Coronary stenosis

Summary

Coronary stenosis (MONDO:0006715) is a disease with 2 cohort genes (10 GWAS associations across 4 studies) and 140 clinical trials. Top therapeutic interventions include esmolol, perflutren, and iodine.

At a glance

• Cohort genes: 2
• GWAS associations: 10
• Clinical trials: 140

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coronary stenosis
Mondo ID	MONDO:0006715
MeSH	D023921
DOID	DOID:4248
SNOMED CT	233970002
UMLS	C0242231
MedGen	66859
MedDRA	10011089
Is cancer (heuristic)	no

Data availability: 10 GWAS associations (4 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › arterial disorder › coronary artery disorder › coronary stenosis

Related subtypes (11): coronary vasospasm, postoperative ventricular dysfunction, coronary aneurysm, coronary thrombosis, intermediate coronary syndrome, coronary artery disease, autosomal dominant, 1, coronary artery disease, autosomal dominant 2, coronary artery congenital malformation, coronary atherosclerosis, nonobstructive coronary artery disease, fibromuscular dysplasia of the coronary arteries

Subtypes (1): coronary restenosis

Genetics & variants

GWAS landscape

10 GWAS associations across 4 studies. Top hits map to 5 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12593069	7e-10	PCSK6	C
rs6778944	7e-10	MTCO1P58 - PLD1	G
rs7835529	7e-10	DLC1 - SGCZ	T
rs9368648	1e-09	SFTA2 - NAPGP2	T
rs17005877	2e-07	PPP1R12A-AS2	G
rs147895362	2e-07	MIR1263 - LINC01324	C	1.14
rs2343305	4e-07	TSPAN14	A
rs76661209	9e-07	RNF182	A	1.06
rs2270836	9e-07	MT1M	T	0.35

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST011564	Wakim V	2021	1,734	0	New susceptibility alleles associated with severe coronary artery stenosis in the Lebanese population.
GCST011565	Wakim V	2021	1,734	0	New susceptibility alleles associated with severe coronary artery stenosis in the Lebanese population.
GCST011566	Wakim V	2021	1,734	0	New susceptibility alleles associated with severe coronary artery stenosis in the Lebanese population.
GCST90104134	Choe EK	2022	0	0	Leveraging deep phenotyping from health check-up cohort with 10,000 Korean individuals for phenome-wide association study of 136 traits.

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	1
Tier 4: intronic/intergenic	8

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	5
intergenic_variant	3
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12593069	15	101355666	C>T	0.05	intron_variant	PCSK6	7e-10	Tier 4: intronic/intergenic
rs6778944	3	171548961	G>T	0.05	intergenic_variant	MTCO1P58 - PLD1	7e-10	Tier 4: intronic/intergenic
rs7835529	8	13664494	T>C,G		intergenic_variant	DLC1 - SGCZ	7e-10	Tier 4: intronic/intergenic
rs9368648	6	30956152	T>C	0.05	regulatory_region_variant	SFTA2 - NAPGP2	1e-09	Tier 3: regulatory
rs17005877	12	79763772	G>A	0.05	intron_variant	PPP1R12A-AS2	2e-07	Tier 4: intronic/intergenic
rs147895362	3	164421765	T>C	0.018	intergenic_variant	MIR1263 - LINC01324	2e-07	Tier 4: intronic/intergenic
rs2343305	10	80468431	A>G		intron_variant	TSPAN14	4e-07	Tier 4: intronic/intergenic
rs76661209	6	13971464	G>A,C	0.018	intron_variant	RNF182	9e-07	Tier 4: intronic/intergenic
rs2270836	16	56633702	C>A,G,T	0.291	intron_variant	MT1M	9e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TSPAN14	HGNC:23303	ENSG00000108219	Q8NG11	Tetraspanin-14	gwas
PCSK6	HGNC:8569	ENSG00000140479	P29122	Proprotein convertase subtilisin/kexin type 6	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TSPAN14	Tetraspanin-14	Part of TspanC8 subgroup, composed of 6 members that interact with the transmembrane metalloprotease ADAM10.
PCSK6	Proprotein convertase subtilisin/kexin type 6	Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif.

Protein-family classification

Druggable: 1 · Difficult: 0 · 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
Protease	1	18.3×	0.108
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TSPAN14	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
PCSK6	Protease	yes	3.4.21.61	Peptidase_S8/S53_dom, EGF, P_dom

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
lower esophagus mucosa	1
right lung	1
C1 segment of cervical spinal cord	1
liver	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TSPAN14	267	ubiquitous	marker	cortical plate, right lung, lower esophagus mucosa
PCSK6	251	ubiquitous	marker	C1 segment of cervical spinal cord, liver, spinal cord

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PCSK6	1,985
TSPAN14	775

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN14	Q8NG11	87.89
PCSK6	P29122	81.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
NGF processing	1	1427.5×	0.005	PCSK6
Assembly of active LPL and LIPC lipase complexes	1	300.5×	0.009	PCSK6
Signaling by NODAL	1	248.3×	0.009	PCSK6
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.010	PCSK6
Amyloid fiber formation	1	51.4×	0.026	TSPAN14
Formation of the cornified envelope	1	43.9×	0.026	PCSK6
Neutrophil degranulation	1	11.5×	0.085	TSPAN14

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
zygotic determination of anterior/posterior axis, embryo	1	4213.0×	0.001	PCSK6
nerve growth factor production	1	4213.0×	0.001	PCSK6
plasma lipoprotein particle remodeling	1	2106.5×	0.002	PCSK6
secretion by cell	1	842.6×	0.004	PCSK6
regulation of BMP signaling pathway	1	601.9×	0.004	PCSK6
glycoprotein metabolic process	1	561.7×	0.004	PCSK6
peptide hormone processing	1	468.1×	0.004	PCSK6
positive regulation of Notch signaling pathway	1	175.5×	0.009	TSPAN14
determination of left/right symmetry	1	127.7×	0.010	PCSK6
protein processing	1	85.1×	0.013	PCSK6
protein maturation	1	81.8×	0.013	TSPAN14
protein localization to plasma membrane	1	54.4×	0.018	TSPAN14

Therapeutics

Drugs indicated for this disease

0 approved, 1 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

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

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Alendronic Acid.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TSPAN14	0	0
PCSK6	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
PCSK6	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PCSK6	3.4.21.61, 3.4.21.B25	Kexin,

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	1	PCSK6
E	Difficult family or no structure, no drug	1	TSPAN14

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TSPAN14	0	—
PCSK6	9	—

Clinical trials & evidence

Clinical trials

Clinical trials: 140.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	119
PHASE4	8
PHASE3	7
PHASE2	3
PHASE2/PHASE3	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00385905	PHASE4	COMPLETED	Excel Drug-Eluting Stent Pilot Clinical Registry
NCT00697372	PHASE4	COMPLETED	SEA-SIDE: Sirolimus Versus Everolimus-eluting Stent Randomized Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
NCT01066650	PHASE4	COMPLETED	The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting Stent Study in Twente
NCT01200693	PHASE4	COMPLETED	Z-SEA-SIDE: Sirolimus Versus Everolimus Versus Zotarolimus-eluting Stent Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
NCT01331707	PHASE4	COMPLETED	DUrable Polymer-based STent CHallenge of Promus Element Versus ReSolute Integrity in an All Comers Population
NCT01899235	PHASE4	TERMINATED	The Treatment of Coronary De-novo Lesions With the Elutax Paclitaxel-eluting Balloon Alone, a Pilot Study
NCT02120859	PHASE4	COMPLETED	Optical Coherence Tomography to Investigate FFR-Guided DEB-only Elective Coronary Angioplasty
NCT02462044	PHASE4	COMPLETED	Contrast Enhancement on Coronary Computed Tomographic Angiography
NCT00258596	PHASE3	COMPLETED	Sirolimus-Eluting Stents for Chronic Total Coronary Occlusions
NCT00301522	PHASE2/PHASE3	COMPLETED	Randomized Trial Evaluating Slow-Release Formulation TAXUS Paclitaxel-Eluting Coronary Stents to Treat De Novo Coronary Lesions
NCT00428454	PHASE3	COMPLETED	Sirolimus-eluting vs Zotarolimus-eluting Stents for Chronic Total Coronary Occlusions
NCT00462631	PHASE2/PHASE3	COMPLETED	Paclitaxel Eluting Balloon Versus Drug Eluting Stent in Native Coronary Artery Stenoses of Diabetic Patients
NCT00473863	PHASE3	UNKNOWN	Coronary Computed Tomographic Angiography in Emergency Department Chest Pain Patients at Intermediate Risk of Acute Coronary Syndrome
NCT00860847	PHASE3	COMPLETED	Firefighter Aged Garlic Extract Investigation With CoQ10 as a Treatment for Heart Disease (FAITH)
NCT01516723	PHASE3	UNKNOWN	Hybrid Sirolimus-eluting Versus Everolimus-eluting Stents for Total Coronary Occlusions
NCT02260453	PHASE3	COMPLETED	Coronary Angiography Before Elective Carotid Endarterectomy in Patients With Asymptomatic Coronary Artery Disease
NCT03452904	PHASE3	UNKNOWN	FrActional Flow Reserve Guided Drug Coated Balloon Only Strategy in De Novo coronarY Lesions (FADDY)
NCT06542393	PHASE2	RECRUITING	PBM as Strategy to CABG Anemic Patients Bypass Graft (CABG)
NCT00176397	PHASE2	UNKNOWN	Percutaneous Coronary Intervention (PCI) With Drug-Eluting Stents (DES) Versus Coronary Artery Bypass Graft (CABG) for Patients With Significant Left Main Stenosis
NCT00404144	PHASE2	COMPLETED	PEPCAD I. The Paclitaxel-Eluting PTCA-Balloon Catheter to Treat Small Vessel
NCT01175876	PHASE1	UNKNOWN	The Effect Of Remote Limb Ischemic Preconditioning For Carotid Artery Stenting
NCT00756379	Not specified	ACTIVE_NOT_RECRUITING	Century Trial, a Randomized Lifestyle Modification Study for Management of Stable Coronary Artery Disease
NCT03412435	Not specified	RECRUITING	Asan Medical Center Myocardial Infarction Registry
NCT03427996	Not specified	RECRUITING	Evaluation of Effectiveness and Safety of Rotational Atherectomy in Routine Clinical Practice
NCT03588481	Not specified	RECRUITING	IRIS- DESyne X2 in the IRIS-DES Registry
NCT03820492	Not specified	RECRUITING	Comparison of Optical Coherence Tomography-derived Minimal Lumen Area, Invasive Fractional Flow Reserve and FFRCT
NCT04014140	Not specified	RECRUITING	iFR Guided Coronary Artery Bypass Grafting Surgery
NCT04192747	Not specified	ACTIVE_NOT_RECRUITING	The Elixir Bioadaptor vs. The Onyx Stent in De Novo Native Coronary Arteries
NCT04634240	Not specified	RECRUITING	Staged Complete Revascularization for Coronary Artery Disease vs Medical Management Alone in Patients With AS Undergoing Transcatheter Aortic Valve Replacement
NCT04951050	Not specified	ACTIVE_NOT_RECRUITING	TARGET-PREMIER Trail in Evaluating the Safety and Efficacy of the Rapamycin Target Eluting Stent in CAS Treatment
NCT05312164	Not specified	RECRUITING	Physio-Anatomy Clinical Data Collection Study
NCT05364697	Not specified	ACTIVE_NOT_RECRUITING	IonMAN Trial- First in Human Study of the IoNIR Ridaforolimus-Eluting Coronary Stent System
NCT05509010	Not specified	RECRUITING	AI Driven National Platform for CT cOronary Angiography for clinicaL and industriaL applicatiOns Registry
NCT05709652	Not specified	RECRUITING	Impact of Fast-rotation Coronary CT in Patients Undergoing Aortic Stenosis Workup
NCT05782738	Not specified	NOT_YET_RECRUITING	Reverse T-stenting and Minimal Protrusion With External Minicrush for Treatment of Complex Coronary Bifurcation
NCT05846893	Not specified	ACTIVE_NOT_RECRUITING	Drug-Coated Balloon vs. Drug-Eluting Stent for Clinical Outcomes in Patients With Large Coronary Artery Disease
NCT06194526	Not specified	ENROLLING_BY_INVITATION	Whole Blood Transcriptomic Signal According to Coronary Atherosclerotic Plaque Burden Assessed by CT Angiography
NCT06348875	Not specified	NOT_YET_RECRUITING	Clinical Evaluation of Radiation Reduction for Optimized Safety
NCT06376630	Not specified	RECRUITING	Study of Microvascular Dysfunction, CFR and Cardioprotective Effect of Early Administration of Esmolol in MI
NCT06471062	Not specified	NOT_YET_RECRUITING	Transit Time Flow Measurement in Coronary Surgery

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ESMOLOL	4	1
PERFLUTREN	4	1
IODINE	3	1
MAXACALCITOL	3	1
UBIDECARENONE	3	1
GLP-1	2	1
GLUCAGON-LIKE PEPTIDE 1	1	1