Systemic sclerosis

Summary

Systemic sclerosis (MONDO:0005100) is a disease (an umbrella term covering 6 Mondo subtypes) with 75 cohort genes (201 GWAS associations across 25 studies) and 606 clinical trials. The dominant Reactome pathway is Phosphorylation of CD3 and TCR zeta chains (8 cohort genes). Top therapeutic interventions include bosentan, 2-mercaptoethanesulfonic acid, and ambrisentan.

At a glance

• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 201
• Phenotypes (HPO): 86
• Clinical trials: 606

Clinical features

Epidemiology

Prevalence records

17 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-5 / 10 000	15.4	Europe	Validated
Annual incidence	>1 / 1000	230	Spain	Validated
Annual incidence	>1 / 1000	110	Greece	Validated
Annual incidence	6-9 / 10 000	72	Japan	Validated
Annual incidence	>1 / 1000	204	Australia	Validated
Annual incidence	1-9 / 100 000	1.09	Taiwan, Province of China	Validated
Annual incidence	1-9 / 100 000	1.7	Italy	Validated
Point prevalence	1-5 / 10 000	27.7	Spain	Validated
Point prevalence	1-9 / 100 000	8.8	United Kingdom	Validated
Point prevalence	1-5 / 10 000	17.3	France	Validated
Point prevalence	1-5 / 10 000	15.4	Greece	Validated
Point prevalence	1-5 / 10 000	30	United States	Validated
Point prevalence	1-5 / 10 000	44.3	Canada	Validated
Point prevalence	1-5 / 10 000	23.3	Australia	Validated
Point prevalence	1-9 / 100 000	5.63	Taiwan, Province of China	Validated
Point prevalence	1-5 / 10 000	22.2	Italy	Validated
Point prevalence	1-9 / 100 000	4.6	Japan	Not yet validated

Signs & symptoms

Clinical features (HPO)

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

HPO ID	Term	Frequency
HP:0001072	Thickened skin	Very frequent (80-99%)
HP:0002829	Arthralgia	Very frequent (80-99%)
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0003493	Antinuclear antibody positivity	Very frequent (80-99%)
HP:0011024	Abnormality of the gastrointestinal tract	Very frequent (80-99%)
HP:0030880	Raynaud phenomenon	Very frequent (80-99%)
HP:0031359	Cutaneous sclerotic plaque	Very frequent (80-99%)
HP:0000077	Abnormality of the kidney	Frequent (30-79%)
HP:0000160	Narrow mouth	Frequent (30-79%)
HP:0001009	Telangiectasia	Frequent (30-79%)
HP:0001232	Nail bed telangiectasia	Frequent (30-79%)
HP:0001324	Muscle weakness	Frequent (30-79%)
HP:0001386	Joint swelling	Frequent (30-79%)
HP:0002031	Abnormal esophagus morphology	Frequent (30-79%)
HP:0002206	Pulmonary fibrosis	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0005590	Spotty hypopigmentation	Frequent (30-79%)
HP:0006121	Acral ulceration	Frequent (30-79%)
HP:0006261	Abnormal phalangeal joint morphology of the hand	Frequent (30-79%)
HP:0006530	Abnormal pulmonary interstitial morphology	Frequent (30-79%)
HP:0007400	Irregular hyperpigmentation	Frequent (30-79%)
HP:0011838	Sclerodactyly	Frequent (30-79%)
HP:0012531	Pain	Frequent (30-79%)
HP:0025131	Finger swelling	Frequent (30-79%)
HP:0025520	Calcinosis cutis	Frequent (30-79%)
HP:0030859	Anti-topoisomerase I antibody positivity	Frequent (30-79%)
HP:0030873	Anticentromere antibody positivity	Frequent (30-79%)
HP:0031293	Digital pitting scar	Frequent (30-79%)
HP:0031917	Digital ulcer	Frequent (30-79%)
HP:0033038	Anti-RNA-polymerase-III-autoantibody positivity	Frequent (30-79%)
HP:0033394	Anti-carbonic anhydrase II antibody positivity	Frequent (30-79%)
HP:0033560	Anti-PM-Scl antibody positivity	Frequent (30-79%)
HP:0034078	Anti-centromere protein A antibody positivity	Frequent (30-79%)
HP:0034079	Anti-centromere protein B antibody positivity	Frequent (30-79%)
HP:0034080	Anti-U3 RNP antibody positivity	Frequent (30-79%)
HP:0034081	Anti-Th/To antibody positivity	Frequent (30-79%)
HP:0034082	Anti-bicaudal D2 antibody positivity	Frequent (30-79%)
HP:0034083	Anti-nucleolus-organizing region antibody positivity	Frequent (30-79%)
HP:0034085	Anti-PM-Scl100 antibody positivity	Frequent (30-79%)
HP:0034086	Anti-PM-Scl75 antibody positivity	Frequent (30-79%)
HP:0034087	Anti-U11/U12 RNP antibody positivity	Frequent (30-79%)
HP:0034088	Anti-Ku antibody positivity	Frequent (30-79%)
HP:0034089	Anti-B23 antibody positivity	Frequent (30-79%)
HP:0034090	Anti-RuvBL1/2 antibody positivity	Frequent (30-79%)
HP:0034091	Anti-platelet derived growth factor receptor	Frequent (30-79%)
HP:0034093	Anti-Ro52/TRIM21 antibody positivity	Frequent (30-79%)
HP:0034094	Anti-angiotensin receptor type-1 antibody positivity	Frequent (30-79%)
HP:0034095	Anti-endothelin-1 type A receptor antibody positivity	Frequent (30-79%)
HP:0034117	Anti-angiotensin-converting enzyme 2 antibody positivity	Frequent (30-79%)
HP:4000170	Anti-platelet antigen antibody positivity	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	systemic sclerosis
Mondo ID	MONDO:0005100
EFO	EFO:0000717
MeSH	D012595
Orphanet	90291
DOID	DOID:418
ICD-10-CM	M34
ICD-11	1084365812
NCIT	C72070
SNOMED CT	89155008
UMLS	C0036421
MedGen	19897
GARD	0009748
MedDRA	10042953
NORD	2007
Is cancer (heuristic)	no

Also known as: diffuse Scleroderma · diffuse sclerosis · Scleroderma · Scleroderma, diffuse · Scleroderma, systemic · SSc · SSc, diffuse sclerosis · Systemic Scleroderma · systemic Scleroderma · systemic scleroderma · systemic sclerosis

Data availability: 201 GWAS associations (25 studies) · 31 cell lines.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › skin disorder › systemic sclerosis

Related subtypes (71): dermatitis, cutaneous mucinosis, skin neoplasm, pyoderma, chronic ulcer of skin, sunburn, severe cutaneous adverse reaction, paronychia, Achenbach syndrome, erythema multiforme, erythematosquamous dermatosis, exanthem, facial dermatosis, hand dermatosis, keratosis, leg dermatosis, lichen disease, lipodystrophy, mongolian spot, reactive cutaneous fibrous lesion, rosacea, scalp dermatosis, sebaceous gland disorder, skin atrophy, skin sarcoidosis, sweat gland disorder, vesiculobullous skin disease, hyperglobulinemic purpura, ainhum, cheilitis glandularis, erythema palmare hereditarium, multiple benign circumferential skin creases on limbs, actinic prurigo, congenital lethal erythroderma, Parana hard-skin syndrome, Bazex-Dupre-Christol syndrome, nephrogenic systemic fibrosis, erosive pustular dermatosis of the scalp, pseudoxanthoma elasticum-like papillary dermal elastolysis, toxic dermatosis, oral erosive lichen, chronic actinic dermatitis, Jessner lymphocytic infiltration of the skin, acquired kinky hair syndrome, primary cutaneous plasmacytosis, cutaneous pseudolymphoma, corticosteroid-sensitive aseptic abscess syndrome, interstitial granulomatous dermatitis with arthritis, epidermal disease, skin pigmentation disorder, skin vascular disease, Wells syndrome, solar urticaria, pellagra, hereditary epidermal appendage anomaly, keratosis pilaris, dermis disorder, aquagenic pruritus, Boudhina Yedes Khiari syndrome, non-neoplastic nevus, cutaneous sclerosis, pityriasis rotunda, hematohidrosis, skin disorder caused by infection, livedoid vasculopathy, prurigo nodularis, granuloma faciale, sclerema neonatorum, hereditary skin disorder, hand-foot syndrome, Nicolau syndrome

Subtypes (6): pulmonary systemic sclerosis, diffuse scleroderma, scleroderma, familial progressive, diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, limited systemic sclerosis

Genetics & variants

GWAS landscape

201 GWAS associations across 25 studies. Top hits map to 31 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2021408	2e-62	HLA-DPB1, HLA-DPA1	C	2.68
rs9275390	3e-54	HLA-DQB1 - MTCO3P1	?	2.38
rs10174238	3e-42	STAT4	?	1.37
rs13238352	1e-38	TNPO3	T	1.44
rs6457617	2e-37	HLA-DQB1 - MTCO3P1	T	1.61
rs4853458	2e-35	STAT4	A	0.14
rs35677470	4e-31	DNASE1L3	A	2.03
rs13239597	1e-29	TPI1P2, TPI1P2	?	1.66
rs6679677	2e-28	PHTF1 - RSBN1	A	1.34
rs2476601	2e-28	AP4B1-AS1, PTPN22	?	1.33
rs3129882	2e-27	HLA-DRA	?	2.17
rs2736340	1e-26	FAM167A - BLK	C	0.1
HLA-DRB1*11:04	2e-24		?	3.14
rs3821236	2e-23	STAT4	A	1.31
rs58721818	5e-23	TNFAIP3 - LINC02865	T	1.64
rs2736337	5e-22	FAM167A - BLK	C	1.23
rs36073657	3e-21	TNPO3	T	1.4
rs443198	9e-21	NOTCH4	?	1.82
rs987870	2e-20	HLA-DPB1, HLA-DPA1	?	2.09
rs11889341	3e-20	STAT4	T	0.16
rs11117420	1e-17	LINC02132 - LINC01082	C	0.09
rs13389408	3e-17	STAT4	C	1.27
rs10954214	7e-17	IRF5	T	1.18
rs4728142	2e-15	IRF5	A	0.09
rs17849502	4e-15	NCF2, SMG7	T	1.36
rs1378942	9e-15	CSK	A	0.07
rs5754467	1e-13	YDJC - CCDC116	G	1.2
rs10488631	2e-13	IRF5 - TNPO3	C	1.5
rs7574865	2e-13	STAT4	T	1.38
rs5029937	2e-13	TNFAIP3	T	0.16

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90319682	Ishikawa Y	2024	9,095	17,584	GWAS for systemic sclerosis identifies six novel susceptibility loci including one in the Fcγ receptor region.
GCST90428834	Yu X	2024	9,095	34,250	Shared genetic architecture between autoimmune disorders and B-cell acute lymphoblastic leukemia: insights from large-scale genome-wide cross-trait analysis.
GCST009131	Lopez-Isac E	2019	9,095	17,584	GWAS for systemic sclerosis identifies multiple risk loci and highlights fibrotic and vasculopathy pathways.
GCST007278	Acosta-Herrera M	2018	4,595	19,704	Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.
GCST009876	Marquez A	2018	3,477	22,308	Meta-analysis of Immunochip data of four autoimmune diseases reveals novel single-disease and cross-phenotype associations.
GCST002069	Martin JE	2013	2,761	7,381	A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
GCST001156	Gorlova O	2011	2,296	5,172	Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
GCST001160	Gorlova O	2011	2,296	5,172	Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.
GCST000650	Radstake TR	2010	2,296	5,171	Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus.
GCST010124	Gonzalez-Serna D	2020	2,281	7,388	A cross-disease meta-GWAS identifies four new susceptibility loci shared between systemic sclerosis and Crohn’s disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	2
Tier 3: regulatory	1
Tier 4: intronic/intergenic	43

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	27
intergenic_variant	13
missense_variant	4
non_coding_transcript_exon_variant	1
unknown	1
synonymous_variant	1
3_prime_UTR_variant	1
regulatory_region_variant	1
splice_donor_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2021408	6	33078949	T>C	0.178	intron_variant	HLA-DPB1, HLA-DPA1	2e-62	Tier 4: intronic/intergenic
rs9275390	6	32701379	T>A,C	0.25	intergenic_variant	HLA-DQB1 - MTCO3P1	3e-54	Tier 4: intronic/intergenic
rs10174238	2	191108308	G>A,T	0.05	intron_variant	STAT4	3e-42	Tier 4: intronic/intergenic
rs13238352	7	129007888	C>A,T	0.05	intron_variant	TNPO3	1e-38	Tier 4: intronic/intergenic
rs6457617	6	32696074	C>A,T	0.5	intergenic_variant	HLA-DQB1 - MTCO3P1	2e-37	Tier 4: intronic/intergenic
rs4853458	2	191094763	A>C,G,T	0.05	intron_variant	STAT4	2e-35	Tier 4: intronic/intergenic
rs35677470	3	58197909	G>A,C	0.059	missense_variant	DNASE1L3	4e-31	Tier 1: coding
rs13239597	7	129055929	C>A	0.05	non_coding_transcript_exon_variant	TPI1P2, TPI1P2	1e-29	Tier 4: intronic/intergenic
rs6679677	1	113761186	C>A,T	0.05	intergenic_variant	PHTF1 - RSBN1	2e-28	Tier 4: intronic/intergenic
rs2476601	1	113834946	A>G,T	0.05	missense_variant	AP4B1-AS1, PTPN22	2e-28	Tier 1: coding
rs3129882	6	32441753	G>A,C	0.44	intron_variant	HLA-DRA	2e-27	Tier 4: intronic/intergenic
rs2736340	8	11486464	C>A,G,T	0.05	intergenic_variant	FAM167A - BLK	1e-26	Tier 4: intronic/intergenic
HLA-DRB1*11:04							2e-24	Tier 4: intronic/intergenic
rs3821236	2	191038032	G>A	0.2	intron_variant	STAT4	2e-23	Tier 4: intronic/intergenic
rs58721818	6	137922602	C>G,T	0.05	intergenic_variant	TNFAIP3 - LINC02865	5e-23	Tier 4: intronic/intergenic
rs2736337	8	11484371	T>A,C,G	0.05	intergenic_variant	FAM167A - BLK	5e-22	Tier 4: intronic/intergenic
rs36073657	7	129011468	C>T	0.1	intron_variant	TNPO3	3e-21	Tier 4: intronic/intergenic
rs443198	6	32222629	A>C,G,T	0.37	synonymous_variant	NOTCH4	9e-21	Tier 4: intronic/intergenic
rs987870	6	33075103	A>C,G,T	0.15	intron_variant	HLA-DPB1, HLA-DPA1	2e-20	Tier 4: intronic/intergenic
rs11889341	2	191079016	C>T	0.299	intron_variant	STAT4	3e-20	Tier 4: intronic/intergenic
rs11117420	16	85938316	G>C,T	0.05	intron_variant	LINC02132 - LINC01082	1e-17	Tier 4: intronic/intergenic
rs13389408	2	191068557	T>C	0.05	intron_variant	STAT4	3e-17	Tier 4: intronic/intergenic
rs10954214	7	128949579	C>T	0.05	3_prime_UTR_variant	IRF5	7e-17	Tier 2: splice/UTR
rs4728142	7	128933913	G>A	0.05	intergenic_variant	IRF5	2e-15	Tier 4: intronic/intergenic
rs17849502	1	183563445	G>A,C,T	0.05	missense_variant	NCF2, SMG7	4e-15	Tier 1: coding
rs1378942	15	74785026	C>A,G,T	0.05	intron_variant	CSK	9e-15	Tier 4: intronic/intergenic
rs5754467	22	21630805	A>G,T	0.05	intergenic_variant	YDJC - CCDC116	1e-13	Tier 4: intronic/intergenic
rs10488631	7	128954129	T>C	0.05	intergenic_variant	IRF5 - TNPO3	2e-13	Tier 4: intronic/intergenic
rs7574865	2	191099907	T>A,G	0.22	intron_variant	STAT4	2e-13	Tier 4: intronic/intergenic
rs5029937	6	137874014	G>A,T	0.05	intron_variant	TNFAIP3	2e-13	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 105 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 12

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

Gene	HGNC	Evidence routes
BLK	BLK	GWAS, Orphanet
STAT4	STAT4	GWAS, Orphanet
TNFAIP3	TNFAIP3	GWAS, Orphanet
TNFSF4	TNFSF4	GWAS, Orphanet
TNIP1	TNIP1	GWAS, Orphanet
PXK	PXK	GWAS, Orphanet
CR2	CR2	GWAS, Orphanet
JAZF1	JAZF1	GWAS, Orphanet
DNASE1L3	DNASE1L3	GWAS, Orphanet
KIAA0319L	KIAA0319L	GWAS, Orphanet
HLA-DQB1	HLA-DQB1	GWAS, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
SOX5	Orphanet:313884	12p12.1 microdeletion syndrome
SOX5	Orphanet:313892	Developmental and speech delay due to SOX5 deficiency
SOX5	Orphanet:626	Large/giant congenital melanocytic nevus
SPINK2	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
STAT1	Orphanet:319595	Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
STAT1	Orphanet:391311	Susceptibility to viral and mycobacterial infections due to STAT1 deficiency
STAT1	Orphanet:391487	STAT1-related autoimmune enteropathy and endocrinopathy-susceptibility to chronic infections syndrome
STAT3	Orphanet:2314	Autosomal dominant hyper-IgE syndrome due to STAT3 deficiency
STAT3	Orphanet:438159	STAT3-related early-onset multisystem autoimmune disease
STAT3	Orphanet:512017	Chronic lymphoproliferative disorder of natural killer cells
STAT3	Orphanet:520	Acute promyelocytic leukemia
STAT3	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
STAT3	Orphanet:86872	T-cell large granular lymphocyte leukemia
STAT3	Orphanet:99885	Isolated permanent neonatal diabetes mellitus
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
TNFAIP3	Orphanet:536	Systemic lupus erythematosus
TNFAIP3	Orphanet:674762	Early-onset autoinflammatory syndrome due to A20 haploinsufficiency
TNFSF4	Orphanet:2073	Narcolepsy type 1
TNFSF4	Orphanet:536	Systemic lupus erythematosus
TREH	Orphanet:103909	Trehalase deficiency
TYK2	Orphanet:300865	Primary cutaneous anaplastic large cell lymphoma
TYK2	Orphanet:331226	Susceptibility to infection due to TYK2 deficiency
TYK2	Orphanet:98842	Lymphomatoid papulosis
IKZF2	Orphanet:697389	Combined immunodeficiency due to HELIOS deficiency
IKZF2	Orphanet:699599	ICHAD syndrome
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
SAMD9L	Orphanet:2585	Ataxia-pancytopenia syndrome
SAMD9L	Orphanet:619367	SAMD9L-associated autoinflammatory syndrome
SAMD9L	Orphanet:631106	Spinocerebellar ataxia type 49
SLC12A5	Orphanet:293181	Epilepsy of infancy with migrating focal seizures
UNC45B	Orphanet:441447	Early-onset posterior subcapsular cataract
UNC45B	Orphanet:98991	Early-onset nuclear cataract
PXDN	Orphanet:289499	Congenital cataract microcornea with corneal opacity
PXDN	Orphanet:699850	2p25.3 microduplication syndrome
FCGR2C	Orphanet:3002	Immune thrombocytopenia
CD247	Orphanet:169160	T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta
CD247	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
CD247	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
TNIP1	Orphanet:536	Systemic lupus erythematosus
TNPO3	Orphanet:186	Primary biliary cholangitis
TNPO3	Orphanet:55595	TNP03-related limb-girdle muscular dystrophy D2

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	75

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RPL41	HGNC:10354	ENSG00000229117	P62945	Small ribosomal subunit protein eS32	gwas
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas
SLC26A1	HGNC:10993	ENSG00000145217	Q9H2B4	Sulfate anion transporter 1	gwas
SOX5	HGNC:11201	ENSG00000134532	P35711	Transcription factor SOX-5	gwas
SPINK2	HGNC:11245	ENSG00000128040	P20155	Serine protease inhibitor Kazal-type 2	gwas
STAT1	HGNC:11362	ENSG00000115415	P42224	Signal transducer and activator of transcription 1-alpha/beta	gwas
STAT3	HGNC:11364	ENSG00000168610	P40763	Signal transducer and activator of transcription 3	gwas
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
TNFSF4	HGNC:11934	ENSG00000117586	P23510	Tumor necrosis factor ligand superfamily member 4	gwas
TREH	HGNC:12266	ENSG00000118094	O43280	Trehalase	gwas
TYK2	HGNC:12440	ENSG00000105397	P29597	Non-receptor tyrosine-protein kinase TYK2	gwas
IKZF2	HGNC:13177	ENSG00000030419	Q9UKS7	Zinc finger protein Helios	gwas
IKZF3	HGNC:13178	ENSG00000161405	Q9UKT9	Zinc finger protein Aiolos	gwas
TIMMDC1	HGNC:1321	ENSG00000113845	Q9NPL8	Complex I assembly factor TIMMDC1, mitochondrial	gwas
GSDMA	HGNC:13311	ENSG00000167914	Q96QA5	Gasdermin-A	gwas
TSPAN32	HGNC:13410	ENSG00000064201	Q96QS1	Tetraspanin-32	gwas
SAMD9L	HGNC:1349	ENSG00000177409	Q8IVG5	Sterile alpha motif domain-containing protein 9-like	gwas
SLC12A5	HGNC:13818	ENSG00000124140	Q9H2X9	Solute carrier family 12 member 5	gwas
UNC45B	HGNC:14304	ENSG00000141161	Q8IWX7	Protein unc-45 homolog B	gwas
PXDN	HGNC:14966	ENSG00000130508	Q92626	Peroxidasin homolog	gwas
FAM167A	HGNC:15549	ENSG00000154319	Q96KS9	Protein FAM167A	gwas
FCGR2C	HGNC:15626	ENSG00000244682	P31995	Low affinity immunoglobulin gamma Fc region receptor II-c	gwas
SCHIP1	HGNC:15678	ENSG00000151967	P0DPB3	Schwannomin-interacting protein 1	gwas
ORMDL3	HGNC:16038	ENSG00000172057	Q8N138	ORM1-like protein 3	gwas
ELMO1	HGNC:16286	ENSG00000155849	Q92556	Engulfment and cell motility protein 1	gwas
CD247	HGNC:1677	ENSG00000198821	P20963	T-cell surface glycoprotein CD3 zeta chain	gwas
NMNAT2	HGNC:16789	ENSG00000157064	Q9BZQ4	Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2	gwas
TNIP1	HGNC:16903	ENSG00000145901	Q15025	TNFAIP3-interacting protein 1	gwas
CD80	HGNC:1700	ENSG00000121594	P33681	T-lymphocyte activation antigen CD80	gwas
TNPO3	HGNC:17103	ENSG00000064419	Q9Y5L0	Transportin-3	gwas
PSORS1C1	HGNC:17202	ENSG00000204540	Q9UIG5	Psoriasis susceptibility 1 candidate gene 1 protein	gwas
ANGPTL5	HGNC:19705	ENSG00000187151	Q86XS5	Angiopoietin-related protein 5	gwas
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	gwas
ZPBP2	HGNC:20678	ENSG00000186075	Q6X784	Zona pellucida-binding protein 2	gwas
SERAC1	HGNC:21061	ENSG00000122335	Q96JX3	Protein SERAC1	gwas
GTF2H5	HGNC:21157	ENSG00000272047	Q6ZYL4	General transcription factor IIH subunit 5	gwas
BLTP3A	HGNC:21216	ENSG00000065060	Q6BDS2	Bridge-like lipid transfer protein family member 3A	gwas
POGLUT1	HGNC:22954	ENSG00000163389	Q8NBL1	Protein O-glucosyltransferase 1	gwas
PXK	HGNC:23326	ENSG00000168297	Q7Z7A4	PX domain-containing protein kinase-like protein	gwas
CR1	HGNC:2334	ENSG00000203710	P17927	Complement receptor type 1	gwas
CR2	HGNC:2336	ENSG00000117322	P20023	Complement receptor type 2	gwas
GSDMB	HGNC:23690	ENSG00000073605	Q8TAX9	Gasdermin-B	gwas
CSK	HGNC:2444	ENSG00000103653	P41240	Tyrosine-protein kinase CSK	gwas
OLFML2B	HGNC:24558	ENSG00000162745	Q68BL8	Olfactomedin-like protein 2B	gwas
RBM43	HGNC:24790	ENSG00000184898	Q6ZSC3	RNA-binding protein 43	gwas
HOPX	HGNC:24961	ENSG00000171476	Q9BPY8	Homeodomain-only protein	gwas
LRP2BP	HGNC:25434	ENSG00000109771	Q9P2M1	LRP2-binding protein	gwas
YDJC	HGNC:27158	ENSG00000161179	A8MPS7	Carbohydrate deacetylase	gwas
DDX6	HGNC:2747	ENSG00000110367	P26196	Probable ATP-dependent RNA helicase DDX6	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RPL41	Small ribosomal subunit protein eS32	Component of the small ribosomal subunit (Ref.8).
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
SLC26A1	Sulfate anion transporter 1	Sodium-independent sulfate anion transporter.
SOX5	Transcription factor SOX-5	Transcription factor involved in chondrocytes differentiation and cartilage formation.
SPINK2	Serine protease inhibitor Kazal-type 2	As a strong inhibitor of acrosin, it is required for normal spermiogenesis.
STAT1	Signal transducer and activator of transcription 1-alpha/beta	Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors.
STAT3	Signal transducer and activator of transcription 3	Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors.
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.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TNFSF4	Tumor necrosis factor ligand superfamily member 4	Cytokine that binds to TNFRSF4.
TREH	Trehalase	Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose.
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.
IKZF2	Zinc finger protein Helios	Transcription factor, which stabilizes the noninflammatory phenotype of regulatory T cells (Tregs).
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).
GSDMA	Gasdermin-A	This form constitutes the precursor of the pore-forming protein and acts as a sensor of infection: upon infection by S.pyogenes, specifically cleaved by S.pyogenes effector protein SpeB in epithelial cells, releasing the N-terminal moiety…
SAMD9L	Sterile alpha motif domain-containing protein 9-like	May be involved in endosome fusion.
SLC12A5	Solute carrier family 12 member 5	Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis.
UNC45B	Protein unc-45 homolog B	Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain.
PXDN	Peroxidasin homolog	Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncro…
FCGR2C	Low affinity immunoglobulin gamma Fc region receptor II-c	Receptor for the Fc region of complexed immunoglobulins gamma.
ORMDL3	ORM1-like protein 3	Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels.
ELMO1	Engulfment and cell motility protein 1	Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
CD247	T-cell surface glycoprotein CD3 zeta chain	Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.
NMNAT2	Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2	Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor.
TNIP1	TNFAIP3-interacting protein 1	Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG.
CD80	T-lymphocyte activation antigen CD80	Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
TNPO3	Transportin-3	Importin, which transports target proteins into the nucleus.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
ZPBP2	Zona pellucida-binding protein 2	Is implicated in sperm-oocyte interaction during fertilization.
SERAC1	Protein SERAC1	Facilitates the transport of serine from the cytosol to the mitochondria by interacting with and stabilizing Sideroflexin-1 (SFXN1), a mitochondrial serine transporter, playing a fundamental role in the one-carbon cycle responsible for the…
GTF2H5	General transcription factor IIH subunit 5	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…
BLTP3A	Bridge-like lipid transfer protein family member 3A	Tube-forming lipid transport protein which probably mediates the transfer of lipids between membranes at organelle contact sites.
POGLUT1	Protein O-glucosyltransferase 1	Dual specificity glycosyltransferase that catalyzes the transfer of glucose and xylose from UDP-glucose and UDP-xylose, respectively, to a serine residue found in the consensus sequence of C-X-S-X-P-C.
PXK	PX domain-containing protein kinase-like protein	Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission.
CR1	Complement receptor type 1	Membrane immune adherence receptor that plays a critical role in the capture and clearance of complement-opsonized pathogens by erythrocytes and monocytes/macrophages.
CR2	Complement receptor type 2	Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1.
GSDMB	Gasdermin-B	Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death.
CSK	Tyrosine-protein kinase CSK	Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response.
HOPX	Homeodomain-only protein	Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development.
LRP2BP	LRP2-binding protein	May act as an adapter that regulates LRP2 function.
YDJC	Carbohydrate deacetylase	Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
DDX6	Probable ATP-dependent RNA helicase DDX6	Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions.
ZBTB9	Zinc finger and BTB domain-containing protein 9	May be involved in transcriptional regulation.
DGKQ	Diacylglycerol kinase theta	Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids.
TMEM175	Endosomal/lysosomal proton channel TMEM175	Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH.
JAZF1	Juxtaposed with another zinc finger protein 1	Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2.
ARHGAP31	Rho GTPase-activating protein 31	Functions as a GTPase-activating protein (GAP) for RAC1 and CDC42.
PRR12	Proline-rich protein 12	May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2.
CEP126	Centrosomal protein of 126 kDa	Participates in cytokinesis.

Protein-family classification

Druggable: 28 · Difficult: 13 · Unknown: 34 · Druggable fraction: 0.37

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	12	4.7×	9e-05
Complement	2	7.2×	0.176
Kinase	5	1.9×	0.491
Phosphatase	1	1.1×	0.974
Transcription factor	10	1.1×	0.974
Transporter	1	1.0×	0.974
Other/Unknown	34	0.8×	0.974
Enzyme (other)	5	0.8×	0.974
Scaffold/PPI	3	0.7×	0.974
Protease	1	0.5×	0.974
GPCR	1	0.3×	0.974

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RPL41	Other/Unknown	no		Ribosomal_eS32
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
SLC26A1	Transporter	yes		SLC26A/SulP_fam, STAS_dom, SLC26A/SulP_dom
SOX5	Transcription factor	no		HMG_box_dom, HMG_box_dom_sf, SOX/SOX-like_TF
SPINK2	Other/Unknown	no		Kazal_dom, Kazal_dom_sf, SPINK2
STAT1	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT3	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
STAT4	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TNFSF4	Other/Unknown	no		TNF_dom, Tumour_necrosis_fac-like_dom, TNF_CS
TREH	Enzyme (other)	yes	3.2.1.28	Glyco_hydro_37, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_sf
TYK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
IKZF2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
IKZF3	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, Ikaros_C2H2-ZF
TIMMDC1	Other/Unknown	no		TIMMDC1
GSDMA	Other/Unknown	no		Gasdermin, Gasdermin_pore, Gasdermin_PUB
TSPAN32	Other/Unknown	no		Tetraspanin_EC2_sf, Tetraspanin/Peripherin, PHEMX_LEL
SAMD9L	Other/Unknown	no		SAM, SAM/pointed_sf
SLC12A5	Other/Unknown	no		KCL_cotranspt, AA-permease/SLC12A_dom, SLC12A_fam
UNC45B	Other/Unknown	no		Armadillo, ARM-like, TPR-like_helical_dom_sf
PXDN	Antibody/Immunoglobulin	yes	1.11.1.7	Cys-rich_flank_reg_C, VWF_dom, Leu-rich_rpt
FAM167A	Other/Unknown	no		FAM167, FAM167_domain
FCGR2C	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
SCHIP1	Other/Unknown	no		SCHIP_1_C, SCHIP_1
ORMDL3	Other/Unknown	no		ORMDL
ELMO1	Scaffold/PPI	no		PH_domain, ELMO_dom, ARM-like
CD247	Other/Unknown	no		Phos_immunorcpt_sig_ITAM, CD3_zeta/IgE_Fc_rcpt_gamma, T-cell_CD3_zeta
NMNAT2	Enzyme (other)	yes	2.7.7.1	Cyt_trans-like, Rossmann-like_a/b/a_fold, NMNAT_euk
TNIP1	Other/Unknown	no
CD80	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
TNPO3	Other/Unknown	no		ARM-like, Exportin-1/Importin-b-like, ARM-type_fold
PSORS1C1	Other/Unknown	no		SEEK1
ANGPTL5	Other/Unknown	no		Fibrinogen_a/b/g_C_dom, Fibrinogen_a/b/g_C_1, Fibrinogen_CS
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
ZPBP2	Antibody/Immunoglobulin	yes		Ig-like_dom, Sp38-bd, Ig-like_fold
SERAC1	Other/Unknown	no		ARM-like, ARM-type_fold, AB_hydrolase_fold
GTF2H5	Other/Unknown	no		TFIIH_TTDA/Tfb5, TFB5-like_sf
BLTP3A	Other/Unknown	no		BLTP3A/B
POGLUT1	Enzyme (other)	yes	2.4.1.376	CAP10, O-Glucosyltr/Glycosyltrsf_90
PXK	Kinase	yes		Prot_kinase_dom, PX_dom, WH2_dom
CR1	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
CR2	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
GSDMB	Other/Unknown	no		Gasdermin, Gasdermin_pore, Gasdermin_PUB
CSK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
OLFML2B	Other/Unknown	no		Olfac-like_dom, Olfactomedin-like_domain
RBM43	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf
HOPX	Transcription factor	no		HD, Homeodomain-like_sf, HOPX
LRP2BP	Other/Unknown	no		Sel1-like, TPR-like_helical_dom_sf, TPR_rpt
YDJC	Enzyme (other)	yes	3.5.1.105	YdjC-like, Glyco_hydro/deAcase_b/a-brl
DDX6	Enzyme (other)	yes	3.6.4.13	RNA-helicase_DEAD-box_CS, Helicase_C-like, DEAD/DEAH_box_helicase_dom

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	13
monocyte	10
mononuclear cell	5
vermiform appendix	5
leukocyte	5
spleen	4
calcaneal tendon	4
sperm	4
left ventricle myocardium	4
stromal cell of endometrium	4
secondary oocyte	4
lymph node	3
male germ line stem cell (sensu Vertebrata) in testis	3
right lobe of liver	3
seminal vesicle	3
middle temporal gyrus	3
right hemisphere of cerebellum	3
cardiac muscle of right atrium	3
pancreatic ductal cell	3
bone marrow cell	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RPL41	134	ubiquitous	marker	ovary, right ovary, left ovary
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
SLC26A1	156	tissue_specific	yes	right adrenal gland cortex, left adrenal gland cortex, right lobe of liver
SOX5	221	ubiquitous	marker	cortical plate, calcaneal tendon, synovial joint
SPINK2	177	broad	marker	corpus epididymis, cauda epididymis, seminal vesicle
STAT1	294	ubiquitous	marker	epithelium of nasopharynx, vermiform appendix, mononuclear cell
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
TNFAIP3	274	ubiquitous	marker	vena cava, mucosa of paranasal sinus, vermiform appendix
TNFSF4	181	broad	marker	primordial germ cell in gonad, monocyte, mononuclear cell
TREH	162	tissue_specific	marker	jejunal mucosa, duodenum, small intestine
TYK2	288	ubiquitous	marker	granulocyte, right hemisphere of cerebellum, adenohypophysis
IKZF2	232	ubiquitous	marker	thymus, palpebral conjunctiva, amniotic fluid
IKZF3	155	broad	marker	granulocyte, lymph node, epithelium of nasopharynx
TIMMDC1	259	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, myocardium
GSDMA	108	tissue_specific	yes	skin of leg, zone of skin, skin of abdomen
TSPAN32	166	broad	marker	granulocyte, apex of heart, monocyte
SAMD9L	231	ubiquitous	marker	pancreatic ductal cell, buccal mucosa cell, leukocyte
SLC12A5	205	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
UNC45B	111	tissue_specific	yes	left ventricle myocardium, cardiac muscle of right atrium, tibialis anterior
PXDN	265	ubiquitous	marker	stromal cell of endometrium, hair follicle, tendon of biceps brachii
FAM167A	207	broad	marker	stromal cell of endometrium, islet of Langerhans, secondary oocyte
FCGR2C	169		marker	granulocyte, monocyte, mononuclear cell
SCHIP1	133	ubiquitous	marker	ventricular zone, prefrontal cortex, Brodmann (1909) area 9
ORMDL3	256	ubiquitous	marker	right lobe of liver, bone marrow cell, granulocyte
ELMO1	248	ubiquitous	marker	prefrontal cortex, C1 segment of cervical spinal cord, corpus callosum
CD247	179	broad	marker	granulocyte, thymus, blood
NMNAT2	208	broad	marker	middle temporal gyrus, cortical plate, frontal pole
TNIP1	298	ubiquitous	marker	lower esophagus mucosa, blood, hindlimb stylopod muscle
CD80	143	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, lower lobe of lung, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 60.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
PXDN	9,915
STAT1	6,459
DDX6	5,922
CHD7	4,819
CSK	4,059
TYK2	3,932
TNFAIP3	3,716
CD80	3,664
HLA-DRB1	3,448

Intra-cohort edges

A	B	Sources
ANGPTL5	CEP126	string_interaction
ARHGAP31	POGLUT1	string_interaction
BLK	FAM167A	string_interaction
BLK	PXK	string_interaction
BLK	STAT3	biogrid_interaction, intact
BLK	STAT4	string_interaction
BLK	TNFAIP3	string_interaction
BLTP3A	JAZF1	string_interaction
BLTP3A	PXK	string_interaction
BLTP3A	TNIP1	string_interaction
CD247	DNASE1L3	intact
CD80	ZPBP2	intact
CR1	CR2	biogrid_interaction
DGKQ	TMEM175	string_interaction
DNASE1L3	PXK	string_interaction
FAM167A	PXK	string_interaction
FAM167A	STAT4	string_interaction
FAM167A	TNFSF4	string_interaction
FAM167A	TNIP1	string_interaction
FAM167A	TNPO3	string_interaction
FCGR2C	GRB2	intact
FLNB	GRB2	intact
GRB10	ZPBP2	string_interaction
GRB2	IKZF3	biogrid_interaction, intact
GSDMA	LRRC3C	string_interaction
GSDMA	ORMDL3	string_interaction
GSDMA	ZPBP2	string_interaction
GSDMB	IKZF3	string_interaction
GSDMB	LRRC3C	string_interaction
GSDMB	ORMDL3	string_interaction
GSDMB	STAT3	biogrid_interaction
GSDMB	ZPBP2	string_interaction
GTF2H5	SERAC1	string_interaction
HLA-DPA1	HLA-DPB1	intact
HLA-DPA1	HLA-DQB1	intact
HLA-DPA1	SLC12A5	biogrid_interaction, intact
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
HLA-DRA	HLA-DRB1	biogrid_interaction, intact, string_interaction
HLA-DRA	SERAC1	intact
HLA-DRA	STAT1	string_interaction
HLA-DRB1	KIAA0319L	biogrid_interaction
IKZF2	IKZF3	biogrid_interaction
IKZF3	LRRC3C	string_interaction
IKZF3	ORMDL3	string_interaction
IKZF3	ZPBP2	string_interaction
KIAA0319L	PXK	string_interaction
LRRC3C	ORMDL3	string_interaction
LRRC3C	ZPBP2	string_interaction
ORMDL3	ZPBP2	string_interaction
POGLUT1	TIMMDC1	string_interaction

Structural data

PDB: 40 · AlphaFold-only: 34 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPL41	P62945	185
HLA-DRA	P01903	140
HLA-DRB1	P01911	108
GRB2	P62993	58
GTF2H5	Q6ZYL4	53
TYK2	P29597	52
CD247	P20963	38
HLA-DQA1	P01909	28
FLNB	O75369	23
ELMO1	Q92556	18
TMEM175	Q9BSA9	18
TNFAIP3	P21580	17
ORMDL3	Q8N138	13
GSDMB	Q8TAX9	11
STAT1	P42224	10
HLA-DPA1	P20036	10
HLA-DPB1	P04440	10
HLA-DQB1	P01920	10
CR2	P20023	9
DDX6	P26196	9
KIAA0319L	Q8IZA0	9
TNIP1	Q15025	8
IKZF2	Q9UKS7	7
CR1	P17927	7
STAT3	P40763	6
CD80	P33681	6
TNPO3	Q9Y5L0	6
POGLUT1	Q8NBL1	6
CSK	P41240	6
GRM7	Q14831	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TREH	O43280	92.80
LRP2BP	Q9P2M1	92.51
YDJC	A8MPS7	91.77
UNC45B	Q8IWX7	88.38
STAT4	Q14765	86.87
ZPBP2	Q6X784	86.81
PXK	Q7Z7A4	86.42
SAMD9L	Q8IVG5	83.85
HOPX	Q9BPY8	83.57
SLC26A1	Q9H2B4	83.13
DGKQ	P52824	82.56
BLK	P51451	81.89
ANGPTL5	Q86XS5	81.80
GSDMA	Q96QA5	80.60
PXDN	Q92626	80.43
NMNAT2	Q9BZQ4	80.34
LRRC3C	A6NJW4	79.40
SERAC1	Q96JX3	78.66
ESYT1	Q9BSJ8	78.29
RBM43	Q6ZSC3	77.12
TSPAN32	Q96QS1	72.74
TIMMDC1	Q9NPL8	72.08
FAM167A	Q96KS9	71.98
JAZF1	Q86VZ6	70.25
BLTP3A	Q6BDS2	67.37
OLFML2B	Q68BL8	63.26
SCHIP1	P0DPB3	61.13
SOX5	P35711	58.95
PSORS1C1	Q9UIG5	55.10
CEP126	Q9P2H0	49.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 510. Enrichment computed across 105 evidence-associated genes (71 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 71 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Phosphorylation of CD3 and TCR zeta chains	8	61.3×	1e-10	CD247, CSK, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, PTPN22
Co-inhibition by PD-1	8	58.5×	1e-10	CD247, CSK, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, PTPN11
Translocation of ZAP-70 to Immunological synapse	7	62.5×	1e-09	CD247, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, PTPN22
Interferon gamma signaling	11	19.4×	1e-09	STAT1, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1, IRF8 (+3 more)
Interleukin-35 Signalling	6	80.4×	4e-09	STAT1, STAT3, STAT4, TYK2, IL12A, IL12RB2
Generation of second messenger molecules	6	29.2×	4e-06	CD247, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1
Signaling by CSF3 (G-CSF)	5	40.2×	8e-06	STAT1, STAT3, TYK2, GRB2, PTPN11
Interleukin-23 signaling	4	71.5×	1e-05	STAT3, STAT4, TYK2, IL12RB1
Signaling by SCF-KIT	6	21.0×	2e-05	STAT1, STAT3, GRB10, GRB2, MMP9, PTPN11
Interferon alpha/beta signaling	7	15.0×	2e-05	STAT1, TYK2, IRF8, IRF1, IRF5, IRF7, PTPN11
Interleukin-20 family signaling	5	29.8×	3e-05	STAT1, STAT3, STAT4, TYK2, PTPN11
Interleukin-6 signaling	4	53.6×	3e-05	STAT1, STAT3, TYK2, PTPN11
Interleukin-12 signaling	5	28.7×	3e-05	STAT4, TYK2, IL12A, IL12RB1, IL12RB2
Cytokine Signaling in Immune system	11	6.3×	4e-05	STAT1, STAT3, STAT4, CD80, IRF8, IRF1, IRF5, IRF7 (+3 more)
Downstream TCR signaling	7	12.7×	4e-05	CD247, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DRA, HLA-DRB1, NFKB1
Interferon Signaling	7	11.8×	6e-05	STAT1, STAT3, IRF8, IRF1, IRF5, IRF7, ATF6
Interleukin-21 signaling	3	48.2×	8e-04	STAT1, STAT3, STAT4
Downstream signal transduction	4	21.4×	9e-04	STAT1, STAT3, GRB2, PTPN11
Interleukin-27 signaling	3	43.9×	1e-03	STAT1, STAT3, TYK2
Signaling by CSF1 (M-CSF) in myeloid cells	4	19.5×	0.001	STAT1, STAT3, GRB2, PTPN11
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	3	37.1×	0.001	STAT1, STAT3, GRB2
Signaling by PDGFRA extracellular domain mutants	3	37.1×	0.001	STAT1, STAT3, GRB2
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	3	37.1×	0.001	STAT1, STAT4, IL12RB2
Interleukin-4 and Interleukin-13 signaling	6	8.7×	0.001	STAT1, STAT3, TYK2, IL12A, ITGAM, MMP9
GAB1 signalosome	3	26.8×	0.003	CSK, GRB2, PTPN11
Signaling by cytosolic FGFR1 fusion mutants	3	26.8×	0.003	STAT1, STAT3, GRB2
Interleukin-2 family signaling	3	26.8×	0.003	STAT1, STAT3, STAT4
Interleukin-10 signaling	4	13.1×	0.004	STAT3, TYK2, CD80, IL12A
Immune System	15	2.7×	0.005	BLK, STAT1, STAT3, STAT4, CD80, IRF8, ATG5, IRF1 (+7 more)
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	3	21.9×	0.006	STAT1, STAT3, GRB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 96 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	6	65.8×	2e-07	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of type II interferon production	9	21.1×	2e-07	TNFSF4, TYK2, HLA-DPA1, HLA-DPB1, IRF8, IL12A, IL12RB1, IL12RB2 (+1 more)
interleukin-12-mediated signaling pathway	5	97.5×	2e-07	STAT4, TYK2, IL12A, IL12RB1, IL12RB2
antigen processing and presentation of exogenous peptide antigen via MHC class II	6	34.0×	4e-06	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of immune response	6	30.1×	8e-06	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of T cell activation	6	27.7×	1e-05	HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, HLA-DRB1
positive regulation of memory T cell differentiation	4	78.0×	1e-05	TNFSF4, HLA-DRA, HLA-DRB1, IL12RB1
immune response	13	6.4×	1e-05	TNFSF4, TYK2, PXDN, FCGR2C, CD80, CR2, HLA-DPA1, HLA-DQA1 (+5 more)
adaptive immune response	9	7.9×	2e-04	CD247, CSK, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, IGHM (+1 more)
interleukin-23-mediated signaling pathway	3	87.8×	3e-04	STAT3, TYK2, IL12RB1
cytokine-mediated signaling pathway	7	9.5×	7e-04	STAT3, STAT4, TYK2, IL12RB1, IL12RB2, IRF5, PTPN11
negative regulation of T cell proliferation	5	17.2×	8e-04	TSPAN32, CD80, CR1, HLA-DRB1, PTPN11
regulation of adaptive immune response	3	58.5×	0.001	TNFSF4, IRF1, IRF7
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	175.5×	0.002	HLA-DRA, HLA-DRB1
regulation of MyD88-dependent toll-like receptor signaling pathway	2	175.5×	0.002	IRF1, IRF7
negative regulation of T cell activation	4	21.9×	0.002	CD80, CSK, PTPN11, PTPN22
positive regulation of T cell mediated cytotoxicity	4	21.3×	0.002	HLA-DRA, HLA-DRB1, IL12A, IL12RB1
positive regulation of T cell proliferation	5	13.5×	0.002	TNFSF4, TYK2, CD80, HLA-DPA1, HLA-DPB1
T cell receptor signaling pathway	6	9.5×	0.002	CD247, CSK, HLA-DPB1, HLA-DQB1, HLA-DRB1, PTPN22
cellular response to lipopolysaccharide	7	7.1×	0.003	TNFAIP3, TNFSF4, TNIP1, CD80, IRF8, MMP9, NFKB1
type II interferon-mediated signaling pathway	3	37.6×	0.003	STAT1, TYK2, IRF1
positive regulation of type I interferon production	4	17.6×	0.003	IRF1, IRF5, IRF7, PTPN22
myeloid dendritic cell antigen processing and presentation	2	117.0×	0.003	HLA-DRA, HLA-DRB1
B cell receptor signaling pathway	4	16.7×	0.003	BLK, GRB2, IGHM, NFKB1
immune system process	4	16.3×	0.003	IRF8, IRF1, IRF5, IRF7
positive regulation of interferon-beta production	4	16.3×	0.003	IRF1, IRF5, IRF7, PTPN11
positive regulation of interleukin-12 production	4	16.3×	0.003	TNFSF4, IRF8, IRF1, IRF5
cellular response to type II interferon	5	10.8×	0.003	STAT1, FLNB, HLA-DPA1, IRF8, IL12RB1
negative regulation of T cell receptor signaling pathway	4	15.3×	0.004	CD80, CSK, PTPN11, PTPN22
response to fungus	2	87.8×	0.005	ATG5, BAK1

Therapeutics

Drugs indicated for this disease

2 approved, 10 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Bosentan	Approved (phase 4)
Tocilizumab	Approved (phase 4)
Divozilimab	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Inebilizumab	Phase 3 (in late-stage trials)
Macitentan	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Nintedanib	Phase 3 (in late-stage trials)
Relaxin	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Sildenafil	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Albumin Human, Belimumab, Bermekimab, Clopidogrel, Fludarabine Phosphate, Guselkumab, Human Immunoglobulin G, Iloprost, Imatinib, Itacitinib, Mycophenolate Mofetil, Nemolizumab, Pirfenidone, Plerixafor, Pomalidomide, Prednisolone, Riociguat, Rituximab, Sirolimus, Sodium Chloride, Tacrolimus Anhydrous, Tadalafil, Tofacitinib, Ziritaxestat.

Drug target analysis

Approved (phase 4): 8 · Phase ≥3: 9 · Phased (≥1): 13 · Undrugged: 62

Druggability breadth: 46 of 105 evidence-associated genes (44%) 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
RPL41	GENTAMICIN SULFATE
BLK	AFATINIB
STAT1	FILGOTINIB
STAT3	MOMELOTINIB
TYK2	FEDRATINIB
IKZF3	POMALIDOMIDE
CSK	PONATINIB
GRB2	DACTINOMYCIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
BLK	62	4
CSK	34	4
STAT3	18	4
STAT1	5	4
IKZF3	5	4
RPL41	1	4
TREH	1	2
ELMO1	1	2
DDX6	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
GENTAMICIN SULFATE	4	RPL41
AFATINIB	4	BLK
FEDRATINIB	4	BLK, CSK, TYK2
AXITINIB	4	BLK, CSK, TYK2
SORAFENIB	4	BLK, CSK
NERATINIB	4	BLK, CSK
IBRUTINIB	4	BLK, CSK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK, CSK
NILOTINIB	4	BLK, CSK
BOSUTINIB	4	BLK, CSK, TYK2
BRIGATINIB	4	BLK, CSK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK, TYK2
NINTEDANIB	4	BLK, TYK2
SUNITINIB	4	BLK, TYK2
DASATINIB	4	BLK, CSK, TYK2
ERLOTINIB	4	BLK, CSK, TYK2
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK, TYK2
MIDOSTAURIN	4	BLK, CSK, TYK2
GEFITINIB	4	BLK
IMATINIB	4	BLK, TYK2
FILGOTINIB	4	STAT1, TYK2
DEUCRAVACITINIB	4	STAT1, STAT3, TYK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 11.

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

Symbol	Assays	Type breakdown
STAT3	1,319	Binding:1304, Functional:12, Unclassified:2, ADMET:1
TYK2	1,083	Binding:1043, Functional:39, ADMET:1
CSK	535	Binding:531, ADMET:2, Functional:2
BLK	483	Binding:477, ADMET:4, Functional:2
STAT1	147	Binding:137, Functional:8, Unclassified:2
GRB2	134	Binding:132, Functional:2
GRM7	110	Binding:56, Functional:54
IKZF3	101	Binding:100, Functional:1
RPL41	89	Binding:89
IKZF2	26	Binding:26
STAT4	20	Binding:20
HLA-DRB1	17	Binding:17
DNPEP	11	Binding:10, ADMET:1
GRB10	9	Binding:9
SLC12A5	6	Functional:4, Binding:2
ELMO1	6	Binding:6
PRR12	6	Binding:6
FLG2	6	Binding:6
DNASE1L3	5	Binding:5
TREH	4	Binding:4
DDX6	4	Binding:4
ZBTB9	3	Binding:3
ESYT1	3	Binding:3
FLNB	2	Binding:2
HLA-DQA1	2	Binding:2
TNFAIP3	1	Binding:1
ORMDL3	1	Binding:1
TNPO3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase
TREH	3.2.1.28	alpha,alpha-trehalase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
PXDN	1.11.1.7	peroxidase
NMNAT2	2.7.7.1, 2.7.7.18	nicotinamide-nucleotide adenylyltransferase, nicotinate-nucleotide adenylyltransferase
POGLUT1	2.4.1.376, 2.4.2.63	EGF-domain serine glucosyltransferase, EGF-domain serine xylosyltransferase
CSK	2.7.10.2	non-specific protein-tyrosine kinase
YDJC	3.5.1.105	chitin disaccharide deacetylase
DDX6	3.6.4.13	RNA helicase
DGKQ	2.7.1.107	diacylglycerol kinase (ATP)
DNPEP	3.4.11.21	aspartyl aminopeptidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483
STAT1	147
STAT3	1,319
TYK2	1,083
IKZF3	101
CSK	535
GRB2	134
GRM7	110

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
GENTAMICIN SULFATE	4	RPL41
AFATINIB	4	BLK
FEDRATINIB	4	BLK, CSK, TYK2
AXITINIB	4	BLK, CSK, TYK2
SORAFENIB	4	BLK, CSK
NERATINIB	4	BLK, CSK
IBRUTINIB	4	BLK, CSK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK
VANDETANIB	4	BLK, CSK
NILOTINIB	4	BLK, CSK
BOSUTINIB	4	BLK, CSK, TYK2
BRIGATINIB	4	BLK, CSK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK, TYK2
SUNITINIB	4	BLK, TYK2
DASATINIB	4	BLK, CSK, TYK2
ERLOTINIB	4	BLK, CSK, TYK2
QUIZARTINIB	4	BLK
CRIZOTINIB	4	BLK, TYK2
MIDOSTAURIN	4	BLK, CSK, TYK2
GEFITINIB	4	BLK
IMATINIB	4	BLK, TYK2
FILGOTINIB	4	STAT1, TYK2
DEUCRAVACITINIB	4	STAT1, STAT3, TYK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	8	RPL41, BLK, STAT1, STAT3, TYK2, IKZF3, CSK, GRB2
B	Phased (≥1) drug, not yet approved	5	TREH, ELMO1, DDX6, PRR12, GRM7
C	Druggable family + PDB, no drug	15	FCGR2C, CD80, POGLUT1, CR1, CR2, DNASE1L3, DNPEP, KIAA0319L, FLNB, HLA-DPA1 (+5 more)
D	Druggable family + AlphaFold only, no drug	7	SLC26A1, PXDN, NMNAT2, ZPBP2, PXK, YDJC, DGKQ
E	Difficult family or no structure, no drug	40	SOX5, SPINK2, STAT4, TNFAIP3, TNFSF4, IKZF2, TIMMDC1, GSDMA, TSPAN32, SAMD9L (+30 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STAT4	20	TYK2, STAT1
FAM167A	0	BLK
FCGR2C	0	GRB2
ZPBP2	0	IKZF3
GSDMB	0	IKZF3
SLC26A1	0	—
SOX5	0	—
SPINK2	0	—
TNFAIP3	1	—
TNFSF4	0	—
IKZF2	26	—
TIMMDC1	0	—
GSDMA	0	—
TSPAN32	0	—
SAMD9L	0	—
SLC12A5	6	—
UNC45B	0	—
PXDN	0	—
SCHIP1	0	—
ORMDL3	1	—
CD247	0	—
NMNAT2	0	—
TNIP1	0	—
CD80	0	—
TNPO3	1	—
PSORS1C1	0	—
ANGPTL5	0	—
CHD7	0	—
SERAC1	0	—
GTF2H5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 606.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	333
PHASE2	81
PHASE1	60
PHASE1/PHASE2	38
PHASE3	31
EARLY_PHASE1	28
PHASE2/PHASE3	18
PHASE4	17

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05300932	PHASE4	ACTIVE_NOT_RECRUITING	A Study Evaluating the Efficacy and Safety of Baricitinib in Systemic Sclerosis
NCT05879419	PHASE4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT06546540	PHASE4	RECRUITING	The Safety and Efficacy of Telitacicept in the Treatment of Systemic Sclerosis
NCT06763783	PHASE4	ENROLLING_BY_INVITATION	Vaccination Against Herpes Zoster in Patients With Inflammatory Rheumatic Diseases
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT00204763	PHASE4	TERMINATED	Comparison of Esophageal and Anorectal Manometry Catheters
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT01051960	PHASE4	COMPLETED	Exercise Induced Pulmonary Hypertension in Systemic Sclerosis and Treatment With Ambrisentan
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01395732	PHASE4	COMPLETED	Bosentan in Systemic Sclerosis
NCT01497743	PHASE4	WITHDRAWN	Probiotics in Patients With Moderate-to-severe Distention/ Bloating From Systemic Sclerosis
NCT02480335	PHASE4	COMPLETED	The Clinical And Subclinical Effects on Arterial Stiffness of Bosentan in Patients With Systemic Sclerosis
NCT03155464	PHASE4	WITHDRAWN	Intraoperative ICG for Systemic Sclerosis
NCT03558854	PHASE4	COMPLETED	Evaluation of Effectiveness of Acetylsalicylic Acid on Markers of Vascular Dysfunction in Scleroderma Patients
NCT03692299	PHASE4	COMPLETED	Effectiveness of Saccharomyces Boulardii for Gastrointestinal Bacterial-overgrowth in Systemic Sclerosis
NCT04464434	PHASE4	COMPLETED	Upfront Autologous HSCT Versus Immunosuppression in Early Diffuse Cutaneous Systemic Sclerosis
NCT07472166	PHASE4	COMPLETED	Efficacy of Tofacitinib on Skin Thickening in Diffuse Cutaneous Systemic Sclerosis: A Comparative Study With Methotrexate
NCT05098704	PHASE2/PHASE3	RECRUITING	Preventive Effect of Clopidogrel on the Systemic Sclerosis Development Risk
NCT05198557	PHASE3	ACTIVE_NOT_RECRUITING	A Study of MT-0551 in Patients With Systemic Sclerosis
NCT05726630	PHASE3	ACTIVE_NOT_RECRUITING	Clinical Study of Divozilimab in Patients With Systemic Scleroderma
NCT05878717	PHASE2/PHASE3	RECRUITING	A Study of the Efficacy and Safety of Belimumab in Adults With Systemic Sclerosis Associated Interstitial Lung Disease
NCT05925803	PHASE3	ACTIVE_NOT_RECRUITING	Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY)
NCT06297096	PHASE3	RECRUITING	Study of the Efficacy of Nintedanib+Tocilizumab in Patients With Systemic Sclerosis and Interstitial Lung Disease
NCT07245238	PHASE3	RECRUITING	Topical Cannabidiol Lotion for Pruritus Relief in Scleroderma
NCT07335562	PHASE3	RECRUITING	A Study to Compare the Efficacy and Safety of BMS-986353 (Zolacabtagene- Autoleucel / Zola-cel), CD19-CAR T Cells, Versus Standard of Care in Participants With Active Systemic Sclerosis
NCT07497087	PHASE3	NOT_YET_RECRUITING	A Study to Test Whether Nerandomilast Helps People With Systemic Sclerosis
NCT00004563	PHASE3	COMPLETED	Scleroderma Lung Disease
NCT00004786	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Oral Iloprost for Raynaud’s Phenomenon Secondary to Systemic Sclerosis
NCT00025818	PHASE3	COMPLETED	Six Month Clinical Research Study for Patients With Moderate or Severe Dry Eye Syndrome
NCT00070590	PHASE2/PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan in Pulmonary Fibrosis Associated With Scleroderma
NCT00077584	PHASE3	COMPLETED	Efficacy and Safety of Oral Bosentan on Healing/Prevention of Digital (Finger) Ulcers in Patients With Scleroderma
NCT00114530	PHASE2/PHASE3	COMPLETED	Scleroderma: Cyclophosphamide or Transplantation
NCT00319033	PHASE2/PHASE3	COMPLETED	Open-label Study With Bosentan in Interstitial Lung Disease
NCT00348296	PHASE3	COMPLETED	Efficacy and Safety Study of GB-0998 for Treatment of Systemic Sclerosis
NCT00419419	PHASE3	COMPLETED	Phase III Study of a Topical Gel Formulation for Treatment and Prevention of Raynaud’s Phenomenon
NCT00428883	PHASE2/PHASE3	UNKNOWN	High Dose Intravenous N-Acetylcysteine Versus Iloprost for Early, Rapidly Progressive Diffuse Systemic Sclerosis
NCT00463125	PHASE2/PHASE3	UNKNOWN	Platelet Gel in Systemic Sclerosis
NCT00498615	PHASE3	COMPLETED	A Rho-kinase Inhibitor (Fasudil) in the Treatment of Raynaud’s Phenomenon
NCT00501995	PHASE3	COMPLETED	High Dose Cyclophosphamide for Treatment of Scleroderma
NCT00704665	PHASE3	COMPLETED	Recombinant Human Relaxin in the Treatment of Diffuse Scleroderma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BOSENTAN	4	10
2-MERCAPTOETHANESULFONIC ACID	4	4
AMBRISENTAN	4	4
TOFACITINIB	4	4
BELIMUMAB	4	3
CYCLOPHOSPHAMIDE ANHYDROUS	4	3
NINTEDANIB	4	3
PIRFENIDONE	4	3
TREPROSTINIL DIOLAMINE	4	3
ANIFROLUMAB	4	2
DASATINIB ANHYDROUS	4	2
FLUDARABINE PHOSPHATE	4	2
ILOPROST	4	2
INDOCYANINE GREEN ACID FORM	4	2
INEBILIZUMAB	4	2
LACTIC ACID	4	2
MYCOPHENOLIC ACID	4	2
NEMOLIZUMAB	4	2
PLERIXAFOR	4	2
RIOCIGUAT	4	2
TADALAFIL	4	2
ABATACEPT	4	1
ACETYLCYSTEINE	4	1
ALBUMIN HUMAN	4	1
BARICITINIB	4	1
BRENTUXIMAB VEDOTIN	4	1
BRODALUMAB	4	1
BUSPIRONE	4	1
CALCIPOTRIENE	4	1
CHOLECALCIFEROL	4	1