Mitral valve stenosis

Summary

Mitral valve stenosis (MONDO:0005852) is a disease with 1 cohort gene and 50 clinical trials. Top therapeutic interventions include warfarin, dabigatran etexilate, and ivabradine.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitral valve stenosis
Mondo ID	MONDO:0005852
EFO	EFO:0007372
MeSH	D008946
DOID	DOID:1754
ICD-11	2115139779
NCIT	C50654
SNOMED CT	79619009
UMLS	C0026269
MedGen	44466
Is cancer (heuristic)	no

Also known as: mitral stenoses · mitral stenosis · mitral valve stenoses · stenoses, mitral · stenoses, mitral valve · stenosis, mitral · stenosis, mitral valve · valve stenoses, mitral · valve stenosis, mitral

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › mitral valve disorder › mitral valve stenosis

Related subtypes (6): mitral valve prolapse, congenital anomaly of the mitral subvalvular apparatus, mitral atresia disorder, inherited mitral valve disease, rheumatic disease of mitral valve, mitral valve insufficiency

Subtypes (1): congenital mitral stenosis

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
623485	NM_014462.3(LSM1):c.231+4A>C	LSM1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
LSM1	HGNC:20472	ENSG00000175324	O15116	U6 snRNA-associated Sm-like protein LSm1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LSM1	U6 snRNA-associated Sm-like protein LSm1	Plays a role in the degradation of histone mRNAs, the only eukaryotic mRNAs that are not polyadenylated.

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)
LSM1	Other/Unknown	no		Sm_dom_euk/arc, LSM_dom_sf, Lsm1

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
gingival epithelium	1
hair follicle	1
parotid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LSM1	296	ubiquitous	marker	parotid gland, gingival epithelium, hair follicle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LSM1	2,060

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LSM1	O15116	89.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Deadenylation-dependent mRNA decay	1	878.5×	0.002	LSM1
mRNA decay by 5’ to 3’ exoribonuclease	1	761.3×	0.002	LSM1
Metabolism of RNA	1	41.7×	0.024	LSM1

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
deadenylation-dependent decapping of nuclear-transcribed mRNA	1	1685.2×	0.002	LSM1
histone mRNA catabolic process	1	1685.2×	0.002	LSM1
RNA splicing, via transesterification reactions	1	624.1×	0.004	LSM1
stem cell population maintenance	1	421.3×	0.005	LSM1
negative regulation of neuron differentiation	1	271.8×	0.006	LSM1
neuron differentiation	1	100.3×	0.013	LSM1
RNA splicing	1	88.2×	0.013	LSM1
mRNA processing	1	78.8×	0.013	LSM1

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Atenolol	Phase 3 (in late-stage trials)
Ivabradine	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LSM1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	LSM1

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)
LSM1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 50.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	38
PHASE4	5
PHASE3	4
PHASE2	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04045093	PHASE4	ACTIVE_NOT_RECRUITING	Dabigatran for Mitral Stenosis Atrial Fibrillation
NCT01201070	PHASE4	UNKNOWN	Study of Administration Of Antithrombin in Patients With Low Plasmatic Levels of Antithrombin After Cardiac Surgery
NCT01641614	PHASE4	COMPLETED	Beating Versus Arrested Heart for Mitral Valve Replacement
NCT03673605	PHASE4	WITHDRAWN	Efficacy and Safety of Rivaroxiban Compare With Vitamin K Antagonist Warfarin
NCT06371222	PHASE4	COMPLETED	Role of Ivabradine on Heart Rate and Quality of Life in Patients With Mitral Stenosis in Sinus Rhythm
NCT01022463	PHASE3	COMPLETED	Effect of Ivabradine on Heart Rate & Effort Tolerance in Mitral Stenosis in Sinus Rhythm
NCT03926156	PHASE3	TERMINATED	RIvoraxaban in Mitral Stenosis
NCT03991910	PHASE3	UNKNOWN	The Effect of Ramipril in Suppressing ST2 Expression in Rheumatic Mitral Stenosis Patients
NCT05618223	PHASE3	UNKNOWN	Dapagliflozin Effect on Rheumatic Mitral Stenosis
NCT00903370	PHASE2	COMPLETED	Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery
NCT01270750	PHASE1/PHASE2	UNKNOWN	Bosentan for Severe Mitral Valve Dysfunction
NCT05540587	PHASE2	UNKNOWN	Efficacy and Safety of Edoxaban in Patients With Atrial Fibrillation and Mitral Stenosis
NCT01406353	Not specified	ACTIVE_NOT_RECRUITING	Early Percutaneous Mitral Intervention in Asymptomatic Moderate Mitral Stenosis
NCT04408430	Not specified	RECRUITING	The MITRAL II Pivotal Trial (Mitral Implantation of TRAnscatheter vaLves).
NCT04577248	Not specified	RECRUITING	The Prospecive OBSERVational Munich Interventional MITRAl-Valve Registry
NCT05526560	Not specified	ACTIVE_NOT_RECRUITING	Real-world Clinical Outcomes of the MITRIS RESILIA Mitral Valve
NCT05625607	Not specified	RECRUITING	Polish Transcatheter Transfemoral Mitral Valve-in-Valve Implantation (Mitral ViV) Registry
NCT06167213	Not specified	NOT_YET_RECRUITING	ALLIANCE Mitral: Safety and Effectiveness of SAPIEN X4 Transcatheter Heart Valve - Mitral
NCT06235385	Not specified	RECRUITING	European Association of Cardiovascular Imaging Multiple and Mixed Valvular Disease Study
NCT06340997	Not specified	NOT_YET_RECRUITING	Impact of Percutaneous Transvenous Mitral Commissurotomy on The Left Atrial Appendage Function in Patients With Mitral Stenosis.
NCT06377449	Not specified	RECRUITING	Influence of Lung Ultrasonography on the Prognosis and Postoperative Outcomes in Cardiac Surgical Patients
NCT06664320	Not specified	NOT_YET_RECRUITING	Mild ANH on Pre-bypass Coagulation Function During Cardiac Surgery
NCT07069673	Not specified	RECRUITING	Abbott Cephea Mitral Valve Disease Registry
NCT07097740	Not specified	RECRUITING	Early Feasibility Study of Surgical Implantation of a Polymer Prosthetic Mitral and Aortic Valve
NCT07175532	Not specified	RECRUITING	Prospective Multicenter Registry of Patients With Mitral Stenosis Undergoing Percutaneous Mitral Balloon Commissurotomy
NCT07244939	Not specified	RECRUITING	Cephea South America Feasibility Study
NCT07267117	Not specified	RECRUITING	Cohort Observing Mechanisms, Progression and Sequelae of Valvular Heart Disease
NCT07394998	Not specified	RECRUITING	Assessment of Exercise Capacity, Muscle Oxygenation and Aortic Stiffness in Patients With Mitral Stenosis
NCT00005199	Not specified	COMPLETED	Balloon Valvuloplasty Registry
NCT00081666	Not specified	COMPLETED	Logical Analysis of Data and Cardiac Surgery Risk
NCT00636987	Not specified	COMPLETED	Aortic or Mitral Valve Replacement With the Biocor and Biocor Supra
NCT00654472	Not specified	UNKNOWN	Mitral Valve Area Assessment: Comparison With Transthoracic Echocardiography and Magnetic Resonance Imaging
NCT01752192	Not specified	COMPLETED	Teledi@Log - Tele-rehabilitation of Heart Patients
NCT01757665	Not specified	COMPLETED	ProspeCtive, nOn-randoMized, MulticENter Clinical Evaluation of Edwards Pericardial Bioprostheses With a New Tissue Treatment Platform (COMMENCE)
NCT02188862	Not specified	COMPLETED	Genetic Susceptibility to Rheumatic Heart Disease in the Pacific Region
NCT02375282	Not specified	COMPLETED	Physical and Functional Recovery From Cardiac Surgery in Hospitalized Patients: A Feasibility Pilot Study
NCT02502448	Not specified	COMPLETED	Acute Normovolemic Hemodilution on ROTEM in Cardiac Surgery
NCT02783248	Not specified	COMPLETED	French National Observatory of Percutaneous Mitral Commissurotomy
NCT02831270	Not specified	COMPLETED	Acute Normovolemic Hemodilution on Serum-creatinine Concentration in Cardiac Surgery
NCT04112108	Not specified	COMPLETED	Late Clinical Outcomes of Percutaneous Mitral Commissurotomy in Patients With Mitral Stenosis

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
WARFARIN	4	5
DABIGATRAN ETEXILATE	4	3
IVABRADINE	4	2
ATENOLOL	4	1
BOSENTAN	4	1
EDOXABAN	4	1
RIVAROXABAN	4	1
ANTITHROMBIN III HUMAN	3	1
MENATETRENONE	3	1
ESATENOLOL	2	1
MENAQUINONE 6	2	1
CHEMBL1230004	0	1
CHEMBL4303203	0	1
CHEMBL4643136	0	1
MENAQUINONE-2	0	1