Aortic valve stenosis

Summary

Aortic valve stenosis (MONDO:0042981) is a disease with 1 cohort gene (3 GWAS associations across 3 studies) and 846 clinical trials. Top therapeutic interventions include bisoprolol, edoxaban, and ferric carboxymaltose.

At a glance

• Cohort genes: 1
• GWAS associations: 3
• ClinVar variants: 1
• Clinical trials: 846

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	aortic valve stenosis
Mondo ID	MONDO:0042981
MeSH	D001024
DOID	DOID:1712
ICD-10-CM	I06.0
ICD-11	956813047
NCIT	C50462
SNOMED CT	60573004, 72011007
UMLS	C0003507
MedGen	1621
Is cancer (heuristic)	no

Also known as: aortic stenosis · AS · rheumatic aortic stenosis · rheumatic aortic valve stenosis · valvular aortic stenosis

Data availability: 1 ClinVar variant · 3 GWAS associations (3 studies) · 1 HPO phenotype · 2 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

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

Related subtypes (4): aortic valve calcification, aortic valve insufficiency, aortic valve prolapse, familial bicuspid aortic valve

Subtypes (4): subvalvular aortic stenosis, supravalvular aortic stenosis, congenital aortic valve stenosis, childhood aortic valve stenosis

Genetics & variants

GWAS landscape

3 GWAS associations across 3 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs576341583	3e-13	LINC01847	A	2.53
rs149553083	4e-12	NPM1P10 - HACE1	G	2.49
rs190698868	4e-11	ANKRD7 - GTF3AP6	A	3.73

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90477834	Verma A	2024	1,613	445,306	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480118	Verma A	2024	283	120,825	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90481965	Verma A	2024	283	120,825	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

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

MAF distribution

Bucket	Variants
common (>=0.05)	0
low_freq (0.01-0.05)	0
rare (<0.01)	3
unknown	0

Functional consequences

Consequence	Count
intergenic_variant	2
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs576341583	5	159805581	A>C	0.001	intron_variant	LINC01847	3e-13	Tier 4: intronic/intergenic
rs149553083	6	104081872	G>A,C,T	0.001	intergenic_variant	NPM1P10 - HACE1	4e-12	Tier 4: intronic/intergenic
rs190698868	7	118524140	A>C,G	0	intergenic_variant	ANKRD7 - GTF3AP6	4e-11	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
973597	GRCh37/hg19 11p11.2(chr11:47997461-48142707)x3	PTPRJ	Uncertain significance	no assertion criteria provided

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
PTPRJ	HGNC:9673	ENSG00000149177	Q12913	Receptor-type tyrosine-protein phosphatase eta	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PTPRJ	Receptor-type tyrosine-protein phosphatase eta	Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of CTNND1, FLT3, PDGFRB, MET, KDR, LYN, SRC, MAPK1, MAPK3, EGFR, TJP1, OCLN, PIK3R1 and PIK3R2.

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
Phosphatase	1	83.9×	0.012

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PTPRJ	Phosphatase	yes	3.1.3.48	PTP_cat, Tyr_Pase_dom, Tyr_Pase_cat

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
ileal mucosa	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PTPRJ	242	ubiquitous	marker	ileal mucosa, leukocyte, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PTPRJ	1,754

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PTPRJ	Q12913	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Negative regulation of FLT3	1	713.8×	0.003	PTPRJ
Phosphorylation of CD3 and TCR zeta chains	1	543.8×	0.003	PTPRJ
Negative regulation of MET activity	1	519.1×	0.003	PTPRJ
Neutrophil degranulation	1	23.1×	0.043	PTPRJ

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
contact inhibition	1	4213.0×	0.005	PTPRJ
positive regulation of Fc receptor mediated stimulatory signaling pathway	1	3370.4×	0.005	PTPRJ
negative regulation of platelet-derived growth factor receptor signaling pathway	1	1872.4×	0.005	PTPRJ
negative regulation of MAP kinase activity	1	1404.3×	0.005	PTPRJ
positive regulation of platelet activation	1	1296.3×	0.005	PTPRJ
negative regulation of vascular permeability	1	1123.5×	0.005	PTPRJ
peptidyl-tyrosine dephosphorylation	1	887.0×	0.005	PTPRJ
positive regulation of macrophage chemotaxis	1	802.5×	0.005	PTPRJ
positive chemotaxis	1	802.5×	0.005	PTPRJ
negative regulation of epidermal growth factor receptor signaling pathway	1	766.0×	0.005	PTPRJ
platelet formation	1	702.2×	0.005	PTPRJ
positive regulation of focal adhesion assembly	1	648.1×	0.005	PTPRJ
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.005	PTPRJ
oligodendrocyte differentiation	1	421.3×	0.006	PTPRJ
positive regulation of calcium-mediated signaling	1	421.3×	0.006	PTPRJ
negative regulation of insulin receptor signaling pathway	1	374.5×	0.006	PTPRJ
negative regulation of T cell receptor signaling pathway	1	366.4×	0.006	PTPRJ
positive regulation of phagocytosis	1	318.0×	0.006	PTPRJ
regulation of cell adhesion	1	306.4×	0.006	PTPRJ
positive regulation of cell adhesion	1	271.8×	0.007	PTPRJ
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	263.3×	0.007	PTPRJ
vasculogenesis	1	255.3×	0.007	PTPRJ
B cell differentiation	1	218.9×	0.007	PTPRJ
blood coagulation	1	173.7×	0.009	PTPRJ
positive regulation of tumor necrosis factor production	1	153.2×	0.009	PTPRJ
T cell receptor signaling pathway	1	151.8×	0.009	PTPRJ
negative regulation of cell growth	1	144.0×	0.010	PTPRJ
cytokine-mediated signaling pathway	1	130.6×	0.010	PTPRJ
glucose homeostasis	1	130.6×	0.010	PTPRJ
negative regulation of cell migration	1	111.6×	0.011	PTPRJ

Therapeutics

Drugs indicated for this disease

0 approved, 15 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Apixaban	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Bivalirudin	Phase 3 (in late-stage trials)
Candesartan	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Dihydralazine	Phase 3 (in late-stage trials)
Edoxaban	Phase 3 (in late-stage trials)
Ezetimibe	Phase 3 (in late-stage trials)
Heparin	Phase 3 (in late-stage trials)
Rivaroxaban	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Spironolactone	Phase 3 (in late-stage trials)
Ticagrelor	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alendronic Acid, Denosumab, Fluvastatin, Pelacarsen, Potassium Chloride.

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
PTPRJ	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PTPRJ	5	Binding:4, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PTPRJ	3.1.3.48	protein-tyrosine-phosphatase

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	PTPRJ
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)
PTPRJ	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 846.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	744
PHASE4	46
PHASE3	26
PHASE2	16
PHASE2/PHASE3	7
PHASE1	3
EARLY_PHASE1	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04913870	PHASE4	RECRUITING	Angiotensin Receptor Blockers in Aortic Stenosis
NCT05672836	PHASE4	RECRUITING	ENAVOgliflozin Outcome Trial in Patients With Severe Aortic Stenosis After Transcatheter Aortic Valve Replacement
NCT05721170	PHASE4	RECRUITING	Impact of Beta Blockers on TAVI (BETA-TAVI)
NCT06007222	PHASE4	RECRUITING	Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation Trial
NCT06818006	PHASE4	NOT_YET_RECRUITING	Application of TAVI at Experienced Interventional Cardiac Centers Without On-site Cardiac Surgery (ATLAS Study)
NCT07087379	PHASE4	NOT_YET_RECRUITING	Perioperative Intensive Statin Therapy for Neuroprotection in TAVR（PISTNT）
NCT07317804	PHASE4	NOT_YET_RECRUITING	Echo-Guided vs Fluoroscopy-Guided Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis（ECHO-TAVR）
NCT07370688	PHASE4	RECRUITING	Iron Infusion in Patients Undergoing Transcatheter Aortic Valve Implantation
NCT07556523	PHASE4	RECRUITING	Patient Quality of Recovery After TAVR With Different Sedation Regimens
NCT00252317	PHASE4	UNKNOWN	Acute Haemodynamic Effects of Treatment With Angiotensin Converting Enzyme (ACE)-Inhibitors in Patients With Symptomatic Aortic Stenosis
NCT00256165	PHASE4	COMPLETED	REST Study: Left Ventricular Regression European Study
NCT00404287	PHASE4	TERMINATED	Randomized Study to Evaluate the Efficacy of Fluvastatin on Inflammatory Markers in Patients With Aortic Stenosis.
NCT00590135	PHASE4	TERMINATED	The Effect of Lipitor on Aortic Stenosis
NCT01060020	PHASE4	COMPLETED	Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
NCT01144039	PHASE4	COMPLETED	Glutamate and Diastolic Function in Patients Undergoing Aortic Valve Repair
NCT01201070	PHASE4	UNKNOWN	Study of Administration Of Antithrombin in Patients With Low Plasmatic Levels of Antithrombin After Cardiac Surgery
NCT01272388	PHASE4	TERMINATED	Aortic Stenosis and PhosphodiEsterase iNhibition With Aortic Valve Replacement (ASPEN-AVR): A Pilot Study
NCT01275339	PHASE4	TERMINATED	Aortic Stenosis and PhosphodiEsterase Type 5 iNhibition (ASPEN): A Pilot Study
NCT01579058	PHASE4	TERMINATED	Effect of Bisoprolol on Progression of Aortic Stenosis
NCT01642134	PHASE4	COMPLETED	Dual Antiplatelet Therapy Versus Oral Anticoagulation for a Short Time to Prevent Cerebral Embolism After TAVI
NCT01994330	PHASE4	COMPLETED	Severe Aortic Stenosis and Acquired Von Willebrand´s Disease: The Impact of Desmopressin in Valve-Replacement Surgery
NCT02019797	PHASE4	UNKNOWN	Desflurane-induced Myocardial Protection
NCT02053818	PHASE4	COMPLETED	Remifentanil/Sufentanil for CABG+/-AVR Evaluated by Recovery, Cognitive Function, Haemodynamics and Biochemical Markers.
NCT02060071	PHASE4	UNKNOWN	Endothelial Progenitors in Aortic Stenosis: Association With Aortic Stenosis Progression and Severity
NCT02224066	PHASE4	COMPLETED	Platelet Reactivity After TAVI: A Multicenter Pilot Study
NCT02308566	PHASE4	COMPLETED	Cerebral Embolic Load in Patients Undergoing Surgical Aortic Valve Replacement: A Comparison of the Conventional With the Minimized Extracorporeal Circulation Technique Using Transcranial Doppler Ultrasound
NCT02486367	PHASE4	COMPLETED	Inflammation and Thrombosis in Patients With Severe Aortic Stenosis After Transcatheter Aortic Valve Replacement (TAVR)
NCT02498639	PHASE4	UNKNOWN	The Pacing vs No Pacing Study - PNP Study
NCT02650388	PHASE4	UNKNOWN	Frailty and Cognitive Function Assessment of TAVI Patients
NCT02838199	PHASE4	WITHDRAWN	TRANscatheter or SurgIcal Aortic Valve ReplacemenT in All-Comers With Severe Aortic Valve Stenosis
NCT02974660	PHASE4	COMPLETED	Protamine Sulfate During Transcatheter Aortic Valve Implantation
NCT02974920	PHASE4	UNKNOWN	Rivaroxaban or Aspirin for Biological Aortic Prosthesis
NCT03284827	PHASE4	COMPLETED	Anticoagulant Versus Dual Antiplatelet Therapy for Preventing Leaflet Thrombosis and Cerebral Embolization After Transcatheter Aortic Valve Replacement
NCT03574311	PHASE4	UNKNOWN	Preoperative Intravenous Ferric Carboxymaltose and Placebo in the Treatment of Patients Undergoing Cardiac Surgery
NCT03666351	PHASE4	COMPLETED	Study to Evaluate the Effect on Improvement of LVH by the Control of BP in Hypertension Patients With AV Disease
NCT03807921	PHASE4	COMPLETED	Anticoagulation for Aortic Bioprosthesis (ANTIPRO)
NCT04346004	PHASE4	UNKNOWN	Effect of Preoperative Iron Isomaltoside 1000 Administration on Hemoglobin Concentration in Patients Undergoing Transcatheter Aortic Valve Implantation
NCT04437303	PHASE4	COMPLETED	Periprocedural Continuation Versus Interruption of Oral Anticoagulant Drugs During Transcatheter Aortic Valve Implantation (POPular PAUSE TAVI)
NCT04573049	PHASE4	UNKNOWN	The Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement
NCT04696185	PHASE4	COMPLETED	Dapagliflozin After Transcatheter Aortic Valve Implantation

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
BISOPROLOL	4	3
EDOXABAN	4	3
FERRIC CARBOXYMALTOSE	4	3
SILDENAFIL	4	3
APIXABAN	4	2
ATORVASTATIN	4	2
COLCHICINE	4	2
FLUVASTATIN	4	2
LOSARTAN	4	2
PROTAMINE SULFATE	4	2
TADALAFIL	4	2
ASPIRIN	4	1
BIVALIRUDIN	4	1
CAPTOPRIL	4	1
CEFTOLOZANE	4	1
CHLORTHALIDONE	4	1
DAPAGLIFLOZIN	4	1
DESFLURANE	4	1
DESMOPRESSIN	4	1
EMPAGLIFLOZIN	4	1
FLUDEOXYGLUCOSE F 18	4	1
ICOSAPENT ETHYL	4	1
METHYLPREDNISOLONE	4	1
MILRINONE	4	1
POTASSIUM CHLORIDE	4	1
POTASSIUM NITRATE	4	1
REMIFENTANIL	4	1
REMIMAZOLAM BESYLATE	4	1
RIVAROXABAN	4	1
SUFENTANIL	4	1