Multiple sclerosis, susceptibility to 1

Summary

Multiple sclerosis, susceptibility to 1 (MONDO:0021571) is a disease with 1 cohort gene and 33 clinical trials. Top therapeutic interventions include psilocybin and mebufotenin.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 33

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	multiple sclerosis, susceptibility to 1
Mondo ID	MONDO:0021571
OMIM	126200
UMLS	C3888106
MedGen	854774
Is cancer (heuristic)	no

Also known as: MS · MS1 · multiple sclerosis, disease progression, modifier of · multiple sclerosis, susceptibility to · multiple sclerosis, susceptibility to, 1

Data availability: 1 ClinVar variant.

Disease family

Classification path: disease susceptibility › inherited disease susceptibility › multiple sclerosis, susceptibility to › multiple sclerosis, susceptibility to 1

Related subtypes (4): multiple sclerosis, susceptibility to, 2, multiple sclerosis, susceptibility to, 3, multiple sclerosis, susceptibility to, 4, multiple sclerosis, susceptibility to, 5

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

1 retrieved; paginated sample, class counts are floors:

1 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
29757	HLA-DRB1, DRB1*1501	HLA-DRB1	risk factor	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
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: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
right lung	1
vermiform appendix	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-DRB1	P01911	108

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Translocation of ZAP-70 to Immunological synapse	1	634.4×	0.004	HLA-DRB1
Phosphorylation of CD3 and TCR zeta chains	1	543.8×	0.004	HLA-DRB1
Co-inhibition by PD-1	1	519.1×	0.004	HLA-DRB1
Generation of second messenger molecules	1	346.1×	0.005	HLA-DRB1
Downstream TCR signaling	1	128.3×	0.009	HLA-DRB1
Interferon gamma signaling	1	125.5×	0.009	HLA-DRB1
MHC class II antigen presentation	1	89.2×	0.011	HLA-DRB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 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	16852.0×	0.001	HLA-DRB1
antigen processing and presentation of endogenous peptide antigen via MHC class II	1	8426.0×	0.001	HLA-DRB1
regulation of interleukin-10 production	1	8426.0×	0.001	HLA-DRB1
myeloid dendritic cell antigen processing and presentation	1	5617.3×	0.001	HLA-DRB1
regulation of T-helper cell differentiation	1	4213.0×	0.001	HLA-DRB1
positive regulation of CD4-positive, alpha-beta T cell activation	1	4213.0×	0.001	HLA-DRB1
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation	1	3370.4×	0.001	HLA-DRB1
positive regulation of T cell mediated immune response to tumor cell	1	2407.4×	0.002	HLA-DRB1
T-helper 1 type immune response	1	1872.4×	0.002	HLA-DRB1
positive regulation of memory T cell differentiation	1	1872.4×	0.002	HLA-DRB1
positive regulation of monocyte differentiation	1	1532.0×	0.002	HLA-DRB1
detection of bacterium	1	1404.3×	0.002	HLA-DRB1
peptide antigen assembly with MHC class II protein complex	1	1053.2×	0.002	HLA-DRB1
inflammatory response to antigenic stimulus	1	936.2×	0.002	HLA-DRB1
protein tetramerization	1	624.1×	0.003	HLA-DRB1
negative regulation of inflammatory response to antigenic stimulus	1	601.9×	0.003	HLA-DRB1
antigen processing and presentation of exogenous peptide antigen via MHC class II	1	543.6×	0.003	HLA-DRB1
positive regulation of T cell mediated cytotoxicity	1	510.7×	0.003	HLA-DRB1
positive regulation of immune response	1	481.5×	0.003	HLA-DRB1
macrophage differentiation	1	468.1×	0.003	HLA-DRB1
positive regulation of T cell activation	1	443.5×	0.003	HLA-DRB1
negative regulation of type II interferon production	1	383.0×	0.003	HLA-DRB1
positive regulation of insulin secretion involved in cellular response to glucose stimulus	1	374.5×	0.003	HLA-DRB1
negative regulation of T cell proliferation	1	330.4×	0.004	HLA-DRB1
humoral immune response	1	280.9×	0.004	HLA-DRB1
epidermis development	1	210.7×	0.005	HLA-DRB1
T cell receptor signaling pathway	1	151.8×	0.007	HLA-DRB1
immune response	1	47.1×	0.022	HLA-DRB1
signal transduction	1	16.1×	0.062	HLA-DRB1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HLA-DRB1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HLA-DRB1	17	Binding:17

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
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