Multiple sclerosis, susceptibility to

Summary

Multiple sclerosis, susceptibility to (MONDO:0007462) is a disease (an umbrella term covering 5 Mondo subtypes) with 4 cohort genes and 33 clinical trials. Top therapeutic interventions include psilocybin and mebufotenin.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 4
• ClinVar variants: 9
• Clinical trials: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple sclerosis, susceptibility to
Mondo ID	MONDO:0007462
OMIM	126200
UMLS	C1868685
MedGen	358269
Is cancer (heuristic)	no

Also known as: MS

Data availability: 9 ClinVar variants.

Disease family

An umbrella term covering 5 Mondo subtypes.

Classification path: disease susceptibility › inherited disease susceptibility › multiple sclerosis, susceptibility to

Related subtypes (283): microvascular complications of diabetes, susceptibility, Mycobacterium tuberculosis, susceptibility, bacteremia, susceptibility, pregnancy loss, recurrent, susceptibility, autoimmune thyroid disease, susceptibility to, susceptibility to HIV infection, appendicitis, proneness to, atherosclerosis susceptibility, dyslexia, susceptibility to, 1, endometriosis, susceptibility to, 1, osteoarthritis susceptibility 2, essential hypertension, genetic, osteoarthritis susceptibility 1, otitis media, susceptibility to, pelvic organ prolapse, susceptibility to, pulmonary edema of mountaineers, susceptibility to, sarcoidosis, susceptibility to, 1, strabismus, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 1, predisposition to invasive fungal disease due to CARD9 deficiency, celiac disease, susceptibility to, 1, hemolytic uremic syndrome, atypical, susceptibility to, 1, hypervitaminosis a, susceptibility to, kuru, susceptibility to, leprosy, susceptibility to, 3, nonarteritic anterior ischemic optic neuropathy, susceptibility to, diabetes mellitus, insulin-dependent, X-linked, susceptibility to, coronary heart disease, susceptibility to, 3, dyslexia, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 15, Leber optic atrophy, susceptibility to, dyslexia, susceptibility to, 2, Helicobacter pylori infection, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 1, inherited susceptibility to asthma, renal dysplasia, cystic, susceptibility to, systemic lupus erythematosus, susceptibility to, 1, leishmaniasis, tegumentary, susceptibility to, xanthomatosis, susceptibility to, hyperlipidemia, combined, 1, urinary tract infections, recurrent, susceptibility to, hypertension, essential, susceptibility to, 1, hepatic fibrosis, severe, susceptibility to, due to Schistosoma mansoni infection, dyslexia, susceptibility to, 3, Ascaris lumbricoides infection, susceptibility to, hypertension, essential, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 3, nephrolithiasis, uric acid, susceptibility to, atrioventricular septal defect, susceptibility to, 2, vitiligo-associated multiple autoimmune disease susceptibility 1, polysubstance abuse, susceptibility to, dyslexia, susceptibility to, 6, glaucoma, normal tension, susceptibility to, anorexia nervosa, susceptibility to, 1, stroke, susceptibility to, 1, dyslexia, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 2, familial meningioma, celiac disease, susceptibility to, 5, systemic lupus erythematosus with hemolytic anemia, susceptibility to, 1, hypertension, essential, susceptibility to, 3, coronary heart disease, susceptibility to, 1, bulimia nervosa, susceptibility to, 1, leprosy, susceptibility to, 2, epilepsy, idiopathic generalized, susceptibility to, 9, Parkinson disease 11, autosomal dominant, susceptibility to, focal segmental glomerulosclerosis 3, susceptibility to, autoimmune disease, susceptibility to, 1, osteoarthritis susceptibility 3, systemic lupus erythematosus with nephritis, susceptibility to, 1, systemic lupus erythematosus with nephritis, susceptibility to, 2, systemic lupus erythematosus with nephritis, susceptibility to, 3, coronary heart disease, susceptibility to, 2, coronary heart disease, susceptibility to, 4, autoimmune disease, susceptibility to, 2, autoimmune disease, susceptibility to, 3, systemic lupus erythematosus, susceptibility to, 4, myocardial infarction, susceptibility to, major depressive disorder 1, legionnaire disease, susceptibility to, myocardial infarction, susceptibility to, 2, major depressive disorder 2, hypertension, essential, susceptibility to, 4, epilepsy, idiopathic generalized, susceptibility to, 3, myoclonic epilepsy, juvenile, susceptibility to, 3, orofacial cleft 6, susceptibility to, coronary heart disease, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 1, attention deficit-hyperactivity disorder, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 3, attention deficit-hyperactivity disorder, susceptibility to, 4, Alzheimer disease 9, susceptibility to respiratory infections associated with CD8alpha chain mutation, dyslexia, susceptibility to, 8, autoimmune disease, susceptibility to, 4, hepatitis C virus, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 4, celiac disease, susceptibility to, 4, celiac disease, susceptibility to, 2, celiac disease, susceptibility to, 3, leprosy, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 5, systemic lupus erythematosus, susceptibility to, 6, opioid dependence, susceptibility to, 1, systemic lupus erythematosus, susceptibility to, 7, systemic lupus erythematosus, susceptibility to, 8, hypertension, essential, susceptibility to, 5, hypertension, essential, susceptibility to, 6, Parkinson disease 13, autosomal dominant, susceptibility to, West Nile virus, susceptibility to, hepatitis B virus, susceptibility to, Buruli ulcer, susceptibility to, osteoarthritis susceptibility 4, systemic lupus erythematosus, susceptibility to, 9, coronary heart disease, susceptibility to, 7, hypertension, essential, susceptibility to, 7, leprosy, susceptibility to, 4, hypertension, essential, susceptibility to, 8, epilepsy, idiopathic generalized, susceptibility to, 13, coronary heart disease, susceptibility to, 8, myoclonic epilepsy, juvenile, susceptibility to, 4, susceptibility to visceral leishmaniasis, 2, susceptibility to visceral leishmaniasis, 3, celiac disease, susceptibility to, 6, epilepsy, idiopathic generalized, susceptibility to, 5, epilepsy, childhood absence, susceptibility to, 6, celiac disease, susceptibility to, 7, celiac disease, susceptibility to, 8, celiac disease, susceptibility to, 9, celiac disease, susceptibility to, 10, celiac disease, susceptibility to, 11, celiac disease, susceptibility to, 12, celiac disease, susceptibility to, 13, coronary heart disease, susceptibility to, 9, systemic lupus erythematosus, susceptibility to, 10, systemic lupus erythematosus, susceptibility to, 11, systemic lupus erythematosus, susceptibility to, 12, epilepsy, childhood absence, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 5, attention deficit-hyperactivity disorder, susceptibility to, 6, systemic lupus erythematosus, susceptibility to, 13, sarcoidosis, susceptibility to, 2, sarcoidosis, susceptibility to, 3, osteoarthritis susceptibility 5, osteoarthritis susceptibility 6, focal segmental glomerulosclerosis 4, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 8, herpes simplex encephalitis, susceptibility to, 2, attention deficit-hyperactivity disorder, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 10, pelvic organ prolapse, susceptibility to, 2, systemic lupus erythematosus, susceptibility to, 14, leprosy, susceptibility to, 5, thyrotoxic periodic paralysis, susceptibility to, 2, hearing loss, cisplatin-induced, susceptibility to, susceptibility to mononeuropathy of the median nerve, mild, fatty liver disease, nonalcoholic, susceptibility to, 2, leprosy, susceptibility to, 6, autoimmune disease, susceptibility to, 6, Parkinson disease 5, autosomal dominant, susceptibility to, aspergillosis, susceptibility to, sick sinus syndrome 3, susceptibility to, Parkinson disease 18, autosomal dominant, susceptibility to, epilepsy, juvenile myoclonic, susceptibility to, 9, dengue virus, susceptibility to, coronary heart disease, susceptibility to, 6, podoconiosis, susceptibility to, peripartum cardiomyopathy, susceptibility to, influenza, severe, susceptibility to, thyrotoxic periodic paralysis, susceptibility to, 3, human herpesvirus 8, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 12, herpes simplex encephalitis, susceptibility to, 3, herpes simplex encephalitis, susceptibility to, 4, pulmonary hypertension, neonatal, susceptibility to, craniosynostosis 5, susceptibility to, melioidosis, susceptibility to, chronic mountain sickness, susceptibility to, herpes simplex encephalitis, susceptibility to, 7, epilepsy, idiopathic generalized, susceptibility to, 14, hereditary neoplastic syndrome, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency, autosomal recessive Mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR2 deficiency, susceptibility to localized juvenile periodontitis, inherited susceptibility to mycobacterial diseases, neural tube defects, susceptibility to, multiple system atrophy 1, susceptibility to, nephrolithiasis susceptibility caused by SLC26A1, myoclonic epilepsy, juvenile, susceptibility to, 1, epilepsy, childhood absence, susceptibility to, 1, autism, susceptiblity to, susceptibility to visceral leishmaniasis, 1, malaria, susceptibility to, spondyloarthropathy, susceptibility to, herpes simplex encephalitis, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 18, epilepsy, idiopathic generalized, susceptibility to, 15, hepatitis, fulminant viral, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 16, autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial jak1 deficiency, aortic aneurysm, familial thoracic 11, susceptibility to, craniosynostosis 7, amyotrophic lateral sclerosis, susceptibility to, 24, amyotrophic lateral sclerosis, susceptibility to, 25, epilepsy, juvenile myoclonic, susceptibility to, 10, susceptibility to angioedema induced by ACE inhibitors, epidermodysplasia verruciformis, susceptibility to, exfoliation syndrome, susceptibility to, basal cell carcinoma, susceptibility to, graft-versus-host disease, susceptibility to, narcolepsy, susceptibility to, pulmonary disease, chronic obstructive, susceptibility to, restless legs syndrome, susceptibility to, psoriasis, susceptibility to, age related macular degeneration, susceptibility to, allergic rhinitis, susceptibility to, dermatitis, atopic, susceptibility to, Hirschsprung disease, susceptibility to, diabetes mellitus, ketosis-prone, schizophrenia, susceptibility to, radioulnar synostosis, nonsyndromic, susceptibility to, lumbar disk herniation, susceptibility to, lumbar disk degeneration, susceptibility to, psoriatic arthritis, susceptibility to, migraine with or without aura, susceptibility to, Alzheimer disease, susceptibility to, mitochondrial, Asperger syndrome, susceptibility to, tobacco addiction, susceptibility to, lipodystrophy, partial, acquired, susceptibility to, Graves disease, susceptibility to, 1, epilepsy, idiopathic generalized, susceptibility to, 17, breast-ovarian cancer, familial, susceptibility to, blepharospasm, benign essential, susceptibility to, hemorrhage, intracerebral, susceptibility to, IgA nephropathy, susceptibility to, hemolytic uremic syndrome, atypical, susceptibility to, 7, vitiligo-associated multiple autoimmune disease susceptibility 6, delayed sleep phase syndrome, susceptibility to, encephalitis, acute, infection-induced, susceptibility to, malignant hyperthermia, susceptibility to, multicentric Castleman disease, susceptibility to, pelvic organ prolapse, susceptibility to, 1, amyotrophic lateral sclerosis, susceptibility to, 13, Graves disease, susceptibility to, X-linked 2, autoimmune thyroid disease, susceptibility to, 5, atrioventricular septal defect, susceptibility to, 1, epilepsy, juvenile myoclonic, susceptibility to, 6, autoimmune disease, susceptibility to, 5, epilepsy, idiopathic generalized, susceptibility to, 6, seasonal affective disorder, susceptibility to, ventricular fibrillation during myocardial infarction, susceptibility to, UV-induced skin damage, susceptibility to, antisocial behavior, susceptibility to, aplastic anemia, susceptibility to, cardiomyopathy, familial hypertrophic, 4, susceptibility to, cirrhosis, noncryptogenic, susceptibility to, coronary artery disease, severe, susceptibility to, dengue fever, susceptibility to, dengue hemorrhagic fever, susceptibility to, dengue shock syndrome, susceptibility to, dyslexia, susceptibility to, 4, dyslexia, susceptibility to, 7, efavirenz central nervous system toxicity, susceptibility to, obesity, susceptibility to, bleeding disorder, platelet-type, 13, susceptibility to, Schistosoma mansoni infection, susceptibility/resistance to, Parkinson disease 24, autosomal dominant, susceptibility to, iron overload, susceptibility to, hydrocephalus, congenital, 5, susceptibility to, hearing loss, noise-induced, susceptibility to, hyperemesis gravidarum, susceptibility to, Parkinson disease 26, autosomal dominant, susceptibility to, epilepsy, idiopathic generalized, susceptibility to, 19, polycystic kidney disease 9, susceptibility to, rhabdomyolysis, susceptibility to, scoliosis, isolated, susceptibility to, dystonia 38, susceptibility to, gallbladder disease 4, epilepsy, juvenile absence, susceptibility to, GBA1-related Parkinson disease, susceptibility, SH2B3-related immune system disorder

Subtypes (5): multiple sclerosis, susceptibility to, 2, multiple sclerosis, susceptibility to, 3, multiple sclerosis, susceptibility to, 4, multiple sclerosis, susceptibility to, 5, multiple sclerosis, susceptibility to 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 1 risk factor, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
265095	NM_000785.4(CYP27B1):c.1286G>C (p.Arg429Pro)	CYP27B1	Pathogenic	criteria provided, multiple submitters, no conflicts
802871	NM_000785.4(CYP27B1):c.1357C>T (p.Arg453Cys)	CYP27B1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3065325	NM_002124.4(HLA-DRB1):c.764-2A>G	HLA-DRB1	Likely pathogenic	criteria provided, single submitter
1338812	NM_001286398.3(RNF217):c.1370G>A (p.Arg457His)	RNF217	risk factor	no assertion criteria provided
260273	NM_012472.6(DNAAF11):c.1391C>T (p.Pro464Leu)	DNAAF11	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3362736	NM_000785.4(CYP27B1):c.1052T>C (p.Leu351Pro)	CYP27B1	Uncertain significance	criteria provided, single submitter
3064715	NM_002124.4(HLA-DRB1):c.125_127del (p.Arg42_Glu43delinsLys)	HLA-DRB1	Uncertain significance	criteria provided, single submitter
3362728	NM_002124.4(HLA-DRB1):c.124_127delinsTATA (p.Arg42_Glu43delinsTyrLys)	HLA-DRB1	Uncertain significance	criteria provided, single submitter
4277631	NM_002124.4(HLA-DRB1):c.115C>T (p.Gln39Ter)	HLA-DRB1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 16 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DNAAF11	Orphanet:244	Primary ciliary dyskinesia
CYP27B1	Orphanet:289157	Hypocalcemic vitamin D-dependent rickets
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
HLA-DRB1	Orphanet:703	Bullous pemphigoid
HLA-DRB1	Orphanet:747	Autoimmune pulmonary alveolar proteinosis
HLA-DRB1	Orphanet:797	Sarcoidosis
HLA-DRB1	Orphanet:83465	Narcolepsy type 2
HLA-DRB1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DNAAF11	HGNC:16725	ENSG00000129295	Q86X45	Dynein axonemal assembly factor 11	clinvar
RNF217	HGNC:21487	ENSG00000146373	Q8TC41	E3 ubiquitin-protein ligase RNF217	clinvar
CYP27B1	HGNC:2606	ENSG00000111012	O15528	25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial	clinvar
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DNAAF11	Dynein axonemal assembly factor 11	Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia.
RNF217	E3 ubiquitin-protein ligase RNF217	E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
CYP27B1	25-hydroxyvitamin D-1 alpha hydroxylase, mitochondrial	A cytochrome P450 monooxygenase involved in vitamin D metabolism and in calcium and phosphorus homeostasis.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.5

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	1	7.3×	0.521
Enzyme (other)	1	3.0×	0.538
Transcription factor	1	2.1×	0.538
Other/Unknown	1	0.5×	0.962

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DNAAF11	Other/Unknown	no		Leu-rich_rpt, U2A’_phosphoprotein32A_C, CS_dom
RNF217	Transcription factor	no		IBR_dom, Znf_RING/FYVE/PHD, E3_UB_ligase_RBR
CYP27B1	Enzyme (other)	yes	1.14.15.18	Cyt_P450, Cyt_P450_E_grp-I, Cyt_P450_CS
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

3 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
epithelium of bronchus	1
right uterine tube	1
left ovary	1
oviduct epithelium	1
upper leg skin	1
kidney epithelium	1
metanephric glomerulus	1
nephron tubule	1
granulocyte	1
right lung	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DNAAF11	219	broad	marker	right uterine tube, bronchial epithelial cell, epithelium of bronchus
RNF217	233	ubiquitous	marker	oviduct epithelium, upper leg skin, left ovary
CYP27B1	175	broad	yes	nephron tubule, metanephric glomerulus, kidney epithelium
HLA-DRB1	131	tissue_specific	marker	vermiform appendix, granulocyte, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HLA-DRB1	3,448
CYP27B1	2,173
DNAAF11	1,331
RNF217	609

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRB1	P01911	108

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CYP27B1	O15528	86.75
DNAAF11	Q86X45	74.44
RNF217	Q8TC41	62.43

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective CYP27B1 causes VDDR1A	1	3806.7×	0.004	CYP27B1
Vitamins	1	634.4×	0.011	CYP27B1
Vitamin D (calciferol) metabolism	1	292.8×	0.013	CYP27B1
Translocation of ZAP-70 to Immunological synapse	1	211.5×	0.013	HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	1	181.3×	0.013	HLA-DRB1
Co-inhibition by PD-1	1	173.0×	0.013	HLA-DRB1
Generation of second messenger molecules	1	115.3×	0.017	HLA-DRB1
Downstream TCR signaling	1	42.8×	0.037	HLA-DRB1
Interferon gamma signaling	1	41.8×	0.037	HLA-DRB1
MHC class II antigen presentation	1	29.7×	0.047	HLA-DRB1
Class I MHC mediated antigen processing & presentation	1	23.4×	0.054	RNF217
Antigen processing: Ubiquitination & Proteasome degradation	1	12.4×	0.092	RNF217
Adaptive Immune System	1	9.9×	0.105	RNF217
Immune System	1	4.3×	0.214	RNF217

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of interleukin-4 production	1	4213.0×	0.008	HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	2106.5×	0.008	HLA-DRB1
regulation of interleukin-10 production	1	2106.5×	0.008	HLA-DRB1
myeloid dendritic cell antigen processing and presentation	1	1404.3×	0.008	HLA-DRB1
calcitriol biosynthetic process from calciol	1	1404.3×	0.008	CYP27B1
vitamin D catabolic process	1	1053.2×	0.008	CYP27B1
regulation of T-helper cell differentiation	1	1053.2×	0.008	HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	1	1053.2×	0.008	HLA-DRB1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	842.6×	0.008	HLA-DRB1
protein localization to motile cilium	1	842.6×	0.008	DNAAF11
vitamin metabolic process	1	702.2×	0.008	CYP27B1
positive regulation of vitamin D receptor signaling pathway	1	702.2×	0.008	CYP27B1
positive regulation of T cell mediated immune response to tumor cell	1	601.9×	0.008	HLA-DRB1
reproductive system development	1	601.9×	0.008	DNAAF11
T-helper 1 type immune response	1	468.1×	0.009	HLA-DRB1
positive regulation of memory T cell differentiation	1	468.1×	0.009	HLA-DRB1
vitamin D metabolic process	1	383.0×	0.009	CYP27B1
positive regulation of monocyte differentiation	1	383.0×	0.009	HLA-DRB1
cellular response to vitamin D	1	383.0×	0.009	CYP27B1
detection of bacterium	1	351.1×	0.009	HLA-DRB1
G1 to G0 transition	1	351.1×	0.009	CYP27B1
epithelial cilium movement involved in determination of left/right asymmetry	1	324.1×	0.009	DNAAF11
peptide antigen assembly with MHC class II protein complex	1	263.3×	0.010	HLA-DRB1
axonemal dynein complex assembly	1	263.3×	0.010	DNAAF11
inflammatory response to antigenic stimulus	1	234.1×	0.011	HLA-DRB1
inner dynein arm assembly	1	221.7×	0.011	DNAAF11
cerebrospinal fluid circulation	1	221.7×	0.011	DNAAF11
response to vitamin D	1	200.6×	0.011	CYP27B1
positive regulation of keratinocyte differentiation	1	200.6×	0.011	CYP27B1
epithelial cilium movement involved in extracellular fluid movement	1	191.5×	0.011	DNAAF11

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
CYP27B1	KETOCONAZOLE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CYP27B1	1	4
DNAAF11	0	0
RNF217	0	0
HLA-DRB1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
KETOCONAZOLE	4	CYP27B1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
HLA-DRB1	17	Binding:17
CYP27B1	7	Binding:6, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CYP27B1	1.14.15.18	calcidiol 1-monooxygenase

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

1 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)
KETOCONAZOLE	4	CYP27B1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CYP27B1
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	HLA-DRB1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	DNAAF11, RNF217

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
DNAAF11	0	—
RNF217	0	—
HLA-DRB1	17	—

Clinical trials & evidence

Clinical trials

Clinical trials: 33.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	26
PHASE2	2
PHASE1	2
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06384976	PHASE2	ACTIVE_NOT_RECRUITING	KYSA-7: A Study of Anti-CD19 CAR T-Cell Therapy, in Subjects With Refractory Primary and Secondary Progressive Multiple Sclerosis
NCT06782724	PHASE2	RECRUITING	Psilocybin Therapy for Psychological Distress in Palliative Patients
NCT00872053	PHASE1/PHASE2	COMPLETED	Effect of Robot-assisted Training on Foot Drop in Multiple Sclerosis
NCT06999434	PHASE1	RECRUITING	Exploring the Utility of [18F]3F4AP for Demyelination Imaging
NCT05102682	PHASE1	COMPLETED	Robotics for Mobility Rehabilitation in MS
NCT06775912	EARLY_PHASE1	RECRUITING	Clinical Study on Targeted CD19/BCMA CAR-T Therapy for Autoimmune Diseases
NCT06548620	EARLY_PHASE1	WITHDRAWN	A Study of RD06-04 in Patients With Active Autoimmune Diseases
NCT04415372	Not specified	ENROLLING_BY_INVITATION	Macromolecular Imaging of White and Gray Matter Pathology in Multiple Sclerosis
NCT05865405	Not specified	ACTIVE_NOT_RECRUITING	A Closed Loop, Doctor to Patient, Mobile Application for Depression in People With Multiple Sclerosis
NCT06770959	Not specified	NOT_YET_RECRUITING	Frequency of Gastrointestinal and Hepatic Manifestations Among Patients with Multiple Sclerosis, a Clinical Hospital Based Study
NCT06849882	Not specified	RECRUITING	Dubousset Functional Test: an Investigation of Its Validity and Reliability in Individuals with Multiple Sclerosis
NCT07087873	Not specified	RECRUITING	Assessment of Transcranial Alternating Current Stimulation’s Clinical Efficacy in Treating Cognitive Impairment of Idiopathic Inflammatory Demyelinating Diseases
NCT07202195	Not specified	RECRUITING	At Home Use of Stimulation Suits for Managing MS Symptoms
NCT07222618	Not specified	RECRUITING	Selfie Videos: A Novel, Patient-centered, Comprehensive Approach to Measuring Function in MS
NCT07235644	Not specified	ACTIVE_NOT_RECRUITING	Comparison of Efficacy and Safety in Patients Switching From MabThera® to Rixathon® in Relapsing-Remitting Multiple Sclerosis
NCT07304960	Not specified	NOT_YET_RECRUITING	Multiple Sclerosis Versus Neuromyelitis Optica Spectrum Disorder
NCT07521384	Not specified	ENROLLING_BY_INVITATION	Real World Outcomes of Intranasal MuSE Exosomes and Stem Cells in Neurological Regenerative Therapy
NCT01128075	Not specified	COMPLETED	Treatment Adherence When Using RebiSmart™ in Relapsing Multiple Sclerosis Subjects
NCT01628276	Not specified	COMPLETED	Brain Functional Connectivity Changes Following Cognitive Rehabilitation in Multiple Sclerosis: an fMRI Study
NCT02490943	Not specified	COMPLETED	A Pilot Study of Warm and Cold Compress to Reduce Injection Site Erythema Due to Peginterferon-beta-1a in MS
NCT03155334	Not specified	UNKNOWN	Understanding Evaluation of Patient Information Sheets by User Testing Method
NCT03316404	Not specified	COMPLETED	Evaluating Multiple Sclerosis Patients ShOWing A GEnomic Signature of Therapy Response
NCT04095377	Not specified	COMPLETED	Development of Automated Analysis to Electroencephelogram (EEG) Data in Patients Treated at the Sagol Hyperbaric Medicine and Research Center at the Years 2017-2019.
NCT04148313	Not specified	WITHDRAWN	A Pilot Study to Explore the Role of Gut Flora in Multiple Sclerosis
NCT04379661	Not specified	COMPLETED	SUNLIGHT Study: Online Support Groups for MS to Address COVID-19
NCT04530955	Not specified	UNKNOWN	Transitioning to a Valve-Gated Intrathecal Drug Delivery System (IDDS)
NCT04822623	Not specified	UNKNOWN	Imaging Evaluation of Central Nervous Autoimmune Diseases
NCT05435404	Not specified	COMPLETED	Qualitative Study Patient & Physician Experiences Botox COVID-19
NCT05857280	Not specified	UNKNOWN	EXOPULSE Mollii Suit, Motor Function & Multiple Sclerosis (EXOSEP 2)
NCT05912595	Not specified	UNKNOWN	EXOPULSE Mollii Suit, Spasticity, Muscular Oxygenation & Multiple Sclerosis (ENNOX 2)
NCT05991297	Not specified	COMPLETED	Effects of Deep Sensory Assisted Rehabilitation on Gait and Balance in Patients With Multiple Sclerosis
NCT06143930	Not specified	UNKNOWN	Blood Flow Restriction Training in Multiple Sclerosis
NCT06199219	Not specified	COMPLETED	Ex-Plissit Model Based Counseling on Sexual Function and Sexual Satisfaction

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PSILOCYBIN	3	1
MEBUFOTENIN	2	1