointerstitial nephritis	Occasional (5-29%)
HP:0002097	Emphysema	Occasional (5-29%)
HP:0002107	Pneumothorax	Occasional (5-29%)
HP:0002110	Bronchiectasis	Occasional (5-29%)
HP:0002150	Hypercalciuria	Occasional (5-29%)
HP:0002206	Pulmonary fibrosis	Occasional (5-29%)
HP:0002240	Hepatomegaly	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0002733	Abnormality of the lymph nodes	Occasional (5-29%)
HP:0002781	Upper airway obstruction	Occasional (5-29%)
HP:0002921	Abnormality of the cerebrospinal fluid	Occasional (5-29%)
HP:0002922	Increased CSF protein concentration	Occasional (5-29%)
HP:0003072	Hypercalcemia	Occasional (5-29%)
HP:0003701	Proximal muscle weakness	Occasional (5-29%)
HP:0004756	Ventricular tachycardia	Occasional (5-29%)
HP:0007734	Enlarged lacrimal glands	Occasional (5-29%)
HP:0009830	Peripheral neuropathy	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sarcoidosis
Mondo ID	MONDO:0019338
MeSH	D012507
Orphanet	797
DOID	DOID:11335
ICD-10-CM	D86
ICD-11	330792642
NCIT	C34995
SNOMED CT	31541009
UMLS	C0036202
MedGen	48554
GARD	0007607
MedDRA	10039486
NORD	1690
Is cancer (heuristic)	no

Also known as: Besnier-Boeck-Schaumann disease · besnier-Boeck-Schaumann syndrome · Boeck sarcoid · Boeck’s sarcoid · Boeck’s sarcoidosis · Darier-Roussy sarcoid · sarcoid · sarcoidosis

Data availability: 284 GWAS associations (41 studies) · 12 cell lines.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › autoinflammatory syndrome › sarcoidosis

Related subtypes (36): cherubism, chronic recurrent multifocal osteomyelitis, Pelger-Huet-like anomaly and episodic fever with abdominal pain, pyogenic arthritis-pyoderma gangrenosum-acne syndrome, psoriasis 14, pustular, autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation, periodic fever syndrome, infantile onset panniculitis with uveitis and systemic granulomatosis, idiopathic recurrent pericarditis, pyoderma gangrenosum-acne-suppurative hidradenitis syndrome, neonatal inflammatory skin and bowel disease, magic syndrome, autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis, Schnitzler syndrome, PFAPA syndrome, pyoderma gangrenosum, SAPHO syndrome, adult-onset Still disease, systemic-onset juvenile idiopathic arthritis, VEXAS syndrome, autoinflammatory syndrome, familial, Behcet-like, CEBPE-associated autoinflammation-immunodeficiency-neutrophil dysfunction syndrome, type 1 interferonopathy, autoinflammatory disease, X-linked, autoinflammatory syndrome with immunodeficiency, early-onset pulmonary and cutaneous vasculitis, autoinflammatory syndrome due to TBK1 deficiency, F12-associated cold autoinflammatory syndrome, neonatal-onset severe multisystemic autoinflammatory disease with increased IL18, SAMD9L-associated autoinflammatory syndrome, autoinflammatory syndrome of childhood, autoinflammatory disease, systemic, with vasculitis, granulomatous autoinflammatory syndrome of childhood, autoinflammatory disease, multisystem, with immune dysregulation, X-linked, PAPASH syndrome, Sharpin-related autoinflammatory syndrome

Subtypes (8): cardiac sarcoidosis, pulmonary sarcoidosis, hypercalcemic sarcoidosis, skin sarcoidosis, uveoparotid fever, Blau syndrome, Löfgren syndrome, neurosarcoidosis

Genetics & variants

GWAS landscape

284 GWAS associations across 41 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12195589	4e-116	HLA-DRB9 - HLA-DRB5	T	0.67
rs3130288	4e-66	ATF6B	A	4.16
rs11202051	6e-58	ANXA11	A	0.78
rs1049550	9e-53	ANXA11	?
rs9271701	2e-39	HLA-DRB1 - HLA-DQA1	T	0.37
rs34859217	2e-36	ZNF70P1 - HTATSF1P1	?
rs2187668	5e-36	HLA-DQA1	A	3.4
rs1265757	1e-33	TSBP1-AS1, TSBP1	A
rs3135394	3e-33	HLA-DRA	G
rs389884	1e-32	WHR1	G
rs1964995	3e-32	HLA-DRB9 - HLA-DRB5	A	1.67
rs915652	4e-32	VARS1	A
chr6:32632783	1e-31		A	0.46
rs3117582	1e-30	APOM, BAG6	C
rs1140310	1e-27	HLA-DQB1	A	0.67
rs2233974	8e-27	C6orf15	C
rs2024825	9e-27	C1orf141	T	1.26
rs3130662	1e-25	HCG20	A
rs2524067	1e-25	USP8P1	G
rs886420	2e-24	GTF2H4	A
rs3184504	1e-23	ATXN2, SH2B3	T	1.17
rs653178	1e-23	ATXN2	?
rs663743	2e-23	CCDC88B	?
rs3130141	4e-23	MICC - TMPOP1	A
rs1480380	6e-23	HLA-DMB - HLA-DMA	A
rs4766578	3e-22	ATXN2	A	0.85
rs34017352	4e-22	C1orf141	A	0.63
chr6:32538333	6e-21		T	0.65
rs8321	1e-20	POLR1HASP, POLR1HASP, POLR1H	C
rs9257809	1e-20	OR5V1	G

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90832116	Ricci A	2025	7,559	1,361,726	Genome-wide association for sarcoidosis identifies novel risk loci and genetic heritability in African and European ancestries: a meta-analysis from the Finngen, Million Veteran Program, UK Biobank, and Biobank Japan datasets.
GCST90832118	Ricci A	2025	7,559	1,361,726	Genome-wide association for sarcoidosis identifies novel risk loci and genetic heritability in African and European ancestries: a meta-analysis from the Finngen, Million Veteran Program, UK Biobank, and Biobank Japan datasets.
GCST90503482	Yuan S	2025	7,554	1,367,006	GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis.
GCST90503483	Yuan S	2025	7,554	1,367,006	GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis.
GCST005563	Liu JZ	2013	6,333	106,357	Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis.
GCST90503484	Yuan S	2025	2,201	159,861	GWAS identifies genetic loci, lifestyle factors and circulating biomarkers that are risk factors for sarcoidosis.
GCST90832117	Ricci A	2025	1,880	126,411	Genome-wide association for sarcoidosis identifies novel risk loci and genetic heritability in African and European ancestries: a meta-analysis from the Finngen, Million Veteran Program, UK Biobank, and Biobank Japan datasets.
GCST90473148	UK Biobank Whole-Genome Sequencing Consortium	2025	1,861	456,579	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90476192	Verma A	2024	1,827	119,828	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480462	Verma A	2024	1,827	119,828	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	7
Tier 3: regulatory	0
Tier 4: intronic/intergenic	39

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	25
intergenic_variant	6
missense_variant	4
non_coding_transcript_exon_variant	4
5_prime_UTR_variant	3
unknown	3
3_prime_UTR_variant	3
synonymous_variant	1
splice_acceptor_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12195589	6	32476807	C>G,T	0.44	intron_variant	HLA-DRB9 - HLA-DRB5	4e-116	Tier 4: intronic/intergenic
rs3130288	6	32128224	C>A,G,T	0.345	5_prime_UTR_variant	ATF6B	4e-66	Tier 2: splice/UTR
rs11202051	10	80193615	A>G	0.41	intron_variant	ANXA11	6e-58	Tier 4: intronic/intergenic
rs1049550	10	80166946	G>A,C,T	0.05	missense_variant	ANXA11	9e-53	Tier 1: coding
rs9271701	6	32625422	T>A,C,G	0.266	intergenic_variant	HLA-DRB1 - HLA-DQA1	2e-39	Tier 4: intronic/intergenic
rs34859217	6	33228620	C>A,T	0.05	intergenic_variant	ZNF70P1 - HTATSF1P1	2e-36	Tier 4: intronic/intergenic
rs2187668	6	32638107	C>A,G,T	0.359	intron_variant	HLA-DQA1	5e-36	Tier 4: intronic/intergenic
rs1265757	6	32334605	C>G,T	0.343	intron_variant	TSBP1-AS1, TSBP1	1e-33	Tier 4: intronic/intergenic
rs3135394	6	32440720	A>G,T	0.344	intron_variant	HLA-DRA	3e-33	Tier 4: intronic/intergenic
rs389884	6	31973120	A>G,T	0.342	intron_variant	WHR1	1e-32	Tier 4: intronic/intergenic
rs1964995	6	32481634	T>A,C,G	0.28	intron_variant	HLA-DRB9 - HLA-DRB5	3e-32	Tier 4: intronic/intergenic
rs915652	6	31781365	G>A,C	0.337	intron_variant	VARS1	4e-32	Tier 4: intronic/intergenic
chr6:32632783				0.267			1e-31	Tier 4: intronic/intergenic
rs3117582	6	31652743	T>A,G	0.34	5_prime_UTR_variant	APOM, BAG6	1e-30	Tier 2: splice/UTR
rs1140310	6	32665006	A>C,T	0.27	synonymous_variant	HLA-DQB1	1e-27	Tier 4: intronic/intergenic
rs2233974	6	31112239	C>A,G	0.377	missense_variant	C6orf15	8e-27	Tier 1: coding
rs2024825	1	67132294	T>A,C,G	0.17	intron_variant	C1orf141	9e-27	Tier 4: intronic/intergenic
rs3130662	6	30746031	C>A	0.334	intron_variant	HCG20	1e-25	Tier 4: intronic/intergenic
rs2524067	6	31278044	A>C,G,T	0.353	non_coding_transcript_exon_variant	USP8P1	1e-25	Tier 4: intronic/intergenic
rs886420	6	30911859	C>G,T	0.311	intron_variant	GTF2H4	2e-24	Tier 4: intronic/intergenic
rs3184504	12	111446804	T>A,C,G	0.41	missense_variant	ATXN2, SH2B3	1e-23	Tier 1: coding
rs653178	12	111569952	C>A,G,T	0.05	intron_variant	ATXN2	1e-23	Tier 4: intronic/intergenic
rs663743	11	64340263	G>A,T	0.05	5_prime_UTR_variant	CCDC88B	2e-23	Tier 2: splice/UTR
rs3130141	6	30464400	C>A,T	0.283	non_coding_transcript_exon_variant	MICC - TMPOP1	4e-23	Tier 4: intronic/intergenic
rs1480380	6	32945469	C>T	0.252	intron_variant	HLA-DMB - HLA-DMA	6e-23	Tier 4: intronic/intergenic
rs4766578	12	111466567	T>A	0.46	intron_variant	ATXN2	3e-22	Tier 4: intronic/intergenic
rs34017352	1	67132522	A>C,G	0.02	intron_variant	C1orf141	4e-22	Tier 4: intronic/intergenic
chr6:32538333				0.382			6e-21	Tier 4: intronic/intergenic
rs8321	6	30064745	A>C,T	0.243	3_prime_UTR_variant	POLR1HASP, POLR1HASP, POLR1H	1e-20	Tier 2: splice/UTR
rs9257809	6	29388554	A>G,T	0.233	intron_variant	OR5V1	1e-20	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 35 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
BTNL2	BTNL2	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN2	Orphanet:803	Amyotrophic lateral sclerosis
ATXN2	Orphanet:98756	Spinocerebellar ataxia type 2
BTNL2	Orphanet:797	Sarcoidosis
TNXB	Orphanet:230839	Classical-like Ehlers-Danlos syndrome type 1
TNXB	Orphanet:289365	Familial vesicoureteral reflux
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
IL23R	Orphanet:117	Behçet disease
SH2B3	Orphanet:3318	Essential thrombocythemia
SH2B3	Orphanet:391366	Growth retardation-mild developmental delay-chronic hepatitis syndrome
TAP2	Orphanet:34592	Immunodeficiency by defective expression of MHC class I
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
HLA-C	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
HLA-DPB1	Orphanet:133	Chronic beryllium disease
HLA-DPB1	Orphanet:900	Granulomatosis with polyangiitis
HLA-DQA1	Orphanet:391490	Adult-onset myasthenia gravis
HLA-DQA1	Orphanet:930	Idiopathic achalasia
HLA-DQB1	Orphanet:2073	Narcolepsy type 1
HLA-DQB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DQB1	Orphanet:703	Bullous pemphigoid
HLA-DQB1	Orphanet:83465	Narcolepsy type 2
HLA-DQB1	Orphanet:930	Idiopathic achalasia
HLA-DRA	Orphanet:505	Graham Little-Piccardi-Lassueur syndrome
ANXA11	Orphanet:803	Amyotrophic lateral sclerosis
IL12B	Orphanet:319558	Mendelian susceptibility to mycobacterial diseases due to complete IL12B deficiency
IL12B	Orphanet:3287	Takayasu arteritis
KCNK4	Orphanet:598603	Facial dysmorphism-hypertrichosis-epilepsy-intellectual disability/developmental delay-gingival overgrowth syndrome
MANBA	Orphanet:118	Beta-mannosidosis
TRIM27	Orphanet:146	Differentiated thyroid carcinoma

Cohort genes → proteins

72 cohort genes, 71 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	72

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
CCL24	HGNC:10623	ENSG00000106178	O00175	C-C motif chemokine 24	gwas
WHR1	HGNC:11398	ENSG00000204344	P49842	Winged helix repair factor 1	gwas
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
TNXB	HGNC:11976	ENSG00000168477	P22105	Tenascin-X	gwas
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gwas
VARS1	HGNC:12651	ENSG00000204394	P26640	Valine–tRNA ligase	gwas
ZNF165	HGNC:12953	ENSG00000197279	P49910	Zinc finger protein 165	gwas
TRIM26	HGNC:12962	ENSG00000234127	Q12899	Tripartite motif-containing protein 26	gwas
ZNF184	HGNC:12975	ENSG00000096654	Q99676	Zinc finger protein 184	gwas
ZSCAN12	HGNC:13172	ENSG00000158691	O43309	Zinc finger and SCAN domain-containing protein 12	gwas
POLR1H	HGNC:13182	ENSG00000066379	Q9P1U0	DNA-directed RNA polymerase I subunit RPA12	gwas
ZKSCAN3	HGNC:13853	ENSG00000189298	Q9BRR0	Zinc finger protein with KRAB and SCAN domains 3	gwas
APOM	HGNC:13916	ENSG00000204444	O95445	Apolipoprotein M	gwas
BAG6	HGNC:13919	ENSG00000204463	P46379	Large proline-rich protein BAG6	gwas
TSBP1	HGNC:13922	ENSG00000204296	Q5SRN2	Testis-expressed basic protein 1	gwas
C6orf15	HGNC:13927	ENSG00000204542	Q6UXA7	Uncharacterized protein C6orf15	gwas
PRRT1	HGNC:13943	ENSG00000204314	Q99946	Proline-rich transmembrane protein 1	gwas
GPSM3	HGNC:13945	ENSG00000213654	Q9Y4H4	G-protein-signaling modulator 3	gwas
FKBPL	HGNC:13949	ENSG00000204315	Q9UIM3	FK506-binding protein-like	gwas
MAS1L	HGNC:13961	ENSG00000204687	P35410	Mas-related G-protein coupled receptor MRG	gwas
OR12D3	HGNC:13963	ENSG00000112462	Q9UGF7	Olfactory receptor 12D3	gwas
FAM117B	HGNC:14440	ENSG00000138439	Q6P1L5	Protein FAM117B	gwas
NCR3	HGNC:19077	ENSG00000204475	O14931	Natural cytotoxicity triggering receptor 3	gwas
IL23R	HGNC:19100	ENSG00000162594	Q5VWK5	Interleukin-23 receptor	gwas
PLAC9	HGNC:19255	ENSG00000189129	Q5JTB6	Placenta-specific protein 9	gwas
LINC01556	HGNC:21195	ENSG00000204709	Q5JQF7	Putative uncharacterized protein encoded by LINC01556	gwas
HCG4	HGNC:21241	ENSG00000176998		HLA complex group 4	gwas
RPP21	HGNC:21300	ENSG00000241370	Q9H633	Ribonuclease P protein subunit p21	gwas
TMEM120A	HGNC:21697	ENSG00000189077	Q9BXJ8	Transmembrane protein 120A	gwas
TSPAN14	HGNC:23303	ENSG00000108219	Q8NG11	Tetraspanin-14	gwas
DYDC2	HGNC:23468	ENSG00000133665	Q96IM9	DPY30 domain-containing protein 2	gwas
ATF6B	HGNC:2349	ENSG00000213676	Q99941	Cyclic AMP-dependent transcription factor ATF-6 beta	gwas
GPR137	HGNC:24300	ENSG00000173264	Q96N19	Integral membrane protein GPR137	gwas
CCDC88B	HGNC:26757	ENSG00000168071	A6NC98	Coiled-coil domain-containing protein 88B	gwas
DDR1	HGNC:2730	ENSG00000204580	Q08345	Epithelial discoidin domain-containing receptor 1	gwas
PRXL2A	HGNC:28651	ENSG00000122378	Q9BRX8	Peroxiredoxin-like 2A	gwas
C10orf67	HGNC:28716	ENSG00000179133	Q8IYJ2	Uncharacterized protein C10orf67, mitochondrial	gwas
SH2B3	HGNC:29605	ENSG00000111252	Q9UQQ2	SH2B adapter protein 3	gwas
AGER	HGNC:320	ENSG00000204305	Q15109	Advanced glycosylation end product-specific receptor	gwas
AIF1	HGNC:352	ENSG00000204472	P55008	Allograft inflammatory factor 1	gwas
TAP2	HGNC:44	ENSG00000204267	Q03519	Antigen peptide transporter 2	gwas
GTF2H4	HGNC:4658	ENSG00000213780	Q92759	General transcription factor IIH subunit 4	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
HLA-C	HGNC:4933	ENSG00000204525	P10321	HLA class I histocompatibility antigen, C alpha chain	gwas
HLA-DMA	HGNC:4934	ENSG00000204257	P28067	HLA class II histocompatibility antigen, DM alpha chain	gwas
HLA-DMB	HGNC:4935	ENSG00000242574	P28068	HLA class II histocompatibility antigen, DM beta chain	gwas
HLA-DOB	HGNC:4937	ENSG00000241106	P13765	HLA class II histocompatibility antigen, DO beta chain	gwas
HLA-DPB1	HGNC:4940	ENSG00000223865	P04440	HLA class II histocompatibility antigen, DP beta 1 chain	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
CCL24	C-C motif chemokine 24	Chemotactic for resting T-lymphocytes, and eosinophils.
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.
TNXB	Tenascin-X	Appears to mediate interactions between cells and the extracellular matrix.
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.
VARS1	Valine–tRNA ligase	Catalyzes the attachment of valine to tRNA(Val).
ZNF165	Zinc finger protein 165	May be involved in transcriptional regulation.
TRIM26	Tripartite motif-containing protein 26	E3 ubiquitin-protein ligase which regulates the IFN-beta production and antiviral response downstream of various DNA-encoded pattern-recognition receptors (PRRs).
ZNF184	Zinc finger protein 184	May be involved in transcriptional regulation.
ZSCAN12	Zinc finger and SCAN domain-containing protein 12	May be involved in transcriptional regulation.
POLR1H	DNA-directed RNA polymerase I subunit RPA12	Core component of RNA polymerase I (Pol I), a DNA-dependent RNA polymerase which synthesizes ribosomal RNA precursors using the four ribonucleoside triphosphates as substrates.
ZKSCAN3	Zinc finger protein with KRAB and SCAN domains 3	Transcriptional factor that binds to the consensus sequence 5’-[GT][AG][AGT]GGGG-3’ and acts as a repressor of autophagy.
APOM	Apolipoprotein M	Probably involved in lipid transport.
BAG6	Large proline-rich protein BAG6	ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins.
PRRT1	Proline-rich transmembrane protein 1	Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function.
GPSM3	G-protein-signaling modulator 3	Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins.
FKBPL	FK506-binding protein-like	May be involved in response to X-ray.
OR12D3	Olfactory receptor 12D3	Odorant receptor.
NCR3	Natural cytotoxicity triggering receptor 3	Cell membrane receptor of natural killer/NK cells that is activated by binding of extracellular ligands including BAG6 and NCR3LG1.
IL23R	Interleukin-23 receptor	Associates with IL12RB1 to form the interleukin-23 receptor.
RPP21	Ribonuclease P protein subunit p21	Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5’-ends.
TMEM120A	Transmembrane protein 120A	Multifunctional protein involved in mechanosensation, and plays an essential role in lipid metabolism and adipocyte differentiation.
TSPAN14	Tetraspanin-14	Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10.
ATF6B	Cyclic AMP-dependent transcription factor ATF-6 beta	Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 beta), which is embedded in the endoplasmic reticulum membrane.
GPR137	Integral membrane protein GPR137	Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.
CCDC88B	Coiled-coil domain-containing protein 88B	Acts as a positive regulator of T-cell maturation and inflammatory function.
DDR1	Epithelial discoidin domain-containing receptor 1	Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell prolifer…
PRXL2A	Peroxiredoxin-like 2A	Involved in redox regulation of the cell.
SH2B3	SH2B adapter protein 3	Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
AGER	Advanced glycosylation end product-specific receptor	Cell surface pattern recognition receptor that senses endogenous stress signals with a broad ligand repertoire including advanced glycation end products, S100 proteins, high-mobility group box 1 protein/HMGB1, amyloid beta/APP oligomers, n…
AIF1	Allograft inflammatory factor 1	Actin-binding protein that enhances membrane ruffling and RAC activation.
TAP2	Antigen peptide transporter 2	ABC transporter associated with antigen processing.
GTF2H4	General transcription factor IIH subunit 4	Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription…
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
HLA-C	HLA class I histocompatibility antigen, C alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule with an important role in reproduction and antiviral immunity.
HLA-DMA	HLA class II histocompatibility antigen, DM alpha chain	Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides.
HLA-DMB	HLA class II histocompatibility antigen, DM beta chain	Plays a critical role in catalyzing the release of class II-associated invariant chain peptide (CLIP) from newly synthesized MHC class II molecules and freeing the peptide binding site for acquisition of antigenic peptides.
HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells.
HLA-DPB1	HLA class II histocompatibility antigen, DP beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQA2	HLA class II histocompatibility antigen, DQ alpha 2 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
HLA-DRB5	HLA class II histocompatibility antigen, DR beta 5 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-E	HLA class I histocompatibility antigen, alpha chain E	Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination.
HLA-G	HLA class I histocompatibility antigen, alpha chain G	Non-classical major histocompatibility class Ib molecule involved in immune regulatory processes at the maternal-fetal interface.
ANXA11	Annexin A11	Binds specifically to calcyclin in a calcium-dependent manner.
IER3	Radiation-inducible immediate-early gene IEX-1	May play a role in the ERK signaling pathway by inhibiting the dephosphorylation of ERK by phosphatase PP2A-PPP2R5C holoenzyme.
IL12B	Interleukin-12 subunit beta	Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.

Protein-family classification

Druggable: 33 · Difficult: 11 · Unknown: 28 · Druggable fraction: 0.46

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
Antibody/Immunoglobulin	21	8.5×	2e-13
GPCR	5	1.7×	0.819
Ion channel	1	1.6×	0.999
Transporter	1	1.1×	0.999
Transcription factor	8	0.9×	0.999
Kinase	2	0.8×	0.999
Scaffold/PPI	3	0.7×	0.999
Other/Unknown	28	0.7×	0.999
Enzyme (other)	3	0.5×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
CCL24	Other/Unknown	no		Chemokine_IL8-like_dom, Interleukin_8-like_sf, Chemokine_b/g/d
WHR1	Other/Unknown	no		STK19-like
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
TNXB	Antibody/Immunoglobulin	yes		EGF, Fibrinogen_a/b/g_C_dom, FN3_dom
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
VARS1	Enzyme (other)	yes	6.1.1.9	aa-tRNA-synth_I_CS, aa-tRNA-synth_Ia, Valyl-tRNA_ligase
ZNF165	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
TRIM26	Transcription factor	no		Znf_B-box, Znf_RING, B30.2/SPRY
ZNF184	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
ZSCAN12	Transcription factor	no		SCAN_dom, Znf_C2H2_type, Znf_C2H2_sf
POLR1H	Transcription factor	no		Znf_TFIIS, Rpa12/Rpb9/Rpc10/TFS, DNA-dir_RNA_pol-M_15_CS
ZKSCAN3	Transcription factor	no		KRAB, SCAN_dom, Znf_C2H2_type
APOM	Other/Unknown	no		Calycin, ApoM
BAG6	Other/Unknown	no		Ubiquitin-like_dom, Ubiquitin_CS, BAG6
TSBP1	Other/Unknown	no		TSBP1
C6orf15	Other/Unknown	no		C6orf15
PRRT1	Other/Unknown	no		CD225/Dispanin_fam, CD225/Dispanin
GPSM3	Other/Unknown	no		GoLoco_motif, TPR-like_helical_dom_sf, GPSM3
FKBPL	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, FKBP4/5/8-like
MAS1L	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, MRGPCRFAMILY
OR12D3	GPCR	yes		GPCR_Rhodpsn, Olfact_rcpt, GPCR_Rhodpsn_7TM
FAM117B	Other/Unknown	no		Glcci1/FAM117
NCR3	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
IL23R	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
PLAC9	Other/Unknown	no		PLAC9
LINC01556	Other/Unknown	no
HCG4	Other/Unknown	no
RPP21	Enzyme (other)	yes	3.1.26.5	Rpr2/Snm1/Rpp21
TMEM120A	Other/Unknown	no		TMEM120A/B
TSPAN14	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
DYDC2	Other/Unknown	no		Dpy-30_motif, Sdc1/DPY30, DYDC-like_DD
ATF6B	Transcription factor	no		bZIP, bZIP_sf, ATF_bZIP_TF
GPR137	Other/Unknown	no		GPR137
CCDC88B	Other/Unknown	no		CH_dom_sf, HOOK_N
DDR1	Kinase	yes	2.7.10.1	FA58C, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
PRXL2A	Other/Unknown	no		PXL2A/B/C
C10orf67	Other/Unknown	no		DUF4709, DUF4724, C10orf67-like
SH2B3	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
AGER	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_sub2, Ig_sub
AIF1	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, AIF1/AIF1L
TAP2	Transporter	yes	7.4.2.14	ABC_transporter-like_ATP-bd, AAA+_ATPase, Tap2/ABCB3
GTF2H4	Other/Unknown	no		TFIIH_p52/Tfb2, Tfb2_C
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
HLA-C	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig_C1-set, Ig-like_dom
HLA-DMA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DMB	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DOB	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DPB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	3
moderate (6-20)	1
broad (>20)	68
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	19
monocyte	11
leukocyte	10
primordial germ cell in gonad	8
male germ line stem cell (sensu Vertebrata) in testis	8
spleen	6
lymph node	6
right lung	6
vermiform appendix	6
colonic epithelium	5
left testis	5
right testis	5
blood	5
ventricular zone	4
testis	4
mucosa of transverse colon	4
lower esophagus mucosa	4
right uterine tube	4
rectum	3
sural nerve	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN2	286	ubiquitous	marker	buccal mucosa cell, colonic epithelium, olfactory bulb
CCL24	133	tissue_specific	yes	rectum, spleen, small intestine Peyer’s patch
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
TNXB	134	ubiquitous	marker	apex of heart, right adrenal gland cortex, right adrenal gland
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
VARS1	134	ubiquitous	marker	right testis, left testis, testis
ZNF165	203	broad	marker	sperm, male germ cell, primordial germ cell in gonad
TRIM26	134	ubiquitous	yes	granulocyte, leukocyte, duodenum
ZNF184	260	ubiquitous	yes	Brodmann (1909) area 23, sperm, hair follicle
ZSCAN12	218	ubiquitous	yes	primordial germ cell in gonad, ventricular zone, ganglionic eminence
POLR1H	133	ubiquitous	marker	granulocyte, mucosa of transverse colon, primordial germ cell in gonad
ZKSCAN3	193	ubiquitous	yes	primordial germ cell in gonad, sperm, hair follicle
APOM	132	ubiquitous	marker	right lobe of liver, liver, adult mammalian kidney
BAG6	144	ubiquitous	marker	right testis, left testis, testis
TSBP1	58	tissue_specific	yes	left testis, testis, right testis
C6orf15	31	tissue_specific	yes	skin of leg, zone of skin, skin of abdomen
PRRT1	134	broad	yes	right hemisphere of cerebellum, cerebellar hemisphere, cerebellum
GPSM3	133	ubiquitous	marker	granulocyte, blood, spleen
FKBPL	132	ubiquitous	yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, lower esophagus mucosa
MAS1L	58		yes	smooth muscle tissue, gall bladder, rectum
OR12D3	1		yes	male germ line stem cell (sensu Vertebrata) in testis, colonic epithelium, ventricular zone
FAM117B	240	ubiquitous	marker	cortical plate, gingiva, gingival epithelium
NCR3	118	tissue_specific	marker	granulocyte, blood, lymph node
IL23R	39	tissue_specific	marker	secondary oocyte, oocyte, adrenal tissue
PLAC9	212	broad	marker	layer of synovial tissue, synovial joint, right coronary artery
LINC01556	109		yes	placenta, skeletal muscle tissue, bone marrow
HCG4	164	broad	yes	amniotic fluid, adenohypophysis, pituitary gland
RPP21	133	ubiquitous	marker	muscle layer of sigmoid colon, lower esophagus mucosa, lower esophagus
TMEM120A	238	ubiquitous	marker	right testis, left testis, right adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 74.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VARS1	5,848
AIF1	4,440
TYK2	3,932
TRIM27	3,746
ATXN2	3,360
HLA-DRA	3,244
HLA-B	3,209
PSMB9	2,896
PRDX5	2,843
NOTCH4	2,670

Intra-cohort edges

A	B	Sources
AIF1	NFKBIL1	string_interaction
ANXA11	BTNL2	string_interaction
ANXA11	C10orf67	string_interaction
ANXA11	PLAC9	string_interaction
APOM	HLA-DQB1	biogrid_interaction, intact
ATF6B	FKBPL	string_interaction
ATF6B	HLA-E	biogrid_interaction
ATF6B	TNXB	string_interaction
ATXN2	SH2B3	string_interaction
BAG6	IER3	intact
BAG6	NCR3	intact, string_interaction
BTNL2	C10orf67	string_interaction
BTNL2	HLA-DQA2	string_interaction
BTNL2	HLA-DQB1	intact
BTNL2	HLA-DRA	string_interaction
BTNL2	HLA-DRB5	string_interaction
BTNL2	TSBP1	string_interaction
C10orf67	CCDC88B	string_interaction
C10orf67	FAM117B	string_interaction
CCDC88B	GPR137	string_interaction
CCDC88B	KCNK4	string_interaction
DYDC2	TSPAN14	string_interaction
FKBPL	GPSM3	string_interaction
FKBPL	PRRT1	string_interaction
GPR137	KCNK4	string_interaction
GPSM3	PRRT1	string_interaction
GTF2H4	OR12D3	string_interaction
HLA-B	HLA-C	biogrid_interaction, intact
HLA-B	HLA-DMA	string_interaction
HLA-B	HLA-DMB	string_interaction
HLA-B	HLA-DOB	string_interaction
HLA-B	HLA-DQA2	string_interaction
HLA-B	HLA-E	biogrid_interaction, intact
HLA-B	HLA-G	biogrid_interaction, intact
HLA-B	NFKBIL1	string_interaction
HLA-B	TAP2	string_interaction
HLA-C	HLA-DQB1	intact
HLA-C	HLA-DRB5	biogrid_interaction
HLA-C	HLA-E	biogrid_interaction, intact
HLA-C	HLA-G	biogrid_interaction
HLA-C	NCR3	biogrid_interaction
HLA-C	PRXL2A	intact
HLA-DMA	HLA-DMB	intact, string_interaction
HLA-DMA	HLA-DOB	intact, string_interaction
HLA-DMA	HLA-DRA	intact
HLA-DMA	HLA-DRB5	string_interaction
HLA-DMB	HLA-DOB	string_interaction
HLA-DMB	HLA-DQA2	string_interaction
HLA-DMB	HLA-DRA	biogrid_interaction, intact, string_interaction
HLA-DMB	PSMB9	string_interaction

Structural data

PDB: 39 · AlphaFold-only: 32 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237
HLA-DRA	P01903	140
TYK2	P29597	52
GTF2H4	Q92759	51
DDR1	Q08345	34
HLA-E	P13747	34
AGER	Q15109	33
HLA-DQA1	P01909	28
TAP2	Q03519	21
IL12B	P29460	20
HLA-C	P10321	13
KCNK4	Q9NYG8	12
PRDX5	P30044	12
BAG6	P46379	10
HLA-DPB1	P04440	10
HLA-DQB1	P01920	10
HLA-G	P17693	10
POLR1H	Q9P1U0	7
PSMB9	P28065	7
BAD	Q92934	6
WHR1	P49842	5
TMEM120A	Q9BXJ8	5
HLA-DMB	P28068	5
NCR3	O14931	4
IL23R	Q5VWK5	4
HLA-DMA	P28067	4
HLA-DRB5	Q30154	4
TNXB	P22105	3
APOM	O95445	3
LTA	P01374	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MANBA	O00462	96.05
HLA-DQA2	P01906	89.29
TRIM27	P14373	89.04
OR2J3	O76001	88.62
PRXL2A	Q9BRX8	88.27
VARS1	P26640	88.12
TSPAN14	Q8NG11	87.89
BTNL2	Q9UIR0	85.97
OR2B3	O76000	85.90
OR12D2	P58182	85.51
TRIM26	Q12899	83.49
OR12D3	Q9UGF7	81.77
PLAC9	Q5JTB6	78.53
NFKBIL1	Q9UBC1	77.75
FKBPL	Q9UIM3	77.00
ZNF184	Q99676	72.56
GPSM3	Q9Y4H4	71.77
C10orf67	Q8IYJ2	71.37
ZSCAN12	O43309	70.20
CCDC88B	A6NC98	70.19
MAS1L	P35410	66.76
GPR137	Q96N19	66.31
IER3	P46695	66.00
SH2B3	Q9UQQ2	63.45
ZKSCAN3	Q9BRR0	60.16
ZNF165	P49910	58.79
ATF6B	Q99941	55.31
LINC01556	Q5JQF7	54.68
FAM117B	Q6P1L5	53.34
PRRT1	Q99946	53.00

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 177. Enrichment computed across 72 evidence-associated genes (50 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 50 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interferon gamma signaling	11	27.6×	2e-11	TRIM26, HLA-B, HLA-C, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA (+3 more)
Translocation of ZAP-70 to Immunological synapse	5	63.4×	1e-06	HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
Phosphorylation of CD3 and TCR zeta chains	5	54.4×	1e-06	HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
Co-inhibition by PD-1	5	51.9×	1e-06	HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
MHC class II antigen presentation	8	14.3×	3e-06	HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
Endosomal/Vacuolar pathway	4	83.0×	3e-06	HLA-B, HLA-C, HLA-E, HLA-G
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	5	39.4×	4e-06	TAP2, HLA-B, HLA-C, HLA-E, HLA-G
Generation of second messenger molecules	5	34.6×	6e-06	HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
ER-Phagosome pathway	6	15.6×	4e-05	TAP2, HLA-B, HLA-C, HLA-E, HLA-G, PSMB9
Interleukin-23 signaling	3	76.1×	1e-04	TYK2, IL23R, IL12B
Interferon alpha/beta signaling	5	15.2×	3e-04	TYK2, HLA-B, HLA-C, HLA-E, HLA-G
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	6	10.5×	3e-04	NCR3, HLA-B, HLA-C, HLA-E, HLA-G, MICB
Downstream TCR signaling	5	12.8×	6e-04	HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DRA, HLA-DRB5
DAP12 interactions	3	28.6×	0.002	HLA-B, HLA-C, HLA-E
SARS-CoV-2 activates/modulates innate and adaptive immune responses	5	8.9×	0.003	TYK2, HLA-B, HLA-C, HLA-E, HLA-G
Interleukin-12 signaling	2	16.3×	0.073	TYK2, IL12B
RNA Polymerase I Transcription Termination	2	13.1×	0.106	POLR1H, GTF2H4
TWIK related potassium channel (TREK)	1	76.1×	0.111	KCNK4
RNA Polymerase I Promoter Clearance	2	11.7×	0.111	POLR1H, GTF2H4
RNA Polymerase I Transcription	2	11.4×	0.111	POLR1H, GTF2H4
Interleukin-4 and Interleukin-13 signaling	3	6.2×	0.111	TYK2, IL23R, IL12B
Negative epigenetic regulation of rRNA expression	2	10.4×	0.127	POLR1H, GTF2H4
Lysosomal oligosaccharide catabolism	1	57.1×	0.128	MANBA
ATF6B (ATF6-beta) activates chaperones	1	57.1×	0.128	ATF6B
Interleukin-10 signaling	2	9.3×	0.137	TYK2, IL12B
RNA Polymerase I Transcription Initiation	2	9.0×	0.142	POLR1H, GTF2H4
Defective LFNG causes SCDO3	1	45.7×	0.142	NOTCH4
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	38.1×	0.164	NOTCH4
Suppression of apoptosis	1	32.6×	0.185	TRIM27
BH3-only proteins associate with and inactivate anti-apoptotic BCL-2 members	1	25.4×	0.229	BAD

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 65 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
peptide antigen assembly with MHC class II protein complex	9	145.8×	6e-16	HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA (+1 more)
positive regulation of T cell activation	10	68.2×	4e-14	CCDC88B, HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1 (+2 more)
antigen processing and presentation of exogenous peptide antigen via MHC class II	9	75.3×	3e-13	HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA (+1 more)
positive regulation of immune response	9	66.7×	8e-13	HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DRA (+1 more)
positive regulation of T cell mediated cytotoxicity	8	62.9×	4e-11	IL23R, TAP2, HLA-B, HLA-C, HLA-DRA, HLA-E, HLA-G, IL12B
adaptive immune response	13	16.9×	5e-11	HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOB, HLA-DPB1, HLA-DQA1, HLA-DQA2 (+5 more)
positive regulation of T cell proliferation	8	31.9×	9e-09	BTNL2, TYK2, IL23R, CCDC88B, AIF1, HLA-DMB, HLA-DPB1, IL12B
immune response	13	9.4×	5e-08	CCL24, TYK2, NCR3, HLA-B, HLA-C, HLA-DQA1, HLA-DQA2, HLA-DQB1 (+5 more)
immune response-activating cell surface receptor signaling pathway	3	259.3×	3e-06	BAG6, NCR3, MICB
positive regulation of natural killer cell proliferation	4	86.4×	5e-06	TYK2, IL23R, HLA-E, IL12B
antigen processing and presentation of endogenous peptide antigen via MHC class Ib	4	79.8×	6e-06	HLA-B, HLA-C, HLA-E, HLA-G
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent	4	79.8×	6e-06	HLA-B, HLA-C, HLA-E, HLA-G
protection from natural killer cell mediated cytotoxicity	3	129.6×	4e-05	HLA-B, HLA-E, HLA-G
positive regulation of memory T cell differentiation	3	86.4×	2e-04	IL23R, HLA-DRA, IL12B
positive regulation of type II interferon production	5	17.3×	3e-04	TYK2, IL23R, HLA-DPB1, IL12B, LTA
positive regulation of T-helper 17 type immune response	3	64.8×	4e-04	TYK2, IL23R, IL12B
positive regulation of interleukin-12 production	4	24.1×	6e-04	IL23R, AGER, HLA-G, IL12B
negative regulation of interleukin-10 production	3	33.8×	0.002	IL23R, AGER, IL12B
positive regulation of activated T cell proliferation	3	31.1×	0.003	IL23R, AGER, IL12B
positive regulation of NK T cell activation	2	103.7×	0.004	IL23R, IL12B
positive regulation of interleukin-17 production	3	27.8×	0.004	TYK2, IL23R, IL12B
interleukin-23-mediated signaling pathway	2	86.4×	0.004	TYK2, IL23R
NK T cell activation	2	86.4×	0.004	BAG6, NCR3
positive regulation of NK T cell proliferation	2	86.4×	0.004	TYK2, IL12B
natural killer cell activation	3	26.8×	0.004	BAG6, NCR3, IL12B
positive regulation of natural killer cell mediated cytotoxicity	3	25.9×	0.004	NCR3, HLA-C, HLA-E
positive regulation of natural killer cell activation	2	64.8×	0.007	HLA-E, IL12B
positive regulation of T-helper 17 cell lineage commitment	2	64.8×	0.007	IL23R, IL12B
positive regulation of natural killer cell cytokine production	2	57.6×	0.008	HLA-E, HLA-G
interleukin-12-mediated signaling pathway	2	57.6×	0.008	TYK2, IL12B

Therapeutics

Drugs indicated for this disease

3 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dexamethasone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Infliximab	Phase 3 (in late-stage trials)
Thalidomide	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Abrocitinib, Adalimumab, Atorvastatin, Azithromycin, Corticotropin, Dapsone, Ethambutol, Golimumab, Metformin, Powdered Cellulose, Rifampin, Rituximab, Sarilumab, Sirolimus, Ustekinumab.

Drug target analysis

Approved (phase 4): 5 · Phase ≥3: 6 · Phased (≥1): 6 · Undrugged: 66

Druggability breadth: 26 of 72 evidence-associated genes (36%) 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
TYK2	FEDRATINIB
DDR1	PONATINIB
PRXL2A	IBRUTINIB
BAD	VENETOCLAX
PSMB9	BORTEZOMIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DDR1	77	4
TYK2	72	4
BAD	8	4
PSMB9	7	4
PRXL2A	1	4
AGER	1	3
ATXN2	0	0
CCL24	0	0
WHR1	0	0
BTNL2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	DDR1, TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
ABROCITINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	DDR1, TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	DDR1, TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	DDR1, TYK2
PEFICITINIB	4	TYK2
CRAVACITINIB	4	TYK2
PAZOPANIB	4	DDR1, TYK2
NINTEDANIB	4	DDR1, TYK2
SUNITINIB	4	DDR1, TYK2
DASATINIB	4	DDR1, TYK2
ERLOTINIB	4	DDR1, TYK2
CRIZOTINIB	4	DDR1, TYK2
MIDOSTAURIN	4	DDR1, TYK2
IMATINIB	4	DDR1, TYK2
PONATINIB	4	DDR1
TIVOZANIB	4	DDR1
LENVATINIB	4	DDR1
SORAFENIB	4	DDR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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

Symbol	Assays	Type breakdown
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
DDR1	422	Binding:422
PSMB9	220	Binding:210, ADMET:7, Functional:3
WHR1	36	Binding:36
BAD	36	Binding:35, Functional:1
AGER	33	Binding:32, Functional:1
KCNK4	18	Binding:18
IL23R	13	Binding:13
MANBA	13	Binding:11, Functional:2
PRDX5	10	Binding:10
VARS1	7	Binding:7
ANXA11	7	Binding:7
TRIM27	6	Binding:6
ATXN2	5	Binding:3, Functional:2
PRXL2A	3	Binding:3
TAP2	3	Binding:3
LTA	3	Binding:3
MAS1L	2	Binding:2
HLA-DQA1	2	Binding:2
NOTCH4	2	Binding:2
BAG6	1	Binding:1
TMEM120A	1	Binding:1
HLA-B	1	Binding:1
HLA-C	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
VARS1	6.1.1.9	valine-tRNA ligase
RPP21	3.1.26.5	ribonuclease P
DDR1	2.7.10.1	receptor protein-tyrosine kinase
TAP2	7.4.2.14, 7.4.2.5	ABC-type antigen peptide transporter, bacterial ABC-type protein transporter
PRDX5	1.11.1.24	thioredoxin-dependent peroxiredoxin

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TYK2	1,083
DDR1	422
PSMB9	220

Pharmacogenomics

Cohort genes with a PharmGKB record: 71; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

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)
FEDRATINIB	4	DDR1, TYK2
RUXOLITINIB	4	TYK2
TOFACITINIB	4	TYK2
UPADACITINIB	4	TYK2
BARICITINIB	4	TYK2
FILGOTINIB	4	TYK2
DEUCRAVACITINIB	4	TYK2
MOMELOTINIB	4	TYK2
AXITINIB	4	DDR1, TYK2
RUXOLITINIB PHOSPHATE	4	TYK2
INFIGRATINIB PHOSPHATE	4	TYK2
INFIGRATINIB	4	TYK2
PACRITINIB	4	DDR1, TYK2
TOFACITINIB CITRATE	4	TYK2
BOSUTINIB	4	DDR1, TYK2
PEFICITINIB	4	TYK2
PAZOPANIB	4	DDR1, TYK2
NINTEDANIB	4	DDR1, TYK2
SUNITINIB	4	DDR1, TYK2
DASATINIB	4	DDR1, TYK2
ERLOTINIB	4	DDR1, TYK2
CRIZOTINIB	4	DDR1, TYK2
MIDOSTAURIN	4	DDR1, TYK2
IMATINIB	4	DDR1, TYK2
PONATINIB	4	DDR1
TIVOZANIB	4	DDR1
LENVATINIB	4	DDR1
SORAFENIB	4	DDR1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	5	TYK2, DDR1, PRXL2A, BAD, PSMB9
B	Phased (≥1) drug, not yet approved	1	AGER
C	Druggable family + PDB, no drug	21	TNXB, NCR3, IL23R, RPP21, TAP2, HLA-B, HLA-C, HLA-DMA, HLA-DMB, HLA-DOB (+11 more)
D	Druggable family + AlphaFold only, no drug	9	BTNL2, VARS1, MAS1L, OR12D3, HLA-DQA2, MANBA, OR12D2, OR2B3, OR2J3
E	Difficult family or no structure, no drug	36	ATXN2, CCL24, WHR1, ZNF165, TRIM26, ZNF184, ZSCAN12, POLR1H, ZKSCAN3, APOM (+26 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TAP2	3	PSMB9
HLA-DOB	0	PSMB9
ATXN2	5	—
CCL24	0	—
WHR1	36	—
BTNL2	0	—
TNXB	0	—
VARS1	7	—
ZNF165	0	—
TRIM26	0	—
ZNF184	0	—
ZSCAN12	0	—
POLR1H	0	—
ZKSCAN3	0	—
APOM	0	—
BAG6	1	—
TSBP1	0	—
C6orf15	0	—
PRRT1	0	—
GPSM3	0	—
FKBPL	0	—
MAS1L	2	—
OR12D3	0	—
FAM117B	0	—
NCR3	0	—
IL23R	13	—
PLAC9	0	—
LINC01556	0	—
HCG4	0	—
RPP21	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 193.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	140
PHASE2	17
PHASE4	14
PHASE2/PHASE3	8
PHASE3	7
PHASE1/PHASE2	3
EARLY_PHASE1	2
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03621553	PHASE4	RECRUITING	Vitamin D Homeostasis in Sarcoidosis
NCT06654934	PHASE4	NOT_YET_RECRUITING	Prednisolone for 12 Versus 6 Months to Treat Pulmonary Sarcoidosis
NCT00361387	PHASE4	COMPLETED	Use of Focalin for Fatigue in Sarcoidosis
NCT00403650	PHASE4	COMPLETED	Inhaled Iloprost for Sarcoidosis-associated Pulmonary Hypertension
NCT00747461	PHASE4	TERMINATED	Interventional Cryotherapy for the Eradication of Benign Airway Disease (ICE the BAD)
NCT01210677	PHASE4	WITHDRAWN	Cardiac Sarcoidosis Response To Steroids Trial
NCT01658280	PHASE4	COMPLETED	Conventional Versus Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Hilar/Mediastinal Lymphadenopathies
NCT01830959	PHASE4	UNKNOWN	Use of Roflumilast to Prevent Exacerbations in Fibrotic Sarcoidosis Patients (REFS)
NCT02188017	PHASE4	UNKNOWN	Acthar Gel for Chronic Pulmonary Sarcoidosis (ACPS)
NCT02246023	PHASE4	COMPLETED	Fractionated Versus Target-controlled Propofol Administration in Bronchoscopy
NCT02523092	PHASE4	TERMINATED	Use of CXCL9 as a Biomarker of Acthar Efficacy
NCT02625558	PHASE4	UNKNOWN	Riociguat for Sarcoidosis Associated Pulmonary Hypertension
NCT02920710	PHASE4	WITHDRAWN	ACTHAR Therapy for Central Nervous System Sarcoidosis
NCT03265405	PHASE4	COMPLETED	Efficacy and Safety of Two Glucocorticoid Regimens in the Treatment of Sarcoidosis
NCT03593759	PHASE3	RECRUITING	Cardiac Sarcoidosis Randomized Trial
NCT05689879	PHASE3	ACTIVE_NOT_RECRUITING	Evaluation of TNF-alpha Antagonists (Infliximab) Withdrawal in Sarcoidosis
NCT00073437	PHASE3	COMPLETED	A Study of Infliximab in Patients With Sarcoidosis
NCT00305552	PHASE3	COMPLETED	SARCOTHAL. Thalidomide in Skin Sarcoidosis
NCT00555347	PHASE2/PHASE3	COMPLETED	Use of Armodafinil for Fatigue in Sarcoidosis
NCT00581607	PHASE2/PHASE3	COMPLETED	Double Blind, Randomized Trial of Bosentan for Sarcoidosis Associated Pulmonary Hypertension
NCT00794274	PHASE2/PHASE3	COMPLETED	The Efficacy and Safety of CC-10004 in Chronic Cutaneous Sarcoidosis
NCT00851929	PHASE2/PHASE3	COMPLETED	Ambrisentan (Letairis) for Sarcoidosis Associated Pulmonary Hypertension
NCT00872612	PHASE3	COMPLETED	Trial for the Diagnosis of Sarcoidosis
NCT01687517	PHASE3	COMPLETED	Efficacy and Safety of Influenza Vaccine During Sarcoidosis
NCT01920919	PHASE3	UNKNOWN	Low-dose Dexamethasone in Newly Diagnosed Pulmonary Sarcoidosis
NCT01955824	PHASE2/PHASE3	COMPLETED	A Trial on Clinical Efficacy of 1% Versus 2% Lignocaine in Cough Suppression and Pain Relief in Patients Undergoing Flexible Bronchoscopy
NCT02155803	PHASE2/PHASE3	UNKNOWN	ACTHAR GEL for Sarcoidosis-Associated Calcium Dysregulation: An Open-label Pilot Study
NCT02348905	PHASE2/PHASE3	UNKNOWN	ACTHAR Gel for Cutaneous Sarcoidosis: An Open Label Trial
NCT02875756	PHASE2/PHASE3	COMPLETED	Effect of the Number of Needle Revolutions Inside the Node on the Diagnostic Yield of EBUS-TBNA in Sarcoidosis
NCT05458492	PHASE2	NOT_YET_RECRUITING	Sirolimus in Cutaneous Sarcoidosis
NCT00000596	PHASE2	COMPLETED	Diffuse Fibrotic Lung Disease
NCT00274352	PHASE2	COMPLETED	A Study of Adalimumab to Treat Sarcoidosis of the Skin
NCT00282438	PHASE1/PHASE2	TERMINATED	Hematopoietic Stem Cell Support in Patients With Refractory Sarcoidosis
NCT00311246	PHASE2	TERMINATED	Trial of Adalimumab in Progressive Sarcoidosis
NCT00690911	PHASE2	WITHDRAWN	Study to Determine the Efficacy of Adalimumab in the Treatment of Cutaneous Sarcoidosis
NCT00731757	PHASE2	WITHDRAWN	Efficacy Study of Humira in the Treatment of Cutaneous Sarcoidosis
NCT00739960	PHASE2	TERMINATED	Safety Study of Abatacept to Treat Refractory Sarcoidosis
NCT00855205	PHASE2	COMPLETED	Rituximab for Pulmonary Sarcoidosis
NCT00926627	PHASE2	TERMINATED	Safety and Efficacy Study of Bosentan in Progressive Pulmonary Sarcoidosis
NCT00955279	PHASE2	COMPLETED	A Study to Evaluate the Safety and Effectiveness of Ustekinumab or Golimumab Administered Subcutaneously (SC) in Patients With Sarcoidosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CORTICOTROPIN	4	3
CRAVACITINIB	4	3
BOSENTAN	4	2
ABATACEPT	4	1
ABROCITINIB	4	1
AMBRISENTAN	4	1
ARMODAFINIL	4	1
DAPSONE	4	1
DIMERCAPROL	4	1
ERGOCALCIFEROL	4	1
GOLIMUMAB	4	1
ILOPROST	4	1
INFLIXIMAB	4	1
OXYGEN	4	1
PREDNISONE	4	1
RIOCIGUAT	4	1
ROFLUMILAST	4	1
SARILUMAB	4	1
THALIDOMIDE	4	1
TREPROSTINIL	4	1
USTEKINUMAB	4	1
BARDOXOLONE METHYL	3	1
QUERCETIN	3	1
RUBIDIUM	3	1
TRANILAST	3	1
LUFENURON	2	1
CHEMBL15720	0	2
CHEMBL50241	0	1
CHEMBL426123	0	1
CHEMBL302753	0	1