Coronary atherosclerosis

Summary

Coronary atherosclerosis (MONDO:0021661) is a disease with 1 cohort gene (196 GWAS associations across 13 studies) and 73 clinical trials. Top therapeutic interventions include adalimumab, pioglitazone, and aliskiren.

At a glance

• Cohort genes: 1
• GWAS associations: 196
• ClinVar variants: 2
• Clinical trials: 73

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coronary atherosclerosis
Mondo ID	MONDO:0021661
DOID	DOID:0061139
ICD-11	1280712786
NCIT	C35505
SNOMED CT	443502000
UMLS	C0010054
MedGen	3623
Anatomy (UBERON)	UBERON:0001621
Is cancer (heuristic)	no

Also known as: arteriosclerosis disorder of coronary artery · atherosclerosis of coronary artery · coronary artery arteriosclerosis (disease) · coronary artery arteriosclerosis disorder · coronary atherosclerosis

Data availability: 2 ClinVar variants · 196 GWAS associations (13 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

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

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

Subtypes (2): arteriolosclerosis, arteriosclerosis obliterans

Genetics & variants

GWAS landscape

196 GWAS associations across 13 studies. Top hits map to 34 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
chr9:22093299	2e-300		A	0.17
rs10455872	1e-234	LPA	A	0.28
rs1537371	3e-166	CDKN2B-AS1	C	0.16
rs9349379	2e-96	PHACTR1	A	0.09
rs12740374	3e-85	CELSR2	G	0.11
rs7528419	8e-58	CELSR2	A	0.1
rs9515203	3e-54	COL4A2	T	0.08
rs28451064	2e-51	KCNE2, MRPS6, LINC00310	G	0.11
chr10:44494546	8e-48		G	0.07
rs142130958	1e-44	SMARCA4 - LDLR	G	0.09
rs12138316	6e-44	AIDA	G	0.07
rs11556924	2e-39	UBE2H-DT, ZC3HC1	C	0.06
rs12190287	2e-38	TCF21, TARID	C	0.06
rs964184	5e-38	ZPR1	G	0.08
rs1412445	9e-38	LIPA	C	0.06
rs10808546	2e-34	TRIB1AL	C	0.05
rs7412	3e-34	APOE	C	0.1
rs494207	8e-34	LINC00841 - LINC03089	G	0.09
chr2:85796101	2e-33		G	0.05
rs12151108	2e-33	SMARCA4 - LDLR	G	0.1
rs148513392	8e-33	WDR12	G	0.08
rs10846744	2e-31	SCARB1	G	0.07
chr8:19855661	2e-31		A	0.06
rs2019090	1e-30	PDGFDDN	A	0.06
rs56375023	3e-29	SMAD3	G	0.06
rs11591147	6e-29	PCSK9	G	0.25
rs62012629	2e-28	ADAMTS7	C	0.06
rs1065853	4e-28	APOE - APOC1	G	0.11
chr4:148378225	2e-25		G	0.07
rs17163360	3e-25	MIA3	T	0.06

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475936	Verma A	2024	124,302	300,039	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90691962	Karczewski KJ	2025	23,888	382,052	Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects.
GCST90475935	Verma A	2024	20,733	93,418	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480132	Verma A	2024	20,733	93,418	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90436075	Zhou W	2018	20,023	377,103	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.
GCST010767	Bi W	2020	19,079	263,792	A Fast and Accurate Method for Genome-Wide Time-to-Event Data Analysis and Its Application to UK Biobank.
GCST90043957	Jiang L	2021	16,041	440,307	A generalized linear mixed model association tool for biobank-scale data.
GCST90475934	Verma A	2024	9,892	47,195	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90651187	Liu TY	2025	9,614	212,336	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.
GCST90692424	Karczewski KJ	2025	1,028	7,496	Pan-UK Biobank genome-wide association analyses enhance discovery and resolution of ancestry-enriched effects.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	6
Tier 3: regulatory	1
Tier 4: intronic/intergenic	40

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	1
rare (<0.01)	2
unknown	0

Functional consequences

Consequence	Count
intron_variant	22
unknown	14
3_prime_UTR_variant	6
missense_variant	3
intergenic_variant	2
regulatory_region_variant	1
non_coding_transcript_exon_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
chr9:22093299				0.488			2e-300	Tier 4: intronic/intergenic
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	1e-234	Tier 4: intronic/intergenic
rs1537371	9	22099569	C>A,G,T	0.421	intron_variant	CDKN2B-AS1	3e-166	Tier 4: intronic/intergenic
rs9349379	6	12903725	A>C,G,T	0.402	intron_variant	PHACTR1	2e-96	Tier 4: intronic/intergenic
rs12740374	1	109274968	G>T	0.219	3_prime_UTR_variant	CELSR2	3e-85	Tier 2: splice/UTR
rs7528419	1	109274570	A>G	0.225	3_prime_UTR_variant	CELSR2	8e-58	Tier 2: splice/UTR
rs9515203	13	110397276	T>C	0.261	intron_variant	COL4A2	3e-54	Tier 4: intronic/intergenic
rs28451064	21	34221526	G>A,T	0.122	intron_variant	KCNE2, MRPS6, LINC00310	2e-51	Tier 4: intronic/intergenic
chr10:44494546				0.347			8e-48	Tier 4: intronic/intergenic
rs142130958	19	11079976	G>A	0.118	intergenic_variant	SMARCA4 - LDLR	1e-44	Tier 4: intronic/intergenic
rs12138316	1	222673540	G>A,C	0.281	intron_variant	AIDA	6e-44	Tier 4: intronic/intergenic
rs11556924	7	130023656	C>A,T	0.384	missense_variant	UBE2H-DT, ZC3HC1	2e-39	Tier 1: coding
rs12190287	6	133893387	C>A,G,T	0.37	3_prime_UTR_variant	TCF21, TARID	2e-38	Tier 2: splice/UTR
rs964184	11	116778201	G>C	0.14	3_prime_UTR_variant	ZPR1	5e-38	Tier 2: splice/UTR
rs1412445	10	89243047	C>A,G,T	0.33	intron_variant	LIPA	9e-38	Tier 4: intronic/intergenic
rs10808546	8	125483576	C>T	0.432	intron_variant	TRIB1AL	2e-34	Tier 4: intronic/intergenic
rs7412	19	44908822	C>T	0.08	missense_variant	APOE	3e-34	Tier 1: coding
rs494207	10	44245808	G>A	0.177	regulatory_region_variant	LINC00841 - LINC03089	8e-34	Tier 3: regulatory
chr2:85796101				0.463			2e-33	Tier 4: intronic/intergenic
rs12151108	19	11086585	G>A,T	0.12	intergenic_variant	SMARCA4 - LDLR	2e-33	Tier 4: intronic/intergenic
rs148513392	2	202879887	G>A,C,T	0.118	3_prime_UTR_variant	WDR12	8e-33	Tier 2: splice/UTR
rs10846744	12	124827879	G>C,T	0.152	intron_variant	SCARB1	2e-31	Tier 4: intronic/intergenic
chr8:19855661				0.265			2e-31	Tier 4: intronic/intergenic
rs2019090	11	103798234	A>C,G,T	0.308	intron_variant	PDGFDDN	1e-30	Tier 4: intronic/intergenic
rs56375023	15	67156025	G>A	0.235	intron_variant	SMAD3	3e-29	Tier 4: intronic/intergenic
rs11591147	1	55039974	G>A,T	0.015	missense_variant	PCSK9	6e-29	Tier 1: coding
rs62012629	15	78778009	C>A,G,T	0.265	intron_variant	ADAMTS7	2e-28	Tier 4: intronic/intergenic
rs1065853	19	44909976	G>A,C,T	0.083	non_coding_transcript_exon_variant	APOE - APOC1	4e-28	Tier 4: intronic/intergenic
chr4:148378225				0.142			2e-25	Tier 4: intronic/intergenic
rs17163360	1	222647448	T>A,C,G	0.39	intron_variant	MIA3	3e-25	Tier 4: intronic/intergenic

ClinVar germline variants

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
2570675	NM_015089.4(CUL9):c.7237C>T (p.Arg2413Trp)	CUL9	Uncertain significance	criteria provided, single submitter
2570677	NM_015089.4(CUL9):c.2732C>T (p.Pro911Leu)	CUL9	Uncertain significance	criteria provided, single submitter

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
CUL9	HGNC:15982	ENSG00000112659	Q8IWT3	Cullin-9	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CUL9	Cullin-9	Core component of a Cul9-RING ubiquitin-protein ligase complex composed of CUL9 and RBX1.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CUL9	Transcription factor	no		Znf_RING, IBR_dom, APC_su10/DOC_dom

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
left testis	1
right frontal lobe	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CUL9	275	ubiquitous	marker	right testis, left testis, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CUL9	1,551

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CUL9	Q8IWT3	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Neddylation	1	47.4×	0.021	CUL9

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 mitotic nuclear division	1	624.1×	0.006	CUL9
microtubule cytoskeleton organization	1	121.2×	0.016	CUL9
ubiquitin-dependent protein catabolic process	1	74.2×	0.018	CUL9
protein ubiquitination	1	41.4×	0.024	CUL9

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
CUL9	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
CUL9	2	Binding:2

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	CUL9

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)
CUL9	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 73.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	45
PHASE4	11
PHASE3	10
PHASE1	4
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06767345	PHASE4	RECRUITING	Comparison of Moderate-Intensity Statin Plus Ezetimibe vs. High-Intensity Statin for Coronary Plaque Stabilization
NCT00155350	PHASE4	UNKNOWN	Treatment of Coronary Atherosclerosis by Insulin Sensitizers in Insulin-Resistant Patients
NCT00294567	PHASE4	COMPLETED	Azelnidipine Anti-Coronary Atherosclerotic Trial in Hypertensive Patients by Serial Volumetric IVUS Analysis(ALPS-J)
NCT00940862	PHASE4	COMPLETED	Effect of Adalimumab on Vascular Inflammation in Patients With Moderate to Severe Plaque Psoriasis
NCT01254552	PHASE4	COMPLETED	Assessment With CCTA and MRI in Asymptomatic Patients With Type 2 Diabetes for Detection of Unrecognized Myocardial Scar in Subclinical Coronary Atherosclerosis
NCT01722214	PHASE4	COMPLETED	Trial on the Effect of Adalimumab on Vascular Inflammation in Patients With Psoriasis
NCT02000661	PHASE4	TERMINATED	Routine Versus Selective Use of FFR to Guide PCI
NCT02360956	PHASE4	UNKNOWN	Efficacy Study of Olmesartan Medoxomil on Coronary Atherosclerosis and Epicardial Adipose Tissue(EAT)
NCT03230851	PHASE4	UNKNOWN	the Efficacy and Safety of Indobufen and Low-dose Aspirin in Different Regimens of Antiplatelet Therapy
NCT04559191	PHASE4	UNKNOWN	Atheroma Progression and Vulnerability Under Continuous Glucose Monitoring
NCT05105750	PHASE4	UNKNOWN	A Comparative Study of Indobufen and Aspirin in Patients With Coronary Atherosclerosis
NCT07474649	PHASE3	NOT_YET_RECRUITING	A Study of Bempedoic Acid/Ezetimibe/High-intensity Statin in Patients Without Cardiovascular Events
NCT00124332	PHASE3	COMPLETED	STRADIVARIUS (Strategy To Reduce Atherosclerosis Development InVolving Administration of Rimonabant - the Intravascular Ultrasound Study)
NCT00358033	PHASE3	COMPLETED	Strategies to Maintain Cardiac Risk Control After Discharge From Cardiovascular Risk Reduction Clinic
NCT00376870	PHASE3	UNKNOWN	PIoglitazone for PrEvention of Restenosis in Diabetic Patients
NCT00620542	PHASE3	COMPLETED	CRESTOR Athero Imaging Head to Head IVUS Study
NCT00853827	PHASE3	COMPLETED	Safety and Efficacy of Aliskiren on the Progression of Atherosclerosis in Coronary Artery Disease Patients
NCT00860847	PHASE3	COMPLETED	Firefighter Aged Garlic Extract Investigation With CoQ10 as a Treatment for Heart Disease (FAITH)
NCT01030328	PHASE3	WITHDRAWN	AFRICA: Atorvastatin Plus Fenofibric Acid (TriLipix) in the Reduction of Intermediate Coronary Atherosclerosis
NCT01182649	PHASE3	COMPLETED	Everolimus Stent in Patients With Coronary Artery Disease (CAD)
NCT01699230	PHASE3	UNKNOWN	Potential Effects of Omega 3 Supplementation on Cardiomyocytes Membranes for Patients With Coronary Atherosclerosis?
NCT00123565	PHASE2	COMPLETED	Hexadecasaccharide (SR123781A) in Patients With Unstable Angina or Non-ST-Segment Elevation Myocardial Infarction
NCT00243308	PHASE2	TERMINATED	Serp-1 for the Treatment of Acute Coronary Syndrome
NCT00790764	PHASE2	SUSPENDED	Phase II Combination Stem Cell Therapy for the Treatment of Severe Coronary Ischemia(CI)
NCT00548613	PHASE1	COMPLETED	Combination Stem Cell (MESENDO) Therapy for Utilization and Rescue of Infarcted Myocardium
NCT00643981	PHASE1	COMPLETED	Combination Stem Cell Therapy for the Treatment of Severe Coronary Ischemia
NCT01581632	PHASE1	COMPLETED	Assessment of Coronary Plaque Composition
NCT01642173	PHASE1	COMPLETED	Assessment of Coronary Plaque Composition Using Optical Coherence Tomography
NCT03504956	Not specified	RECRUITING	Coronary Atherosclerosis T1-Weighted Characterization (CATCH)
NCT05660798	Not specified	RECRUITING	Effects of Switching From Cigarettes to Tobacco Heating System on Coronary Atherosclerosis Progression
NCT06831409	Not specified	RECRUITING	Using CTA Measures to Define Cardiac Risk In NFL Alumni
NCT06855394	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing of CYP2C19 in Prognostic Evaluation of Long-Term Major Adverse Cardiac and Vascular Events
NCT06860295	Not specified	NOT_YET_RECRUITING	Immunoregulation in Atherosclerosis: A Single-Cell RNA Sequencing Study
NCT07091682	Not specified	RECRUITING	Safety and Clinical Performance of the Freesolve Resorbable Magnesium Scaffold System in the Treatment of Subjects With Long de Novo Lesions
NCT07117084	Not specified	ACTIVE_NOT_RECRUITING	Imaging Markers of High-Risk Plaque Phenotype for Predicting Post-PCI Outcomes
NCT00353795	Not specified	COMPLETED	Coronary Atherosclerosis Evaluation by Arterial Wall Magnetic Resonance Imaging (MRI)
NCT00431717	Not specified	COMPLETED	Coronary Computed Tomography Angiography and SPECT in Asymptomatic Diabetes
NCT00431860	Not specified	UNKNOWN	Subclinical COronary Atheroscleorosis Updated With Coronary cT Angiography (SCOUT Study)
NCT00431977	Not specified	COMPLETED	Validation Study of Coronary CT Angiography as a Screening Tool in Asymptomatic Diabetes
NCT00455793	Not specified	COMPLETED	Subclinical Atherosclerosis in HIV-infected Patients

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ADALIMUMAB	4	2
PIOGLITAZONE	4	2
ALISKIREN	4	1
BEMPEDOIC ACID	4	1
CHOLINE FENOFIBRATE	4	1
EZETIMIBE	4	1
GADOTERATE MEGLUMINE	4	1
OLMESARTAN MEDOXOMIL	4	1
RIMONABANT	4	1
IOBITRIDOL	3	1
SERINE	3	1
UBIDECARENONE	3	1