Relapsing-remitting multiple sclerosis

Summary

Relapsing-remitting multiple sclerosis (MONDO:0005314) is a disease with 1 cohort gene and 279 clinical trials. Top therapeutic interventions include fingolimod, dimethyl fumarate, and natalizumab.

At a glance

• Cohort genes: 1
• ClinVar variants: 7
• Clinical trials: 279

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	relapsing-remitting multiple sclerosis
Mondo ID	MONDO:0005314
EFO	EFO:0003929
MeSH	D020529
DOID	DOID:2378
ICD-11	799053936
NCIT	C165675
SNOMED CT	426373005
UMLS	C0751967
MedGen	155669
Is cancer (heuristic)	no

Data availability: 7 ClinVar variants · 27 cell lines.

Disease family

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 › relapsing-remitting multiple sclerosis

Related subtypes (3): chronic progressive multiple sclerosis, Marburg acute multiple sclerosis, pediatric multiple sclerosis

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

7 retrieved; paginated sample, class counts are floors:

3 likely benign, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
135597	NM_031157.4(HNRNPA1):c.982A>C (p.Met328Leu)	HNRNPA1	Likely pathogenic	no assertion criteria provided
135599	NM_031157.4(HNRNPA1):c.995A>G (p.Asn332Ser)	HNRNPA1	Likely pathogenic	no assertion criteria provided
135590	NM_031157.4(HNRNPA1):c.911G>A (p.Ser304Asn)	HNRNPA1	Uncertain significance	no assertion criteria provided
135591	NM_031157.4(HNRNPA1):c.931A>G (p.Ser311Gly)	HNRNPA1	Uncertain significance	no assertion criteria provided
135610	NM_031157.4(HNRNPA1):c.1093A>G (p.Ser365Gly)	HNRNPA1	Likely benign	no assertion criteria provided
135611	NM_031157.4(HNRNPA1):c.1096T>C (p.Tyr366His)	HNRNPA1	Likely benign	no assertion criteria provided
135614	NM_031157.4(HNRNPA1):c.1111A>G (p.Arg371Gly)	HNRNPA1	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNRNPA1	Orphanet:399086	HNRNPA1-related adult-onset distal myopathy
HNRNPA1	Orphanet:52430	Inclusion body myopathy with Paget disease of bone and frontotemporal dementia
HNRNPA1	Orphanet:803	Amyotrophic lateral sclerosis

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
HNRNPA1	HGNC:5031	ENSG00000135486	P09651	Heterogeneous nuclear ribonucleoprotein A1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNRNPA1	Heterogeneous nuclear ribonucleoprotein A1	Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HNRNPA1	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, HnRNPA1/A2_C

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
embryo	1
ganglionic eminence	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNRNPA1	295	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPA1	6,616

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNRNPA1	P09651	73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. 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
FGFR2 alternative splicing	1	423.0×	0.015	HNRNPA1
Signaling by FGFR2	1	407.9×	0.015	HNRNPA1
Signaling by FGFR	1	346.1×	0.015	HNRNPA1
SARS-CoV-1 modulates host translation machinery	1	308.6×	0.015	HNRNPA1
SARS-CoV-1-host interactions	1	175.7×	0.020	HNRNPA1
SARS-CoV-1 Infection	1	142.8×	0.021	HNRNPA1
mRNA Splicing	1	109.8×	0.023	HNRNPA1
mRNA Polyadenylation	1	87.8×	0.024	HNRNPA1
Processing of Capped Intron-Containing Pre-mRNA	1	82.2×	0.024	HNRNPA1
SARS-CoV Infections	1	55.4×	0.029	HNRNPA1
mRNA Splicing - Major Pathway	1	54.6×	0.029	HNRNPA1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.029	HNRNPA1
Dengue Virus-Host Interactions	1	45.7×	0.030	HNRNPA1
Metabolism of RNA	1	41.7×	0.031	HNRNPA1
Viral Infection Pathways	1	30.8×	0.039	HNRNPA1
Infectious disease	1	24.8×	0.045	HNRNPA1
Disease	1	13.1×	0.081	HNRNPA1
Signal Transduction	1	10.2×	0.098	HNRNPA1

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
cellular response to sodium arsenite	1	3370.4×	0.002	HNRNPA1
import into nucleus	1	2407.4×	0.002	HNRNPA1
nuclear export	1	1532.0×	0.003	HNRNPA1
RNA export from nucleus	1	936.2×	0.003	HNRNPA1
negative regulation of telomere maintenance via telomerase	1	732.7×	0.003	HNRNPA1
positive regulation of telomere maintenance via telomerase	1	732.7×	0.003	HNRNPA1
alternative mRNA splicing, via spliceosome	1	674.1×	0.003	HNRNPA1
cellular response to glucose starvation	1	337.0×	0.004	HNRNPA1
mRNA transport	1	263.3×	0.005	HNRNPA1
regulation of alternative mRNA splicing, via spliceosome	1	244.2×	0.005	HNRNPA1
regulation of RNA splicing	1	218.9×	0.005	HNRNPA1
mRNA splicing, via spliceosome	1	91.6×	0.011	HNRNPA1

Therapeutics

Drugs indicated for this disease

9 approved, 31 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Daclizumab	Approved (phase 4)
Dimethyl Fumarate	Approved (phase 4)
Diroximel Fumarate	Approved (phase 4)
Natalizumab	Approved (phase 4)
Ocrelizumab	Approved (phase 4)
Ofatumumab	Approved (phase 4)
Ponesimod	Approved (phase 4)
Teriflunomide	Approved (phase 4)
Ublituximab	Approved (phase 4)
Alemtuzumab	Phase 3 (in late-stage trials)
Caffeine	Phase 3 (in late-stage trials)
Cholecalciferol	Phase 3 (in late-stage trials)
Cladribine	Phase 3 (in late-stage trials)
Corticotropin	Phase 3 (in late-stage trials)
Dalfampridine	Phase 3 (in late-stage trials)
Dextromethorphan	Phase 3 (in late-stage trials)
Evobrutinib	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fingolimod	Phase 3 (in late-stage trials)
Glatiramer Acetate	Phase 3 (in late-stage trials)
Human Immunoglobulin G	Phase 3 (in late-stage trials)
INTERFERON BETA-1A	Phase 3 (in late-stage trials)
INTERFERON BETA-1B	Phase 3 (in late-stage trials)
Influenza Virus Vaccine	Phase 3 (in late-stage trials)
Laquinimod	Phase 3 (in late-stage trials)
Metenkefalin	Phase 3 (in late-stage trials)
Methylprednisolone	Phase 3 (in late-stage trials)
Midazolam	Phase 3 (in late-stage trials)
Omeprazole	Phase 3 (in late-stage trials)
Ozanimod	Phase 3 (in late-stage trials)
PEGINTERFERON BETA-1A	Phase 3 (in late-stage trials)
Pertussis Vaccine	Phase 3 (in late-stage trials)
Pravastatin	Phase 3 (in late-stage trials)
Rituximab	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Tridecactide	Phase 3 (in late-stage trials)
Vidofludimus	Phase 3 (in late-stage trials)
Vitamin K	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abatacept, Albumin Human, Atorvastatin, Carmustine, Clemastine, Cytarabine, Dirucotide, Domperidone, Estriol, Etoposide, Flupirtine, Inosine, Lamotrigine, Melatonin, Melphalan, Methylprednisolone Hemisuccinate, Minocycline, Mitoxantrone, Norethindrone, Orelabrutinib, Prednisone, Raltegravir, Secukinumab, Siponimod, Tabalumab, Temsirolimus, Tricaprilin.

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
HNRNPA1	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
HNRNPA1	7	Binding:7

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	HNRNPA1

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)
HNRNPA1	7	—

Clinical trials & evidence

Clinical trials

Clinical trials: 279.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	100
PHASE4	51
PHASE2	50
PHASE3	49
PHASE1	22
PHASE1/PHASE2	3
PHASE2/PHASE3	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05090371	PHASE4	ACTIVE_NOT_RECRUITING	A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation
NCT06733922	PHASE4	RECRUITING	ELIOS - Investigational Biomarkers to Track Disease Modification in Active RRMS
NCT00078338	PHASE4	COMPLETED	Rebif® Versus Copaxone® in the Treatment of Relapsing Remitting Multiple Sclerosis
NCT00101959	PHASE4	WITHDRAWN	Implementation Study of Treatment Optimization Recommendations on Relapsing-Remitting Multiple Sclerosis (RR MS) Subjects
NCT00168766	PHASE4	COMPLETED	Avonex (Interferon-beta-1a) and Avonex Plus Methylprednisolone for the Treatment of Relapsing-remitting MS
NCT00202995	PHASE4	TERMINATED	Randomized Study Designed to Look at Disease Progression Using 2 Currently FDA Approved Drugs for the Treatment of RRMS
NCT00203021	PHASE4	COMPLETED	Glatiramer Acetate (Copaxone®) Study to Follow Participants From the First Original Study for Safety and Effectiveness
NCT00203047	PHASE4	TERMINATED	Assessment Study of Steroid Effect in Relapsing Multiple Sclerosis Subjects Treated With Glatiramer Acetate
NCT00315367	PHASE4	COMPLETED	A fMRI(Functional Magnetic Resonance Imaging) Research Study to Learn More About Multiple Sclerosis and Individuals Potentially Experiencing Memory Difficulties
NCT00317941	PHASE4	COMPLETED	Safety Study in Relapsing-remitting Multiple Sclerosis (RRMS) Patients Receiving Betaferon or Rebif
NCT00367484	PHASE4	COMPLETED	Study To Evaluate The Immunogenicity And Safety Of r-hIFN Beta-1a (Rebif®) Using Clone 484-39 In Multiple Sclerosis
NCT00492466	PHASE4	COMPLETED	Investigating if Interferon-Beta Can be Used in Patients With MS After They Have Developed Neutralizing Antibodies
NCT00493116	PHASE4	COMPLETED	Is IFN-beta Treatment in MS Useful After a Washout Period in Patients With Neutralizing Antibodies to Interferon Beta
NCT00534261	PHASE4	COMPLETED	Does Quality of Life Improve in Multiple Sclerosis Patients Treated With Interferon Beta-1a?
NCT00574041	PHASE4	TERMINATED	How Side Effects of Avonex Are Affected by Gradually Increasing to Full Dose vs Starting at Full Dose
NCT00771043	PHASE4	WITHDRAWN	A Proof-of-Concept Study to Correlate Retinal Nerve Fiber Layer Changes in Patients With Multiple Sclerosis Treated With Natalizumab or Interferon Beta 1-a
NCT00871780	PHASE4	COMPLETED	A Prospective, Open-label, Non-randomized, Clinical Trial to Determine if Natalizumab (Tysabri®) Improves Ambulatory Measures in Relapsing-remitting Multiple Sclerosis (RRMS) Patients
NCT01144052	PHASE4	COMPLETED	Natalizumab De-escalation With Interferon Beta-1b
NCT01225289	PHASE4	COMPLETED	Impact of Vitamin A Supplementation on Immune System in Multiple Sclerosis Patients
NCT01310166	PHASE4	COMPLETED	Biomarker Study After Initiation of Treatment With Fingolimod (FTY720) in Patients With Relapsing-remitting Multiple Sclerosis
NCT01317004	PHASE4	COMPLETED	Patients With Relapse Remitting Multiple Sclerosis (RRMS): Candidates for MS Therapy Change
NCT01407211	PHASE4	UNKNOWN	Impact of Vitamin A on Gene Expression, in Multiple Sclerosis Patient
NCT01417273	PHASE4	UNKNOWN	Impact of Vitamin A on Multiple Sclerosis (MS)
NCT01436643	PHASE4	TERMINATED	Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression
NCT01498887	PHASE4	COMPLETED	Efficacy of Fingolimod in de Novo Patients Versus Fingolimod in Patients Previously Treated With a First Line Disease Modifying Therapy
NCT01534182	PHASE4	COMPLETED	Evaluation of Patient Reported Outcomes in RRMS Patients Candidates for MS Therapy Change and Transitioned to Fingolimod 0.5 mg (EPOC)
NCT01623596	PHASE4	COMPLETED	Evaluation of Patient Retention of Fingolimod vs. Currently Approved Disease Modifying Therapy in Patients With Relapsing Remitting Multiple Sclerosis.
NCT01701856	PHASE4	TERMINATED	Natalizumab De-escalation to Interferon-beta-1b in Patients With Relapsing-remitting Multiple Sclerosis
NCT01705457	PHASE4	UNKNOWN	Impact of Vitamin A on RAR Gene Expression in Multiple Sclerosis
NCT01709812	PHASE4	WITHDRAWN	Effect of an Individualized Patient Support Program on Treatment Satisfaction in Fingolimod-treated Patients With RRMS
NCT01755871	PHASE4	TERMINATED	Long-term Effect of Fingolimod on Circulating Immunocompetent Mononuclear Cells in Patients With Multiple Sclerosis
NCT01842191	PHASE4	COMPLETED	Efficacy of Fish Oil in Multiple Sclerosis
NCT01930708	PHASE4	COMPLETED	A Study Evaluating the Effectiveness of Tecfidera (Dimethyl Fumarate) on Multiple Sclerosis (MS) Disease Activity and Patient-Reported Outcomes
NCT02090348	PHASE4	WITHDRAWN	Study to Evaluate Fatigue in Participants With Relapsing Remitting Multiple Sclerosis When Treated With Dimethyl Fumarate
NCT02090413	PHASE4	COMPLETED	Phase 4 Study of Effect of Aspirin on Flushing in Dimethyl Fumarate-Treated Participants With Relapsing-Remitting Multiple Sclerosis
NCT02125604	PHASE4	COMPLETED	Gastrointestinal Tolerability Study Of Dimethyl Fumarate In Participants With Relapsing-Remitting Multiple Sclerosis In Germany
NCT02142205	PHASE4	COMPLETED	Safety and Efficacy of Natalizumab (BG00002, Tysabri®) in Russian Participants With Relapsing Remitting Multiple Sclerosis (RRMS)
NCT02205489	PHASE4	COMPLETED	Management Of The Infusion-Associated Reactions In RRMS Patients Treated With LEMTRADA
NCT02217982	PHASE4	TERMINATED	Pilot Study to Assess Dimethyl Fumarate Related GI Symptom Mitigation
NCT02255656	PHASE4	COMPLETED	Phase IIIB-IV Long-Term Follow-up Study for Patients Who Participated in CAMMS03409

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FINGOLIMOD	4	36
DIMETHYL FUMARATE	4	20
NATALIZUMAB	4	17
GLATIRAMER ACETATE	4	15
INTERFERON BETA-1A	4	13
OCRELIZUMAB	4	7
INTERFERON BETA-1B	4	5
MONOMETHYL FUMARATE	4	4
PEGINTERFERON BETA-1A	4	4
CITALOPRAM	4	3
DEXTROMETHORPHAN	4	3
FEXOFENADINE	4	3
FLUOXETINE	4	3
LOPERAMIDE	4	3
METHYLPREDNISOLONE	4	3
RETINOL	4	3
TERIFLUNOMIDE	4	3
VENLAFAXINE	4	3
ALEMTUZUMAB	4	2
CLADRIBINE	4	2
DIROXIMEL FUMARATE	4	2
ESTRIOL	4	2
SIPONIMOD	4	2
ACYCLOVIR	4	1
BRIMONIDINE TARTRATE	4	1
CAFFEINE	4	1
CETIRIZINE	4	1
CORTICOTROPIN	4	1
DACLIZUMAB	4	1
ESOMEPRAZOLE	4	1