Systemic lupus erythematosus

Summary

Systemic lupus erythematosus (MONDO:0007915) is a disease (an umbrella term covering 12 Mondo subtypes) caused by variants in SAT1 and TREX1, with 72 cohort genes (1,562 GWAS associations across 88 studies) and 1,027 clinical trials. The dominant Reactome pathway is Cytokine Signaling in Immune system (17 cohort genes). Top therapeutic interventions include belimumab, anifrolumab, and cravacitinib.

At a glance

• Prevalence: 1-5 / 10 000 (Worldwide) [Orphanet-validated]
• Causal genes: SAT1 (GenCC Strong), TREX1 (GenCC Strong)
• Umbrella term: 12 Mondo subtypes
• Cohort genes: 72
• GWAS associations: 1,562
• ClinVar variants: 85
• Phenotypes (HPO): 44
• Clinical trials: 1,027

Clinical features

Epidemiology

Prevalence records

11 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	5.14	Worldwide	Validated
Point prevalence	1-5 / 10 000	43.7	Worldwide	Validated
Point prevalence	1-5 / 10 000		Europe	Validated
Annual incidence	6-9 / 10 000	81.84	Poland	Validated
Point prevalence	1-5 / 10 000	47	France	Validated
Point prevalence	6-9 / 10 000	64.2	Martinique	Validated
Point prevalence	1-5 / 10 000	14.7	New Zealand	Validated
Point prevalence	1-5 / 10 000	20.6	Korea, Republic of	Validated
Point prevalence	1-5 / 10 000	53.6	United States	Validated
Point prevalence	1-5 / 10 000	37	Taiwan, Province of China	Validated
Point prevalence	1-5 / 10 000	28	Finland	Validated

Signs & symptoms

Clinical features (HPO)

44 HPO clinical features (Orphanet curated; top 44 by frequency):

HPO ID	Term	Frequency
HP:0000093	Proteinuria	Very frequent (80-99%)
HP:0001824	Weight loss	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002039	Anorexia	Very frequent (80-99%)
HP:0003493	Antinuclear antibody positivity	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0033834	Malaise	Very frequent (80-99%)
HP:0033726	Lupus nephritis	Frequent (30-79%)
HP:0034076	Anti-ribosome Po antibody positivity	Frequent (30-79%)
HP:0034077	Anti-complement component C1q antibody positivity	Frequent (30-79%)
HP:0045042	Decreased circulating complement C4 concentration	Frequent (30-79%)
HP:5000038	Anti-titin antibody positivity	Frequent (30-79%)
HP:0000790	Hematuria	Frequent (30-79%)
HP:0000822	Hypertension	Frequent (30-79%)
HP:0001369	Arthritis	Frequent (30-79%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0001882	Leukopenia	Frequent (30-79%)
HP:0003453	Antineutrophil antibody positivity	Frequent (30-79%)
HP:0005421	Decreased circulating complement C3 concentration	Frequent (30-79%)
HP:0005764	Polyarticular arthritis	Frequent (30-79%)
HP:0012085	Pyuria	Frequent (30-79%)
HP:0025300	Malar rash	Frequent (30-79%)
HP:0030880	Raynaud phenomenon	Frequent (30-79%)
HP:0000155	Oral ulcer	Occasional (5-29%)
HP:0000716	Depression	Occasional (5-29%)
HP:0000992	Cutaneous photosensitivity	Occasional (5-29%)
HP:0001250	Seizure	Occasional (5-29%)
HP:0001873	Thrombocytopenia	Occasional (5-29%)
HP:0001878	Hemolytic anemia	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0007417	Discoid lupus rash	Occasional (5-29%)
HP:0020151	Anti-dsDNA antibody positivity	Occasional (5-29%)
HP:0032235	Anti-La/SS-B antibody positivity	Occasional (5-29%)
HP:0033028	Anti-U1 ribonucleoprotein antibody positivity	Occasional (5-29%)
HP:0033040	Anti-Sm antibody positivity	Occasional (5-29%)
HP:0033556	Anti-nucleoporin 62 antibody positivity	Occasional (5-29%)
HP:0034093	Anti-Ro52/TRIM21 antibody positivity	Occasional (5-29%)
HP:0034096	Anti-phosphatidic acid antibody positivity	Occasional (5-29%)
HP:0045073	Serositis	Occasional (5-29%)
HP:0100669	Abnormal pigmentation of the oral mucosa	Occasional (5-29%)
HP:0100755	Abnormality of salivation	Occasional (5-29%)
HP:0100825	Cheilitis	Occasional (5-29%)
HP:0000488	Retinopathy	Very rare (<1-4%)
HP:0002072	Chorea	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	systemic lupus erythematosus
Mondo ID	MONDO:0007915
MeSH	D008180
OMIM	152700, 601744
Orphanet	536
DOID	DOID:9074
ICD-10-CM	M32
ICD-11	749596428
NCIT	C3201
SNOMED CT	55464009
UMLS	C0024141
MedGen	6146
NORD	1380
Is cancer (heuristic)	no

Also known as: disseminated lupus erythematosus · lupus erythematosus, systemic · SLE · SLE - lupus erythematosus, systemic · systemic lupus erythematosus · systemic lupus erythematosus (disease) · systemic lupus erythematosus susceptibility to

Data availability: 85 ClinVar variants · 1,562 GWAS associations (88 studies) · 38 GenCC gene-disease records · 1 HPO phenotype · 61 cell lines.

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › connective tissue disorder › rheumatic disorder › lupus erythematosus › systemic lupus erythematosus

Related subtypes (2): cutaneous lupus erythematosus, drug-induced lupus erythematosus

Subtypes (12): autosomal systemic lupus erythematosus type 16, neonatal lupus erythematosus, pediatric systemic lupus erythematosus, central nervous system lupus, bullous systemic lupus erythematosus, systemic lupus erythematosus related to C4A, systemic lupus erythematosus 17, systemic lupus erythematosus related to C1QA, systemic lupus erythematosus related to C1S, systemic lupus erythematosus 18, systemic lupus erythematosus related to C1QC, systemic lupus erythematosus related to C1QB

Genetics & variants

GWAS landscape

1,562 GWAS associations across 88 studies. Top hits map to 24 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs117026326	2e-298	GTF2I-AS1, GTF2I	T	2.14
rs7800325	1e-280	GTF2I-AS1	T	0.45
rs199789198	3e-194	NCF1	A	3.1
rs1270942	2e-165	CFB	C	2.28
rs11889341	5e-123	STAT4	T	1.41
rs1150755	6e-117	TNXB	?	1.3
DQA1*05:01	9e-112		?	1.74
DQB1*02:01	1e-110		?	1.75
rs10488631	9e-110	IRF5 - TNPO3	C	1.92
DRB1*03:01	2e-109		?	1.73
rs1150757	6e-107	TNXB	A	2.33
B*08:01	9e-105		?	1.94
rs35000415	1e-99	IRF5	?	1.82
rs114092478	3e-93	MTCO3P1 - HLA-DQB3	T	2
rs114090659	6e-92	NAPGP2 - MUC21	C	1.99
rs2205960	3e-90	TNFSF4	T	1.37
rs17849501	3e-88	SMG7, NCF2	T	2.1
rs34572943	9e-85	ITGAM	?	1.68
rs9494894	3e-84	TNFAIP3 - LINC02865	T	0.59
rs73366469	3e-81	GTF2I-AS1	C	2.52
rs3757387	9e-79	IRF5	T	0.69
rs7568275	1e-77	STAT4	?	1.42
C*07:01	6e-74		?	1.47
rs28359827	2e-71	MICA-AS1	A	2.92
rs12706861	4e-71	TNPO3	?	1.76
rs2736332	2e-70	FAM167A - BLK	C	1.36
rs7582694	4e-69	STAT4	?	1.56
rs34723256	4e-68	HLA-DQB1 - MTCO3P1	A	2.28
rs143176121	2e-66	GTF2I-AS1, GTF2I	T	0.29
rs1143679	3e-62	ITGAM	?	1.72

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011956	Yin X	2020	13,377	194,993	Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus.
GCST005752	Langefeld CD	2017	6,748	11,516	Transancestral mapping and genetic load in systemic lupus erythematosus.
GCST007400	Langefeld CD	2017	6,748	11,516	Transancestral mapping and genetic load in systemic lupus erythematosus.
GCST003155	Bentham J	2015	5,201	9,066	Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.
GCST003156	Bentham J	2015	5,201	9,066	Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.
GCST011661	Zhang F	2020	4,943	8,483	Independent Replication on Genome-Wide Association Study Signals Identifies IRF3 as a Novel Locus for Systemic Lupus Erythematosus.
GCST005831	Julia A	2018	4,943	8,483	Genome-wide association study meta-analysis identifies five new loci for systemic lupus erythematosus.
GCST011491	Song Q	2021	4,734	9,425	Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus.
GCST011493	Song Q	2021	4,734	9,425	Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus.
GCST007278	Acosta-Herrera M	2018	4,595	19,704	Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	3
Tier 3: regulatory	0
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	39
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	9
unknown	6
splice_region_variant	2
synonymous_variant	2
missense_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs117026326	7	74711703	C>T	0.175	intron_variant	GTF2I-AS1, GTF2I	2e-298	Tier 4: intronic/intergenic
rs7800325	7	74618332	T>C	0.174	intron_variant	GTF2I-AS1	1e-280	Tier 4: intronic/intergenic
rs199789198	7	74781840	C>A	0.073	intron_variant	NCF1	3e-194	Tier 4: intronic/intergenic
rs1270942	6	31951083	A>C,G,T	0.05	splice_region_variant	CFB	2e-165	Tier 2: splice/UTR
rs11889341	2	191079016	C>T	0.348	intron_variant	STAT4	5e-123	Tier 4: intronic/intergenic
rs1150755	6	32070773	C>A,G,T	0.05	intron_variant	TNXB	6e-117	Tier 4: intronic/intergenic
DQA1*05:01							9e-112	Tier 4: intronic/intergenic
DQB1*02:01							1e-110	Tier 4: intronic/intergenic
rs10488631	7	128954129	T>C	0.05	intergenic_variant	IRF5 - TNPO3	9e-110	Tier 4: intronic/intergenic
DRB1*03:01							2e-109	Tier 4: intronic/intergenic
rs1150757	6	32061428	G>A,C	0.05	synonymous_variant	TNXB	6e-107	Tier 4: intronic/intergenic
B*08:01							9e-105	Tier 4: intronic/intergenic
rs35000415	7	128945562	C>T	0.05	intron_variant	IRF5	1e-99	Tier 4: intronic/intergenic
rs114092478	6	32714358			intergenic_variant	MTCO3P1 - HLA-DQB3	3e-93	Tier 4: intronic/intergenic
rs114090659	6	30973212			intergenic_variant	NAPGP2 - MUC21	6e-92	Tier 4: intronic/intergenic
rs2205960	1	173222336	G>A,T	0.265	intron_variant	TNFSF4	3e-90	Tier 4: intronic/intergenic
rs17849501	1	183573188	C>T	0.05	synonymous_variant	SMG7, NCF2	3e-88	Tier 4: intronic/intergenic
rs34572943	16	31261032	G>A	0.05	intron_variant	ITGAM	9e-85	Tier 4: intronic/intergenic
rs9494894	6	137907383	T>A,C	0.059	intergenic_variant	TNFAIP3 - LINC02865	3e-84	Tier 4: intronic/intergenic
rs73366469	7	74619286	T>C	0.18	intron_variant	GTF2I-AS1	3e-81	Tier 4: intronic/intergenic
rs3757387	7	128936032	T>C	0.137	intergenic_variant	IRF5	9e-79	Tier 4: intronic/intergenic
rs7568275	2	191101726	G>C,T	0.05	intron_variant	STAT4	1e-77	Tier 4: intronic/intergenic
C*07:01							6e-74	Tier 4: intronic/intergenic
rs28359827	6	31392867	ATT>A,AT,ATTT,ATTTT,ATTTTT,ATTTTTT,ATTTTTTT	0.077	intron_variant	MICA-AS1	2e-71	Tier 4: intronic/intergenic
rs12706861	7	128976528	C>T	0.05	intron_variant	TNPO3	4e-71	Tier 4: intronic/intergenic
rs2736332	8	11482456	G>C,T	0.266	intergenic_variant	FAM167A - BLK	2e-70	Tier 4: intronic/intergenic
rs7582694	2	191105394	C>G	0.05	intron_variant	STAT4	4e-69	Tier 4: intronic/intergenic
rs34723256	6	32690917	T>A,C,G	0.059	intergenic_variant	HLA-DQB1 - MTCO3P1	4e-68	Tier 4: intronic/intergenic
rs143176121	7	74694107	T>C	0.02	intron_variant	GTF2I-AS1, GTF2I	2e-66	Tier 4: intronic/intergenic
rs1143679	16	31265490	G>A,T	0.05	missense_variant	ITGAM	3e-62	Tier 1: coding

ClinVar germline variants

85 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 17 conflicting classifications of pathogenicity, 13 benign, 12 benign/likely benign, 10 pathogenic/likely pathogenic, 7 pathogenic, 4 likely pathogenic, 1 association

ClinVar	Variant (HGVS)	Gene	Classification	Review
126389	NM_033629.6(TREX1):c.500del (p.Ser167fs)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
225499	NM_033629.6(TREX1):c.294dup (p.Cys99fs)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282766	NM_033629.6(TREX1):c.144dup (p.Thr49fs)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282767	NM_033629.6(TREX1):c.152_153del (p.Gln51fs)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4179	NM_033629.6(TREX1):c.341G>A (p.Arg114His)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
839889	NM_033629.6(TREX1):c.236_243dup (p.Ser82fs)	ATRIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
619204	NM_001715.3(BLK):c.1048T>C (p.Tyr350His)	BLK	Pathogenic	no assertion criteria provided
619203	NM_001715.3(BLK):c.919C>G (p.Pro307Ala)	BLK-AS1	Pathogenic	no assertion criteria provided
161109	NM_005214.5(CTLA4):c.151C>T (p.Arg51Ter)	CTLA4	Pathogenic	reviewed by expert panel
636389	NM_005214.5(CTLA4):c.457G>A (p.Asp153Asn)	CTLA4	Pathogenic	reviewed by expert panel
977215	NM_003745.2(SOCS1):c.64C>T (p.Arg22Trp)	LOC130058479	Pathogenic/Likely pathogenic	no assertion criteria provided
977216	NM_003745.2(SOCS1):c.460T>C (p.Tyr154His)	SOCS1	Pathogenic/Likely pathogenic	no assertion criteria provided
1330375	NM_016562.4(TLR7):c.1521T>G (p.Phe507Leu)	TLR7	Pathogenic	no assertion criteria provided
4086267	NM_016562.4(TLR7):c.1520T>C (p.Phe507Ser)	TLR7	Pathogenic	no assertion criteria provided
126393	NM_033629.6(TREX1):c.868_885del (p.Pro290_Ala295del)	TREX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2939141	NM_033629.6(TREX1):c.294_296dup (p.Cys99Ter)	TREX1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
930977	NM_033629.6(TREX1):c.856_865dup (p.Ala289fs)	TREX1	Pathogenic	criteria provided, single submitter
4181	NM_033629.6(TREX1):c.599_601dup (p.Asp200dup)	ATRIP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4183	NM_033629.6(TREX1):c.375dup (p.Gly126fs)	ATRIP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
432079	NM_005214.5(CTLA4):c.410C>T (p.Pro137Leu)	CTLA4	Likely pathogenic	reviewed by expert panel
3067943	NM_005223.4(DNASE1):c.91C>T (p.Gln31Ter)	DNASE1	Likely pathogenic	criteria provided, single submitter
209198	NM_033629.6(TREX1):c.340C>T (p.Arg114Cys)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
225498	NM_033629.6(TREX1):c.290G>A (p.Arg97His)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
381689	NM_033629.6(TREX1):c.667G>A (p.Ala223Thr)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
522920	NM_033629.6(TREX1):c.218C>T (p.Pro73Leu)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
931952	NM_033629.6(TREX1):c.1A>G (p.Met1Val)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
953494	NM_033629.6(TREX1):c.23dup (p.Pro10fs)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96242	NM_033629.6(TREX1):c.797A>G (p.Glu266Gly)	ATRIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361476	NM_001715.3(BLK):c.187G>A (p.Val63Met)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
361491	NM_001715.3(BLK):c.1057C>T (p.Arg353Cys)	BLK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 108 · Orphanet: 133 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 23

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

Gene	HGNC	Evidence routes
BLK	BLK	GWAS, GenCC, Orphanet
BANK1	BANK1	GWAS, GenCC, Orphanet
CTLA4	CTLA4	GWAS, GenCC, Orphanet
IRF5	IRF5	GWAS, GenCC, Orphanet
STAT4	STAT4	GWAS, GenCC, Orphanet
TNFAIP3	TNFAIP3	GWAS, GenCC, Orphanet
TNFSF4	TNFSF4	GWAS, GenCC, Orphanet
UBE2L3	UBE2L3	GWAS, GenCC, Orphanet
TNIP1	TNIP1	GWAS, GenCC, Orphanet
SOCS1	SOCS1	GWAS, Orphanet
PXK	PXK	GWAS, GenCC, Orphanet
JAZF1	JAZF1	GWAS, GenCC, Orphanet
KIAA0319L	KIAA0319L	GWAS, GenCC, Orphanet
ETS1	ETS1	GWAS, GenCC, Orphanet
FCGR2A	FCGR2A	GWAS
FCGR2B	FCGR2B	GWAS, GenCC, Orphanet
FCGR3B	FCGR3B	GWAS, GenCC, Orphanet
HLA-DRB1	HLA-DRB1	GWAS, GenCC, Orphanet
IL10	IL10	GWAS, GenCC, Orphanet
IRAK1	IRAK1	GWAS, GenCC, Orphanet
ITGAM	ITGAM	GWAS, GenCC, Orphanet
MECP2	MECP2	GWAS, GenCC, Orphanet
PTPN22	PTPN22	GWAS, GenCC, Orphanet

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
SAT1	Strong	X-linked	systemic lupus erythematosus
SLC38A1	Strong	X-linked	systemic lupus erythematosus	2
TREX1	Strong	Autosomal dominant	retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations	17
P2RY8	Moderate	Autosomal dominant	systemic lupus erythematosus
TLR7	Moderate	X-linked	systemic lupus erythematosus 17	5
BANK1	Supportive	Unknown	systemic lupus erythematosus
BLK	Supportive	Unknown	systemic lupus erythematosus	5
C4A	Supportive	Unknown	systemic lupus erythematosus	6
C4B	Supportive	Unknown	systemic lupus erythematosus	3
CR2	Supportive	Unknown	systemic lupus erythematosus	5
CTLA4	Supportive	Unknown	systemic lupus erythematosus	4
CXXC1	Supportive	Unknown	systemic lupus erythematosus
DNASE1	Supportive	Autosomal dominant	autosomal systemic lupus erythematosus type 16	4
ETS1	Supportive	Unknown	systemic lupus erythematosus	4
FCGR2B	Supportive	Unknown	systemic lupus erythematosus	3
FCGR3B	Supportive	Unknown	systemic lupus erythematosus
HLA-DRB1	Supportive	Unknown	systemic lupus erythematosus
IL10	Supportive	Unknown	systemic lupus erythematosus	5
IRAK1	Supportive	Unknown	systemic lupus erythematosus	2
IRF5	Supportive	Unknown	systemic lupus erythematosus
ITGAM	Supportive	Unknown	systemic lupus erythematosus
JAZF1	Supportive	Unknown	systemic lupus erythematosus
KIAA0319L	Supportive	Unknown	systemic lupus erythematosus
MECP2	Supportive	Unknown	systemic lupus erythematosus	13
PTPN22	Supportive	Unknown	systemic lupus erythematosus	4
PXK	Supportive	Unknown	systemic lupus erythematosus
SPP1	Supportive	Unknown	systemic lupus erythematosus
STAT4	Supportive	Unknown	systemic lupus erythematosus	3
TNFAIP3	Supportive	Unknown	systemic lupus erythematosus	5
TNFSF4	Supportive	Unknown	systemic lupus erythematosus	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BLK	Orphanet:536	Systemic lupus erythematosus
BLK	Orphanet:552	MODY
BANK1	Orphanet:536	Systemic lupus erythematosus
CTLA4	Orphanet:2584	Classic mycosis fungoides
CTLA4	Orphanet:3162	Sézary syndrome
CTLA4	Orphanet:391490	Adult-onset myasthenia gravis
CTLA4	Orphanet:436159	Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency
CTLA4	Orphanet:536	Systemic lupus erythematosus
CTLA4	Orphanet:900	Granulomatosis with polyangiitis
IRF5	Orphanet:186	Primary biliary cholangitis
IRF5	Orphanet:220393	Diffuse cutaneous systemic sclerosis
IRF5	Orphanet:220402	Limited cutaneous systemic sclerosis
IRF5	Orphanet:536	Systemic lupus erythematosus
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
TREX1	Orphanet:247691	Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations
TREX1	Orphanet:481662	Familial Chilblain lupus
TREX1	Orphanet:51	Aicardi-Goutières syndrome
TREX1	Orphanet:536	Systemic lupus erythematosus
UBE2L3	Orphanet:536	Systemic lupus erythematosus
TLR7	Orphanet:536	Systemic lupus erythematosus
TNIP1	Orphanet:536	Systemic lupus erythematosus
SOCS1	Orphanet:619948	Early-onset autoimmunity-autoinflammation-immunodeficiency syndrome due to SOCS1 haploinsufficiency
PXK	Orphanet:536	Systemic lupus erythematosus
JAZF1	Orphanet:213711	Endometrial stromal sarcoma
JAZF1	Orphanet:536	Systemic lupus erythematosus
DNASE1	Orphanet:300345	Autosomal systemic lupus erythematosus
DNASE1	Orphanet:536	Systemic lupus erythematosus
KIAA0319L	Orphanet:220402	Limited cutaneous systemic sclerosis
KIAA0319L	Orphanet:536	Systemic lupus erythematosus
ETS1	Orphanet:536	Systemic lupus erythematosus
FCGR2B	Orphanet:536	Systemic lupus erythematosus
FCGR3B	Orphanet:464370	Neonatal alloimmune neutropenia
FCGR3B	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:2073	Narcolepsy type 1
HLA-DRB1	Orphanet:220393	Diffuse cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220402	Limited cutaneous systemic sclerosis
HLA-DRB1	Orphanet:220407	Limited systemic sclerosis
HLA-DRB1	Orphanet:3437	Vogt-Koyanagi-Harada disease
HLA-DRB1	Orphanet:397	Giant cell arteritis
HLA-DRB1	Orphanet:477738	Pediatric multiple sclerosis
HLA-DRB1	Orphanet:536	Systemic lupus erythematosus
HLA-DRB1	Orphanet:545	Follicular lymphoma

Cohort genes → proteins

72 cohort genes, 72 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	38
gwas_and_gencc	17
gwas_and_clinvar	2
multi_evidence	15

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BLK	HGNC:1057	ENSG00000136573	P51451	Tyrosine-protein kinase Blk	gwas,gencc,clinvar
BANK1	HGNC:18233	ENSG00000153064	Q8NDB2	B-cell scaffold protein with ankyrin repeats	gwas,gencc,clinvar
CTLA4	HGNC:2505	ENSG00000163599	P16410	Cytotoxic T-lymphocyte protein 4	gwas,gencc,clinvar
IRF5	HGNC:6120	ENSG00000128604	Q13568	Interferon regulatory factor 5	gwas,gencc,clinvar
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas,gencc
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas,gencc
TNFSF4	HGNC:11934	ENSG00000117586	P23510	Tumor necrosis factor ligand superfamily member 4	gwas,gencc
TREX1	HGNC:12269	ENSG00000213689	Q9NSU2	Three-prime repair exonuclease 1	gencc,clinvar
UBE2L3	HGNC:12488	ENSG00000185651	P68036	Ubiquitin-conjugating enzyme E2 L3	gwas,gencc
TLR7	HGNC:15631	ENSG00000196664	Q9NYK1	Toll-like receptor 7	gencc,clinvar
TNIP1	HGNC:16903	ENSG00000145901	Q15025	TNFAIP3-interacting protein 1	gwas,gencc
SOCS1	HGNC:19383	ENSG00000185338	O15524	Suppressor of cytokine signaling 1	gwas,clinvar
PXK	HGNC:23326	ENSG00000168297	Q7Z7A4	PX domain-containing protein kinase-like protein	gwas,gencc
JAZF1	HGNC:28917	ENSG00000153814	Q86VZ6	Juxtaposed with another zinc finger protein 1	gwas,gencc
DNASE1	HGNC:2956	ENSG00000213918	P24855	Deoxyribonuclease-1	gencc,clinvar
KIAA0319L	HGNC:30071	ENSG00000142687	Q8IZA0	Dyslexia-associated protein KIAA0319-like protein	gwas,gencc
ETS1	HGNC:3488	ENSG00000134954	P14921	Protein C-ets-1	gwas,gencc
FCGR2A	HGNC:3616	ENSG00000143226	P12318	Low affinity immunoglobulin gamma Fc region receptor II-a	gwas,clinvar
FCGR2B	HGNC:3618	ENSG00000072694	P31994	Low affinity immunoglobulin gamma Fc region receptor II-b	gwas,gencc
FCGR3B	HGNC:3620	ENSG00000162747	O75015	Low affinity immunoglobulin gamma Fc region receptor III-B	gwas,gencc
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas,gencc
IL10	HGNC:5962	ENSG00000136634	P22301	Interleukin-10	gwas,gencc
IRAK1	HGNC:6112	ENSG00000184216	P51617	Interleukin-1 receptor-associated kinase 1	gwas,gencc
ITGAM	HGNC:6149	ENSG00000169896	P11215	Integrin alpha-M	gwas,gencc
MECP2	HGNC:6990	ENSG00000169057	P51608	Methyl-CpG-binding protein 2	gwas,gencc
PTPN22	HGNC:9652	ENSG00000134242	Q9Y2R2	Tyrosine-protein phosphatase non-receptor type 22	gwas,gencc
SAT1	HGNC:10540	ENSG00000130066	P21673	Diamine acetyltransferase 1	gencc
SPP1	HGNC:11255	ENSG00000118785	P10451	Osteopontin	gencc
C4A	HGNC:1323	ENSG00000244731	P0C0L4	Complement C4-A	gencc
C4B	HGNC:1324	ENSG00000224389	P0C0L5	Complement C4-B	gencc
SLC38A1	HGNC:13447	ENSG00000111371	Q9H2H9	Sodium-coupled neutral amino acid symporter 1	gencc
P2RY8	HGNC:15524	ENSG00000182162	Q86VZ1	S-geranylgeranyl-glutathione receptor P2RY8	gencc
CR2	HGNC:2336	ENSG00000117322	P20023	Complement receptor type 2	gencc
CXXC1	HGNC:24343	ENSG00000154832	Q9P0U4	CXXC-type zinc finger protein 1	gencc
RPS20	HGNC:10405	ENSG00000008988	P60866	Small ribosomal subunit protein uS10	gwas
BIN1	HGNC:1052	ENSG00000136717	O00499	Myc box-dependent-interacting protein 1	gwas
ATXN1	HGNC:10548	ENSG00000124788	P54253	Ataxin-1	gwas
ATXN2	HGNC:10555	ENSG00000204842	Q99700	Ataxin-2	gwas
SCN10A	HGNC:10582	ENSG00000185313	Q9Y5Y9	Sodium channel protein type 10 subunit alpha	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
CCL22	HGNC:10621	ENSG00000102962	O00626	C-C motif chemokine 22	gwas
ST8SIA4	HGNC:10871	ENSG00000113532	Q92187	CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase	gwas
SIGLEC5	HGNC:10874	ENSG00000105501	O15389	Sialic acid-binding Ig-like lectin 5	gwas
SKP1	HGNC:10899	ENSG00000113558	P63208	S-phase kinase-associated protein 1	gwas
SLC12A1	HGNC:10910	ENSG00000074803	Q13621	Solute carrier family 12 member 1	gwas
SLC17A4	HGNC:10932	ENSG00000146039	Q9Y2C5	Probable small intestine urate exporter	gwas
SLC1A7	HGNC:10945	ENSG00000162383	O00341	Excitatory amino acid transporter 5	gwas
SLC7A8	HGNC:11066	ENSG00000092068	Q9UHI5	Large neutral amino acids transporter small subunit 2	gwas
SNRPC	HGNC:11157	ENSG00000124562	P09234	U1 small nuclear ribonucleoprotein C	gwas
STAT1	HGNC:11362	ENSG00000115415	P42224	Signal transducer and activator of transcription 1-alpha/beta	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BLK	Tyrosine-protein kinase Blk	Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.
BANK1	B-cell scaffold protein with ankyrin repeats	Involved in B-cell receptor (BCR)-induced Ca(2+) mobilization from intracellular stores.
CTLA4	Cytotoxic T-lymphocyte protein 4	Inhibitory receptor acting as a major negative regulator of T-cell responses.
IRF5	Interferon regulatory factor 5	Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9.
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.
TREX1	Three-prime repair exonuclease 1	Major cellular 3’-to-5’ DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3’ termini.
UBE2L3	Ubiquitin-conjugating enzyme E2 L3	Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases.
TLR7	Toll-like receptor 7	Endosomal receptor that plays a key role in innate and adaptive immunity.
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.
SOCS1	Suppressor of cytokine signaling 1	Essential negative regulator of type I and type II interferon (IFN) signaling, as well as that of other cytokines, including IL2, IL4, IL6 and leukemia inhibitory factor (LIF).
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.
JAZF1	Juxtaposed with another zinc finger protein 1	Acts as a transcriptional corepressor of orphan nuclear receptor NR2C2.
DNASE1	Deoxyribonuclease-1	Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs.
KIAA0319L	Dyslexia-associated protein KIAA0319-like protein	Possible role in axon guidance through interaction with RTN4R.
ETS1	Protein C-ets-1	Transcription factor.
FCGR2A	Low affinity immunoglobulin gamma Fc region receptor II-a	Binds to the Fc region of immunoglobulins gamma.
FCGR2B	Low affinity immunoglobulin gamma Fc region receptor II-b	Receptor for the Fc region of complexed or aggregated immunoglobulins gamma.
FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	Receptor for the Fc region of immunoglobulins gamma.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IRAK1	Interleukin-1 receptor-associated kinase 1	Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.
ITGAM	Integrin alpha-M	Integrin ITGAM/ITGB2 is implicated in various adhesive interactions of monocytes, macrophages and granulocytes as well as in mediating the uptake of complement-coated particles and pathogens.
MECP2	Methyl-CpG-binding protein 2	Chromosomal protein that binds to methylated DNA.
PTPN22	Tyrosine-protein phosphatase non-receptor type 22	Acts as a negative regulator of T-cell receptor (TCR) signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules.
SAT1	Diamine acetyltransferase 1	Enzyme which catalyzes the acetylation of polyamines.
SPP1	Osteopontin	Major non-collagenous bone protein that binds tightly to hydroxyapatite.
C4A	Complement C4-A	Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune sy…
C4B	Complement C4-B	Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune sy…
SLC38A1	Sodium-coupled neutral amino acid symporter 1	Symporter that cotransports short-chain neutral amino acids and sodium ions from the extracellular to the intracellular side of the cell membrane.
P2RY8	S-geranylgeranyl-glutathione receptor P2RY8	G protein-coupled receptor for S-geranylgeranyl-glutathione (GGG), an endogenous metabolite present in lymphoid tissues.
CR2	Complement receptor type 2	Serves as a receptor for various ligands including complement component CD3d, HNRNPU OR IFNA1.
CXXC1	CXXC-type zinc finger protein 1	Transcriptional activator that exhibits a unique DNA binding specificity for CpG unmethylated motifs with a preference for CpGG.
RPS20	Small ribosomal subunit protein uS10	Component of the small ribosomal subunit.
BIN1	Myc box-dependent-interacting protein 1	Is a key player in the control of plasma membrane curvature, membrane shaping and membrane remodeling.
ATXN1	Ataxin-1	Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor.
ATXN2	Ataxin-2	Involved in EGFR trafficking, acting as negative regulator of endocytic EGFR internalization at the plasma membrane.
SCN10A	Sodium channel protein type 10 subunit alpha	Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes.
CXCR5	C-X-C chemokine receptor type 5	Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
CCL22	C-C motif chemokine 22	May play a role in the trafficking of activated/effector T-lymphocytes to inflammatory sites and other aspects of activated T-lymphocyte physiology.
ST8SIA4	CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferase	Catalyzes the transfer of a sialic acid from a CMP-linked sialic acid donor onto a terminal alpha-2,3-, alpha-2,6-, or alpha-2,8-linked sialic acid of an N-linked glycan protein acceptor through alpha-2,8-linkages.
SIGLEC5	Sialic acid-binding Ig-like lectin 5	Putative adhesion molecule that mediates sialic-acid dependent binding to cells.
SKP1	S-phase kinase-associated protein 1	Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription.
SLC12A1	Solute carrier family 12 member 1	Renal sodium, potassium and chloride non-electrogenic ion symporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation.
SLC17A4	Probable small intestine urate exporter	Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions.
SLC1A7	Excitatory amino acid transporter 5	Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate.
SLC7A8	Large neutral amino acids transporter small subunit 2	Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1.
SNRPC	U1 small nuclear ribonucleoprotein C	Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5’ splice-site and the subsequent assembly of the spliceosome.
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.

Protein-family classification

Druggable: 29 · Difficult: 13 · Unknown: 30 · Druggable fraction: 0.4

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	9	3.6×	0.008
Complement	3	11.2×	0.014
Phosphatase	2	2.3×	0.575
Transporter	2	2.2×	0.575
Kinase	4	1.5×	0.575
Scaffold/PPI	5	1.2×	0.741
Ion channel	1	1.6×	0.751
Enzyme (other)	6	1.0×	0.773
Transcription factor	8	0.9×	0.803
GPCR	2	0.7×	0.890
Other/Unknown	30	0.8×	0.994

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BLK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
BANK1	Scaffold/PPI	no		TIR_dom, DBB_domain, Toll_tir_struct_dom_sf
CTLA4	Antibody/Immunoglobulin	yes		Ig_sub, CTLA4, Ig_V-set
IRF5	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_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
TREX1	Enzyme (other)	yes	3.1.11.2	RNaseH-like_sf, Ribonucl_H, RNaseH_sf
UBE2L3	Enzyme (other)	yes	2.3.2.23	UBC, UBQ-conjugating_enzyme/RWD, UBQ-conjugating_AS
TLR7	Other/Unknown	no		TIR_dom, Cys-rich_flank_reg_C, Leu-rich_rpt
TNIP1	Other/Unknown	no
SOCS1	Scaffold/PPI	no		SH2, SOCS_box, SOCS1_SH2
PXK	Kinase	yes		Prot_kinase_dom, PX_dom, WH2_dom
JAZF1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZnF-Chromatin_assoc
DNASE1	Phosphatase	yes	3.1.21.1	Endo/exonuclease/phosphatase, DNase_I, Deoxyribonuclease-1_AS
KIAA0319L	Antibody/Immunoglobulin	yes		PKD_dom, Ig-like_fold, MANSC_dom
ETS1	Other/Unknown	no		Ets_dom, Pointed_dom, SAM/pointed_sf
FCGR2A	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
FCGR2B	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
FCGR3B	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig-like_fold
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IL10	Other/Unknown	no		IL-10, 4_helix_cytokine-like_core, IL-10_CS
IRAK1	Kinase	yes	2.7.10.2	Death_dom, Prot_kinase_dom, Ser/Thr_kinase_AS
ITGAM	Antibody/Immunoglobulin	yes		Integrin_alpha, VWF_A, FG-GAP
MECP2	Other/Unknown	no		Methyl_CpG_DNA-bd, DNA-bd_dom_sf, Me_CpG-bd_MeCP2
PTPN22	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat
SAT1	Enzyme (other)	yes	2.3.1.57	GNAT_dom, Acyl_CoA_acyltransferase, Diverse_Substrate_AcTransf
SPP1	Other/Unknown	no		Osteopontin, Osteopontin_CS
C4A	Complement	yes		Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2
C4B	Complement	yes		Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2
SLC38A1	Other/Unknown	no		AA_transpt_TM
P2RY8	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, P2Y8_rcpt
CR2	Complement	yes		Sushi_SCR_CCP_dom, Sushi/SCR/CCP_sf, SEZ6_CSMD_C4BPB_Regulators
CXXC1	Transcription factor	no		Znf_PHD, Znf_CXXC, Znf_FYVE_PHD
RPS20	Other/Unknown	no		Ribosomal_uS10, Ribosomal_uS10_euk/arc, Ribosomal_uS10_CS
BIN1	Scaffold/PPI	no		SH3_domain, Amphiphysin, Amphiphysin_2
ATXN1	Other/Unknown	no		Ataxin_AXH_dom, Ataxin-1_N, Ataxin_AXH_dom_sf
ATXN2	Other/Unknown	no		LsmAD_domain, PAM2_motif, LSM_dom_sf
SCN10A	Ion channel	yes		Na_channel_asu, Ion_trans_dom, Na_trans_assoc_dom
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
CCL22	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
ST8SIA4	Enzyme (other)	yes	2.4.99.8	Glyco_trans_29, Sialyl_trans, GT29-like_sf
SIGLEC5	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
SKP1	Other/Unknown	no		SKP1-like, SKP1/BTB/POZ_sf, Skp1_comp_dimer
SLC12A1	Other/Unknown	no		SLC12A1/SLC12A2, Slc12a1, AA-permease/SLC12A_dom
SLC17A4	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
SLC1A7	Other/Unknown	no		Na-dicarboxylate_symporter, Na-dicarboxylate_symporter_CS, Na:dicarbo_symporter_sf
SLC7A8	Transporter	yes		AA/rel_permease1, L_AA_transporter, AminoAcid_Transporter
SNRPC	Transcription factor	no		Matrin/U1-C_Znf_C2H2, Matrin/U1-like-C_Znf_C2H2, U1-CZ_Znf_C2H2
STAT1	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	72
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	10
monocyte	9
blood	9
lymph node	8
vermiform appendix	7
spleen	6
mononuclear cell	6
type B pancreatic cell	6
male germ line stem cell (sensu Vertebrata) in testis	5
leukocyte	5
right adrenal gland cortex	5
olfactory bulb	5
buccal mucosa cell	4
jejunal mucosa	4
right lobe of liver	4
middle temporal gyrus	3
sperm	3
mucosa of transverse colon	3
hindlimb stylopod muscle	3
cartilage tissue	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BLK	145	tissue_specific	marker	spleen, male germ line stem cell (sensu Vertebrata) in testis, lymph node
BANK1	205	broad	marker	lymph node, spleen, vermiform appendix
CTLA4	164	tissue_specific	marker	lymph node, vermiform appendix, buccal mucosa cell
IRF5	214	broad	marker	monocyte, mononuclear cell, granulocyte
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
TREX1	134	ubiquitous	yes	olfactory segment of nasal mucosa, granulocyte, leukocyte
UBE2L3	287	ubiquitous	marker	oocyte, secondary oocyte, mucosa of transverse colon
TLR7	163	broad	marker	monocyte, mononuclear cell, leukocyte
TNIP1	298	ubiquitous	marker	lower esophagus mucosa, blood, hindlimb stylopod muscle
SOCS1	211	ubiquitous	marker	type B pancreatic cell, sperm, endocervix
PXK	256	ubiquitous	marker	corpus callosum, inferior vagus X ganglion, C1 segment of cervical spinal cord
JAZF1	251	ubiquitous	marker	trabecular bone tissue, cauda epididymis, right adrenal gland cortex
DNASE1	226	ubiquitous	marker	duodenum, jejunal mucosa, small intestine Peyer’s patch
KIAA0319L	271	ubiquitous	marker	right uterine tube, body of pancreas, adrenal tissue
ETS1	263	ubiquitous	marker	visceral pleura, parietal pleura, tibia
FCGR2A	144	broad	marker	blood, monocyte, leukocyte
FCGR2B	217		marker	placenta, right coronary artery, blood
FCGR3B	203	tissue_specific	marker	blood, periodontal ligament, trabecular bone tissue
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung
IL10	158	broad	marker	vermiform appendix, gall bladder, cartilage tissue
IRAK1	288	ubiquitous	marker	parotid gland, pancreatic ductal cell, cervix squamous epithelium
ITGAM	236	broad	marker	monocyte, mononuclear cell, leukocyte
MECP2	277	ubiquitous	marker	paraflocculus, Brodmann (1909) area 10, sural nerve
PTPN22	190	broad	marker	bone marrow cell, bone marrow, monocyte
SAT1	295	ubiquitous	marker	nasal cavity epithelium, epithelium of nasopharynx, monocyte
SPP1	267	broad	marker	gall bladder, middle frontal gyrus, inferior vagus X ganglion
C4A	134		marker	right lobe of liver, liver, right adrenal gland cortex
C4B	134		marker	right lobe of liver, right adrenal gland cortex, liver

Protein interactions among cohort

Intra-cohort edges: 71.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
STAT1	6,459
IL10	6,185
TERT	5,717
MECP2	5,688
ITGAM	4,816
ATXN1	4,465
IRAK1	4,382
FASLG	4,373
TLR7	4,103

Intra-cohort edges

A	B	Sources
ATXN1	ATXN2	string_interaction
BANK1	BLK	intact, string_interaction
BANK1	DNASE1	string_interaction
BANK1	IRF5	string_interaction
BANK1	PTPN22	string_interaction
BANK1	PXK	string_interaction
BANK1	TNFAIP3	string_interaction
BANK1	TNFSF4	string_interaction
BLK	FCGR2A	string_interaction
BLK	IRF5	string_interaction
BLK	PXK	string_interaction
BLK	STAT3	biogrid_interaction, intact
BLK	STAT4	string_interaction
BLK	TNFAIP3	string_interaction
C4A	C4B	biogrid_interaction, intact
CD40	CD40LG	biogrid_interaction, intact, string_interaction
CD40	CTLA4	string_interaction
CD40	FASLG	string_interaction
CD40	TNFSF4	string_interaction
CD40	TRAF3	biogrid_interaction, string_interaction
CD40LG	TNFSF4	string_interaction
CTLA4	PTPN22	string_interaction
CTLA4	TNFSF18	string_interaction
DNASE1	FCGR2A	string_interaction
DNASE1	FCGR2B	string_interaction
FASLG	TNFRSF6B	biogrid_interaction, intact, string_interaction
FCGR2A	FCGR2B	biogrid_interaction, intact
FCGR2A	ITGAM	string_interaction
FCGR2B	ITGAM	string_interaction
FCGR3B	ITGAM	string_interaction
HLA-DRB1	IRF5	string_interaction
HLA-DRB1	KIAA0319L	biogrid_interaction
HLA-DRB1	PTPN22	string_interaction
IL10	IRF5	string_interaction
IRAK1	IRF5	string_interaction
IRAK1	SOCS1	string_interaction
IRAK1	TLR7	string_interaction
IRAK1	TRAF3	string_interaction
IRF5	PTPN22	string_interaction
IRF5	PXK	string_interaction
IRF5	STAT1	string_interaction
IRF5	STAT4	string_interaction
IRF5	TNFAIP3	string_interaction
IRF5	TNIP1	string_interaction
IRF5	TYK2	string_interaction
KIAA0319L	PXK	string_interaction
PTPN22	PXK	string_interaction
PTPN22	STAT4	string_interaction
PTPN22	TNFAIP3	string_interaction
PTPN22	TRAF3	string_interaction

Structural data

PDB: 55 · AlphaFold-only: 17 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RPS20	P60866	199
HLA-DRB1	P01911	108
SKP1	P63208	72
TYK2	P29597	52
TNKS	O95271	42
ITGAM	P11215	31
SYT1	P21579	24
TERT	O14746	23
CTLA4	P16410	22
UBE2L3	P68036	21
ETS1	P14921	21
TNFAIP3	P21580	17
PTPN22	Q9Y2R2	14
CD40	P25942	14
TREX1	Q9NSU2	12
C4A	P0C0L4	12
SAT1	P21673	10
STAT1	P42224	10
TRAF3	Q13114	10
KIAA0319L	Q8IZA0	9
FCGR2A	P12318	9
IL10	P22301	9
MECP2	P51608	9
CR2	P20023	9
TNIP1	Q15025	8
SCN10A	Q9Y5Y9	8
TNFRSF6B	O95407	8
CD40LG	P29965	8
BIN1	O00499	7
ATXN1	P54253	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ACOX2	Q99424	94.49
EIPR1	Q53HC9	89.26
CCL22	O00626	88.21
STAT4	Q14765	86.87
PXK	Q7Z7A4	86.42
SOCS1	O15524	84.20
SLC17A4	Q9Y2C5	83.87
BLK	P51451	81.89
CXCR5	P32302	80.85
SLC38A1	Q9H2H9	79.81
TCP11	Q8WWU5	78.50
SLC12A1	Q13621	78.39
SLC1A7	O00341	77.54
RASSF7	Q02833	75.00
JAZF1	Q86VZ6	70.25
BANK1	Q8NDB2	61.25
TCF7	P36402	58.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 726. Enrichment computed across 250 evidence-associated genes (156 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 156 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cytokine Signaling in Immune system	17	4.4×	2e-04	IRF5, STAT4, SOCS1, IRAK1, ITGAM, CCL22, SKP1, STAT1 (+9 more)
TNFs bind their physiological receptors	6	15.2×	6e-04	TNFSF4, TNFRSF6B, TNFSF15, TNFSF18, FASLG, TNFRSF13B
Immune System	30	2.5×	6e-04	BLK, IRF5, STAT4, SOCS1, IRAK1, ITGAM, CCL22, SKP1 (+22 more)
Interleukin-23 signaling	4	32.5×	7e-04	STAT4, STAT3, TYK2, IL23R
Interleukin-35 Signalling	4	24.4×	0.002	STAT4, STAT1, STAT3, TYK2
Interleukin-4 and Interleukin-13 signaling	9	5.9×	0.002	SOCS1, IL10, ITGAM, CCL22, STAT1, STAT3, FASLG, TYK2 (+1 more)
Interleukin-10 signaling	6	9.0×	0.005	IL10, CCL22, STAT3, TYK2, CD80, CD86
Signaling by CSF3 (G-CSF)	4	14.6×	0.012	SOCS1, STAT1, STAT3, TYK2
Signaling by Interleukins	10	4.1×	0.013	STAT4, SOCS1, IRAK1, ITGAM, CCL22, SKP1, STAT1, STAT3 (+2 more)
Activation of C3 and C5	3	24.4×	0.014	C2, C4A, C4B
Ovarian tumor domain proteases	5	8.9×	0.015	TNFAIP3, TNIP1, TRAF3, IFIH1, TNIP2
Interferon gamma signaling	7	5.6×	0.015	IRF5, SOCS1, HLA-DRB1, STAT1, CAMK2G, TRIM31, CD44
Interleukin-21 signaling	3	22.0×	0.016	STAT4, STAT1, STAT3
Interleukin-27 signaling	3	20.0×	0.018	STAT1, STAT3, TYK2
Regulation of IFNA/IFNB signaling	4	11.3×	0.018	SOCS1, STAT1, TYK2, USP18
Inactivation of CSF3 (G-CSF) signaling	4	11.3×	0.018	SOCS1, STAT1, STAT3, TYK2
Interleukin-6 signaling	3	18.3×	0.019	STAT1, STAT3, TYK2
Interleukin-20 family signaling	4	10.8×	0.019	STAT4, STAT1, STAT3, TYK2
Synthesis of PC	4	10.5×	0.019	SLC44A4, CEPT1, CSNK2A2, CSNK2B
Regulation of Complement cascade	5	7.5×	0.019	C2, C4A, C4B, C9, CR2
CD28 dependent Vav1 pathway	3	16.9×	0.022	CD28, CD80, CD86
Co-stimulation by CD28	4	9.8×	0.023	CTLA4, CD28, CD80, CD86
PI3K/AKT Signaling in Cancer	4	9.4×	0.025	CD28, CD80, CD86, CDKN1B
TRAF3-dependent IRF activation pathway	3	14.6×	0.029	TRAF3, IKBKE, IFIH1
Maturation of hRSV A proteins	3	14.6×	0.029	XPO1, CSNK2A2, CSNK2B
Dengue virus activates/modulates innate and adaptive immune responses	4	8.6×	0.032	C4A, C4B, IKBKE, IFIH1
Negative regulators of DDX58/IFIH1 signaling	4	8.4×	0.034	TNFAIP3, TRAF3, IKBKE, IFIH1
Organic anion transport by SLC22 transporters	2	29.3×	0.037	SLC22A12, SLC22A11
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	3	12.9×	0.037	CD40, CD40LG, TRAF3
Interleukin-2 family signaling	3	12.2×	0.037	STAT4, STAT1, STAT3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 222 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of T cell activation	7	16.6×	2e-04	CTLA4, PTPN22, DUSP22, SOCS6, CD80, CD86, CSK
type I interferon-mediated signaling pathway	8	12.4×	2e-04	TREX1, IRAK1, STAT1, TRAF3, TYK2, IKBKE, IFIH1, CR2
antibody-dependent cellular cytotoxicity	4	50.6×	2e-04	FCGR2A, FCGR2B, FCGR3B, FCGR2C
B cell activation	7	14.4×	2e-04	BANK1, CXCR5, CD40, SKAP2, CD86, FCRL5, CR2
cell surface receptor signaling pathway via JAK-STAT	8	10.5×	3e-04	STAT4, SOCS1, STAT1, STAT3, CD40, TYK2, SOCS6, IL23R
immune response	18	3.8×	3e-04	CTLA4, TNFSF4, ETS1, FCGR3B, HLA-DRB1, IL10, CXCR5, CCL22 (+10 more)
cell surface receptor signaling pathway	14	4.0×	0.002	FCGR2A, FCGR2B, FCGR3B, TNFSF15, CD40LG, TRAF3, FCGR2C, SIRPB1 (+6 more)
complement activation, GZMK pathway	4	23.4×	0.004	C2, C4A, C4B, C9
positive regulation of T cell proliferation	7	8.2×	0.004	TNFSF4, CD40LG, TYK2, CD28, CD80, CD86, IL23R
negative regulation of T cell receptor signaling pathway	6	9.9×	0.004	CTLA4, PTPN22, DUSP22, CD80, CD86, CSK
inflammatory response	18	3.1×	0.004	IRF5, TNFAIP3, TNFSF4, TLR7, TNIP1, PXK, FCGR2B, CCL22 (+10 more)
interleukin-23-mediated signaling pathway	3	38.0×	0.005	STAT3, TYK2, IL23R
complement activation, classical pathway	5	12.2×	0.006	C2, C4A, C4B, C9, CR2
negative regulation of B cell activation	3	32.5×	0.007	BANK1, TNFAIP3, FCGR2B
positive regulation of apoptotic cell clearance	3	32.5×	0.007	C2, C4A, C4B
negative regulation of B cell proliferation	4	16.9×	0.007	CTLA4, FCGR2B, IL10, TNFRSF13B
defense response to virus	12	3.8×	0.008	IRF5, TREX1, TLR7, STAT1, CD40, TRAF3, IKBKE, TRIM31 (+4 more)
regulation of adaptive immune response	3	25.3×	0.013	TNFSF4, FCGR2B, ADCY7
positive regulation of memory T cell differentiation	3	25.3×	0.013	TNFSF4, HLA-DRB1, IL23R
positive regulation of T cell receptor signaling pathway	4	13.8×	0.013	CD28, CD226, CD80, CD86
positive regulation of type I interferon production	5	9.5×	0.013	IRF5, IRAK1, PTPN22, TRAF3, IKBKE
CD40 signaling pathway	3	22.8×	0.017	CD40, CD40LG, TNIP2
positive regulation of interleukin-12 production	5	8.8×	0.017	IRF5, TNFSF4, CD40, CD40LG, IL23R
T cell costimulation	5	8.4×	0.019	CD40LG, CD28, CD80, CD86, CSK
urate metabolic process	3	20.7×	0.020	SLC22A12, SLC22A11, CARMIL1
positive regulation of interferon-alpha production	4	11.7×	0.020	IRF5, TLR7, STAT1, IFIH1
complement activation	4	11.2×	0.022	C2, C4A, C4B, C9
negative regulation of interleukin-6 production	5	7.9×	0.022	BANK1, TNFAIP3, IL10, PTPN22, CSK
interleukin-10-mediated signaling pathway	3	19.0×	0.022	IL10, STAT3, TYK2
positive regulation of T-helper 17 type immune response	3	19.0×	0.022	TYK2, CARD9, IL23R

Therapeutics

Drugs indicated for this disease

6 approved, 30 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Anifrolumab	Approved (phase 4)
Belimumab	Approved (phase 4)
Cortisone Acetate	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisone	Approved (phase 4)
Abetimus Sodium	Phase 3 (in late-stage trials)
Acetaminophen	Phase 3 (in late-stage trials)
Aldesleukin	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Baricitinib	Phase 3 (in late-stage trials)
Blisibimod	Phase 3 (in late-stage trials)
Cenerimod	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Dapirolizumab Pegol	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Emapalumab	Phase 3 (in late-stage trials)
Epratuzumab	Phase 3 (in late-stage trials)
Estrogens, Conjugated	Phase 3 (in late-stage trials)
Folic Acid	Phase 3 (in late-stage trials)
Forigerimod	Phase 3 (in late-stage trials)
Hydroxychloroquine	Phase 3 (in late-stage trials)
Litifilimab	Phase 3 (in late-stage trials)
Medroxyprogesterone Acetate	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Mycophenolic Acid	Phase 3 (in late-stage trials)
Obinutuzumab	Phase 3 (in late-stage trials)
Ocrelizumab	Phase 3 (in late-stage trials)
Prasterone	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Tabalumab	Phase 3 (in late-stage trials)
Telitacicept	Phase 3 (in late-stage trials)
Ustekinumab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Acetylcysteine, Arsenic Trioxide, Artenimol, Aspirin, Atacicept, Benazepril, Brentuximab Vedotin, Brepocitinib, Calcitriol, Chloroquine, Curcumin, Cytarabine, Daratumumab, Dazukibart, Epigalocatechin Gallate, Etonogestrel, Evobrutinib, Fenebrutinib, Filgotinib, Filgrastim, Fish Oil, Fludarabine Phosphate, Fulvestrant, Human Immunoglobulin G, Icosapent, Lactobacillus Acidophilus, Laquinimod, Leflunomide, Lenabasum, Lisinopril Anhydrous, Memantine, Nelfinavir, Niacinamide, Obexelimab, Olive Oil, Orelabrutinib, Pravastatin, Ramipril, Sirolimus, Upadacitinib, Voclosporin.

Drug target analysis

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

Druggability breadth: 97 of 250 evidence-associated genes (39%) 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
BLK	AFATINIB
TLR7	IMIQUIMOD
DNASE1	GENTIAN VIOLET
IRAK1	PONATINIB
SAT1	PENTAMIDINE
RPS20	GENTAMICIN SULFATE
SCN10A	IMIPRAMINE
SKP1	SELEXIPAG
STAT1	FILGOTINIB
STAT3	MOMELOTINIB
STIM1	TERIFLUNOMIDE
TERT	BERBERINE
PARP11	TALAZOPARIB
TNKS	NIRAPARIB
TYK2	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
BLK	62	4
IRAK1	50	4
SCN10A	21	4
STAT3	18	4
TERT	10	4
TLR7	9	4
TNKS	9	4
STAT1	5	4
PARP11	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AFATINIB	4	BLK, IRAK1
FEDRATINIB	4	BLK, IRAK1, TYK2
AXITINIB	4	BLK, IRAK1, TYK2
SORAFENIB	4	BLK, IRAK1
NERATINIB	4	BLK, IRAK1
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK, IRAK1
VANDETANIB	4	BLK, IRAK1
NILOTINIB	4	BLK
BOSUTINIB	4	BLK, IRAK1, TYK2
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK, IRAK1, TYK2
NINTEDANIB	4	BLK, IRAK1, TYK2
SUNITINIB	4	BLK, IRAK1, TYK2
DASATINIB	4	BLK, TYK2
ERLOTINIB	4	BLK, TYK2
QUIZARTINIB	4	BLK, IRAK1
CRIZOTINIB	4	BLK, IRAK1, TYK2
MIDOSTAURIN	4	BLK, TYK2
GEFITINIB	4	BLK, IRAK1
IMATINIB	4	BLK, IRAK1, TYK2
IMIQUIMOD	4	TLR7
HYDROXYCHLOROQUINE	4	TLR7
GENTIAN VIOLET	4	DNASE1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 12.

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
BLK	483	Binding:477, ADMET:4, Functional:2
TERT	391	Binding:389, Functional:2
IRAK1	363	Binding:361, Functional:1, ADMET:1
TLR7	356	Binding:321, Functional:35
TNKS	226	Binding:223, Functional:3
STAT1	147	Binding:137, Functional:8, Unclassified:2
SCN10A	144	Binding:124, Functional:16, ADMET:4
PTPN22	137	Binding:122, Functional:10, ADMET:5
RPS20	90	Binding:90
STIM1	35	Binding:33, Functional:1, ADMET:1
CXCR5	33	Binding:21, Functional:12
PARP11	28	Binding:28
SAT1	22	ADMET:12, Binding:10
STAT4	20	Binding:20
HLA-DRB1	17	Binding:17
ITGAM	14	Binding:12, Functional:2
CD40	10	Binding:10
CD40LG	8	Binding:8
TCF7	7	Binding:7
ATXN2	5	Binding:3, Functional:2
DNASE1	4	Binding:4
SKP1	4	Binding:4
SLC7A8	3	Binding:3
UBE2L3	2	Binding:2
SLC38A1	2	Binding:2
P2RY8	2	Binding:2
FASLG	2	Binding:2
CTLA4	1	Binding:1
TNFAIP3	1	Binding:1
FCGR2A	1	Binding:1
FCGR3B	1	Binding:1
MECP2	1	Binding:1
CXXC1	1	Binding:1
CCL22	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BLK	2.7.10.2	non-specific protein-tyrosine kinase
TREX1	3.1.11.2	exodeoxyribonuclease III
UBE2L3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
DNASE1	3.1.21.1	deoxyribonuclease I
IRAK1	2.7.10.2	non-specific protein-tyrosine kinase
PTPN22	3.1.3.48	protein-tyrosine-phosphatase
SAT1	2.3.1.57	diamine N-acetyltransferase
ST8SIA4	2.4.99.8	alpha-N-acetylneuraminate alpha-2,8-sialyltransferase
SUOX	1.8.3.1	sulfite oxidase
PARP11	2.4.2.30	NAD+ ADP-ribosyltransferase
TNKS	2.4.2.30	NAD+ ADP-ribosyltransferase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BLK	483
TLR7	356
IRAK1	363
PTPN22	137
SCN10A	144
STAT1	147
STAT3	1,319
TERT	391
TNKS	226
TYK2	1,083

Pharmacogenomics

Cohort genes with a PharmGKB record: 72; 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)
AFATINIB	4	BLK, IRAK1
FEDRATINIB	4	BLK, IRAK1, TYK2
AXITINIB	4	BLK, IRAK1, TYK2
SORAFENIB	4	BLK, IRAK1
NERATINIB	4	BLK, IRAK1
IBRUTINIB	4	BLK
ENTRECTINIB	4	BLK
BELUMOSUDIL	4	BLK
AFATINIB DIMALEATE	4	BLK, IRAK1
VANDETANIB	4	BLK, IRAK1
NILOTINIB	4	BLK
BOSUTINIB	4	BLK, IRAK1, TYK2
BRIGATINIB	4	BLK
ACALABRUTINIB	4	BLK
ZANUBRUTINIB	4	BLK
TIRABRUTINIB	4	BLK
RITLECITINIB	4	BLK
PAZOPANIB	4	BLK, IRAK1, TYK2
NINTEDANIB	4	BLK, IRAK1, TYK2
SUNITINIB	4	BLK, IRAK1, TYK2
DASATINIB	4	BLK, TYK2
ERLOTINIB	4	BLK, TYK2
QUIZARTINIB	4	BLK, IRAK1
CRIZOTINIB	4	BLK, IRAK1, TYK2
MIDOSTAURIN	4	BLK, TYK2
GEFITINIB	4	BLK, IRAK1
IMATINIB	4	BLK, IRAK1, TYK2
IMIQUIMOD	4	TLR7
GENTIAN VIOLET	4	DNASE1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	15	BLK, TLR7, DNASE1, IRAK1, SAT1, RPS20, SCN10A, SKP1, STAT1, STAT3 (+5 more)
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	19	CTLA4, TREX1, UBE2L3, KIAA0319L, FCGR2A, FCGR2B, FCGR3B, HLA-DRB1, ITGAM, PTPN22 (+9 more)
D	Druggable family + AlphaFold only, no drug	3	PXK, CXCR5, SLC17A4
E	Difficult family or no structure, no drug	35	BANK1, IRF5, STAT4, TNFAIP3, TNFSF4, TNIP1, SOCS1, JAZF1, ETS1, IL10 (+25 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BANK1	0	BLK
IRF5	0	IRAK1, TYK2
STAT4	20	TYK2, STAT1
SOCS1	0	TYK2
PTPN22	137	—
CTLA4	1	—
TNFAIP3	1	—
TNFSF4	0	—
TREX1	0	—
UBE2L3	2	—
TNIP1	0	—
PXK	0	—
JAZF1	0	—
KIAA0319L	0	—
ETS1	0	—
FCGR2A	1	—
FCGR2B	0	—
FCGR3B	1	—
HLA-DRB1	17	—
IL10	0	—
ITGAM	14	—
MECP2	1	—
SPP1	0	—
C4A	0	—
C4B	0	—
SLC38A1	2	—
P2RY8	2	—
CR2	0	—
CXXC1	1	—
BIN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1,027.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	436
PHASE1	188
PHASE2	165
PHASE3	86
PHASE4	53
PHASE1/PHASE2	53
EARLY_PHASE1	32
PHASE2/PHASE3	14

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05879419	PHASE4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT05916781	PHASE4	RECRUITING	Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus
NCT06411249	PHASE4	RECRUITING	A Study Describing the Efficacy and Safety of Belimumab Administered in Adult Participants With Early Systemic Lupus Erythematosus (SLE)
NCT06594068	PHASE4	RECRUITING	Prospective Registry Investigating Maternal, Infant, and Lactation Outcomes in Anifrolumab Users
NCT06677801	PHASE4	ACTIVE_NOT_RECRUITING	Immune Cell Subsets in SLE Patients Treated with Telitacicept
NCT06763783	PHASE4	ENROLLING_BY_INVITATION	Vaccination Against Herpes Zoster in Patients With Inflammatory Rheumatic Diseases
NCT06875960	PHASE4	RECRUITING	A Study to Continue the Administration of Deucravacitinib in Participants With Systemic Lupus Erythematosus (SLE) or Discoid and/or Subacute Cutaneous Lupus Erythematosus (DLE/SCLE) Who Have Completed Study IM011074 or Study IM011132
NCT07077486	PHASE4	RECRUITING	Effects of Telitacicept vs Cyclophosphamide on Lupus Related Interstitial Lung Disease
NCT07087912	PHASE4	RECRUITING	Safety and Immunogenicity of the Live Attenuated Tetravalent Butantan-Dengue Vaccine in Autoimmune Rheumatic Diseases
NCT07381465	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of IL-1 Inhibitors in Mild to Moderate Systemic Lupus Erythematosus
NCT07611747	PHASE4	RECRUITING	Carotid Ultrasound-Based Strategy for Primary Prevention of Cardiovascular Events in Inflammatory Rheumatic Disease (PREVENER)
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BELIMUMAB	4	37
ANIFROLUMAB	4	19
CRAVACITINIB	4	12
CYCLOPHOSPHAMIDE ANHYDROUS	4	6
PRASTERONE	4	6
ABATACEPT	4	4
ATORVASTATIN	4	4
AZATHIOPRINE	4	4
BARICITINIB	4	4
DIPHENHYDRAMINE	4	4
ROSUVASTATIN	4	4
ACETAMINOPHEN	4	3
ALDESLEUKIN	4	3
HYDROXYCHLOROQUINE	4	3
MYCOPHENOLATE MOFETIL	4	3
UPADACITINIB	4	3
CALCITRIOL	4	2
CORTICOTROPIN	4	2
HUMAN PAPILLOMAVIRUS, L1 PROTEIN VIRUS LIKE PARTICLES	4	2
MEDROXYPROGESTERONE ACETATE	4	2
MOSUNETUZUMAB	4	2
NORETHINDRONE	4	2
OBINUTUZUMAB	4	2
OCRELIZUMAB	4	2
RAMIPRIL	4	2
RITUXIMAB	4	2
SIMVASTATIN	4	2
TOFACITINIB CITRATE	4	2
USTEKINUMAB	4	2
VARICELLA ZOSTER VIRUS ENVELOPE GLYCOPROTEIN E	4	2