Multiple sclerosis

Summary

Multiple sclerosis (MONDO:0005301) is a disease with 75 cohort genes (1,039 GWAS associations across 83 studies) and 2,743 clinical trials. The dominant Reactome pathway is Signaling by Interleukins (11 cohort genes). Top therapeutic interventions include fingolimod, teriflunomide, and ocrelizumab.

At a glance

• Cohort genes: 75
• GWAS associations: 1,039
• ClinVar variants: 24
• Clinical trials: 2,743

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple sclerosis
Mondo ID	MONDO:0005301
MeSH	D009103
Orphanet	802
DOID	DOID:2377
ICD-10-CM	G35
ICD-11	1298865187
NCIT	C3243
SNOMED CT	24700007
UMLS	C0026769
MedGen	10123
Is cancer (heuristic)	no

Also known as: generalised multiple sclerosis · generalized multiple sclerosis

Data availability: 24 ClinVar variants · 1,039 GWAS associations (83 studies) · 111 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › autoimmune disorder of central nervous system › multiple sclerosis

Related subtypes (7): Miller Fisher syndrome, autoimmune encephalopathy with parasomnia and obstructive sleep apnea, lymphocytic hypophysitis, autoimmune encephalitis, autoimmune optic neuritis, central nervous system lupus, autoimmune epilepsy

Subtypes (4): chronic progressive multiple sclerosis, relapsing-remitting multiple sclerosis, Marburg acute multiple sclerosis, pediatric multiple sclerosis

Genetics & variants

GWAS landscape

1,039 GWAS associations across 83 studies. Top hits map to 26 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs3104373	1e-234	HLA-DQA1	T	2.9
rs3135388	4e-225	HLA-DRA - HLA-DRB9	A	2.75
rs3129889	1e-206	HLA-DRA - HLA-DRB9	G	2.97
rs9271366	7e-184	HLA-DRB1 - HLA-DQA1	G	2.78
DRB*15:01	1e-132		?	3.08
chr6:32620082	2e-109		T	2.34
rs9268925	1e-95	HLA-DRB9	A	0.82
chr6:32513714	1e-89		A	0.86
chr16:11213951	4e-71		C	1.2
rs10801908	5e-70	CD58	C	1.3
rs11256593	3e-65	RPL32P23 - RBM17	T	1.21
rs4640926	7e-62	HLA-DRB9 - HLA-DRB5	T	0.96
rs438613	2e-49	LINC01967	C	1.15
rs2104286	2e-47	IL2RA	A	1.22
rs1800693	2e-47	TNFRSF1A	C	1.15
rs12927355	6e-46	CLEC16A	G	1.2
chr3:121765368	7e-43		C	1.14
rs6677309	5e-42	CD58	A	1.29
chr6:31610048	1e-40		A	1.67
rs6670198	2e-36	PRXL2B	T	1.14
rs62420820	9e-36	IL20RA - IL22RA2	A	1.14
rs1738074	3e-35	TAGAP-AS1, TAGAP	C	1.13
rs35540610	3e-33	SP140	C	1.14
rs1323292	4e-33	RGS2-AS1	A	1.16
rs1077667	8e-33	TNFSF14	C	1.15
rs1813375	2e-32	LINC01967	A	1.15
rs35486093	2e-31	C1orf52 - Y_RNA	G	1.21
rs2150879	4e-31	VMP1	G	1.12
rs701006	1e-30	OS9-AS1, OS9	G	1.12
chr14:88523488	2e-30		C	1.33

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST009597	International Multiple Sclerosis Genetics Consortium	2019	14,802	26,703	Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility.
GCST005531	Beecham AH	2013	14,498	24,091	Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
GCST001198	Sawcer S	2011	9,772	16,849	Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.
GCST003340	Zhou Y	2016	5,545	12,153	Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis.
GCST001341	Patsopoulos NA	2011	5,545	12,153	Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.
GCST003566	Andlauer TF	2016	4,888	10,395	Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.
GCST002274	Goris A	2013	4,088	12,030	No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis.
GCST008722	Din L	2019	3,617	24,813	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST008718	Din L	2019	2,686	25,256	Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.
GCST000424	De Jager PL	2009	2,624	7,220	Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	3
Tier 3: regulatory	1
Tier 4: intronic/intergenic	46

MAF distribution

Bucket	Variants
common (>=0.05)	42
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	8

Functional consequences

Consequence	Count
intron_variant	29
unknown	9
intergenic_variant	8
3_prime_UTR_variant	2
5_prime_UTR_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs3104373	6	32632598	T>A,C,G	0.05	intergenic_variant	HLA-DQA1	1e-234	Tier 4: intronic/intergenic
rs3135388	6	32445274	A>C,G,T	0.22	intron_variant	HLA-DRA - HLA-DRB9	4e-225	Tier 4: intronic/intergenic
rs3129889	6	32445768	G>A,C,T	0.2	intron_variant	HLA-DRA - HLA-DRB9	1e-206	Tier 4: intronic/intergenic
rs9271366	6	32619077	G>A,C,T	0.15	intergenic_variant	HLA-DRB1 - HLA-DQA1	7e-184	Tier 4: intronic/intergenic
DRB*15:01							1e-132	Tier 4: intronic/intergenic
chr6:32620082							2e-109	Tier 4: intronic/intergenic
rs9268925	6	32465192	A>C,G,T	0.109	intron_variant	HLA-DRB9	1e-95	Tier 4: intronic/intergenic
chr6:32513714				0.144			1e-89	Tier 4: intronic/intergenic
chr16:11213951							4e-71	Tier 4: intronic/intergenic
rs10801908	1	116547871	C>G,T	0.05	intron_variant	CD58	5e-70	Tier 4: intronic/intergenic
rs11256593	10	6075359	C>T	0.05	intergenic_variant	RPL32P23 - RBM17	3e-65	Tier 4: intronic/intergenic
rs4640926	6	32479216	T>A,C,G	0.117	intron_variant	HLA-DRB9 - HLA-DRB5	7e-62	Tier 4: intronic/intergenic
rs438613	3	28030595	T>A,C,G	0.05	intron_variant	LINC01967	2e-49	Tier 4: intronic/intergenic
rs2104286	10	6057082	T>A,C,G	0.27	intron_variant	IL2RA	2e-47	Tier 4: intronic/intergenic
rs1800693	12	6330843	T>A,C,G	0.05	intron_variant	TNFRSF1A	2e-47	Tier 4: intronic/intergenic
rs12927355	16	11100914	C>A,T	0.31	intron_variant	CLEC16A	6e-46	Tier 4: intronic/intergenic
chr3:121765368							7e-43	Tier 4: intronic/intergenic
rs6677309	1	116537544	A>C,T	0.12	intron_variant	CD58	5e-42	Tier 4: intronic/intergenic
chr6:31610048							1e-40	Tier 4: intronic/intergenic
rs6670198	1	2589088	T>A,C	0.05	intron_variant	PRXL2B	2e-36	Tier 4: intronic/intergenic
rs62420820	6	137116920	G>A	0.05	intergenic_variant	IL20RA - IL22RA2	9e-36	Tier 4: intronic/intergenic
rs1738074	6	159044945	T>A,C,G	0.05	5_prime_UTR_variant	TAGAP-AS1, TAGAP	3e-35	Tier 2: splice/UTR
rs35540610	2	230257114	T>C	0.05	intron_variant	SP140	3e-33	Tier 4: intronic/intergenic
rs1323292	1	192571891	G>A,C,T	0.05	intron_variant	RGS2-AS1	4e-33	Tier 4: intronic/intergenic
rs1077667	19	6668961	C>G,T	0.05	intron_variant	TNFSF14	8e-33	Tier 4: intronic/intergenic
rs1813375	3	28037080	G>T	0.49	intron_variant	LINC01967	2e-32	Tier 4: intronic/intergenic
rs35486093	1	85264137	A>G	0.05	intergenic_variant	C1orf52 - Y_RNA	2e-31	Tier 4: intronic/intergenic
rs2150879	17	59781849	G>A,C,T	0.05	intron_variant	VMP1	4e-31	Tier 4: intronic/intergenic
rs701006	12	57713053	A>G	0.05	intron_variant	OS9-AS1, OS9	1e-30	Tier 4: intronic/intergenic
chr14:88523488							2e-30	Tier 4: intronic/intergenic

ClinVar germline variants

24 retrieved; paginated sample, class counts are floors:

6 uncertain significance, 6 benign/likely benign, 4 conflicting classifications of pathogenicity, 4 likely pathogenic, 2 pathogenic, 2 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
226296	NM_005693.4(NR1H3):c.1244G>A (p.Arg415Gln)	NR1H3	Pathogenic	no assertion criteria provided
12336	NM_001065.4(TNFRSF1A):c.236C>T (p.Thr79Met)	TNFRSF1A	Pathogenic	criteria provided, multiple submitters, no conflicts
3600999	NM_001374736.1(DST):c.4322A>G (p.His1441Arg)	DST	Likely pathogenic	no assertion criteria provided
3601001	NM_002291.3(LAMB1):c.2383C>T (p.Arg795Trp)	LAMB1	Likely pathogenic	no assertion criteria provided
3600998	NM_201384.3(PLEC):c.3160C>A (p.Pro1054Thr)	PLEC	Likely pathogenic	no assertion criteria provided
3601002	NM_201384.3(PLEC):c.934G>T (p.Glu312Ter)	PLEC	Likely pathogenic	no assertion criteria provided
357589	NM_001723.7(DST):c.3336G>C (p.Glu1112Asp)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
809956	NM_001374736.1(DST):c.14495A>G (p.Glu4832Gly)	DST	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
252602	NM_002291.3(LAMB1):c.476C>G (p.Thr159Ser)	LAMB1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
436328	NM_201384.3(PLEC):c.13247C>T (p.Thr4416Met)	PLEC	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1027084	NM_001374736.1(DST):c.15406T>G (p.Leu5136Val)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
809958	NM_001374736.1(DST):c.13499T>C (p.Leu4500Pro)	DST	Uncertain significance	criteria provided, multiple submitters, no conflicts
1442403	NM_005560.6(LAMA5):c.5512C>T (p.Arg1838Trp)	LAMA5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3601000	NM_005560.6(LAMA5):c.4106G>A (p.Arg1369Gln)	LAMA5	Uncertain significance	criteria provided, single submitter
196854	NM_201384.3(PLEC):c.12992C>T (p.Pro4331Leu)	PLEC	Uncertain significance	criteria provided, multiple submitters, no conflicts
2063149	NM_201384.3(PLEC):c.12736C>T (p.Arg4246Cys)	PLEC	Uncertain significance	criteria provided, multiple submitters, no conflicts
3257589	NM_133493.5(CD109):c.1709C>T (p.Pro570Leu)	CD109	Likely benign	criteria provided, single submitter
357584	NM_001723.7(DST):c.3809A>G (p.Lys1270Arg)	DST	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
357622	NM_001723.7(DST):c.25C>T (p.Arg9Cys)	DST	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
714023	NM_000213.5(ITGB4):c.1924G>A (p.Glu642Lys)	ITGB4	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
289396	NM_001378452.1(ITPR1):c.5621T>G (p.Val1874Gly)	ITPR1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
196717	NM_201384.3(PLEC):c.4651C>T (p.Arg1551Cys)	PLEC	Likely benign	criteria provided, multiple submitters, no conflicts
287621	NM_201384.3(PLEC):c.7951C>T (p.Arg2651Trp)	PLEC	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
471582	NM_201384.3(PLEC):c.3869A>G (p.Lys1290Arg)	PLEC	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 88 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 2

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

Gene	HGNC	Evidence routes
TNFRSF1A	TNFRSF1A	GWAS, Orphanet
ITPR1	ITPR1	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TNFRSF1A	Orphanet:32960	Tumor necrosis factor receptor 1 associated periodic syndrome
TNFRSF1A	Orphanet:329967	Intermittent hydrarthrosis
ITPR1	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
ITPR1	Orphanet:208513	Spinocerebellar ataxia type 29
ITPR1	Orphanet:98769	Spinocerebellar ataxia type 15/16
BCL6	Orphanet:480541	High grade B-cell lymphoma with MYC and/ or BCL2 and/or BCL6 rearrangement
BCL6	Orphanet:545	Follicular lymphoma
BCL6	Orphanet:98838	Primary mediastinal large B-cell lymphoma
BCL6	Orphanet:98839	Intravascular large B-cell lymphoma
RNASEL	Orphanet:1331	Familial prostate cancer
RORA	Orphanet:528084	Non-specific syndromic intellectual disability
RPL5	Orphanet:124	Diamond-Blackfan anemia
RREB1	Orphanet:567	22q11.2 deletion syndrome
ATXN1	Orphanet:98755	Spinocerebellar ataxia type 1
SCO2	Orphanet:1561	Fatal infantile cytochrome C oxidase deficiency
SCO2	Orphanet:521411	Autosomal recessive axonal Charcot-Marie-Tooth disease due to copper metabolism defect
SCO2	Orphanet:98619	Rare isolated myopia
SGCD	Orphanet:154	Familial isolated dilated cardiomyopathy
SGCD	Orphanet:219	Delta-sarcoglycan-related limb-girdle muscular dystrophy R6
SH3BP2	Orphanet:184	Cherubism
DST	Orphanet:314381	Hereditary sensory and autonomic neuropathy type 6
DST	Orphanet:412181	Epidermolysis bullosa simplex due to BP230 deficiency
SMARCA4	Orphanet:1465	Coffin-Siris syndrome
SMARCA4	Orphanet:231108	Rhabdoid tumor predisposition syndrome
SMARCA4	Orphanet:370396	Small cell carcinoma of the ovary
SMARCA4	Orphanet:466962	SMARCA4-deficient sarcoma of thorax
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
BTNL2	Orphanet:797	Sarcoidosis
SYK	Orphanet:695807	Immunodeficiency-systemic inflammation-lymphoma predisposition syndrome
TBX6	Orphanet:1797	Autosomal dominant spondylocostal dysostosis
TBX6	Orphanet:2311	Autosomal recessive spondylocostal dysostosis
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma

Cohort genes → proteins

75 cohort genes, 75 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	72
gwas_and_clinvar	2
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TNFRSF1A	HGNC:11916	ENSG00000067182	P19438	Tumor necrosis factor receptor superfamily member 1A	gwas,clinvar
ITPR1	HGNC:6180	ENSG00000150995	Q14643	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	gwas,clinvar
BCL6	HGNC:1001	ENSG00000113916	P41182	B-cell lymphoma 6 protein	gwas
RNASEL	HGNC:10050	ENSG00000135828	Q05823	2-5A-dependent ribonuclease	gwas
RORA	HGNC:10258	ENSG00000069667	P35398	Nuclear receptor ROR-alpha	gwas
RPL5	HGNC:10360	ENSG00000122406	P46777	Large ribosomal subunit protein uL18	gwas
RPS6KA5	HGNC:10434	ENSG00000100784	O75582	Ribosomal protein S6 kinase alpha-5	gwas
RPS6KB1	HGNC:10436	ENSG00000108443	P23443	Ribosomal protein S6 kinase beta-1	gwas
RREB1	HGNC:10449	ENSG00000124782	Q92766	Ras-responsive element-binding protein 1	gwas
BHLHE40	HGNC:1046	ENSG00000134107	O14503	Class E basic helix-loop-helix protein 40	gwas
RUNX3	HGNC:10473	ENSG00000020633	Q13761	Runt-related transcription factor 3	gwas
BICD1	HGNC:1049	ENSG00000151746	Q96G01	Protein bicaudal D homolog 1	gwas
ATXN1	HGNC:10548	ENSG00000124788	P54253	Ataxin-1	gwas
SCAMP2	HGNC:10564	ENSG00000140497	O15127	Secretory carrier-associated membrane protein 2	gwas
CXCR5	HGNC:1060	ENSG00000160683	P32302	C-X-C chemokine receptor type 5	gwas
SCO2	HGNC:10604	ENSG00000284194	O43819	Cytochrome c oxidase assembly factor SCO2	gwas
CCL22	HGNC:10621	ENSG00000102962	O00626	C-C motif chemokine 22	gwas
SCAF11	HGNC:10784	ENSG00000139218	Q99590	Protein SCAF11	gwas
SGCD	HGNC:10807	ENSG00000170624	Q92629	Delta-sarcoglycan	gwas
SH3BP2	HGNC:10825	ENSG00000087266	P78314	SH3 domain-binding protein 2	gwas
SH3GL2	HGNC:10831	ENSG00000107295	Q99962	Endophilin-A1	gwas
SHMT1	HGNC:10850	ENSG00000176974	P34896	Serine hydroxymethyltransferase, cytosolic	gwas
DST	HGNC:1090	ENSG00000151914	Q03001	Dystonin	clinvar
SLAMF1	HGNC:10903	ENSG00000117090	Q13291	Signaling lymphocytic activation molecule	gwas
SLC15A2	HGNC:10921	ENSG00000163406	Q16348	Solute carrier family 15 member 2	gwas
SLC7A10	HGNC:11058	ENSG00000130876	Q9NS82	Asc-type amino acid transporter 1	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
SMARCA4	HGNC:11100	ENSG00000127616	P51532	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	gwas
SOX8	HGNC:11203	ENSG00000005513	P57073	Transcription factor SOX-8	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
BTNL2	HGNC:1142	ENSG00000204290	Q9UIR0	Butyrophilin-like protein 2	gwas
SVIL	HGNC:11480	ENSG00000197321	O95425	Supervillin	gwas
SYK	HGNC:11491	ENSG00000165025	P43405	Tyrosine-protein kinase SYK	gwas
TBX21	HGNC:11599	ENSG00000073861	Q9UL17	T-box transcription factor TBX21	gwas
TBX6	HGNC:11605	ENSG00000149922	O95947	T-box transcription factor TBX6	gwas
TCF7	HGNC:11639	ENSG00000081059	P36402	Transcription factor 7	gwas
TEF	HGNC:11722	ENSG00000167074	Q10587	Thyrotroph embryonic factor	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
TG	HGNC:11764	ENSG00000042832	P01266	Thyroglobulin	gwas
TGFBR3	HGNC:11774	ENSG00000069702	Q03167	Transforming growth factor beta receptor type 3	gwas
TLL1	HGNC:11843	ENSG00000038295	O43897	Tolloid-like protein 1	gwas
TNFAIP3	HGNC:11896	ENSG00000118503	P21580	Tumor necrosis factor alpha-induced protein 3	gwas
TNFRSF14	HGNC:11912	ENSG00000157873	Q92956	Tumor necrosis factor receptor superfamily member 14	gwas
CD40	HGNC:11919	ENSG00000101017	P25942	Tumor necrosis factor receptor superfamily member 5	gwas
TNFSF14	HGNC:11930	ENSG00000125735	O43557	Tumor necrosis factor ligand superfamily member 14	gwas
TNP2	HGNC:11952	ENSG00000178279	Q05952	Nuclear transition protein 2	gwas
TRAF3	HGNC:12033	ENSG00000131323	Q13114	TNF receptor-associated factor 3	gwas
TREH	HGNC:12266	ENSG00000118094	O43280	Trehalase	gwas
ZNHIT3	HGNC:12309	ENSG00000273611	Q15649	Zinc finger HIT domain-containing protein 3	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TNFRSF1A	Tumor necrosis factor receptor superfamily member 1A	Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.
ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1	Inositol 1,4,5-trisphosphate-gated calcium channel that, upon inositol 1,4,5-trisphosphate binding, mediates calcium release from the endoplasmic reticulum (ER).
BCL6	B-cell lymphoma 6 protein	Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions.
RNASEL	2-5A-dependent ribonuclease	Endoribonuclease that functions in the interferon (IFN) antiviral response.
RORA	Nuclear receptor ROR-alpha	Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5’-AGGTCA-3’ preceded by a short A-T-rich sequence.
RPL5	Large ribosomal subunit protein uL18	Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
RPS6KA5	Ribosomal protein S6 kinase alpha-5	Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factors RELA, STAT3 and ETV1/ER81, and that contribu…
RPS6KB1	Ribosomal protein S6 kinase beta-1	Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression.
RREB1	Ras-responsive element-binding protein 1	Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
BHLHE40	Class E basic helix-loop-helix protein 40	Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes.
RUNX3	Runt-related transcription factor 3	Forms the heterodimeric complex core-binding factor (CBF) with CBFB.
BICD1	Protein bicaudal D homolog 1	Regulates coat complex coatomer protein I (COPI)-independent Golgi-endoplasmic reticulum transport by recruiting the dynein-dynactin motor complex.
ATXN1	Ataxin-1	Chromatin-binding factor that repress Notch signaling in the absence of Notch intracellular domain by acting as a CBF1 corepressor.
SCAMP2	Secretory carrier-associated membrane protein 2	Functions in post-Golgi recycling pathways.
CXCR5	C-X-C chemokine receptor type 5	Cytokine receptor that binds to B-lymphocyte chemoattractant (BLC).
SCO2	Cytochrome c oxidase assembly factor SCO2	Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2); together with SCO1, facilitates the incorporation of copper into the Cu(A) site of MT-CO2/COX2.
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.
SCAF11	Protein SCAF11	Plays a role in pre-mRNA alternative splicing by regulating spliceosome assembly.
SGCD	Delta-sarcoglycan	Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
SH3BP2	SH3 domain-binding protein 2	Binds differentially to the SH3 domains of certain proteins of signal transduction pathways.
SH3GL2	Endophilin-A1	Implicated in synaptic vesicle endocytosis.
SHMT1	Serine hydroxymethyltransferase, cytosolic	Pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylene THF, serving as a critical component of the folate cycle and facilitating one-carbon bio…
DST	Dystonin	Cytoskeletal linker protein.
SLAMF1	Signaling lymphocytic activation molecule	Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family.
SLC15A2	Solute carrier family 15 member 2	Proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
SLC7A10	Asc-type amino acid transporter 1	Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane.
ZFP36L1	mRNA decay activator protein ZFP36L1	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
SMARCA4	SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 4	ATPase involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
SOX8	Transcription factor SOX-8	Transcription factor that may play a role in central nervous system, limb and facial development.
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.
BTNL2	Butyrophilin-like protein 2	Negative regulator of T-cell proliferation.
SVIL	Supervillin	Forms a high-affinity link between the actin cytoskeleton and the membrane.
SYK	Tyrosine-protein kinase SYK	Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR).
TBX21	T-box transcription factor TBX21	Lineage-defining transcription factor which initiates Th1 lineage development from naive Th precursor cells both by activating Th1 genetic programs and by repressing the opposing Th2 and Th17 genetic programs.
TBX6	T-box transcription factor TBX6	T-box transcription factor that plays an essential role in the determination of the fate of axial stem cells: neural vs mesodermal.
TCF7	Transcription factor 7	Transcriptional activator involved in T-cell lymphocyte differentiation.
TEF	Thyrotroph embryonic factor	Transcription factor that binds to and transactivates the TSHB promoter.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TG	Thyroglobulin	Acts as a substrate for the production of iodinated thyroid hormones thyroxine (T4) and triiodothyronine (T3).
TGFBR3	Transforming growth factor beta receptor type 3	Cell surface receptor that regulates diverse cellular processes including cell proliferation, differentiation, migration, and apoptosis.
TLL1	Tolloid-like protein 1	Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase.
TNFAIP3	Tumor necrosis factor alpha-induced protein 3	Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities.
TNFRSF14	Tumor necrosis factor receptor superfamily member 14	Receptor for four distinct ligands: The TNF superfamily members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the immunoglobulin superfamily members BTLA and CD160, altogether defining a complex stimulatory and inhibitory signal…
CD40	Tumor necrosis factor receptor superfamily member 5	Receptor for TNFSF5/CD40LG.
TNFSF14	Tumor necrosis factor ligand superfamily member 14	Cytokine that binds to TNFRSF3/LTBR.
TNP2	Nuclear transition protein 2	Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals.
TRAF3	TNF receptor-associated factor 3	Cytoplasmic E3 ubiquitin ligase that regulates various signaling pathways, such as the NF-kappa-B, mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) pathways, and thus controls a lot of biological processes in…
TREH	Trehalase	Intestinal trehalase is probably involved in the hydrolysis of ingested trehalose.
TSFM	Elongation factor Ts, mitochondrial	Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP.

Protein-family classification

Druggable: 20 · Difficult: 26 · Unknown: 29 · Druggable fraction: 0.27

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	19	2.1×	0.014
Kinase	7	2.6×	0.101
Nuclear receptor	1	5.2×	0.487
Scaffold/PPI	7	1.6×	0.487
Transporter	2	2.1×	0.552
Ion channel	1	1.5×	0.773
Antibody/Immunoglobulin	3	1.2×	0.773
Other/Unknown	29	0.7×	0.999
Enzyme (other)	4	0.6×	0.999
Protease	1	0.5×	0.999
GPCR	1	0.3×	0.999

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TNFRSF1A	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
ITPR1	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom
BCL6	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
RNASEL	Kinase	yes	4.6.1.19	Prot_kinase_dom, Ankyrin_rpt, KEN_dom
RORA	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt, Nuclear_hrmn_rcpt
RPL5	Other/Unknown	no		Rbsml_uL18_euk_arc, Ribosomal_uL18_C_euk, Ribosomal_L18
RPS6KA5	Kinase	yes		Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RPS6KB1	Kinase	yes	2.7.11.1	Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS
RREB1	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, RREB1
BHLHE40	Transcription factor	no		Orange_dom, bHLH_dom, HLH_DNA-bd_sf
RUNX3	Transcription factor	no		AML1_Runt, p53-like_TF_DNA-bd_sf, p53/RUNT-type_TF_DNA-bd_sf
BICD1	Other/Unknown	no		BICD
ATXN1	Other/Unknown	no		Ataxin_AXH_dom, Ataxin-1_N, Ataxin_AXH_dom_sf
SCAMP2	Other/Unknown	no		SCAMP
CXCR5	GPCR	yes		GPCR_Rhodpsn, Chemokine_CXCR5, GPCR_Rhodpsn_7TM
SCO2	Other/Unknown	no		SCO1/SenC, Thioredoxin_domain, Synth_of_cyt-c-oxidase_Sco1/2
CCL22	Other/Unknown	no		Chemokine_CC_CS, Chemokine_IL8-like_dom, Interleukin_8-like_sf
SCAF11	Transcription factor	no		Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
SGCD	Other/Unknown	no		Sarcoglycan, Sarcoglycan_gamma/delta/zeta
SH3BP2	Scaffold/PPI	no		SH2, PH_domain, PH-like_dom_sf
SH3GL2	Scaffold/PPI	no		SH3_domain, BAR_dom, AH/BAR_dom_sf
SHMT1	Enzyme (other)	yes	2.1.2.1	Ser_HO-MeTrfase, PyrdxlP-dep_Trfase_major, PyrdxlP-dep_Trfase_small
DST	Scaffold/PPI	no		Plectin_repeat, SH3_domain, Actinin_actin-bd_CS
SLAMF1	Antibody/Immunoglobulin	yes		Ig-like_dom, Sig_lymph_act_molc_N, Ig-like_fold
SLC15A2	Transporter	yes		POT_fam, Oligopep_transport, PTR2_symporter_CS
SLC7A10	Transporter	yes		AA/rel_permease1, AminoAcid_Transporter
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
SMARCA4	Other/Unknown	no		SNF2_N, Bromodomain, Helicase_C-like
SOX8	Transcription factor	no		HMG_box_dom, Sox_N, HMG_box_dom_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
BTNL2	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig_sub, Ig-like_dom
SVIL	Other/Unknown	no		Villin_headpiece, Villin/Gelsolin, Gelsolin-like_dom
SYK	Kinase	yes	2.7.10.2	Prot_kinase_dom, SH2, Ser-Thr/Tyr_kinase_cat_dom
TBX21	Transcription factor	no		TF_T-box, p53-like_TF_DNA-bd_sf, TF_T-box_CS
TBX6	Transcription factor	no		TF_T-box, TF_Brachyury, p53-like_TF_DNA-bd_sf
TCF7	Other/Unknown	no		HMG_box_dom, CTNNB1-bd_N, TCF/LEF
TEF	Other/Unknown	no		bZIP, PAR_bZIP, bZIP_sf
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TG	Other/Unknown	no		Thyroglobulin_1, CarbesteraseB, Tyr-kin_ephrin_A/B_rcpt-like
TGFBR3	Other/Unknown	no		ZP_dom, ZP_dom_CS, ZP-C_dom
TLL1	Protease	yes		EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
TNFAIP3	Transcription factor	no		Znf_A20, OTU_dom, OTU_Deubiquitinase
TNFRSF14	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_14, TNFRSF14/UL144_N
CD40	Other/Unknown	no		TNFR/NGFR_Cys_rich_reg, TNFR_5, TNFRSF5_N
TNFSF14	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
TNP2	Other/Unknown	no		TP2
TRAF3	Transcription factor	no		Znf_TRAF, Znf_RING, MATH/TRAF_dom
TREH	Enzyme (other)	yes	3.2.1.28	Glyco_hydro_37, 6-hairpin_glycosidase_sf, 6hp_glycosidase-like_sf
ZNHIT3	Transcription factor	no		Znf_HIT, ZNHIT3_C, BCD1

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
granulocyte	11
Brodmann (1909) area 23	5
primordial germ cell in gonad	5
buccal mucosa cell	5
lymph node	5
ganglionic eminence	5
ventricular zone	5
left testis	5
blood	4
endothelial cell	4
monocyte	4
male germ line stem cell (sensu Vertebrata) in testis	4
right testis	4
germinal epithelium of ovary	3
palpebral conjunctiva	3
lower esophagus mucosa	3
sural nerve	3
skeletal muscle tissue of rectus abdominis	3
mucosa of transverse colon	3
spleen	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TNFRSF1A	292	ubiquitous	marker	tendon of biceps brachii, gall bladder, left uterine tube
ITPR1	284	ubiquitous	marker	cauda epididymis, Brodmann (1909) area 23, primary visual cortex
BCL6	300	ubiquitous	marker	gastrocnemius, mucosa of stomach, blood
RNASEL	249	ubiquitous	marker	amniotic fluid, palpebral conjunctiva, germinal epithelium of ovary
RORA	284	ubiquitous	marker	upper leg skin, lateral nuclear group of thalamus, skin of hip
RPL5	292	ubiquitous	marker	germinal epithelium of ovary, primordial germ cell in gonad, parietal pleura
RPS6KA5	283	ubiquitous	marker	secondary oocyte, cauda epididymis, nipple
RPS6KB1	275	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, calcaneal tendon
RREB1	278	ubiquitous	marker	buccal mucosa cell, epithelium of nasopharynx, oral cavity
BHLHE40	302	ubiquitous	marker	saphenous vein, vena cava, lower esophagus mucosa
RUNX3	220	broad	marker	granulocyte, buccal mucosa cell, lymph node
BICD1	259	ubiquitous	marker	ventricular zone, sural nerve, ganglionic eminence
ATXN1	295	ubiquitous	marker	endothelial cell, Brodmann (1909) area 23, skeletal muscle tissue of rectus abdominis
SCAMP2	288	ubiquitous	marker	rectum, mucosa of transverse colon, lower esophagus mucosa
CXCR5	172	tissue_specific	marker	granulocyte, spleen, lymph node
SCO2	260	ubiquitous	yes	right uterine tube, granulocyte, mucosa of transverse colon
CCL22	131	broad	marker	type B pancreatic cell, olfactory bulb, vermiform appendix
SCAF11	295	ubiquitous	marker	buccal mucosa cell, colonic epithelium, tendon of biceps brachii
SGCD	247	broad	marker	left ventricle myocardium, skeletal muscle tissue of rectus abdominis, heart right ventricle
SH3BP2	213	ubiquitous	marker	granulocyte, sural nerve, monocyte
SH3GL2	193	broad	marker	Brodmann (1909) area 23, middle temporal gyrus, endothelial cell
SHMT1	134	ubiquitous	marker	right lobe of liver, liver, adult mammalian kidney
DST	305	ubiquitous	marker	corpus callosum, calcaneal tendon, medial globus pallidus
SLAMF1	159	broad	marker	thymus, lymph node, granulocyte
SLC15A2	245	broad	marker	nasal cavity epithelium, bronchial epithelial cell, epithelium of bronchus
SLC7A10	138	broad	yes	omental fat pad, peritoneum, adipose tissue of abdominal region
ZFP36L1	289	ubiquitous	marker	mucosa of paranasal sinus, endocervix, mucosa of stomach
SMARCA4	295	ubiquitous	marker	ganglionic eminence, cortical plate, cervix squamous epithelium
SOX8	194	broad	marker	inferior vagus X ganglion, lateral globus pallidus, subthalamic nucleus
STAT3	301	ubiquitous	marker	type B pancreatic cell, pericardium, lower lobe of lung

Protein interactions among cohort

Intra-cohort edges: 41.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STAT3	10,108
SMARCA4	8,138
RNASEL	6,889
RPL5	6,028
WWOX	5,892
TERT	5,717
RPS6KB1	5,474
SYK	5,172
VCAM1	5,031
TNFRSF1A	4,523

Intra-cohort edges

A	B	Sources
BCL6	CXCR5	string_interaction
BCL6	TBX21	string_interaction
BICD1	STAT3	intact
BTNL2	TSBP1	string_interaction
CD40	TRAF3	biogrid_interaction, string_interaction
DLEU1	SHMT1	intact
DST	YWHAG	intact
IKZF1	IKZF2	biogrid_interaction, intact
IKZF1	RUNX3	string_interaction
IKZF1	SH3BP2	biogrid_interaction
IKZF1	TXK	biogrid_interaction, intact
IKZF2	IKZF3	biogrid_interaction
IKZF2	TBX21	string_interaction
IKZF3	RUNX3	string_interaction
PRM3	TNP2	string_interaction
RPS6KA5	SMARCA4	string_interaction
RUNX3	TBX21	string_interaction
RUNX3	TCF7	intact
SCAF11	STAT3	intact
SH3BP2	SYK	intact, string_interaction
SH3BP2	VAV2	intact
SLC15A2	WWOX	biogrid_interaction, intact
SMARCA4	SOX8	string_interaction
SMARCA4	TERT	intact, string_interaction
STAT3	SYK	biogrid_interaction, intact
STAT3	TYK2	string_interaction
STAT4	TBX21	string_interaction
STAT4	TYK2	string_interaction
SVIL	YWHAG	intact
SYK	TNFRSF1A	biogrid_interaction
SYK	VAV2	string_interaction
TBX21	TCF7	string_interaction
TBX21	TXK	string_interaction
TBX6	ZIC1	string_interaction
TNFAIP3	TNFRSF1A	biogrid_interaction
TNFAIP3	TRAF3	string_interaction
TNFAIP3	YWHAG	intact
TNFRSF14	TNFSF14	biogrid_interaction, intact, string_interaction
TNFRSF14	TRAF3	biogrid_interaction, intact
TNFSF14	TRAF3	biogrid_interaction
YWHAG	ZFP36L1	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BCL6	P41182	246
RPL5	P46777	184
SYK	P43405	93
TYK2	P29597	52
SMARCA4	P51532	31
TERT	O14746	23
RPS6KB1	P23443	22
YWHAG	P61981	22
TNFAIP3	P21580	17
CD40	P25942	14
TNFRSF1A	P19438	13
UCK2	Q9BZX2	11
TRAF3	Q13114	10
IKZF1	Q13422	10
RPS6KA5	O75582	8
SHMT1	P34896	8
TNFRSF14	Q92956	8
ATXN1	P54253	7
TNFSF14	O43557	7
VAV2	P52735	7
IKZF2	Q9UKS7	7
SLAMF1	Q13291	6
STAT3	P40763	6
RNASEL	Q05823	5
SH3GL2	Q99962	4
SLC7A10	Q9NS82	4
ZNF217	O75362	4
RORA	P35398	3
SLC15A2	Q16348	3
TG	P01266	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TREH	O43280	92.80
CCL22	O00626	88.21
STAT4	Q14765	86.87
BTNL2	Q9UIR0	85.97
WNT9B	O14905	84.50
SGCD	Q92629	81.43
CXCR5	P32302	80.85
SLC6A16	Q9GZN6	80.51
SCAMP2	O15127	77.30
WDR7	Q9Y4E6	74.31
GCFC2	P16383	74.12
BICD1	Q96G01	72.36
TIMMDC1	Q9NPL8	72.08
SMIM29	Q86T20	71.70
ESPN	B1AK53	68.76
TBX6	O95947	66.18
TBX21	Q9UL17	61.95
BHLHE40	O14503	60.60
SOX8	P57073	59.57
TNP2	Q05952	59.17
PRM3	Q9NNZ6	58.43
TCF7	P36402	58.11
ZIC1	Q15915	55.77
DLEU1	O43261	55.08
RREB1	Q92766	48.28
IKZF3	Q9UKT9	48.06
TSBP1	Q5SRN2	45.58
SCAF11	Q99590	42.56
ITPR1	Q14643

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 713. Enrichment computed across 250 evidence-associated genes (151 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 151 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by Interleukins	11	4.7×	0.017	BCL6, RORA, RPS6KA5, CCL22, SMARCA4, STAT3, STAT4, SYK (+3 more)
Signaling by CSF3 (G-CSF)	4	15.1×	0.029	STAT3, SYK, TYK2, SOCS1
Cytokine Signaling in Immune system	13	3.5×	0.029	BCL6, RNASEL, RORA, RPS6KA5, CCL22, SMARCA4, STAT3, STAT4 (+5 more)
Interleukin-23 signaling	3	25.2×	0.030	STAT3, STAT4, TYK2
Immune System	25	2.1×	0.030	ITPR1, BCL6, RNASEL, RORA, RPS6KA5, CCL22, SH3GL2, SMARCA4 (+17 more)
Interleukin-35 Signalling	3	18.9×	0.033	STAT3, STAT4, TYK2
Inactivation of CSF3 (G-CSF) signaling	4	11.6×	0.033	STAT3, SYK, TYK2, SOCS1
Interleukin-20 family signaling	4	11.2×	0.033	STAT3, STAT4, TYK2, IL22RA2
C-type lectin receptors (CLRs)	5	7.9×	0.033	ITPR1, RPS6KA5, SYK, CASP8, CARD11
Interleukin-10 signaling	5	7.7×	0.033	TNFRSF1A, CCL22, STAT3, TYK2, CD86
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	3	17.4×	0.038	RUNX3, STAT4, TBX21
Interleukin-4 and Interleukin-13 signaling	7	4.8×	0.039	BCL6, RORA, CCL22, STAT3, TYK2, VCAM1, SOCS1
FCERI mediated Ca+2 mobilization	4	9.4×	0.043	ITPR1, SYK, TXK, VAV2
TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway	3	13.3×	0.068	CD40, TNFSF14, TRAF3
Interleukin-2 family signaling	3	12.6×	0.069	STAT3, STAT4, SYK
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	4.0×	0.069	CD40, VCAM1, CLEC2D, CD226, SLAMF6, SLAMF7, CD200R1
Adaptive Immune System	13	2.6×	0.069	ITPR1, SH3GL2, BTNL2, SYK, CARD11, CD28, CD226, CD86 (+5 more)
Signal Transduction	27	1.8×	0.069	ITPR1, RPS6KA5, RPS6KB1, RUNX3, CCL22, SH3GL2, SMARCA4, STAT3 (+19 more)
Ovarian tumor domain proteases	4	7.4×	0.076	TNFAIP3, TRAF3, TNIP2, TNIP3
Signaling by WNT	6	4.5×	0.082	ITPR1, RUNX3, SMARCA4, TCF7, TERT, BCL9L
TNFR1-induced proapoptotic signaling	3	8.7×	0.160	TNFRSF1A, TNFAIP3, CASP8
Binding of TCF/LEF:CTNNB1 to target gene promoters	2	15.1×	0.173	RUNX3, TCF7
RUNX3 regulates WNT signaling	2	15.1×	0.173	RUNX3, TCF7
Interleukin-21 signaling	2	15.1×	0.173	STAT3, STAT4
Synthesis of PC	3	8.1×	0.173	LPIN3, SLC44A2, LPCAT1
TNFs bind their physiological receptors	3	7.8×	0.173	TNFRSF1A, TNFRSF14, TNFSF14
Anti-inflammatory response favouring Leishmania parasite infection	3	7.8×	0.173	ITPR1, SYK, ADCY3
Leishmania parasite growth and survival	3	7.8×	0.173	ITPR1, SYK, ADCY3
Co-stimulation by CD28	3	7.6×	0.173	CD28, CD86, CTLA4
Interferon gamma signaling	5	4.2×	0.173	VCAM1, CAMK2G, TRIM2, TRIM14, SOCS1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 232 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	20	4.1×	2e-04	CXCR5, CCL22, SLAMF1, TCF7, TGFBR3, TNFRSF14, TNFSF14, TYK2 (+12 more)
regulation of B cell differentiation	4	22.4×	0.008	ZFP36L1, IKZF3, CARD11, FCRL3
T cell costimulation	6	9.7×	0.008	TNFRSF14, TNFSF14, CARD11, CD28, CD5, CD86
cell surface receptor signaling pathway via JAK-STAT	7	8.8×	0.008	TNFRSF1A, STAT3, STAT4, CD40, TYK2, SOCS1, CSF2RB
positive regulation of T cell proliferation	7	7.8×	0.008	BTNL2, TYK2, VCAM1, CD28, CD6, CD86, CLECL1
T cell activation	7	7.8×	0.008	TNFSF14, CASP8, CD2, CD28, CD86, SLAMF6, SLAMF7
negative regulation of canonical NF-kappaB signal transduction	8	5.9×	0.013	TNFRSF1A, RORA, STAT3, TGFBR3, TNFAIP3, CASP8, TNIP2, TNIP3
negative regulation of CD40 signaling pathway	2	72.6×	0.025	SLAMF1, TNFAIP3
CD4-positive, alpha-beta T cell proliferation	3	24.2×	0.025	CARD11, CD28, NDFIP1
positive regulation of T cell receptor signaling pathway	4	13.2×	0.025	CARD11, CD28, CD226, CD86
B cell activation	5	9.8×	0.025	CXCR5, CD40, CASP8, CD86, FCRL1
positive regulation of transcription by RNA polymerase II	31	2.0×	0.025	TNFRSF1A, RNASEL, RORA, RPS6KA5, RREB1, ATXN1, SMARCA4, SOX8 (+23 more)
regulation of tumor necrosis factor-mediated signaling pathway	4	12.1×	0.033	TNFRSF1A, SYK, TNFAIP3, CASP8
positive regulation of isotype switching to IgG isotypes	3	19.8×	0.035	TBX21, CD40, CD28
positive regulation of canonical NF-kappaB signal transduction	11	3.4×	0.035	TNFRSF1A, STAT3, CD40, TNFSF14, CASP8, CARD11, SLC44A2, NDFIP1 (+3 more)
regulation of transcription by RNA polymerase II	36	1.8×	0.035	RORA, RREB1, BHLHE40, RUNX3, SMARCA4, STAT3, STAT4, TBX21 (+28 more)
adaptive immune response	10	3.6×	0.037	SLAMF1, SYK, TNFRSF14, TXK, CD6, CD86, SLAMF7, THEMIS (+2 more)
negative regulation of DNA-templated transcription	18	2.5×	0.037	BCL6, RPS6KA5, BHLHE40, ATXN1, SMARCA4, SOX8, TBX21, ZNF217 (+10 more)
negative regulation of CD8-positive, alpha-beta T cell differentiation	2	48.4×	0.038	ZBTB7B, SOCS1
regulation of lymphocyte differentiation	2	48.4×	0.038	IKZF3, NDFIP1
negative regulation of isotype switching to IgE isotypes	2	48.4×	0.038	BCL6, NDFIP1
natural killer cell activation	4	10.0×	0.038	CASP8, CD2, CD48, SLAMF7
heterotypic cell-cell adhesion	4	10.0×	0.038	VCAM1, CD2, CD58, CD200R1
positive regulation of type II interferon production	6	5.8×	0.038	SLAMF1, TXK, TYK2, CD2, CD226, SLAMF6
positive regulation of interleukin-4 production	4	9.7×	0.041	SYK, CD28, CD86, CLECL1
granulocyte differentiation	3	15.6×	0.043	CBFA2T3, ZBTB46, L3MBTL3
regulation of T cell differentiation	3	15.6×	0.043	TBX21, CD2, CARD11
phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	5.5×	0.043	ZFP36L1, STAT3, CD40, CD28, RGCC, PRR5L
macrophage differentiation	4	8.1×	0.070	CASP8, ZBTB46, SOCS1, L3MBTL3
positive regulation of interleukin-2 production	4	8.1×	0.070	BTNL2, CARD11, CD28, CD86

Therapeutics

Drugs indicated for this disease

26 approved, 52 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alemtuzumab	Approved (phase 4)
Baclofen	Approved (phase 4)
Cladribine	Approved (phase 4)
Corticotropin	Approved (phase 4)
Daclizumab	Approved (phase 4)
Dalfampridine	Approved (phase 4)
Dexamethasone	Approved (phase 4)
Dimethyl Fumarate	Approved (phase 4)
Diroximel Fumarate	Approved (phase 4)
Glatiramer Acetate	Approved (phase 4)
INTERFERON BETA-1A	Approved (phase 4)
INTERFERON BETA-1B	Approved (phase 4)
Lincomycin	Approved (phase 4)
Methylprednisolone	Approved (phase 4)
Monomethyl Fumarate	Approved (phase 4)
Natalizumab	Approved (phase 4)
Ocrelizumab	Approved (phase 4)
Ofatumumab	Approved (phase 4)
PEGINTERFERON BETA-1A	Approved (phase 4)
Ponesimod	Approved (phase 4)
Prednisolone	Approved (phase 4)
Prednisolone Acetate	Approved (phase 4)
Prednisone	Approved (phase 4)
Siponimod	Approved (phase 4)
Teriflunomide	Approved (phase 4)
Triamcinolone Acetonide	Approved (phase 4)
Acetaminophen	Phase 3 (in late-stage trials)
Amantadine	Phase 3 (in late-stage trials)
Amifampridine	Phase 3 (in late-stage trials)
Arbaclofen Placarbil	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Biotin	Phase 3 (in late-stage trials)
Cetirizine	Phase 3 (in late-stage trials)
Charcoal, Activated	Phase 3 (in late-stage trials)
Cholestyramine	Phase 3 (in late-stage trials)
Desloratadine	Phase 3 (in late-stage trials)
Dextromethorphan	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Diphenhydramine	Phase 3 (in late-stage trials)
Donepezil	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Estradiol	Phase 3 (in late-stage trials)
Evobrutinib	Phase 3 (in late-stage trials)
Fenebrutinib	Phase 3 (in late-stage trials)
Fingolimod	Phase 3 (in late-stage trials)
Frexalimab	Phase 3 (in late-stage trials)
Human Immunoglobulin G	Phase 3 (in late-stage trials)
Ibuprofen	Phase 3 (in late-stage trials)
Influenza Virus Vaccine	Phase 3 (in late-stage trials)
Interferon Beta	Phase 3 (in late-stage trials)
Keyhole Limpet Hemocyanin	Phase 3 (in late-stage trials)
Laquinimod	Phase 3 (in late-stage trials)
Levocarnitine	Phase 3 (in late-stage trials)
Masitinib	Phase 3 (in late-stage trials)
Memantine	Phase 3 (in late-stage trials)
Methotrexate	Phase 3 (in late-stage trials)
Methylphenidate	Phase 3 (in late-stage trials)
Minocycline	Phase 3 (in late-stage trials)
Mitoxantrone	Phase 3 (in late-stage trials)
Modafinil	Phase 3 (in late-stage trials)
Nabiximols	Phase 3 (in late-stage trials)
Naltrexone	Phase 3 (in late-stage trials)
Naproxen	Phase 3 (in late-stage trials)
Nomegestrol Acetate	Phase 3 (in late-stage trials)
Onabotulinumtoxina	Phase 3 (in late-stage trials)
Ozanimod	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Pertussis Vaccine	Phase 3 (in late-stage trials)
Quinidine	Phase 3 (in late-stage trials)
Ranitidine	Phase 3 (in late-stage trials)
Remibrutinib	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Terfenadine	Phase 3 (in late-stage trials)
Tetanus Toxoid	Phase 3 (in late-stage trials)
Tolebrutinib	Phase 3 (in late-stage trials)
Ublituximab	Phase 3 (in late-stage trials)
Vidofludimus	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Acetazolamide, Acetylcysteine, Alfuzosin, Armodafinil, Atacicept, Atorvastatin, Azithromycin, Belimumab, Briakinumab, Cannabidiol, Cannabinol, Celecoxib, Cholecalciferol, Clemastine, Curcumin, Dexrazoxane, Dextroamphetamine, Dronabinol, Duloxetine, Emtricitabine, Epigalocatechin Gallate, Epoetin Beta, Famciclovir, Fish Oil, Fludarabine, Gabapentin, Ginseng, American, Histamine, Hydroxyurea, Ianalumab, Icosapent, Incomplete Freund’S Adjuvant, Ketoprofen, Lipoic Acid, Alpha, Lisdexamfetamine, Mecasermin, Metformin, Mycophenolate Mofetil, Oxcarbazepine, Pirtobrutinib, Rifampin, Riluzole, Secukinumab, Sodium Chloride, Tacrolimus Anhydrous, Testosterone, Topiramate, Ustekinumab.

Drug target analysis

Approved (phase 4): 13 · Phase ≥3: 14 · Phased (≥1): 19 · Undrugged: 56

Druggability breadth: 81 of 250 evidence-associated genes (32%) 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
RORA	TRETINOIN
RPL5	GENTAMICIN SULFATE
RPS6KA5	FEDRATINIB
RPS6KB1	FEDRATINIB
SHMT1	PEMETREXED
SLC15A2	CYCLACILLIN
STAT3	MOMELOTINIB
SYK	FEDRATINIB
TERT	BERBERINE
TXK	AFATINIB
TYK2	FEDRATINIB
IKZF1	POMALIDOMIDE
IKZF3	POMALIDOMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TYK2	72	4
SYK	54	4
RPS6KB1	39	4
TXK	31	4
RPS6KA5	25	4
STAT3	18	4
TERT	10	4
SLC15A2	8	4
IKZF3	5	4
IKZF1	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
TRETINOIN	4	RORA
GENTAMICIN SULFATE	4	RPL5
FEDRATINIB	4	RPS6KA5, RPS6KB1, SYK, TXK, TYK2
RUXOLITINIB	4	RPS6KA5, TYK2
NINTEDANIB	4	RPS6KA5, RPS6KB1, TXK, TYK2
SUNITINIB	4	RPS6KA5, RPS6KB1, TYK2
MIDOSTAURIN	4	RPS6KA5, RPS6KB1, SYK, TYK2
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1, TXK
BOSUTINIB	4	RPS6KB1, SYK, TXK, TYK2
CRIZOTINIB	4	RPS6KB1, SYK, TXK, TYK2
PEMETREXED	4	SHMT1
CYCLACILLIN	4	SLC15A2
CEFTIBUTEN	4	SLC15A2
CEFADROXIL	4	SLC15A2
CEPHALEXIN ANHYDROUS	4	SLC15A2
AMPICILLIN	4	SLC15A2
CEFACLOR ANHYDROUS	4	SLC15A2
MOMELOTINIB	4	STAT3, TYK2
NITAZOXANIDE	4	STAT3
NICLOSAMIDE	4	STAT3
DIGOXIN	4	STAT3
BARICITINIB	4	STAT3, TYK2
DIGITOXIN	4	STAT3
DEUCRAVACITINIB	4	STAT3, TYK2
NERATINIB	4	SYK, TXK
INFIGRATINIB PHOSPHATE	4	SYK, TYK2
INFIGRATINIB	4	SYK, TYK2
ENTRECTINIB	4	SYK
FOSTAMATINIB	4	SYK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

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
SYK	873	Binding:863, Functional:10
RPS6KA5	659	Binding:656, ADMET:2, Functional:1
RPS6KB1	585	Binding:582, Functional:2, ADMET:1
TERT	391	Binding:389, Functional:2
TXK	290	Binding:286, ADMET:3, Functional:1
SMARCA4	230	Binding:207, ADMET:12, Functional:11
BCL6	209	Binding:202, Functional:7
RORA	115	Binding:111, Functional:3, Unclassified:1
IKZF1	106	Binding:105, Functional:1
IKZF3	101	Binding:100, Functional:1
RPL5	90	Binding:90
RNASEL	43	Binding:42, Functional:1
CXCR5	33	Binding:21, Functional:12
IKZF2	26	Binding:26
UCK2	25	Binding:25
TNFRSF1A	24	Binding:23, Functional:1
SLC15A2	20	Functional:16, ADMET:4
STAT4	20	Binding:20
VCAM1	16	Binding:15, Functional:1
ITPR1	13	Binding:12, Functional:1
YWHAG	12	Binding:11, Functional:1
CD40	10	Binding:10
SHMT1	9	Binding:9
TCF7	7	Binding:7
TLL1	5	Binding:5
TREH	4	Binding:4
SCAMP2	1	Binding:1
SCO2	1	Binding:1
CCL22	1	Binding:1
TNFAIP3	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNASEL	4.6.1.19	ribonuclease T2
RPS6KB1	2.7.11.1	non-specific serine/threonine protein kinase
SHMT1	2.1.2.1	glycine hydroxymethyltransferase
SYK	2.7.10.2, 2.7.12.1	non-specific protein-tyrosine kinase, dual-specificity kinase
TREH	3.2.1.28	alpha,alpha-trehalase
ACP5	3.1.3.2	acid phosphatase
TXK	2.7.10.2	non-specific protein-tyrosine kinase
TYK2	2.7.10.2	non-specific protein-tyrosine kinase
UBE2E3	2.3.2.23, 2.3.2.24	E2 ubiquitin-conjugating enzyme, (E3-independent) E2 ubiquitin-conjugating enzyme
UCK2	2.7.1.48	uridine/cytidine kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
BCL6	209
RORA	115
RPS6KA5	659
RPS6KB1	585
SMARCA4	230
STAT3	1,319
SYK	873
TERT	391
TXK	290
TYK2	1,083
IKZF1	106
IKZF3	101

Pharmacogenomics

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

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

Chemical tractability of cohort targets

30 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)
TRETINOIN	4	RORA
GENTAMICIN SULFATE	4	RPL5
FEDRATINIB	4	RPS6KA5, RPS6KB1, SYK, TXK, TYK2
RUXOLITINIB	4	RPS6KA5, TYK2
NINTEDANIB	4	RPS6KA5, RPS6KB1, TXK, TYK2
SUNITINIB	4	RPS6KA5, RPS6KB1, TYK2
MIDOSTAURIN	4	RPS6KA5, RPS6KB1, SYK, TYK2
SORAFENIB	4	RPS6KB1
VANDETANIB	4	RPS6KB1, TXK
BOSUTINIB	4	RPS6KB1, SYK, TXK, TYK2
CRIZOTINIB	4	RPS6KB1, SYK, TXK, TYK2
PEMETREXED	4	SHMT1
CYCLACILLIN	4	SLC15A2
CEFTIBUTEN	4	SLC15A2
CEFADROXIL	4	SLC15A2
CEPHALEXIN ANHYDROUS	4	SLC15A2
AMPICILLIN	4	SLC15A2
CEFACLOR ANHYDROUS	4	SLC15A2
MOMELOTINIB	4	STAT3, TYK2
NITAZOXANIDE	4	STAT3
NICLOSAMIDE	4	STAT3
DIGOXIN	4	STAT3
BARICITINIB	4	STAT3, TYK2
DIGITOXIN	4	STAT3
DEUCRAVACITINIB	4	STAT3, TYK2
NERATINIB	4	SYK, TXK
INFIGRATINIB PHOSPHATE	4	SYK, TYK2
INFIGRATINIB	4	SYK, TYK2
ENTRECTINIB	4	SYK
FOSTAMATINIB	4	SYK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	13	RORA, RPL5, RPS6KA5, RPS6KB1, SHMT1, SLC15A2, STAT3, SYK, TERT, TXK (+3 more)
B	Phased (≥1) drug, not yet approved	6	TNFRSF1A, BCL6, SMARCA4, TREH, VCAM1, YWHAG
C	Druggable family + PDB, no drug	7	RNASEL, SLAMF1, SLC7A10, TLL1, ACP5, UBE2E3, UCK2
D	Druggable family + AlphaFold only, no drug	3	ITPR1, CXCR5, BTNL2
E	Difficult family or no structure, no drug	46	RREB1, BHLHE40, RUNX3, BICD1, ATXN1, SCAMP2, SCO2, CCL22, SCAF11, SGCD (+36 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RUNX3	0	IKZF1
SH3BP2	0	SYK
STAT4	20	TYK2
ITPR1	13	—
RNASEL	43	—
RREB1	0	—
BHLHE40	0	—
BICD1	0	—
ATXN1	0	—
SCAMP2	1	—
CXCR5	33	—
SCO2	1	—
CCL22	1	—
SCAF11	0	—
SGCD	0	—
SH3GL2	0	—
DST	0	—
SLAMF1	0	—
SLC7A10	0	—
ZFP36L1	0	—
SOX8	0	—
BTNL2	0	—
SVIL	0	—
TBX21	0	—
TBX6	0	—
TCF7	7	—
TEF	0	—
TG	0	—
TGFBR3	0	—
TLL1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,743.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	282
PHASE2	214
PHASE3	187
PHASE4	143
PHASE1	142
PHASE1/PHASE2	75
PHASE2/PHASE3	34
EARLY_PHASE1	23

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT04178005	PHASE4	ACTIVE_NOT_RECRUITING	Cladribine Tablets After Treatment With Natalizumab (CLADRINA)
NCT04387734	PHASE4	ACTIVE_NOT_RECRUITING	Effects of Ocrevus in Relapsing Multiple Sclerosis
NCT04466150	PHASE4	ACTIVE_NOT_RECRUITING	Impact of Ocrelizumab on Cerebrospinal Fluid Biomarkers at Multiple Sclerosis Onset
NCT04480853	PHASE4	RECRUITING	Safety and Efficacy Study of Fingolimod in Taiwanese Adults (≥ 20years) With Relapsing Remitting Multiple Sclerosis
NCT04601233	PHASE4	NOT_YET_RECRUITING	Testosterone Treatment for Erectile Dysfunction and Multiple Sclerosis
NCT04650321	PHASE4	RECRUITING	Home Based Infusions for Ocrelizumab
NCT05285891	PHASE4	RECRUITING	Ocrelizumab Discontinuation in Relapsing Multiple Sclerosis
NCT06136728	PHASE4	RECRUITING	Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
NCT06396039	PHASE4	ACTIVE_NOT_RECRUITING	A Study to Assess the Effectiveness and Safety of Ozanimod in Chinese Adults With Relapsing Multiple Sclerosis
NCT06444113	PHASE4	ACTIVE_NOT_RECRUITING	Concentration of Ofatumumab in the Breast Milk of Lactating Women With Relapsing Forms of Multiple Sclerosis
NCT06529406	PHASE4	RECRUITING	Prospective Evaluation of Sequencing From antiCD-20 Therapies to Ozanimod
NCT07087106	PHASE4	RECRUITING	Glucose Consumption in MS Using [F-18]FDG-PET
NCT07138833	PHASE4	NOT_YET_RECRUITING	A Phase IV Study of Dimethyl Fumarate Enteric-coated Capsules for Relapsing Multiple Sclerosis (RMS)
NCT07225361	PHASE4	RECRUITING	Ublituximab (Briumvi) for Early Forms of Relapsing Multiple Sclerosis
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT07303582	PHASE4	RECRUITING	Individualised Cryoneurolysis to Treat Pain in the Context of Spasticity in the Upper and Lower Extremities
NCT07389590	PHASE4	RECRUITING	Study of Ublituximab for Ocrelizumab Wearing-Off in Multiple Sclerosis
NCT07483450	PHASE4	RECRUITING	A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Ocrelizumab in Participants With Relapsing Multiple Sclerosis and Primary Progressive Multiple Sclerosis
NCT07609719	PHASE4	NOT_YET_RECRUITING	A Study of Ocrelizumab Administered Subcutaneously in Participants With Multiple Sclerosis Who Switch From an Approved Anti-CD20 Therapy
NCT07614321	PHASE4	RECRUITING	Silodosin for Urinary Symptoms in Female Patients With Multiple Sclerosis
NCT00037102	PHASE4	COMPLETED	Combination Therapy With Avonex and BiMonthly High Dose Intravenous Methotrexate in Multiple Sclerosis
NCT00037115	PHASE4	WITHDRAWN	Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.
NCT00146068	PHASE4	COMPLETED	EARLY IFNB-1a and Simvastatin Combination Therapy in Clinically Isolated Syndrome Suggestive of Multiple Sclerosis
NCT00151294	PHASE4	TERMINATED	The Efficacy and Safety of Escitalopram for Depression in Multiple Sclerosis
NCT00176592	PHASE4	COMPLETED	Phase IV Study, Betaseron Versus Copaxone for Relapsing Remitting or CIS Forms of MS Using Triple Dose Gad 3 T MRI
NCT00179478	PHASE4	COMPLETED	Long Term Study of Avonex Therapy Following a First Attack of Multiple Sclerosis
NCT00220922	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Using Alcohol Wipes Prior to Daily Injections of Copaxone®.
NCT00239993	PHASE4	COMPLETED	A Study to Evaluate the Impact of Using Warm Compress Prior to Daily Injections of Copaxone®
NCT00240006	PHASE4	COMPLETED	A Study Comparing Shared Solutions® Plus MS Center Support Versus Shared Solutions® Alone
NCT00240032	PHASE4	COMPLETED	A Study to Evaluate the Impact on Skin (Injection Site) Reactions of Taking an Antihistamine (Zyrtec®) or Placebo Prior to Daily Injections of Copaxone®.
NCT00246324	PHASE4	COMPLETED	Safety and Efficacy Study of Doxycycline in Combination With Interferon-B-1a to Treat Multiple Sclerosis
NCT00267319	PHASE4	COMPLETED	FOCUS Fatigue Outcome in Copaxone USers
NCT00381264	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Multiple Sclerosis
NCT00414453	PHASE4	TERMINATED	Trial of Analgesia With Lidocaine or Extended-release Oxycodone for Neuropathic Pain Treatment in Multiple Sclerosis
NCT00423527	PHASE4	COMPLETED	Levetiracetam in Central Pain in Multiple Sclerosis(MS)
NCT00480181	PHASE4	COMPLETED	Efficacy and Safety Evaluation of Nabilone as Adjunctive Therapy to Gabapentin for the Management of Neuropathic Pain in Multiple Sclerosis
NCT00492765	PHASE4	COMPLETED	Simvastatin as an Add-on Treatment to Interferon-beta-1a for the Treatment of Relapsing-Remitting Multiple Sclerosis
NCT00493077	PHASE4	COMPLETED	Safety of Avonex Treatment in Multiple Sclerosis Patients With Neutralizing Antibodies to Interferon Beta Therapy
NCT00536120	PHASE4	COMPLETED	The Effects of Tysabri Treatment on Vaccination Response and Lymphocyte Subsets in Subjects With Relapsing Forms of Multiple Sclerosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FINGOLIMOD	4	46
TERIFLUNOMIDE	4	33
OCRELIZUMAB	4	28
INTERFERON BETA-1A	4	25
DIMETHYL FUMARATE	4	15
NATALIZUMAB	4	15
DALFAMPRIDINE	4	14
GLATIRAMER ACETATE	4	12
OFATUMUMAB	4	12
CLADRIBINE	4	10
OZANIMOD	4	9
CORTICOTROPIN	4	7
UBLITUXIMAB	4	7
CLEMASTINE	4	6
DEXCHLORPHENIRAMINE	4	6
ALEMTUZUMAB	4	5
PEGINTERFERON BETA-1A	4	5
ACYCLOVIR	4	4
METHYLPREDNISOLONE	4	4
PONESIMOD	4	4
CETIRIZINE	4	3
CHOLESTYRAMINE	4	3
CYCLOPHOSPHAMIDE	4	3
MEMANTINE	4	3
METHOTREXATE	4	3
BACLOFEN	4	2
CHOLECALCIFEROL	4	2
DACLIZUMAB	4	2
DIPHENHYDRAMINE	4	2
GINKGO	4	2