Cerebral arterial disease

Summary

Cerebral arterial disease (MONDO:0006693) is a disease with 3 cohort genes and 14 clinical trials. Top therapeutic interventions include gadoterate meglumine, esmolol, and ganirelix acetate.

At a glance

• Cohort genes: 3
• ClinVar variants: 4
• Clinical trials: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cerebral arterial disease
Mondo ID	MONDO:0006693
EFO	EFO:1000859
MeSH	D002539
DOID	DOID:3527
UMLS	C0007774
MedGen	2963
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › cerebrovascular disorder › intracranial arterial disease › cerebral arterial disease

Subtypes (4): brain aneurysm, middle cerebral artery infarction, posterior cerebral artery infarction, Moyamoya disease

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

4 retrieved; paginated sample, class counts are floors:

2 uncertain significance, 1 likely pathogenic, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
419978	NM_000435.3(NOTCH3):c.3182G>A (p.Cys1061Tyr)	NOTCH3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1910224	NM_002775.5(HTRA1):c.497G>A (p.Arg166His)	HTRA1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4075136	NM_001288705.3(CSF1R):c.2309C>T (p.Ala770Val)	CSF1R	Uncertain significance	criteria provided, single submitter
4075142	NM_000435.3(NOTCH3):c.5769A>C (p.Glu1923Asp)	NOTCH3	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 9 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSF1R	Orphanet:313808	Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
CSF1R	Orphanet:556985	Early-onset calcifying leukoencephalopathy-skeletal dysplasia
NOTCH3	Orphanet:136	Cerebral autosomal dominant arteriopathy-subcortical infarcts-leukoencephalopathy
NOTCH3	Orphanet:2591	Infantile myofibromatosis
NOTCH3	Orphanet:2789	Lateral meningocele syndrome
HTRA1	Orphanet:199354	Cerebral autosomal recessive arteriopathy-subcortical infarcts-leukoencephalopathy
HTRA1	Orphanet:252128	Malignant peripheral nerve sheath tumor with perineurial differentiation
HTRA1	Orphanet:252212	Malignant triton tumor
HTRA1	Orphanet:482077	HTRA1-related autosomal dominant cerebral small vessel disease

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CSF1R	HGNC:2433	ENSG00000182578	P07333	Macrophage colony-stimulating factor 1 receptor	clinvar
NOTCH3	HGNC:7883	ENSG00000074181	Q9UM47	Neurogenic locus notch homolog protein 3	clinvar
HTRA1	HGNC:9476	ENSG00000166033	Q92743	Serine protease HTRA1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF1R	Macrophage colony-stimulating factor 1 receptor	Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes…
NOTCH3	Neurogenic locus notch homolog protein 3	Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination.
HTRA1	Serine protease HTRA1	Serine protease with a variety of targets, including extracellular matrix proteins such as fibronectin.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.67

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	12.2×	0.157
Kinase	1	9.2×	0.157
Scaffold/PPI	1	5.8×	0.164

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSF1R	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS
NOTCH3	Scaffold/PPI	no		EGF-type_Asp/Asn_hydroxyl_site, EGF, Notch_dom
HTRA1	Protease	yes	3.4.21.107	IGFBP-like, PDZ, Peptidase_S1C

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1
popliteal artery	1
right coronary artery	1
tibial artery	1
metanephric glomerulus	1
renal glomerulus	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF1R	245	broad	marker	granulocyte, monocyte, leukocyte
NOTCH3	273	ubiquitous	marker	popliteal artery, tibial artery, right coronary artery
HTRA1	287	ubiquitous	marker	tendon of biceps brachii, renal glomerulus, metanephric glomerulus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NOTCH3	4,403
CSF1R	4,392
HTRA1	2,843

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSF1R	P07333	26
HTRA1	Q92743	18
NOTCH3	Q9UM47	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective LFNG causes SCDO3	1	761.3×	0.008	NOTCH3
Pre-NOTCH Processing in the Endoplasmic Reticulum	1	634.4×	0.008	NOTCH3
Noncanonical activation of NOTCH3	1	475.8×	0.008	NOTCH3
Pre-NOTCH Processing in Golgi	1	211.5×	0.011	NOTCH3
Other interleukin signaling	1	158.6×	0.011	CSF1R
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	158.6×	0.011	NOTCH3
NOTCH3 Intracellular Domain Regulates Transcription	1	146.4×	0.011	NOTCH3
Notch-HLH transcription pathway	1	135.9×	0.011	NOTCH3
Signaling by CSF1 (M-CSF) in myeloid cells	1	115.3×	0.012	CSF1R
Transcriptional Regulation by VENTX	1	88.5×	0.014	CSF1R
Pre-NOTCH Transcription and Translation	1	40.9×	0.025	NOTCH3
Degradation of the extracellular matrix	1	39.2×	0.025	HTRA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
forebrain neuron differentiation	1	1872.4×	0.008	CSF1R
macrophage colony-stimulating factor signaling pathway	1	1872.4×	0.008	CSF1R
glomerular capillary formation	1	1872.4×	0.008	NOTCH3
regulation of macrophage migration	1	1404.3×	0.008	CSF1R
cellular response to macrophage colony-stimulating factor stimulus	1	1123.5×	0.008	CSF1R
positive regulation of macrophage proliferation	1	1123.5×	0.008	CSF1R
chorionic trophoblast cell differentiation	1	936.2×	0.008	HTRA1
mammary gland duct morphogenesis	1	802.5×	0.008	CSF1R
neuroblast differentiation	1	702.2×	0.008	NOTCH3
positive regulation of protein tyrosine kinase activity	1	702.2×	0.008	CSF1R
cell-cell junction maintenance	1	624.1×	0.008	CSF1R
microglial cell proliferation	1	624.1×	0.008	CSF1R
axon guidance	2	60.4×	0.008	CSF1R, NOTCH3
regulation of bone resorption	1	510.7×	0.008	CSF1R
host-mediated activation of viral process	1	468.1×	0.008	CSF1R
programmed cell death	1	432.1×	0.008	HTRA1
ruffle organization	1	432.1×	0.008	CSF1R
positive regulation of macrophage chemotaxis	1	267.5×	0.011	CSF1R
monocyte differentiation	1	267.5×	0.011	CSF1R
neuron fate commitment	1	267.5×	0.011	NOTCH3
olfactory bulb development	1	255.3×	0.011	CSF1R
positive regulation of cell motility	1	255.3×	0.011	CSF1R
positive regulation of tyrosine phosphorylation of STAT protein	1	244.2×	0.011	CSF1R
artery morphogenesis	1	224.7×	0.011	NOTCH3
cellular response to cytokine stimulus	1	181.2×	0.013	CSF1R
macrophage differentiation	1	156.0×	0.015	CSF1R
regulation of MAPK cascade	1	151.8×	0.015	CSF1R
placenta development	1	147.8×	0.015	HTRA1
peptidyl-tyrosine phosphorylation	1	140.4×	0.015	CSF1R
positive regulation of chemokine production	1	124.8×	0.016	CSF1R

Therapeutics

Drugs indicated for this disease

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

Drug	Development status
Esmolol	Phase 3 (in late-stage trials)
Propofol	Phase 3 (in late-stage trials)
Sevoflurane	Phase 3 (in late-stage trials)

Drug target analysis

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

Druggability breadth: 3 of 3 evidence-associated genes (100%) 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
CSF1R	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSF1R	79	4
NOTCH3	1	2
HTRA1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	CSF1R
FEDRATINIB	4	CSF1R
AXITINIB	4	CSF1R
SORAFENIB	4	CSF1R
DASATINIB ANHYDROUS	4	CSF1R
SUNITINIB MALATE	4	CSF1R
NERATINIB	4	CSF1R
IBRUTINIB	4	CSF1R
ENTRECTINIB	4	CSF1R
PACRITINIB	4	CSF1R
VANDETANIB	4	CSF1R
NILOTINIB	4	CSF1R
BOSUTINIB	4	CSF1R
FILGOTINIB	4	CSF1R
BRIGATINIB	4	CSF1R
PEXIDARTINIB	4	CSF1R
PAZOPANIB	4	CSF1R
NINTEDANIB	4	CSF1R
SUNITINIB	4	CSF1R
DASATINIB	4	CSF1R
QUIZARTINIB	4	CSF1R
CRIZOTINIB	4	CSF1R
MIDOSTAURIN	4	CSF1R
IMATINIB	4	CSF1R
VATALANIB	3	CSF1R
DACTOLISIB	3	CSF1R
MASITINIB	3	CSF1R
LINIFANIB	3	CSF1R
SEMAXANIB	3	CSF1R
BRIVANIB	3	CSF1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
CSF1R	897	Binding:879, Functional:17, ADMET:1
HTRA1	28	Binding:28
NOTCH3	3	Binding:3

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CSF1R	2.7.10.1	receptor protein-tyrosine kinase
HTRA1	3.4.21.107, 3.4.21.108	peptidase Do, HtrA2 peptidase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CSF1R	897

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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)
PONATINIB	4	CSF1R
FEDRATINIB	4	CSF1R
AXITINIB	4	CSF1R
SORAFENIB	4	CSF1R
DASATINIB ANHYDROUS	4	CSF1R
SUNITINIB MALATE	4	CSF1R
NERATINIB	4	CSF1R
IBRUTINIB	4	CSF1R
ENTRECTINIB	4	CSF1R
PACRITINIB	4	CSF1R
VANDETANIB	4	CSF1R
NILOTINIB	4	CSF1R
BOSUTINIB	4	CSF1R
FILGOTINIB	4	CSF1R
BRIGATINIB	4	CSF1R
PEXIDARTINIB	4	CSF1R
PAZOPANIB	4	CSF1R
NINTEDANIB	4	CSF1R
SUNITINIB	4	CSF1R
DASATINIB	4	CSF1R
QUIZARTINIB	4	CSF1R
CRIZOTINIB	4	CSF1R
MIDOSTAURIN	4	CSF1R
IMATINIB	4	CSF1R
VATALANIB	3	CSF1R
DACTOLISIB	3	CSF1R
MASITINIB	3	CSF1R
LINIFANIB	3	CSF1R
SEMAXANIB	3	CSF1R
BRIVANIB	3	CSF1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CSF1R
B	Phased (≥1) drug, not yet approved	1	NOTCH3
C	Druggable family + PDB, no drug	1	HTRA1
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)
HTRA1	28	—

Clinical trials & evidence

Clinical trials

Clinical trials: 14.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	10
PHASE3	3
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01010932	PHASE3	COMPLETED	Carotid and Vertebral Magnetic Resonance Angiography (MRA) Study Comparing Dotarem and Time Of Flight (TOF)
NCT01012674	PHASE3	COMPLETED	Carotid and Vertebral Magnetic Resonance Angiography (MRA) Study Comparing Dotarem and Time Of Flight (TOF)
NCT02455440	PHASE3	COMPLETED	Esmolol Infusion in Patients Undergoing Craniotomy
NCT04265053	EARLY_PHASE1	COMPLETED	Human Cerebral Blood Flow Regulation
NCT04927156	Not specified	RECRUITING	Safety, Performance and Usability of BALT Medical Devices: The EVIDENCE Post Marketing Clinical Follow-up Platform
NCT06052969	Not specified	RECRUITING	Pulse Endovascular ReperFUSION for Acute Ischemic Stroke
NCT06494358	Not specified	RECRUITING	Liquid Biopsies for the Detection of Somatic Mutations in bAVMs
NCT06980064	Not specified	NOT_YET_RECRUITING	Wearable Devices Assist in the Detection, Screening, and Management of Major Diseases in Middle-aged and Elderly Populations
NCT07126821	Not specified	RECRUITING	A Vision-Language Foundation Model for Brain Disease Diagnosis From Multimodal Data
NCT00512447	Not specified	COMPLETED	Normal Values of Brain Oxygenation
NCT02914288	Not specified	UNKNOWN	Prospective Observation for Serial Changes of Acute Intracranial Artery Dissection Using High Resolution MRI
NCT03632564	Not specified	UNKNOWN	Modulation of Brain Blood Flow Using Dichoptic Visual and Auditory Stimulation
NCT04364074	Not specified	COMPLETED	Acute Probiotic Supplementation and Endothelial Function
NCT06067113	Not specified	UNKNOWN	Hemodynamic and Functional Characteristics of the Cerebral Circulation in Obesity

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
GADOTERATE MEGLUMINE	4	2
ESMOLOL	4	1
GANIRELIX ACETATE	4	1
INDOMETHACIN	4	1
SEVOFLURANE	4	1