Carotid stenosis

Summary

Carotid stenosis (MONDO:0001612) is a disease with 1 cohort gene and 249 clinical trials. Top therapeutic interventions include clopidogrel, dexmedetomidine, and terazosin.

At a glance

• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 249

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	carotid stenosis
Mondo ID	MONDO:0001612
MeSH	D016893
DOID	DOID:13001
NCIT	C95804
SNOMED CT	64586002
UMLS	C0007282
MedGen	785
Is cancer (heuristic)	no

Also known as: carotid artery stenosis

Data availability: 1 ClinVar variant · 1 HPO phenotype.

Disease family

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

Related subtypes (5): carotid artery occlusion, carotid artery dissection, carotid artery thrombosis, autonomic facial cephalgia, extracranial carotid artery aneurysm

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 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
523426	NM_001256071.3(RNF213):c.11659A>G (p.Lys3887Glu)	RNF213	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF213	Orphanet:2573	Moyamoya disease

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
RNF213	HGNC:14539	ENSG00000173821	Q63HN8	E3 ubiquitin-protein ligase RNF213	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF213	E3 ubiquitin-protein ligase RNF213	Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity.

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)
RNF213	Transcription factor	no		Znf_RING, AAA+_ATPase, Znf_RING/FYVE/PHD

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
granulocyte	1
metanephros cortex	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF213	252	ubiquitous	marker	granulocyte, metanephros cortex, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RNF213	2,368

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RNF213	Q63HN8	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
Suppression of apoptosis	1	1631.4×	0.004	RNF213
Response of Mtb to phagocytosis	1	1427.5×	0.004	RNF213
Infection with Mycobacterium tuberculosis	1	1142.0×	0.004	RNF213
Bacterial Infection Pathways	1	335.9×	0.010	RNF213
Signaling by ALK in cancer	1	271.9×	0.010	RNF213
Signaling by ALK fusions and activated point mutants	1	150.3×	0.014	RNF213
Class I MHC mediated antigen processing & presentation	1	70.1×	0.027	RNF213
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.029	RNF213
Antigen processing: Ubiquitination & Proteasome degradation	1	37.2×	0.039	RNF213
Adaptive Immune System	1	29.8×	0.044	RNF213
Infectious disease	1	24.8×	0.048	RNF213
Disease	1	13.1×	0.077	RNF213
Immune System	1	13.0×	0.077	RNF213

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
lipid ubiquitination	1	16852.0×	8e-04	RNF213
negative regulation of non-canonical Wnt signaling pathway	1	3370.4×	0.002	RNF213
xenophagy	1	2407.4×	0.002	RNF213
lipid droplet formation	1	991.3×	0.003	RNF213
sprouting angiogenesis	1	481.5×	0.005	RNF213
regulation of lipid metabolic process	1	432.1×	0.005	RNF213
immune system process	1	391.9×	0.005	RNF213
protein K63-linked ubiquitination	1	267.5×	0.006	RNF213
protein autoubiquitination	1	234.1×	0.006	RNF213
defense response to bacterium	1	108.0×	0.012	RNF213
ubiquitin-dependent protein catabolic process	1	74.2×	0.016	RNF213
angiogenesis	1	62.4×	0.017	RNF213
protein ubiquitination	1	41.4×	0.024	RNF213

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
RNF213	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
RNF213	1	Binding: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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RNF213

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)
RNF213	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 249.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	192
PHASE4	22
PHASE3	15
PHASE2	15
PHASE1	3
PHASE2/PHASE3	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06873321	PHASE4	RECRUITING	VTE Incidence After Rivaroxaban + Aspirin or SAPT After Lower-limb Revascularization
NCT07036991	PHASE4	NOT_YET_RECRUITING	Clinical Trial of PCSK9 Inhibitor and Statin Treatment for Carotid Artery Stenosis
NCT00178672	PHASE4	COMPLETED	A Single Center of Carotid Stenting With Distal Protection for the Treatment of Obstructive Carotid Artery Disease
NCT00287508	PHASE4	COMPLETED	Emboshield® and Xact® Post Approval Carotid Stent Trial (The EXACT Study)
NCT00335972	PHASE4	TERMINATED	The Effects of Dexmedetomidine and Remifentanil on Carotid Patients
NCT00478673	PHASE4	TERMINATED	Post-Approval Study of the NexStent Carotid Stent System and the FilterWire EZ Embolic Protection System: SONOMA
NCT00772278	PHASE4	COMPLETED	Comparing Carotid Stenting With Endarterectomy in Severe Asymptomatic Carotid Stenosis
NCT00805311	PHASE4	TERMINATED	Aggressive Medical Treatment Evaluation for Asymptomatic Carotid Artery Stenosis
NCT01146301	PHASE4	COMPLETED	Platelet Inhibition and Transcranial Doppler (TCD)-Detected Microemboli During and After Carotid Artery Stenting (CAS) in Asymptomatic Patients Prior to Cardiac Surgery
NCT01210937	PHASE4	UNKNOWN	Early Warning and Optimization Strategy in Carotid Endarterectomy
NCT01236508	PHASE4	TERMINATED	Relation of Carotid Artery Plaque Inflammation, Covert Stroke and White Matter Disease
NCT01572623	PHASE4	UNKNOWN	Clopidogrel and Atorvastatin Treatment During Carotid Artery Stenting
NCT02224209	PHASE4	UNKNOWN	Comparison of Staged Angioplasty and Routine Single-stage Stenting (CAS) in the Treatment of Carotid Artery Stenosis
NCT02609087	PHASE4	COMPLETED	Effect on Cerebral Oxygenation by Sevoflurane or Propofol Using Near-infrared Spectroscopy in Carotid Endarterectomy
NCT03079115	PHASE4	UNKNOWN	High Dose Atorvastatin for Preventing Periprocedural Ischemic Brain Damage During Carotid Artery Stenting
NCT03115034	PHASE4	COMPLETED	Melatonin in Patients Under Carotid Endarterectomy
NCT03419767	PHASE4	UNKNOWN	Insulin Resistance in Patients After Carotid Revascularization
NCT03931161	PHASE4	UNKNOWN	Effect of Evolocumab on Carotid Plaque Composition in Asymptomatic Carotid Artery Stenosis (EVOCAR-1)
NCT03996148	PHASE4	COMPLETED	Time to Post-Anesthesia Neurological Evaluation With Three Different Anesthetic Techniques
NCT04539223	PHASE4	UNKNOWN	A Study of Evolocumab on Carotid Artery Atherosclerotic Plaque Morphology Prior to Carotid EndArterectomy
NCT04662177	PHASE4	COMPLETED	Co-administration of Dexmedetomidine in Carotid Endarterectomy (CEA)
NCT05797376	PHASE4	COMPLETED	Effects of aSPIrin Versus Aspirin Plus Low-dose RIvaroxaban on Carotid aTherosclerotic Plaque Inflammation
NCT06511089	PHASE3	RECRUITING	Carotid Artery Stenting During Endovascular Treatment of Acute Stroke
NCT07586540	PHASE3	NOT_YET_RECRUITING	Alirocumab for Stabilisation of Symptomatic Vulnerable Carotid Plaque
NCT00190398	PHASE3	COMPLETED	EVA3S: Endarterectomy Versus Angioplasty in Patients With Severe Symptomatic Carotid Stenosis
NCT00318851	PHASE3	COMPLETED	Carotid Artery Stenting With Protection Registry
NCT00395785	PHASE2/PHASE3	TERMINATED	Evaluation of the TriActiv ProGuard System During Carotid Artery Stenting
NCT00417963	PHASE3	COMPLETED	ViVEXX Carotid Revascularization Trial (VIVA)
NCT00594100	PHASE3	COMPLETED	GORE Embolic Protection With Reverse Flow
NCT00654394	PHASE3	COMPLETED	Progression of Carotid Artery Atheroma in Moderately Hypercholesterolemic Subjects
NCT00766493	PHASE3	COMPLETED	GORE® Embolic Filter in Carotid Stenting for High Risk Surgical Subjects (EMBOLDEN)
NCT01331473	PHASE3	UNKNOWN	PROximal Protection VErsus NON-Protection in Carotid Artery Stenting
NCT01344447	PHASE3	COMPLETED	Gadobutrol Enhanced MRA of the Supra-aortic Vessels
NCT02133989	PHASE3	UNKNOWN	Clopidogrel Resistance and Embolism in Carotid Artery Stenting
NCT02260453	PHASE3	COMPLETED	Coronary Angiography Before Elective Carotid Endarterectomy in Patients With Asymptomatic Coronary Artery Disease
NCT02850081	PHASE3	TERMINATED	Statin Neuroprotection and Carotid Endarterectomy: Safety, Feasibility and Outcomes
NCT05126238	PHASE3	TERMINATED	A Lithium-Based Medication to Improve Neurological Outcomes After Surgical Carotid Reconstruction
NCT05905848	PHASE3	UNKNOWN	Pre-operative Antihypertension Strategies-Carotid Artery Stenting
NCT05850247	PHASE2	RECRUITING	Plaque and Brain Inflammation in Symptomatic Carotid Stenosis: Role of the Ficolin-2
NCT00000469	PHASE2	COMPLETED	Asymptomatic Carotid Artery Plaque Study (ACAPS)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CLOPIDOGREL	4	6
DEXMEDETOMIDINE	4	3
TERAZOSIN	4	3
INDOCYANINE GREEN ACID FORM	4	2
LOSARTAN	4	2
MELATONIN	4	2
REMIFENTANIL	4	2
ABCIXIMAB	4	1
ALIROCUMAB	4	1
AMLODIPINE	4	1
ASPIRIN	4	1
ATORVASTATIN	4	1
DESFLURANE	4	1
DIPYRIDAMOLE	4	1
EPHEDRINE	4	1
EVOLOCUMAB	4	1
GADOPENTETATE DIMEGLUMINE	4	1
LITHIUM CARBONATE	4	1
LOVASTATIN	4	1
MINOCYCLINE	4	1
PERFLUTREN	4	1
RIVAROXABAN	4	1
SEVOFLURANE	4	1
SODIUM FLUORIDE	4	1
SULFUR HEXAFLUORIDE	4	1
TICLOPIDINE	4	1
MEDETOMIDINE	3	1
EGAPTIVON PEGOL	2	1
FASUDIL HYDROCHLORIDE	2	1
CHEMBL4587343	0	1