Cervical artery dissection

Summary

Cervical artery dissection (MONDO:0006061) is a disease with 5 cohort genes (16 GWAS associations across 3 studies) and 6 clinical trials. Top therapeutic interventions include aspirin and dipyridamole.

At a glance

• Cohort genes: 5
• GWAS associations: 16
• Clinical trials: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cervical artery dissection
Mondo ID	MONDO:0006061
EFO	EFO:1000059
UMLS	C5396999
MedGen	1709179
Anatomy (UBERON)	UBERON:0012320
Is cancer (heuristic)	no

Data availability: 16 GWAS associations (3 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 › cervical artery dissection

Related subtypes (29): vertebral artery insufficiency, splenic artery aneurysm, basilar artery insufficiency, arteriosclerosis disorder, 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, 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 (2): familial cervical artery dissection, vertebral artery dissection

Genetics & variants

GWAS landscape

16 GWAS associations across 3 studies. Top hits map to 10 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11172113	9e-42	LRP1	?	0.33
rs9349379	2e-25	PHACTR1	?	0.25
rs9486725	1e-23	FHL5	?	0.25
rs2971603	9e-22	FHL5	?	0.27
rs7940646	1e-11	IRAG1	?	0.17
rs11187838	2e-11	PLCE1, PLCE1-AS1	?	0.16
rs57866767	5e-11	PLCE1	?	0.16
rs6693567	3e-09	FALEC - ADAMTSL4-AS2	?	0.16
rs6820391	2e-08	LNX1, LNX1-AS1	A	1.24
rs12402265	2e-07	JUN-DT, FGGY-DT	A	1.23
rs6741522	2e-06	ZNF804A - ELF2P4	A	1.26

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90103794	Daghals I	2022	59,674	330,494	Migraine, Stroke, and Cervical Arterial Dissection: Shared Genetics for a Triad of Brain Disorders With Vascular Involvement.
GCST90269767	Daghals I	2022	8,348	154,038	Migraine, Stroke, and Cervical Arterial Dissection: Shared Genetics for a Triad of Brain Disorders With Vascular Involvement.
GCST002700	Debette S	2014	1,393	14,416	Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	10

MAF distribution

Bucket	Variants
common (>=0.05)	11
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	8
non_coding_transcript_exon_variant	1
regulatory_region_variant	1
intergenic_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11172113	12	57133500	T>C,G	0.05	intron_variant	LRP1	9e-42	Tier 4: intronic/intergenic
rs9349379	6	12903725	A>C,G,T	0.05	intron_variant	PHACTR1	2e-25	Tier 4: intronic/intergenic
rs9486725	6	96613283	C>G,T	0.05	intron_variant	FHL5	1e-23	Tier 4: intronic/intergenic
rs2971603	6	96587542	C>G,T	0.05	intron_variant	FHL5	9e-22	Tier 4: intronic/intergenic
rs7940646	11	10647681	T>A,C,G	0.05	intron_variant	IRAG1	1e-11	Tier 4: intronic/intergenic
rs11187838	10	94278929	G>A,C,T	0.05	non_coding_transcript_exon_variant	PLCE1, PLCE1-AS1	2e-11	Tier 4: intronic/intergenic
rs57866767	10	94263320	T>C,G	0.05	intron_variant	PLCE1	5e-11	Tier 4: intronic/intergenic
rs6693567	1	150538184	C>T	0.05	regulatory_region_variant	FALEC - ADAMTSL4-AS2	3e-09	Tier 3: regulatory
rs6820391	4	53548529	C>A	0.29	intron_variant	LNX1, LNX1-AS1	2e-08	Tier 4: intronic/intergenic
rs12402265	1	59224930	G>A	0.27	intron_variant	JUN-DT, FGGY-DT	2e-07	Tier 4: intronic/intergenic
rs6741522	2	184971171	G>A	0.13	intergenic_variant	ZNF804A - ELF2P4	2e-06	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
PHACTR1	Orphanet:697160	Infantile epileptic spasms syndrome
LRP1	Orphanet:2340	Keratosis follicularis spinulosa decalvans
LRP1	Orphanet:79100	Atrophoderma vermiculata

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PHACTR1	HGNC:20990	ENSG00000112137	Q9C0D0	Phosphatase and actin regulator 1	gwas
ZNF804A	HGNC:21711	ENSG00000170396	Q7Z570	Zinc finger protein 804A	gwas
FGGY	HGNC:25610	ENSG00000172456	Q96C11	FGGY carbohydrate kinase domain-containing protein	gwas
LNX1	HGNC:6657	ENSG00000072201	Q8TBB1	E3 ubiquitin-protein ligase LNX	gwas
LRP1	HGNC:6692	ENSG00000123384	Q07954	Prolow-density lipoprotein receptor-related protein 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PHACTR1	Phosphatase and actin regulator 1	Binds actin monomers (G actin) and plays a role in multiple processes including the regulation of actin cytoskeleton dynamics, actin stress fibers formation, cell motility and survival, formation of tubules by endothelial cells, and regula…
FGGY	FGGY carbohydrate kinase domain-containing protein	Catalyzes ATP-dependent phosphorylation of D-ribulose at C-5 to form D-ribulose 5-phosphate.
LNX1	E3 ubiquitin-protein ligase LNX	E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB.
LRP1	Prolow-density lipoprotein receptor-related protein 1	Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells.

Protein-family classification

Druggable: 1 · Difficult: 2 · Unknown: 2 · Druggable fraction: 0.2

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
Kinase	1	5.5×	0.252
Transcription factor	2	3.3×	0.252
Other/Unknown	2	0.7×	0.877

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PHACTR1	Other/Unknown	no		RPEL_repeat
ZNF804A	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF804A-like/GPATCH8
FGGY	Kinase	yes	2.7.1.47	Carb_kinase_FGGY, FGGY_RbtK-like, FGGY_N
LNX1	Transcription factor	no		PDZ, Znf_RING, Znf_RING/FYVE/PHD
LRP1	Other/Unknown	no		LDLR_classB_rpt, EGF-type_Asp/Asn_hydroxyl_site, EGF

Expression context

Cohort genes with no expression data: 0.

5 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
nucleus accumbens	1
postcentral gyrus	1
Brodmann (1909) area 10	1
Brodmann (1909) area 23	1
ganglionic eminence	1
gastrocnemius	1
hindlimb stylopod muscle	1
right lobe of liver	1
esophagus squamous epithelium	1
middle temporal gyrus	1
parotid gland	1
ascending aorta	1
descending thoracic aorta	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PHACTR1	210	ubiquitous	marker	cortical plate, postcentral gyrus, nucleus accumbens
ZNF804A	144	broad	marker	ganglionic eminence, Brodmann (1909) area 10, Brodmann (1909) area 23
FGGY	213	ubiquitous	marker	right lobe of liver, hindlimb stylopod muscle, gastrocnemius
LNX1	256	broad	marker	esophagus squamous epithelium, middle temporal gyrus, parotid gland
LRP1	293	ubiquitous	marker	stromal cell of endometrium, descending thoracic aorta, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LNX1	5,295
LRP1	2,662
FGGY	2,121
PHACTR1	986
ZNF804A	967

Structural data

PDB: 3 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LRP1	Q07954	7
PHACTR1	Q9C0D0	6
LNX1	Q8TBB1	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FGGY	Q96C11	96.13
ZNF804A	Q7Z570	45.51

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 5 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Scavenging of heme from plasma	1	439.2×	0.021	LRP1
Binding and Uptake of Ligands by Scavenger Receptors	1	271.9×	0.021	LRP1
Metabolism of fat-soluble vitamins	1	190.3×	0.021	LRP1
Visual phototransduction	1	129.8×	0.021	LRP1
Retinoid metabolism and transport	1	124.1×	0.021	LRP1
Metabolism of vitamins and cofactors	1	58.3×	0.037	LRP1
Sensory Perception	1	47.6×	0.039	LRP1
Class I MHC mediated antigen processing & presentation	1	35.0×	0.046	LNX1
Antigen processing: Ubiquitination & Proteasome degradation	1	18.6×	0.074	LNX1
Vesicle-mediated transport	1	17.4×	0.074	LRP1
Adaptive Immune System	1	14.9×	0.078	LNX1
Immune System	1	6.5×	0.161	LNX1
Metabolism	1	5.8×	0.165	LRP1

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of transcytosis	1	3370.4×	0.007	LRP1
pentose metabolic process	1	1685.2×	0.007	FGGY
positive regulation of lipid transport	1	1685.2×	0.007	LRP1
positive regulation of reverse cholesterol transport	1	1685.2×	0.007	LRP1
astrocyte activation involved in immune response	1	842.6×	0.008	LRP1
negative regulation of platelet-derived growth factor receptor-beta signaling pathway	1	842.6×	0.008	LRP1
regulation of extracellular matrix disassembly	1	674.1×	0.008	LRP1
positive regulation of dendritic spine maintenance	1	674.1×	0.008	ZNF804A
positive regulation of lysosomal protein catabolic process	1	674.1×	0.008	LRP1
amyloid-beta clearance by transcytosis	1	481.5×	0.009	LRP1
carbohydrate phosphorylation	1	421.3×	0.009	FGGY
amyloid-beta clearance by cellular catabolic process	1	421.3×	0.009	LRP1
positive regulation of amyloid-beta clearance	1	421.3×	0.009	LRP1
dendrite arborization	1	374.5×	0.009	PHACTR1
regulation of extracellular matrix organization	1	374.5×	0.009	LRP1
transcytosis	1	337.0×	0.009	LRP1
negative regulation of smooth muscle cell migration	1	306.4×	0.010	LRP1
enzyme-linked receptor protein signaling pathway	1	259.3×	0.011	LRP1
lipoprotein transport	1	198.3×	0.012	LRP1
synapse maturation	1	187.2×	0.012	LNX1
amyloid-beta clearance	1	187.2×	0.012	LRP1
aorta morphogenesis	1	177.4×	0.012	LRP1
apoptotic cell clearance	1	177.4×	0.012	LRP1
positive regulation of endocytosis	1	160.5×	0.013	LRP1
stress fiber assembly	1	153.2×	0.013	PHACTR1
lysosomal transport	1	140.4×	0.014	LRP1
positive regulation of cholesterol efflux	1	124.8×	0.014	LRP1
regulation of neuron migration	1	124.8×	0.014	PHACTR1
negative regulation of SMAD protein signal transduction	1	120.4×	0.014	LRP1
actomyosin structure organization	1	112.3×	0.015	PHACTR1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PHACTR1	0	0
ZNF804A	0	0
FGGY	0	0
LNX1	0	0
LRP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
FGGY	2.7.1.47	D-ribulokinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	1	FGGY
E	Difficult family or no structure, no drug	4	PHACTR1, ZNF804A, LNX1, LRP1

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)
PHACTR1	0	—
ZNF804A	0	—
FGGY	0	—
LNX1	0	—
LRP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 6.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	4
PHASE3	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00238667	PHASE3	COMPLETED	To Determine the Feasibility of a Clinical Trial Comparing Anticoagulants Versus Antiplatelets in the Acute Treatment of Patients With Cervical Artery Dissection
NCT02046460	PHASE3	COMPLETED	Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection - TREAT-CAD
NCT01967511	Not specified	RECRUITING	Defining the Basis of Fibromuscular Dysplasia (FMD)
NCT06258109	Not specified	RECRUITING	Risk of Recurrent CeAD After Pregnancy
NCT00657969	Not specified	UNKNOWN	Looking For Genetic and Environmental Risk Factors and Therapeutic Aspects in Cervical Artery Dissections
NCT04253535	Not specified	COMPLETED	Risk of Recurrence of Cervical Artery Dissection During Pregnancy and Puerperium

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ASPIRIN	4	1
DIPYRIDAMOLE	4	1