Arteriosclerosis disorder

Summary

Arteriosclerosis disorder (MONDO:0002277) is a disease (an umbrella term covering 5 Mondo subtypes) with 1 cohort gene and 110 clinical trials. Top therapeutic interventions include alendronic acid, aspirin, and ammonia solution, strong.

At a glance

• Umbrella term: 5 Mondo subtypes
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 110

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	arteriosclerosis disorder
Mondo ID	MONDO:0002277
MeSH	D001161
DOID	DOID:2348, DOID:2349
NCIT	C34398, C34403
SNOMED CT	72092001
UMLS	C0003850
MedGen	2076
Is cancer (heuristic)	no

Also known as: arterial sclerosis · arteriosclerosis · arteriosclerotic cardiovascular disease · vascular sclerosis

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

An umbrella term covering 5 Mondo subtypes.

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

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, subclavian artery aneurysm, pulmonary artery choriocarcinoma, pulmonary artery leiomyosarcoma, coronary artery disorder, hypertensive disorder, carotid artery disorder, pulmonary embolism, peripheral arterial disease, hypotensive disorder, large artery stroke, aortic disorder, cervical artery dissection, anterior spinal artery syndrome, fibromuscular dysplasia, retinal arterial tortuosity, Sneddon syndrome, celiac trunk compression syndrome, pediatric arterial ischemic stroke, absence of the pulmonary artery, arterial occlusion, aberrant subclavian artery, anterior spinal artery stroke, arteritis, pulmonary artery disease, fibromuscular dysplasia, multifocal, carotid web

Subtypes (5): intracranial arteriosclerosis, Monckeberg arteriosclerosis, intermittent vascular claudication, atherosclerosis, arteriosclerotic retinopathy

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 risk factor

ClinVar	Variant (HGVS)	Gene	Classification	Review
441163	NM_005114.4(HS3ST1):c.-108-6848A>G	HS3ST1	risk factor	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
HS3ST1	HGNC:5194	ENSG00000002587	O14792	Heparan sulfate glucosamine 3-O-sulfotransferase 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HS3ST1	Heparan sulfate glucosamine 3-O-sulfotransferase 1	Sulfotransferase that utilizes 3’-phospho-5’-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan.

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
HS3ST1	Enzyme (other)	yes	2.8.2.23	Sulfotransferase_dom, P-loop_NTPase, NST/OST

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
bronchial epithelial cell	1
epithelium of bronchus	1
nasal cavity epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HS3ST1	247	broad	marker	nasal cavity epithelium, bronchial epithelial cell, epithelium of bronchus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HS3ST1	749

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HS3ST1	O14792	1

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
HS-GAG biosynthesis	1	346.1×	0.003	HS3ST1

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
glycosaminoglycan biosynthetic process	1	842.6×	0.002	HS3ST1
heparan sulfate proteoglycan biosynthetic process	1	561.7×	0.002	HS3ST1

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Dextroamphetamine	Approved (phase 4)
Clopidogrel	Phase 3 (in late-stage trials)
Rimonabant	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
HS3ST1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
HS3ST1	2.8.2.23	[heparan sulfate]-glucosamine 3-sulfotransferase 1

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	HS3ST1
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)
HS3ST1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 110.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	81
PHASE4	13
PHASE3	7
PHASE2	4
PHASE1	3
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07237308	PHASE4	NOT_YET_RECRUITING	BEACON-AA: Apixaban With or Without Clopidogrel in Stroke Patients With Atrial Fibrillation and Cerebral Atherosclerosis
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00154180	PHASE4	UNKNOWN	Kronos Early Estrogen Prevention Study (KEEPS)
NCT00161070	PHASE4	COMPLETED	ESPRIT: European/Australasian Stroke Prevention in Reversible Ischaemia Trial
NCT00211939	PHASE4	COMPLETED	CARE-2 (Calcium Acetate [PhosLo®]/Sevelamer[Renagel®] Evaluation Study 2) for Heart Calcification in Dialysis Patients
NCT00395382	PHASE4	COMPLETED	Study of the Effect of Alendronate on Vascular Calcification and Arterial Stiffness in Chronic Kidney Disease
NCT00657943	PHASE4	COMPLETED	The Copenhagen Insulin and Metformin Therapy Trial
NCT02212470	PHASE4	COMPLETED	Drug Eluting Balloon Angioplasty Versus Nitinol Stent Implantation in the Superficial Femoral Artery
NCT02423265	PHASE4	WITHDRAWN	Efficacy of Ranolazine in Patients With Chronic Total Occlusions of Coronary Arteries
NCT02510547	PHASE4	COMPLETED	Comparison of a CrossBoss First Versus Standard Wire Escalation Strategy for Crossing Coronary Chronic Total Occlusion: the CrossBoss First Trial
NCT02601664	PHASE4	TERMINATED	Randomized-controlled Trial of a Combined vs. Conventional Percutaneous Intervention for Near-Infrared Spectroscopy Defined High-Risk Native Coronary Artery Lesions
NCT04624854	PHASE4	COMPLETED	Dual Anti-Platelet Therapy in Patients With Coronary Multi-Vessel Disease (DAPT-MVD)
NCT05942352	PHASE4	UNKNOWN	Clinical Study of Ligustrazine in Treating Alcohol Addiction
NCT06008756	PHASE3	ACTIVE_NOT_RECRUITING	Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) Cardiovascular Outcomes Study (MK-0616-015) CORALreef Outcomes
NCT06708000	PHASE3	ENROLLING_BY_INVITATION	Personalized Evaluation of Susptected Myocardial Ischemia
NCT00050817	PHASE3	COMPLETED	Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA)
NCT00228176	PHASE3	TERMINATED	Atherosclerosis Underlying Development Assessed by Intima-Media Thickness in Patients on Rimonabant
NCT00247208	PHASE3	COMPLETED	The SOS (Stenting Of Saphenous Vein Grafts) Trial
NCT00934037	PHASE3	COMPLETED	Combined Non-invasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography
NCT02452736	PHASE3	COMPLETED	Acute Safety, Deliverability and Efficacy of the Medtronic Resolute Integrity™ Zotarolimus-Eluting Coronary Stent System in the Treatment of Suitable Patients According to Indication for Use (CHINA RESOLUTE INTEGRITY STUDY)
NCT00174902	PHASE1/PHASE2	UNKNOWN	The Effect of Beta-Blockers and Aspirin on Hemostasis and Endothelial Function After Acute Mental Stress
NCT00930813	PHASE1/PHASE2	COMPLETED	LEVANT I, The Lutonix Paclitaxel-Coated Balloon for the Prevention of Femoropopliteal Restenosis
NCT01275092	PHASE2	COMPLETED	Evaluation of the Safety and Effectiveness of the CorPath 200 System in Percutaneous Coronary Interventions (PCI)
NCT01537315	PHASE2	TERMINATED	Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
NCT01774058	PHASE2	UNKNOWN	The Arterial Measurement of the Blood Flow Volume After Iloprost Stimulation
NCT02561000	PHASE2	COMPLETED	Safety of PZ-128 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention
NCT00029575	PHASE1	COMPLETED	Magnetic Resonance Imaging of Narrowed Arteries
NCT00080392	PHASE1	COMPLETED	EW-A-401 to Treat Intermittent Claudication
NCT02685098	PHASE1	COMPLETED	A Clinical and Histological Analysis of Mesenchymal Stem Cells in Amputation
NCT03466151	Not specified	ACTIVE_NOT_RECRUITING	RESOLUTE ONYX China RCT Study
NCT03471845	Not specified	ACTIVE_NOT_RECRUITING	RESOLUTE ONYX China Single Arm Study
NCT04353232	Not specified	ACTIVE_NOT_RECRUITING	Impact of Lifetime Exposure to Air and Noise Pollution on Cardiovascular Disease and Mortality - the AIRCARD Study.
NCT05620095	Not specified	RECRUITING	Durg Coated Balloon Angioplasty in Infrapopliteal Lesions
NCT05884840	Not specified	RECRUITING	New Cardiovascular Risk Screening Strategy.
NCT05985447	Not specified	RECRUITING	Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity
NCT06394934	Not specified	RECRUITING	Home Blood Pressure Variability and Its Link to Arteriosclerosis and Metabolic Dysfunction in Hypertensive Patients
NCT06603363	Not specified	RECRUITING	Changes in Plaque Characteristics After Short-term Statin Therapy as Assessed With Coronary CT
NCT06670768	Not specified	RECRUITING	Myocardial Perfusion Quantification With SPECT Using Multi-Pinhole Collimator Compared to Photon-Counting Coronary CTA
NCT06754956	Not specified	RECRUITING	Imaging of Intracranial and Extracranial Arterial Atherosclerotic Plaques Using Different Field Strength MRIs
NCT07258290	Not specified	NOT_YET_RECRUITING	Safety and Clinical Performance of the Freesolve Resorbable Magnesium Scaffold (RMS) System in Subjects With Coronary Artery Lesions

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALENDRONIC ACID	4	3
ASPIRIN	4	3
AMMONIA SOLUTION, STRONG	4	1
APIXABAN	4	1
ATORVASTATIN	4	1
CALCIUM ACETATE	4	1
DIPYRIDAMOLE	4	1
ILOPROST	4	1
INSULIN ASPART	4	1
INSULIN DETEMIR	4	1
METFORMIN	4	1
PROGESTERONE	4	1
RANOLAZINE	4	1
RIMONABANT	4	1
SEVELAMER	4	1
ENLICITIDE DECANOATE	3	1
MENAQUINONE 7	2	1
PZ-128	2	1
CHEMBL5282669	0	2
CHEMBL4587343	0	1