autosomal dominant Ehlers-Danlos syndrome, vascular type

Summary

autosomal dominant Ehlers-Danlos syndrome, vascular type (MONDO:0007524) is a disease caused by COL3A1 (GenCC Definitive), with 1 cohort gene and 4 clinical trials. Top therapeutic interventions include celiprolol and irbesartan.

At a glance

• Causal gene: COL3A1 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 4
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant Ehlers-Danlos syndrome, vascular type
Mondo ID	MONDO:0007524
OMIM	130050
DOID	DOID:14756
UMLS	C0268339
MedGen	541286
GARD	0024560
Is cancer (heuristic)	no

Also known as: autosomal dominant Ehlers-Danlos syndrome, vascular type · EDS 4 · EDSVASC · Ehlers-Danlos syndrome, type IV, autosomal dominant · Ehlers-Danlos syndrome, vascular type · Ehlers-Danlos syndrome, vascular type, autosomal dominant

Data availability: 4 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal dominant disease › autosomal dominant Ehlers-Danlos syndrome, vascular type

Related subtypes (191): autosomal dominant polycystic liver disease, cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 1, tuberous sclerosis, Treacher-Collins syndrome, hereditary breast ovarian cancer syndrome, autosomal dominant polycystic kidney disease, Lynch syndrome, branchio-oto-renal syndrome, autosomal dominant Aarskog syndrome, acroosteolysis dominant type, ADULT syndrome, autosomal dominant Alport syndrome, amelogenesis imperfecta type 1B, Townes-Brocks syndrome, nevoid basal cell carcinoma syndrome, blepharophimosis, ptosis, and epicanthus inversus syndrome, autosomal dominant brachyolmia, branchiooculofacial syndrome, pheochromocytoma/paraganglioma syndrome 4, cataract-aberrant oral frenula-growth delay syndrome, cherubism, autosomal dominant chondrodysplasia punctata, autosomal dominant popliteal pterygium syndrome, blepharocheilodontic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Beare-Stevenson cutis gyrata syndrome, autosomal dominant vibratory urticaria, neurohypophyseal diabetes insipidus, autosomal dominant Kenny-Caffey syndrome, Rapp-Hodgkin syndrome, Ehlers-Danlos syndrome, classic type, multiple endocrine neoplasia type 1, Coffin-Siris syndrome 1, isolated congenital adermatoglyphia, Flynn-Aird syndrome, Frasier syndrome, hand-foot-genital syndrome, Holt-Oram syndrome, hyperkeratosis-hyperpigmentation syndrome, autosomal dominant ichthyosis vulgaris, hyper-IgE recurrent infection syndrome 1, autosomal dominant, autosomal dominant keratitis, autosomal dominant keratitis-ichthyosis-hearing loss syndrome, LADD syndrome, trichorhinophalangeal syndrome type II, Noonan syndrome with multiple lentigines, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, Marfan syndrome, melanoma, cutaneous malignant, susceptibility to, 2, autosomal dominant primary microcephaly, autosomal dominant progressive external ophthalmoplegia, monilethrix, Muir-Torre syndrome, autosomal dominant myoglobinuria, autosomal dominant centronuclear myopathy, nail-patella syndrome, multiple endocrine neoplasia type 2B, autosomal dominant omodysplasia, pheochromocytoma/paraganglioma syndrome 1, Pelger-Huet anomaly, multiple endocrine neoplasia type 2A, piebaldism, autosomal dominant medullary cystic kidney disease with or without hyperuricemia, generalized juvenile polyposis/juvenile polyposis coli, juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Peutz-Jeghers syndrome, contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A, autosomal dominant distal renal tubular acidosis, retinoschisis, autosomal dominant, autosomal dominant Robinow syndrome, scapuloperoneal spinal muscular atrophy, autosomal dominant, autosomal dominant sideroblastic anemia, spondyloepiphyseal dysplasia tarda, autosomal dominant, proximal symphalangism, calcaneonavicular coalition, thanatophoric dysplasia type 1, trichorhinophalangeal syndrome type I, Muckle-Wells syndrome, autosomal dominant hypophosphatemic rickets, von Hippel-Lindau disease, Denys-Drash syndrome, autosomal dominant severe congenital neutropenia, Costello syndrome, EEC syndrome, multiple cutaneous and mucosal venous malformations, diffuse nonepidermolytic palmoplantar keratoderma, Timothy syndrome, pheochromocytoma/paraganglioma syndrome 2, spondyloepimetaphyseal dysplasia with multiple dislocations, Brooke-Spiegler syndrome, macrocephaly-autism syndrome, pheochromocytoma/paraganglioma syndrome 3, Duane-radial ray syndrome, PCWH syndrome, heart-hand syndrome, Slovenian type, congenital stationary night blindness autosomal dominant 3, mandibulofacial dysostosis-microcephaly syndrome, multiple endocrine neoplasia type 4, juvenile cataract-microcornea-renal glucosuria syndrome, Crouzon syndrome-acanthosis nigricans syndrome, Birk-Barel syndrome, thrombophilia due to protein S deficiency, autosomal dominant, dyskeratosis congenita, autosomal dominant 2, dyskeratosis congenita, autosomal dominant 3, colorectal cancer, hereditary nonpolyposis, type 6, colorectal cancer, hereditary nonpolyposis, type 7, brain small vessel disease 2A, autosomal dominant, intellectual disability, autosomal dominant 14, intellectual disability, autosomal dominant 15, intellectual disability, autosomal dominant 16, hypopigmentation-punctate palmoplantar keratoderma syndrome, intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, intellectual developmental disorder with microcephaly and with or without ocular malformations or hypogonadotropic hypogonadism, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, Houge-Janssens syndrome 2, severe achondroplasia-developmental delay-acanthosis nigricans syndrome, dyskeratosis congenita, autosomal dominant 6, epidermolysis bullosa simplex 6, generalized, with scarring and hair loss, autosomal dominant complex spastic paraplegia, early-onset autosomal dominant Alzheimer disease, muscular dystrophy, limb-girdle, autosomal dominant, Feingold syndrome, Carney complex, neuronopathy, distal hereditary motor, autosomal dominant, autosomal dominant coarctation of aorta, autosomal dominant spondylocostal dysostosis, autosomal dominant hypohidrotic ectodermal dysplasia, Cowden disease, autosomal dominant distal myopathy, autosomal dominant rhegmatogenous retinal detachment, palmoplantar keratoderma-spastic paralysis syndrome, Alagille syndrome due to a JAG1 point mutation, PTEN hamartoma tumor syndrome, gastric adenocarcinoma and proximal polyposis of the stomach, autosomal dominant proximal renal tubular acidosis, autosomal dominant spastic ataxia, Waardenburg syndrome, hereditary retinoblastoma, autosomal dominant hypocalcemia, Li-Fraumeni syndrome, Loeys-Dietz syndrome, hereditary hemorrhagic telangiectasia, hereditary inclusion body myopathy-joint contractures-ophthalmoplegia syndrome, microcephalic osteodysplastic dysplasia, Saul-Wilson type, autosomal dominant intermediate Charcot-Marie-Tooth disease, autosomal dominant cutis laxa, autosomal dominant nonsyndromic hearing loss, autosomal dominant optic atrophy, autosomal dominant Emery-Dreifuss muscular dystrophy, autosomal dominant cerebellar ataxia, autosomal dominant osteopetrosis, autosomal dominant epidermolytic ichthyosis, ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome, distal arthrogryposis type 2B1, neurofibromatosis, autosomal dominant cataract, arthrogryposis, distal, type 2B2, arthrogryposis, distal, type 2B3, Charcot-Marie-Tooth disease, demyelinating, type 1G, Delpire-McNeill syndrome, LAMA5-related multisystemic syndrome, autosomal dominant oculocutaneous albinism, Charcot-Marie-tooth disease, axonal, type 2DD, Pilarowski-Bjornsson syndrome, intellectual disability, autosomal dominant, fatty acyl-CoA reductase 1 upregulation, GUCY2D-related dominant retinopathy, RPE65-related dominant retinopathy, autosomal dominant titinopathy, NOG-related symphalangism spectrum disorder, ALPL-related autosomal dominant hypophosphatasia, MYH10-related neurodevelopmental disorder with congenital anomalies, spastic paraplegia 30A, autosomal dominant, TMEM127-related tumor predisposition, MAX-related tumor predisposition, BMPR1A-related juvenile polyposis syndrome, RP1-related dominant retinopathy, Birt-Hogg-Dube syndrome, inclusion body myopathy and brain white matter abnormalities, KINSSHIP syndrome, autosomal dominant nebulin-related myopathy, IMPG1-related dominant retinopathy, PROM1-related dominant retinopathy, PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome, ALG8-related autosomal dominant polycystic kidney and/or liver disease, NOTCH1-related AOS spectrum disorder, FLNB-associated autosomal dominant filamin related bone disorder, familial antiphospholipid 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

4 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
101449	NM_000090.4(COL3A1):c.2402G>A (p.Gly801Asp)	COL3A1	Pathogenic	criteria provided, single submitter
529320	NM_000090.4(COL3A1):c.3208G>T (p.Ala1070Ser)	COL3A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
924824	NM_000090.4(COL3A1):c.884C>T (p.Ala295Val)	COL3A1	Uncertain significance	criteria provided, multiple submitters, no conflicts
960219	NM_000090.4(COL3A1):c.3271C>A (p.Arg1091Ser)	COL3A1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 5 · 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
COL3A1	Definitive	Autosomal dominant	autosomal dominant Ehlers-Danlos syndrome, vascular type	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL3A1	Orphanet:231160	Familial cerebral saccular aneurysm
COL3A1	Orphanet:2500	Acrogeria
COL3A1	Orphanet:286	Vascular Ehlers-Danlos syndrome
COL3A1	Orphanet:636941	Vascular Ehlers-Danlos-polymicrogyria syndrome
COL3A1	Orphanet:86	Familial abdominal aortic aneurysm

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
COL3A1	HGNC:2201	ENSG00000168542	P02461	Collagen alpha-1(III) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL3A1	Collagen alpha-1(III) chain	Collagen type III occurs in most soft connective tissues along with type I collagen.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL3A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen

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
parietal pleura	1
skin of hip	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL3A1	281	ubiquitous	marker	skin of hip, parietal pleura, visceral pleura

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL3A1	3,629

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL3A1	P02461	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
Scavenging by Class A Receptors	1	601.0×	0.008	COL3A1
Fibronectin matrix formation	1	571.0×	0.008	COL3A1
Syndecan interactions	1	423.0×	0.008	COL3A1
MET activates PTK2 signaling	1	380.7×	0.008	COL3A1
Collagen chain trimerization	1	259.6×	0.008	COL3A1
Signaling by PDGF	1	253.8×	0.008	COL3A1
NCAM1 interactions	1	248.3×	0.008	COL3A1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	COL3A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.008	COL3A1
Collagen degradation	1	175.7×	0.008	COL3A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.008	COL3A1
Non-integrin membrane-ECM interactions	1	154.3×	0.008	COL3A1
ECM proteoglycans	1	150.3×	0.008	COL3A1
Integrin cell surface interactions	1	134.3×	0.008	COL3A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.011	COL3A1

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
transforming growth factor beta1 production	1	5617.3×	0.002	COL3A1
limb joint morphogenesis	1	5617.3×	0.002	COL3A1
endochondral bone morphogenesis	1	4213.0×	0.002	COL3A1
aorta smooth muscle tissue morphogenesis	1	4213.0×	0.002	COL3A1
response to angiotensin	1	1872.4×	0.003	COL3A1
elastic fiber assembly	1	1532.0×	0.003	COL3A1
peptide cross-linking	1	1404.3×	0.003	COL3A1
negative regulation of neuron migration	1	1404.3×	0.003	COL3A1
response to radiation	1	1203.7×	0.003	COL3A1
layer formation in cerebral cortex	1	1123.5×	0.003	COL3A1
negative regulation of immune response	1	1053.2×	0.003	COL3A1
supramolecular fiber organization	1	1053.2×	0.003	COL3A1
positive regulation of Rho protein signal transduction	1	581.1×	0.004	COL3A1
tissue homeostasis	1	561.7×	0.004	COL3A1
digestive tract development	1	526.6×	0.004	COL3A1
basement membrane organization	1	510.7×	0.004	COL3A1
skin development	1	443.5×	0.004	COL3A1
fibroblast proliferation	1	391.9×	0.005	COL3A1
response to cytokine	1	374.5×	0.005	COL3A1
cellular response to amino acid stimulus	1	306.4×	0.005	COL3A1
chondrocyte differentiation	1	300.9×	0.005	COL3A1
platelet activation	1	267.5×	0.006	COL3A1
wound healing	1	227.7×	0.006	COL3A1
collagen fibril organization	1	224.7×	0.006	COL3A1
cerebral cortex development	1	205.5×	0.006	COL3A1
lung development	1	198.3×	0.006	COL3A1
cell-matrix adhesion	1	163.6×	0.007	COL3A1
integrin-mediated signaling pathway	1	160.5×	0.007	COL3A1
transforming growth factor beta receptor signaling pathway	1	159.0×	0.007	COL3A1
multicellular organism growth	1	137.0×	0.008	COL3A1

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
COL3A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	COL3A1

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)
COL3A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE4	1
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00190411	PHASE4	COMPLETED	Celiprolol in Patients With Ehlers-Danlos Syndrome, Vascular Type
NCT02597361	PHASE3	COMPLETED	Angiotensin II Receptor Blockade in Vascular Ehlers Danlos Syndrome (ARCADE)
NCT05976841	Not specified	ACTIVE_NOT_RECRUITING	SEDVasc (RaDiCo Cohort) (RaDiCo-SEDVasc)
NCT06546137	Not specified	RECRUITING	National Network for Cardiovascular Genomics: Advancing Cardiovascular Healthcare for Hereditary Diseases in Brazil’s Unified Health System Through a Multicenter Registry

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CELIPROLOL	4	1
IRBESARTAN	4	1
CHEMBL443232	0	1