Atherosclerosis

Summary

Atherosclerosis (MONDO:0005311) is a disease (an umbrella term covering 6 Mondo subtypes) with 8 cohort genes (74 GWAS associations across 34 studies) and 921 clinical trials. Top therapeutic interventions include rosuvastatin, simvastatin, and atorvastatin.

At a glance

• Umbrella term: 6 Mondo subtypes
• Cohort genes: 8
• GWAS associations: 74
• Clinical trials: 921

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	atherosclerosis
Mondo ID	MONDO:0005311
EFO	EFO:0003914
MeSH	D050197
DOID	DOID:1936
ICD-10-CM	I70
ICD-11	109367356
NCIT	C35768
SNOMED CT	441574008
UMLS	C0004153
MedGen	13948
Is cancer (heuristic)	no

Also known as: atherosclerosis of artery

Data availability: 74 GWAS associations (34 studies).

Disease family

An umbrella term covering 6 Mondo subtypes.

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

Related subtypes (4): intracranial arteriosclerosis, Monckeberg arteriosclerosis, intermittent vascular claudication, arteriosclerotic retinopathy

Subtypes (6): aortic atherosclerosis, generalized atherosclerosis, cerebral atherosclerosis, coronary atherosclerosis, autoimmune atherosclerosis, atherosclerotic cardiovascular disease

Genetics & variants

GWAS landscape

74 GWAS associations across 34 studies. Top hits map to 16 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1333049	2e-61	CDKN2B-AS1	G	0.16
rs183130	3e-54	HERPUD1 - CETP	?	0.21
rs74617384	2e-48	LPA	A	0.28
rs1333047	6e-47	CDKN2B-AS1	A	0.15
rs55730499	5e-41	LPA	C	0.29
rs10455872	3e-40	LPA	A	0.34
rs2107595	3e-24	HDAC9 - TWIST1	G	0.13
chr7:19052733	1e-20		G	0.13
rs17486278	5e-20	CHRNA5	A	0.1
rs10774624	2e-17	LINC02356	G	0.1
rs4766578	2e-16	ATXN2	T	0.08
rs8040868	5e-16	CHRNA3	T	0.08
rs72740955	2e-15	PSMA4 - CHRNA5	C	0.1
rs12151108	2e-15	SMARCA4 - LDLR	G	0.12
chr19:11196886	5e-15		T	0.12
rs72957606	2e-14	PRMT5P1 - EDNRA	A	0.1
rs7903146	2e-13	TCF7L2	C	0.18
rs61194703	2e-13	SMARCA4 - LDLR	A	0.12
rs6841581	2e-13	PRMT5P1 - EDNRA	G	0.11
rs62053262	5e-13	WWP2	C	0.2
rs227419	7e-13	SMOC1	T	0.1
rs12914385	1e-12	CHRNA3	C	0.1
rs77140532	1e-12	SMARCA4 - LDLR	A	0.14
rs17398575	2e-12	CCDC71L - LINC02577	A	0.16
chr4:148407652	2e-12		C	0.1
rs548102413	6e-12	CLASP2 - SDAD1P3	C	1.34
rs1878406	7e-12	PRMT5P1 - EDNRA	T	0.2
rs73015020	7e-12	SMARCA4 - LDLR	G	0.13
chr11:102744087	9e-12		C	0.1
rs2917677	9e-12	NQO1	C	0.07

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475989	Verma A	2024	20,858	405,668	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475990	Verma A	2024	15,036	423,003	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475991	Verma A	2024	9,984	432,329	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478005	Verma A	2024	5,248	110,792	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480200	Verma A	2024	5,248	110,792	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478007	Verma A	2024	4,282	113,972	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90480198	Verma A	2024	4,282	113,972	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90473596	UK Biobank Whole-Genome Sequencing Consortium	2025	4,148	454,292	Whole-genome sequencing of 490,640 UK Biobank participants.
GCST90478009	Verma A	2024	2,865	446,086	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90478011	Verma A	2024	2,794	116,274	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	1
Tier 3: regulatory	2
Tier 4: intronic/intergenic	47

MAF distribution

Bucket	Variants
common (>=0.05)	41
low_freq (0.01-0.05)	1
rare (<0.01)	3
unknown	5

Functional consequences

Consequence	Count
intron_variant	17
intergenic_variant	16
unknown	12
regulatory_region_variant	2
synonymous_variant	1
non_coding_transcript_exon_variant	1
splice_donor_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1333049	9	22125504	G>A,C	0.484	intergenic_variant	CDKN2B-AS1	2e-61	Tier 4: intronic/intergenic
rs183130	16	56957451	C>T	0.05	intergenic_variant	HERPUD1 - CETP	3e-54	Tier 4: intronic/intergenic
rs74617384	6	160576086	A>C,G,T	0.067	intron_variant	LPA	2e-48	Tier 4: intronic/intergenic
rs1333047	9	22124505	A>C,G,T	0.424	intergenic_variant	CDKN2B-AS1	6e-47	Tier 4: intronic/intergenic
rs55730499	6	160584578	C>T	0.056	intron_variant	LPA	5e-41	Tier 4: intronic/intergenic
rs10455872	6	160589086	A>G	0.069	intron_variant	LPA	3e-40	Tier 4: intronic/intergenic
rs2107595	7	19009765	G>A,C,T	0.18	regulatory_region_variant	HDAC9 - TWIST1	3e-24	Tier 3: regulatory
chr7:19052733				0.16			1e-20	Tier 4: intronic/intergenic
rs17486278	15	78575140	A>C	0.32	intron_variant	CHRNA5	5e-20	Tier 4: intronic/intergenic
rs10774624	12	111395984	G>A,C	0.491	intron_variant	LINC02356	2e-17	Tier 4: intronic/intergenic
rs4766578	12	111466567	T>A	0.495	intron_variant	ATXN2	2e-16	Tier 4: intronic/intergenic
rs8040868	15	78618839	T>A,C	0.396	synonymous_variant	CHRNA3	5e-16	Tier 4: intronic/intergenic
rs72740955	15	78557437	C>T	0.334	intergenic_variant	PSMA4 - CHRNA5	2e-15	Tier 4: intronic/intergenic
rs12151108	19	11086585	G>A,T	0.121	intergenic_variant	SMARCA4 - LDLR	2e-15	Tier 4: intronic/intergenic
chr19:11196886				0.119			5e-15	Tier 4: intronic/intergenic
rs72957606	4	147478859	A>G	0.166	intergenic_variant	PRMT5P1 - EDNRA	2e-14	Tier 4: intronic/intergenic
rs7903146	10	112998590	C>G,T	0.292	intron_variant	TCF7L2	2e-13	Tier 4: intronic/intergenic
rs61194703	19	11081517	A>T	0.14	intergenic_variant	SMARCA4 - LDLR	2e-13	Tier 4: intronic/intergenic
rs6841581	4	147480038	G>A,C,T	0.166	regulatory_region_variant	PRMT5P1 - EDNRA	2e-13	Tier 3: regulatory
rs62053262	16	69935396	C>G	0.042	intron_variant	WWP2	5e-13	Tier 4: intronic/intergenic
rs227419	14	69992653	T>C	0.413	intron_variant	SMOC1	7e-13	Tier 4: intronic/intergenic
rs12914385	15	78606381	C>A,G,T	0.382	intron_variant	CHRNA3	1e-12	Tier 4: intronic/intergenic
rs77140532	19	11082155	A>G,T	0.161	intergenic_variant	SMARCA4 - LDLR	1e-12	Tier 4: intronic/intergenic
rs17398575	7	106769006	G>A	0.25	intergenic_variant	CCDC71L - LINC02577	2e-12	Tier 4: intronic/intergenic
chr4:148407652				0.137			2e-12	Tier 4: intronic/intergenic
rs548102413	3	33764732	C>T	0.002	intergenic_variant	CLASP2 - SDAD1P3	6e-12	Tier 4: intronic/intergenic
rs1878406	4	147472512	C>A,G,T	0.13	intergenic_variant	PRMT5P1 - EDNRA	7e-12	Tier 4: intronic/intergenic
rs73015020	19	11081874	G>A,C	0.121	intergenic_variant	SMARCA4 - LDLR	7e-12	Tier 4: intronic/intergenic
chr11:102744087				0.181			9e-12	Tier 4: intronic/intergenic
rs2917677	16	69716946	C>A,G,T	0.364	intron_variant	NQO1	9e-12	Tier 4: intronic/intergenic

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
EDNRA	Orphanet:443995	Mandibulofacial dysostosis with alopecia
EDNRA	Orphanet:586	Cystic fibrosis
LDLR	Orphanet:391665	Homozygous familial hypercholesterolemia

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC17A4	HGNC:10932	ENSG00000146039	Q9Y2C5	Probable small intestine urate exporter	gwas
LRIG1	HGNC:17360	ENSG00000144749	Q96JA1	Leucine-rich repeats and immunoglobulin-like domains protein 1	gwas
ZHX2	HGNC:18513	ENSG00000178764	Q9Y6X8	Zinc fingers and homeoboxes protein 2	gwas
PINX1	HGNC:30046	ENSG00000254093	Q96BK5	PIN2/TERF1-interacting telomerase inhibitor 1	gwas
EDNRA	HGNC:3179	ENSG00000151617	P25101	Endothelin-1 receptor	gwas
APOC1	HGNC:607	ENSG00000130208	P02654	Apolipoprotein C-I	gwas
LDLR	HGNC:6547	ENSG00000130164	P01130	Low-density lipoprotein receptor	gwas
PIK3CG	HGNC:8978	ENSG00000105851	P48736	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC17A4	Probable small intestine urate exporter	Acts as a membrane potential-dependent organic anion transporter, the transport requires a low concentration of chloride ions.
LRIG1	Leucine-rich repeats and immunoglobulin-like domains protein 1	Acts as a feedback negative regulator of signaling by receptor tyrosine kinases, through a mechanism that involves enhancement of receptor ubiquitination and accelerated intracellular degradation.
ZHX2	Zinc fingers and homeoboxes protein 2	Acts as a transcriptional repressor.
PINX1	PIN2/TERF1-interacting telomerase inhibitor 1	Microtubule-binding protein essential for faithful chromosome segregation.
EDNRA	Endothelin-1 receptor	Receptor for endothelin-1.
APOC1	Apolipoprotein C-I	Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor.
LDLR	Low-density lipoprotein receptor	Binds low density lipoprotein /LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis.
PIK3CG	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3).

Protein-family classification

Druggable: 4 · Difficult: 1 · Unknown: 3 · 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
Transporter	1	9.7×	0.434
Antibody/Immunoglobulin	1	3.6×	0.434
Kinase	1	3.5×	0.434
GPCR	1	3.0×	0.434
Transcription factor	1	1.0×	0.773
Other/Unknown	3	0.7×	0.919

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC17A4	Transporter	yes		MFS, MFS_dom, MFS_trans_sf
LRIG1	Antibody/Immunoglobulin	yes		LRRNT, Cys-rich_flank_reg_C, Leu-rich_rpt
ZHX2	Transcription factor	no		HD, Homeodomain-like_sf, Znf_C2H2_type
PINX1	Other/Unknown	no		G_patch_dom, PINX1
EDNRA	GPCR	yes		GPCR_Rhodpsn, Endthln_rcpt, ETA_rcpt
APOC1	Other/Unknown	no		ApoC-I, ApoC-1_sf
LDLR	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF
PIK3CG	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom

Expression context

Cohort genes with no expression data: 0.

8 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
jejunal mucosa	1
mucosa of transverse colon	1
rectum	1
bronchial epithelial cell	1
secondary oocyte	1
ventricular zone	1
dorsal motor nucleus of vagus nerve	1
saphenous vein	1
superficial temporal artery	1
kidney epithelium	1
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
cauda epididymis	1
seminal vesicle	1
visceral pleura	1
left adrenal gland cortex	1
liver	1
right lobe of liver	1
adrenal tissue	1
lower lobe of lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC17A4	60	tissue_specific	marker	mucosa of transverse colon, jejunal mucosa, rectum
LRIG1	290	ubiquitous	marker	secondary oocyte, bronchial epithelial cell, ventricular zone
ZHX2	293	ubiquitous	marker	superficial temporal artery, dorsal motor nucleus of vagus nerve, saphenous vein
PINX1	244	ubiquitous	marker	kidney epithelium, oocyte, male germ line stem cell (sensu Vertebrata) in testis
EDNRA	253	ubiquitous	marker	cauda epididymis, seminal vesicle, visceral pleura
APOC1	257	broad	marker	right lobe of liver, liver, left adrenal gland cortex
LDLR	281	ubiquitous	marker	adrenal tissue, lower lobe of lung, right adrenal gland
PIK3CG	201	broad	marker	bone marrow, trabecular bone tissue, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PIK3CG	2,964
EDNRA	2,013
LRIG1	1,843
ZHX2	1,500
PINX1	1,466
APOC1	1,437
LDLR	1,426
SLC17A4	547

Intra-cohort edges

A	B	Sources
SLC17A4	ZHX2	string_interaction

Structural data

PDB: 6 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PIK3CG	P48736	107
LDLR	P01130	36
APOC1	P02654	8
EDNRA	P25101	5
LRIG1	Q96JA1	2
ZHX2	Q9Y6X8	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SLC17A4	Q9Y2C5	83.87
PINX1	Q96BK5	65.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 40. Enrichment computed across 8 evidence-associated genes (5 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 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Plasma lipoprotein clearance	2	190.3×	0.002	APOC1, LDLR
Plasma lipoprotein assembly, remodeling, and clearance	2	91.4×	0.004	APOC1, LDLR
VLDL assembly	1	456.8×	0.021	APOC1
Chylomicron clearance	1	456.8×	0.021	LDLR
VLDL clearance	1	380.7×	0.021	APOC1
Co-stimulation by ICOS	1	207.6×	0.030	PIK3CG
Erythropoietin activates Phosphoinositide-3-kinase (PI3K)	1	190.3×	0.030	PIK3CG
Plasma lipoprotein assembly	1	142.8×	0.034	APOC1
LDL clearance	1	108.8×	0.034	LDLR
Negative regulation of MET activity	1	103.8×	0.034	LRIG1
G beta:gamma signalling through PI3Kgamma	1	87.8×	0.034	PIK3CG
CD28 dependent PI3K/Akt signaling	1	78.8×	0.034	PIK3CG
NR1H2 and NR1H3-mediated signaling	1	78.8×	0.034	APOC1
Metabolism of fat-soluble vitamins	1	76.1×	0.034	LDLR
Signaling by EGFR	1	65.3×	0.034	LRIG1
Signaling by MET	1	63.4×	0.034	LRIG1
GPVI-mediated activation cascade	1	61.7×	0.034	PIK3CG
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	1	61.7×	0.034	APOC1
Transport of small molecules	2	10.1×	0.034	APOC1, LDLR
Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin	1	55.7×	0.036	LRIG1
Visual phototransduction	1	51.9×	0.036	LDLR
Retinoid metabolism and transport	1	49.6×	0.036	LDLR
Developmental Cell Lineages	1	44.8×	0.038	LRIG1
Synthesis of PIPs at the plasma membrane	1	42.3×	0.039	PIK3CG
Constitutive Signaling by Aberrant PI3K in Cancer	1	25.4×	0.062	PIK3CG
Metabolism of vitamins and cofactors	1	23.3×	0.065	LDLR
Cargo recognition for clathrin-mediated endocytosis	1	20.9×	0.069	LDLR
Signaling by Nuclear Receptors	1	20.4×	0.069	APOC1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	19.4×	0.069	PIK3CG
Sensory Perception	1	19.0×	0.069	LDLR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of triglyceride catabolic process	2	702.2×	6e-04	APOC1, PIK3CG
negative regulation of phosphatidylcholine catabolic process	1	2106.5×	0.012	APOC1
regulation of protein localization to cell leading edge	1	2106.5×	0.012	EDNRA
regulation of phosphatidylcholine catabolic process	1	1053.2×	0.012	LDLR
natural killer cell chemotaxis	1	1053.2×	0.012	PIK3CG
cellular response to human chorionic gonadotropin stimulus	1	1053.2×	0.012	EDNRA
receptor-mediated endocytosis involved in cholesterol transport	1	1053.2×	0.012	LDLR
podocyte apoptotic process	1	1053.2×	0.012	EDNRA
cardiac chamber formation	1	702.2×	0.012	EDNRA
secretory granule localization	1	702.2×	0.012	PIK3CG
negative regulation of astrocyte activation	1	702.2×	0.012	LDLR
endothelin receptor signaling pathway involved in heart process	1	702.2×	0.012	EDNRA
semaphorin-plexin signaling pathway involved in axon guidance	1	702.2×	0.012	EDNRA
respiratory burst involved in defense response	1	526.6×	0.012	PIK3CG
left ventricular cardiac muscle tissue morphogenesis	1	526.6×	0.012	EDNRA
atrial cardiac muscle tissue development	1	526.6×	0.012	EDNRA
negative regulation of very-low-density lipoprotein particle clearance	1	526.6×	0.012	APOC1
neural crest cell fate commitment	1	526.6×	0.012	EDNRA
negative regulation of cholesterol transport	1	526.6×	0.012	APOC1
plasma lipoprotein particle remodeling	1	526.6×	0.012	APOC1
plasma lipoprotein particle clearance	1	526.6×	0.012	LDLR
negative regulation of cardiac muscle contraction	1	526.6×	0.012	PIK3CG
sympathetic neuron axon guidance	1	526.6×	0.012	EDNRA
positive regulation of cation channel activity	1	526.6×	0.012	EDNRA
negative regulation of receptor recycling	1	421.3×	0.012	LDLR
otolith morphogenesis	1	421.3×	0.012	LRIG1
very-low-density lipoprotein particle clearance	1	421.3×	0.012	APOC1
negative regulation of lipid metabolic process	1	421.3×	0.012	APOC1
glomerular endothelium development	1	421.3×	0.012	EDNRA
renal albumin absorption	1	421.3×	0.012	EDNRA

Therapeutics

Drugs indicated for this disease

5 approved, 49 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Alirocumab	Approved (phase 4)
Bempedoic Acid	Approved (phase 4)
Inclisiran Sodium	Approved (phase 4)
Lovastatin	Approved (phase 4)
Niacin	Approved (phase 4)
Acarbose	Phase 3 (in late-stage trials)
Amlodipine	Phase 3 (in late-stage trials)
Anacetrapib	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atorvastatin	Phase 3 (in late-stage trials)
Benazepril	Phase 3 (in late-stage trials)
Canakinumab	Phase 3 (in late-stage trials)
Candesartan Cilexetil	Phase 3 (in late-stage trials)
Carvedilol	Phase 3 (in late-stage trials)
Chlorothiazide	Phase 3 (in late-stage trials)
Chlorthalidone	Phase 3 (in late-stage trials)
Cilostazol	Phase 3 (in late-stage trials)
Clopidogrel	Phase 3 (in late-stage trials)
Corn Oil	Phase 3 (in late-stage trials)
Darapladib	Phase 3 (in late-stage trials)
Diltiazem	Phase 3 (in late-stage trials)
Ezetimibe	Phase 3 (in late-stage trials)
Felodipine	Phase 3 (in late-stage trials)
Fenofibrate	Phase 3 (in late-stage trials)
Furosemide	Phase 3 (in late-stage trials)
Glimepiride	Phase 3 (in late-stage trials)
Glipizide	Phase 3 (in late-stage trials)
Hydralazine	Phase 3 (in late-stage trials)
Hydrochlorothiazide	Phase 3 (in late-stage trials)
Inclisiran	Phase 3 (in late-stage trials)
Insulin Aspart	Phase 3 (in late-stage trials)
Insulin Detemir	Phase 3 (in late-stage trials)
Insulin Glargine	Phase 3 (in late-stage trials)
Insulin Human	Phase 3 (in late-stage trials)
Insulin Susp Isophane Recombinant Human	Phase 3 (in late-stage trials)
Insulin Susp Isophane Semisynthetic Purified Human	Phase 3 (in late-stage trials)
Lisinopril Anhydrous	Phase 3 (in late-stage trials)
Lycopene	Phase 3 (in late-stage trials)
Metformin	Phase 3 (in late-stage trials)
Metoprolol	Phase 3 (in late-stage trials)
Obicetrapib	Phase 3 (in late-stage trials)
Olmesartan Medoxomil	Phase 3 (in late-stage trials)
Pioglitazone	Phase 3 (in late-stage trials)
Ramipril	Phase 3 (in late-stage trials)
Repaglinide	Phase 3 (in late-stage trials)
Reserpine	Phase 3 (in late-stage trials)
Rosiglitazone	Phase 3 (in late-stage trials)
Rosuvastatin	Phase 3 (in late-stage trials)
Simvastatin	Phase 3 (in late-stage trials)
Terazosin	Phase 3 (in late-stage trials)
Tirofiban	Phase 3 (in late-stage trials)
Triamterene	Phase 3 (in late-stage trials)
Valsartan	Phase 3 (in late-stage trials)
Warfarin	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aliskiren, Ascorbic Acid, Colchicine, Cyanocobalamin, Estradiol, Folic Acid, Losmapimod, Pyridoxine, Vitamin E.

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 3 · Undrugged: 5

Druggability breadth: 3 of 8 evidence-associated genes (38%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
EDNRA	AMBRISENTAN
LDLR	NILOTINIB
PIK3CG	FEDRATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PIK3CG	56	4
EDNRA	31	4
LDLR	1	4
SLC17A4	0	0
LRIG1	0	0
ZHX2	0	0
PINX1	0	0
APOC1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMBRISENTAN	4	EDNRA
GRAMICIDIN	4	EDNRA
NITAZOXANIDE	4	EDNRA
IRBESARTAN	4	EDNRA
ACYCLOVIR	4	EDNRA
MACITENTAN	4	EDNRA
APROCITENTAN	4	EDNRA
SITAXENTAN	4	EDNRA
FLUOXETINE	4	EDNRA
SULFATHIAZOLE	4	EDNRA
SULFISOXAZOLE	4	EDNRA
SUNITINIB	4	EDNRA, PIK3CG
SPARSENTAN	4	EDNRA
PIOGLITAZONE	4	EDNRA
MELOXICAM	4	EDNRA
AMIODARONE	4	EDNRA
ENOXACIN	4	EDNRA
BOSENTAN	4	EDNRA
NILOTINIB	4	LDLR
FEDRATINIB	4	PIK3CG
IDELALISIB	4	PIK3CG
ALPELISIB	4	PIK3CG
DUVELISIB	4	PIK3CG
COPANLISIB	4	PIK3CG
COPANLISIB HYDROCHLORIDE	4	PIK3CG
LENIOLISIB	4	PIK3CG
UMBRALISIB	4	PIK3CG
INAVOLISIB	4	PIK3CG
CLAZOSENTAN	3	EDNRA
ZIBOTENTAN	3	EDNRA

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
PIK3CG	899	Binding:888, ADMET:8, Functional:2, Toxicity:1
EDNRA	418	Binding:342, Functional:73, Toxicity:2, ADMET:1
LDLR	55	Binding:54, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PIK3CG	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
EDNRA	418
PIK3CG	899

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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.

Compound	Max phase	Cohort target (bioactivity)
AMBRISENTAN	4	EDNRA
GRAMICIDIN	4	EDNRA
NITAZOXANIDE	4	EDNRA
IRBESARTAN	4	EDNRA
ACYCLOVIR	4	EDNRA
MACITENTAN	4	EDNRA
APROCITENTAN	4	EDNRA
SITAXENTAN	4	EDNRA
FLUOXETINE	4	EDNRA
SULFATHIAZOLE	4	EDNRA
SULFISOXAZOLE	4	EDNRA
SUNITINIB	4	EDNRA, PIK3CG
SPARSENTAN	4	EDNRA
PIOGLITAZONE	4	EDNRA
MELOXICAM	4	EDNRA
AMIODARONE	4	EDNRA
ENOXACIN	4	EDNRA
BOSENTAN	4	EDNRA
NILOTINIB	4	LDLR
FEDRATINIB	4	PIK3CG
IDELALISIB	4	PIK3CG
ALPELISIB	4	PIK3CG
DUVELISIB	4	PIK3CG
COPANLISIB	4	PIK3CG
COPANLISIB HYDROCHLORIDE	4	PIK3CG
LENIOLISIB	4	PIK3CG
UMBRALISIB	4	PIK3CG
INAVOLISIB	4	PIK3CG
CLAZOSENTAN	3	EDNRA
ZIBOTENTAN	3	EDNRA

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	EDNRA, LDLR, PIK3CG
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	LRIG1
D	Druggable family + AlphaFold only, no drug	1	SLC17A4
E	Difficult family or no structure, no drug	3	ZHX2, PINX1, APOC1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC17A4	0	—
LRIG1	0	—
ZHX2	0	—
PINX1	0	—
APOC1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 921.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	609
PHASE4	114
PHASE3	62
PHASE2	54
PHASE1	45
PHASE2/PHASE3	20
EARLY_PHASE1	9
PHASE1/PHASE2	8

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02915198	PHASE4	RECRUITING	Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes
NCT05365425	PHASE4	RECRUITING	Choline Fenofibrate and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia
NCT05365438	PHASE4	RECRUITING	Atmeg (Atorvastatin and Omega-3 Combination) and Carotid Atherosclerosis in Patients With Type 2 Diabetes and Combined Dyslipidemia
NCT05708859	PHASE4	RECRUITING	Effect of Tirzepatide on Progression of Coronary Atherosclerosis Using MDCT
NCT05932472	PHASE4	RECRUITING	Randomized Comparison of Morning Versus Bedtime Administration of Aspirin: A Cardiovascular Circadian Chronotherapy (C3) Trial
NCT06402747	PHASE4	RECRUITING	Clopidogrel Versus Cilostazol on Vessels
NCT06785974	PHASE4	NOT_YET_RECRUITING	Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis
NCT07611747	PHASE4	RECRUITING	Carotid Ultrasound-Based Strategy for Primary Prevention of Cardiovascular Events in Inflammatory Rheumatic Disease (PREVENER)
NCT07614230	PHASE4	RECRUITING	SGLT2 Inhibitors on Coronary Atherosclerosis Progression Via Perivascular Adipose Tissue in Diabetes
NCT00079638	PHASE4	COMPLETED	Comparative Efficacy Evaluation of Lipids When Treated With Niaspan & Statin or Other Lipid-Modifying Therapies-COMPELL
NCT00130039	PHASE4	COMPLETED	Trial of Cilostazol in Symptomatic Intracranial Arterial Stenosis II
NCT00166530	PHASE4	COMPLETED	EASEGO Study: Doubling of Atorvastatin/Simvastatin or INEGY in Patients With Hypercholesterolemia and Coronary Artery Disease(CAD)(0653A-089)
NCT00217178	PHASE4	UNKNOWN	Homocysteine Lowering and Atherosclerosis Reduction Trial (HART)
NCT00222261	PHASE4	COMPLETED	Aspirin Non-responsiveness and Clopidogrel Endpoint Trial.
NCT00241904	PHASE4	COMPLETED	Reducing Total Cardiovascular Risk in an Urban Community
NCT00243672	PHASE4	WITHDRAWN	Early Therapeutic Effects of Statins and Fibrates on Unstable Atherosclerotic Plaques
NCT00247494	PHASE4	UNKNOWN	Effects of Mycophenolate Mofetil (MMF) on Surrogate Markers for Cardiovascular Disease in HIV-1 Infected Patients
NCT00247507	PHASE4	UNKNOWN	The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
NCT00272311	PHASE4	COMPLETED	Aspirin Dose and Atherosclerosis in Patients With Metabolic Syndrome
NCT00272337	PHASE4	COMPLETED	Aspirin Dose and Atherosclerosis in Patients With Heart Disease
NCT00281060	PHASE4	COMPLETED	Vienna Absolute Trial: Balloon Angioplasty Versus Stenting in the Superficial Femoral Artery
NCT00287508	PHASE4	COMPLETED	Emboshield® and Xact® Post Approval Carotid Stent Trial (The EXACT Study)
NCT00287586	PHASE4	COMPLETED	Testosterone Replacement in Older Men and Atherosclerosis Progression
NCT00328536	PHASE4	COMPLETED	Omacor for the Treatment of Vascular Dysfunction in Patients With Type 2 Diabetes Mellitus
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00397657	PHASE4	TERMINATED	Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis
NCT00400543	PHASE4	COMPLETED	Early Signs of Atherosclerosis in Obstructive Sleep Apnea: Effects of Treatment
NCT00437905	PHASE4	TERMINATED	Balloon Angioplasty vs. Cutting Balloon Angioplasty of Femoropopliteal Arteries- a Randomized Controlled Trial
NCT00457405	PHASE4	COMPLETED	Does a Seven Day Treatment With Dipyridamole Induce Protection Against Ischemia-Reperfusion Injury?
NCT00470808	PHASE4	UNKNOWN	The Effect of a Natural Polyphenolic Extract From Pomegrnate (POMX) on the Development of Atherosclerosis in Diabetic Patients
NCT00484965	PHASE4	UNKNOWN	Erythrocyte-Mediated Drug Delivery for the Prevention of Stent Restenosis
NCT00560170	PHASE4	COMPLETED	Vascular Effects of Ezetimibe/Simvastatin and Simvastatin on Atherosclerosis
NCT00574457	PHASE4	COMPLETED	Improving Cardiovascular Risk Prediction Using Hand Held Carotid Ultrasonography Study
NCT00578578	PHASE4	TERMINATED	Trial to Study the Effects of Supplementary Omega-3 on Serum C-Reactive Protein Levels
NCT00605605	PHASE4	COMPLETED	Vascular Endothelial Protection Effects of Dextromethorphan
NCT00640744	PHASE4	UNKNOWN	Effect of Short Term Atorvastatin Treatment,80mg/Day on Early Regression of Carotid Artery Atherosclerotic Lesions
NCT00650663	PHASE4	COMPLETED	Ezetimibe Plus Simvastatin Versus Simvastatin Alone in African-American Subjects With Primary Hypercholesterolemia (P03377)
NCT00651014	PHASE4	TERMINATED	Ezetimibe Plus Simvastatin Versus Simvastatin in Patients With Hypercholesterolemia and Coronary Risk Factors (P03405)
NCT00651274	PHASE4	COMPLETED	Comparison of Co-administration of Ezetimibe Plus Simvastatin Versus Simvastatin Alone in Primary Hypercholesterolemia (P03476)
NCT00651378	PHASE4	TERMINATED	Switching to Rosuvastatin Versus Adding Ezetimibe to Atorvastatin Versus Doubling the Dose of Atorvastatin in Patients With Hypercholesterolemia and Risk Factors (P03708)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ROSUVASTATIN	4	18
SIMVASTATIN	4	15
ATORVASTATIN	4	11
EZETIMIBE	4	9
NIACIN	4	8
CANGRELOR	4	6
CLOPIDOGREL	4	6
ENALAPRIL	4	6
ASPIRIN	4	5
ROSIGLITAZONE	4	5
COLCHICINE	4	4
VORAPAXAR	4	4
ALIROCUMAB	4	3
CILOSTAZOL	4	3
DEXTROMETHORPHAN	4	3
RAMIPRIL	4	3
SITAGLIPTIN	4	3
BEMPEDOIC ACID	4	2
CANAKINUMAB	4	2
DIPYRIDAMOLE	4	2
EVOLOCUMAB	4	2
GLYCINE	4	2
ICOSAPENT ETHYL	4	2
LEVOTHYROXINE	4	2
LOVASTATIN	4	2
OLIVE OIL	4	2
PENTOXIFYLLINE	4	2
RETINOL	4	2
RIVAROXABAN	4	2
TICAGRELOR	4	2