Idiopathic spontaneous coronary artery dissection

Summary

Idiopathic spontaneous coronary artery dissection (MONDO:0007385) is a disease with 3 cohort genes.

At a glance

• Prevalence: Unknown (Europe)
• Cohort genes: 3
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	idiopathic spontaneous coronary artery dissection
Mondo ID	MONDO:0007385
MeSH	C565153
OMIM	122455
Orphanet	458718
UMLS	C1852540
MedGen	377701
GARD	0010822
Is cancer (heuristic)	no

Also known as: idiopathic SCAD

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records · 15 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › vascular disorder › idiopathic spontaneous coronary artery dissection

Related subtypes (59): arterial disorder, ischemic colitis, thrombotic disease, capillary disorder, angiodysplasia, hepatic vascular disorder, vascular hemostatic disease, vein disorder, ischemic disease, peripheral vascular disease, venous thromboembolism, ocular vascular disorder, cholesterol embolism, thoracic outlet syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, angioosteohypertrophic syndrome, Bannayan-Riley-Ruvalcaba syndrome, arterial tortuosity syndrome, hereditary arterial and articular multiple calcification syndrome, pulmonary venoocclusive disease, multiple cutaneous and mucosal venous malformations, arterial dissection-lentiginosis syndrome, patent ductus arteriosus, multisystemic smooth muscle dysfunction syndrome, STING-associated vasculopathy with onset in infancy, capillary malformation, Ehlers-Danlos syndrome, vascular-like type, calciphylaxis, neonatal Marfan syndrome, Ehlers-Danlos syndrome, vascular type, lethal arteriopathy syndrome due to fibulin-4 deficiency, congenital portosystemic shunt, arterial calcification of infancy, vasculitis, Loeys-Dietz syndrome, skin vascular disease, lymphatic malformation, familial thoracic aortic aneurysm and aortic dissection, congenital anomaly of superior vena cava, congenital anomaly of the inferior vena cava, congenital anomaly of hepatic vein, congenital renal artery stenosis, internal carotid agenesis, coronary sinus stenosis, coronary sinus atresia, vascular occlusion disorder, vascular insufficiency disorder, blood vessel neoplasm, vascular ectasia, vascular disorder of penis, fibrocartilaginous embolism, vascular malformation, lymphatic vessel neoplasm, neurovascular disorder, superior vena cava syndrome, coronary microvascular disorder, segmental arterial mediolysis, bleeding disorder, vascular-type, arterial tortuosity-bone fragility syndrome

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
213800	NM_005902.4(SMAD3):c.278G>A (p.Arg93Gln)	SMAD3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
TLN1	Moderate	Autosomal dominant	idiopathic spontaneous coronary artery dissection	2
TSR1	Limited	Autosomal dominant	idiopathic spontaneous coronary artery dissection

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SMAD3	Orphanet:284984	Aneurysm-osteoarthritis syndrome
SMAD3	Orphanet:60030	Loeys-Dietz syndrome
SMAD3	Orphanet:91387	Familial thoracic aortic aneurysm and aortic dissection

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
TLN1	HGNC:11845	ENSG00000137076	Q9Y490	Talin-1	gencc
TSR1	HGNC:25542	ENSG00000167721	Q2NL82	Pre-rRNA-processing protein TSR1 homolog	gencc
SMAD3	HGNC:6769	ENSG00000166949	P84022	SMAD family member 3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TLN1	Talin-1	High molecular weight cytoskeletal protein concentrated at regions of cell-matrix and cell-cell contacts.
TSR1	Pre-rRNA-processing protein TSR1 homolog	Required during maturation of the 40S ribosomal subunit in the nucleolus.
SMAD3	SMAD family member 3	Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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
Other/Unknown	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TLN1	Other/Unknown	no		FERM_domain, IRS_PTB, ILWEQ_dom
TSR1	Other/Unknown	no		BMS1_TSR1_C, AARP2CN, G_Bms1/Tsr1_dom
SMAD3	Other/Unknown	no		SMAD_dom, MAD_homology1_Dwarfin-type, SMAD_FHA_dom_sf

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
ascending aorta	1
popliteal artery	1
tibial artery	1
cervix squamous epithelium	1
mucosa of paranasal sinus	1
nipple	1
cartilage tissue	1
hindlimb stylopod muscle	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TLN1	269	ubiquitous	marker	popliteal artery, tibial artery, ascending aorta
TSR1	300	ubiquitous	marker	cervix squamous epithelium, nipple, mucosa of paranasal sinus
SMAD3	288	ubiquitous	marker	tendon of biceps brachii, cartilage tissue, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMAD3	6,440
TLN1	3,215
TSR1	3,130

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TSR1	Q2NL82	17
SMAD3	P84022	12
TLN1	Q9Y490	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 70. 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
Loss of Function of SMAD4 in Cancer	1	1268.9×	0.012	SMAD3
SMAD4 MH2 Domain Mutants in Cancer	1	1268.9×	0.012	SMAD3
SMAD2/3 MH2 Domain Mutants in Cancer	1	1268.9×	0.012	SMAD3
Loss of Function of TGFBR1 in Cancer	1	761.3×	0.012	SMAD3
RUNX3 regulates BCL2L11 (BIM) transcription	1	761.3×	0.012	SMAD3
Loss of Function of SMAD2/3 in Cancer	1	634.4×	0.012	SMAD3
Signaling by TGF-beta Receptor Complex in Cancer	1	634.4×	0.012	SMAD3
SMAD2/3 Phosphorylation Motif Mutants in Cancer	1	634.4×	0.012	SMAD3
TGFBR1 KD Mutants in Cancer	1	634.4×	0.012	SMAD3
RUNX3 regulates CDKN1A transcription	1	543.8×	0.013	SMAD3
Formation of axial mesoderm	1	271.9×	0.016	SMAD3
Signaling by Activin	1	253.8×	0.016	SMAD3
p130Cas linkage to MAPK signaling for integrins	1	253.8×	0.016	TLN1
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion	1	253.8×	0.016	TLN1
GRB2:SOS provides linkage to MAPK signaling for Integrins	1	237.9×	0.016	TLN1
Formation of definitive endoderm	1	237.9×	0.016	SMAD3
FOXO-mediated transcription of cell cycle genes	1	223.9×	0.016	SMAD3
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	1	223.9×	0.016	SMAD3
Germ layer formation at gastrulation	1	223.9×	0.016	SMAD3
NOTCH4 Intracellular Domain Regulates Transcription	1	190.3×	0.018	SMAD3
Interleukin-37 signaling	1	173.0×	0.018	SMAD3
Signaling by NODAL	1	165.5×	0.018	SMAD3
Signaling by NOTCH4	1	165.5×	0.018	SMAD3
TGFBR3 expression	1	152.3×	0.019	SMAD3
Integrin signaling	1	141.0×	0.019	TLN1
Downregulation of TGF-beta receptor signaling	1	135.9×	0.019	SMAD3
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	126.9×	0.019	SMAD3
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	122.8×	0.019	SMAD3
Downregulation of SMAD2/3:SMAD4 transcriptional activity	1	122.8×	0.019	SMAD3
Signaling by TGFBR3	1	122.8×	0.019	SMAD3

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
negative regulation of lung blood pressure	1	5617.3×	0.009	SMAD3
regulation of miRNA transcription	1	5617.3×	0.009	SMAD3
positive regulation of transforming growth factor beta3 production	1	2808.7×	0.010	SMAD3
paraxial mesoderm morphogenesis	1	1872.4×	0.010	SMAD3
endonucleolytic cleavage of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	1404.3×	0.010	TSR1
immune system development	1	1404.3×	0.010	SMAD3
regulation of transforming growth factor beta2 production	1	1404.3×	0.010	SMAD3
cell-substrate junction assembly	1	936.2×	0.010	TLN1
regulation of striated muscle tissue development	1	936.2×	0.010	SMAD3
trophoblast cell migration	1	802.5×	0.010	SMAD3
transdifferentiation	1	702.2×	0.010	SMAD3
cortical microtubule organization	1	624.1×	0.010	TLN1
pericardium development	1	624.1×	0.010	SMAD3
positive regulation of extracellular matrix assembly	1	624.1×	0.010	SMAD3
negative regulation of cardiac muscle hypertrophy in response to stress	1	624.1×	0.010	SMAD3
response to angiotensin	1	624.1×	0.010	SMAD3
embryonic foregut morphogenesis	1	561.7×	0.010	SMAD3
negative regulation of osteoblast proliferation	1	510.7×	0.010	SMAD3
response to alcohol	1	510.7×	0.010	SMAD3
integrin activation	1	468.1×	0.010	TLN1
positive regulation of positive chemotaxis	1	468.1×	0.010	SMAD3
primary miRNA processing	1	432.1×	0.010	SMAD3
negative regulation of cytosolic calcium ion concentration	1	432.1×	0.010	SMAD3
negative regulation of wound healing	1	432.1×	0.010	SMAD3
nodal signaling pathway	1	374.5×	0.011	SMAD3
lens fiber cell differentiation	1	351.1×	0.011	SMAD3
osteoblast development	1	330.4×	0.011	SMAD3
regulation of epithelial cell proliferation	1	312.1×	0.011	SMAD3
activin receptor signaling pathway	1	295.6×	0.011	SMAD3
regulation of dendritic spine morphogenesis	1	280.9×	0.011	SMAD3

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 3 evidence-associated genes (67%) 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
SMAD3	FLUORESCEIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SMAD3	2	4
TLN1	0	0
TSR1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FLUORESCEIN	4	SMAD3
ELLAGIC ACID	2	SMAD3

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
SMAD3	24	Binding:18, Functional:6
TLN1	1	Binding:1

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

2 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)
FLUORESCEIN	4	SMAD3
ELLAGIC ACID	2	SMAD3

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	SMAD3
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	2	TLN1, TSR1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TLN1	1	—
TSR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.