Ehlers-Danlos/osteogenesis imperfecta syndrome

Summary

Ehlers-Danlos/osteogenesis imperfecta syndrome (MONDO:0016470) is a disease with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Europe)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	<1 / 1 000 000		Europe	Not yet validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Ehlers-Danlos/osteogenesis imperfecta syndrome
Mondo ID	MONDO:0016470
MeSH	C565178
OMIM	619115
Orphanet	230857
UMLS	C4518787
MedGen	1386497
GARD	0017156
Is cancer (heuristic)	no

Also known as: EDS/OI syndrome

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

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › Ehlers-Danlos/osteogenesis imperfecta syndrome

Related subtypes (24): Ehlers-Danlos syndrome, classic type, Ehlers-Danlos syndrome, hypermobility type, Ehlers-Danlos syndrome, arthrochalasia type, Ehlers-Danlos syndrome, spondylodysplastic type, Ehlers-Danlos syndrome, periodontitis type, Ehlers-Danlos syndrome, autosomal dominant, type unspecified, joint laxity, familial, Ehlers-Danlos syndrome, fibronectinemic type, Ehlers-Danlos syndrome, dermatosparaxis type, brittle cornea syndrome, X-linked Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, musculocontractural type, Ehlers-Danlos syndrome due to tenascin-X deficiency, Ehlers-Danlos syndrome, Beasley-Cohen type, Ehlers-Danlos syndrome, kyphoscoliotic type, 2, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Ehlers-Danlos syndrome, vascular-like type, Ehlers-Danlos syndrome, vascular type, spondylodysplastic Ehlers-Danlos syndrome, Bethlem myopathy 2, Ehlers-Danlos syndrome, classic-like, 2, COL1A1-related Ehlers-Danlos syndrome, COL1A2-related Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic-like, 3

Subtypes (2): combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1, combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

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
196607	NM_000088.4(COL1A1):c.1984-5C>A	COL1A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 41 · Orphanet: 18 · 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
COL1A1	Definitive	Autosomal dominant	Ehlers-Danlos syndrome, classic type	20
COL1A2	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, cardiac valvular type	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL1A1	Orphanet:1310	Caffey disease
COL1A1	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A1	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A1	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A1	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A1	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A1	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A1	Orphanet:287	Classical Ehlers-Danlos syndrome
COL1A1	Orphanet:31112	Dermatofibrosarcoma protuberans
COL1A1	Orphanet:314029	High bone mass osteogenesis imperfecta
COL1A2	Orphanet:1899	Arthrochalasia Ehlers-Danlos syndrome
COL1A2	Orphanet:216796	Osteogenesis imperfecta type 1
COL1A2	Orphanet:216804	Osteogenesis imperfecta type 2
COL1A2	Orphanet:216812	Osteogenesis imperfecta type 3
COL1A2	Orphanet:216820	Osteogenesis imperfecta type 4
COL1A2	Orphanet:230851	Cardiac-valvular Ehlers-Danlos syndrome
COL1A2	Orphanet:230857	Ehlers-Danlos/osteogenesis imperfecta syndrome
COL1A2	Orphanet:314029	High bone mass osteogenesis imperfecta

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	gencc,clinvar
COL1A2	HGNC:2198	ENSG00000164692	P08123	Collagen alpha-2(I) chain	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL1A1	Collagen alpha-1(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).
COL1A2	Collagen alpha-2(I) chain	Type I collagen is a member of group I collagen (fibrillar forming collagen).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL1A1	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
periodontal ligament	2
skin of hip	2
stromal cell of endometrium	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL1A1	298	ubiquitous	marker	stromal cell of endometrium, skin of hip, periodontal ligament
COL1A2	295	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL1A1	5,341
COL1A2	179

Intra-cohort edges

A	B	Sources
COL1A1	COL1A2	intact

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL1A1	P02452	14
COL1A2	P08123	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 2 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
Defective VWF binding to collagen type I	2	3806.7×	9e-07	COL1A1, COL1A2
Enhanced cleavage of VWF variant by ADAMTS13	2	2855.0×	9e-07	COL1A1, COL1A2
Defective VWF cleavage by ADAMTS13 variant	2	2855.0×	9e-07	COL1A1, COL1A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	2	1631.4×	2e-06	COL1A1, COL1A2
Defective binding of VWF variant to GPIb:IX:V	2	1631.4×	2e-06	COL1A1, COL1A2
GP1b-IX-V activation signalling	2	951.7×	5e-06	COL1A1, COL1A2
Anchoring fibril formation	2	761.3×	6e-06	COL1A1, COL1A2
Platelet Adhesion to exposed collagen	2	671.8×	7e-06	COL1A1, COL1A2
Scavenging by Class A Receptors	2	601.0×	7e-06	COL1A1, COL1A2
Fibronectin matrix formation	2	571.0×	7e-06	COL1A1, COL1A2
Crosslinking of collagen fibrils	2	571.0×	7e-06	COL1A1, COL1A2
Platelet Aggregation (Plug Formation)	2	439.2×	1e-05	COL1A1, COL1A2
Syndecan interactions	2	423.0×	1e-05	COL1A1, COL1A2
MET activates PTK2 signaling	2	380.7×	1e-05	COL1A1, COL1A2
GPVI-mediated activation cascade	2	308.6×	2e-05	COL1A1, COL1A2
Collagen chain trimerization	2	259.6×	3e-05	COL1A1, COL1A2
Developmental Lineage of Pancreatic Ductal Cells	2	228.4×	3e-05	COL1A1, COL1A2
Assembly of collagen fibrils and other multimeric structures	2	200.3×	4e-05	COL1A1, COL1A2
Collagen degradation	2	175.7×	5e-05	COL1A1, COL1A2
Collagen biosynthesis and modifying enzymes	2	170.4×	5e-05	COL1A1, COL1A2
Non-integrin membrane-ECM interactions	2	154.3×	6e-05	COL1A1, COL1A2
ECM proteoglycans	2	150.3×	6e-05	COL1A1, COL1A2
Integrin cell surface interactions	2	134.3×	7e-05	COL1A1, COL1A2
Cell surface interactions at the vascular wall	2	95.2×	1e-04	COL1A1, COL1A2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	2	87.2×	1e-04	COL1A1, COL1A2
RUNX2 regulates osteoblast differentiation	1	228.4×	0.005	COL1A1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	154.3×	0.007	COL1A2
Interleukin-4 and Interleukin-13 signaling	1	51.4×	0.019	COL1A2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skin morphogenesis	2	1404.3×	2e-05	COL1A1, COL1A2
blood vessel development	2	374.5×	2e-04	COL1A1, COL1A2
cellular response to amino acid stimulus	2	306.4×	2e-04	COL1A1, COL1A2
collagen fibril organization	2	224.7×	2e-04	COL1A1, COL1A2
skeletal system development	2	125.8×	6e-04	COL1A1, COL1A2
protein heterotrimerization	1	8426.0×	8e-04	COL1A2
cellular response to vitamin E	1	8426.0×	8e-04	COL1A1
cellular response to fluoride	1	4213.0×	0.001	COL1A1
tooth mineralization	1	2808.7×	0.002	COL1A1
cellular response to acetaldehyde	1	1685.2×	0.003	COL1A1
intramembranous ossification	1	1404.3×	0.003	COL1A1
cartilage development involved in endochondral bone morphogenesis	1	1203.7×	0.003	COL1A1
bone trabecula formation	1	1053.2×	0.004	COL1A1
collagen-activated tyrosine kinase receptor signaling pathway	1	648.1×	0.005	COL1A1
response to hyperoxia	1	561.7×	0.005	COL1A1
negative regulation of cell-substrate adhesion	1	526.6×	0.005	COL1A1
collagen metabolic process	1	526.6×	0.005	COL1A2
collagen biosynthetic process	1	526.6×	0.005	COL1A1
extracellular matrix assembly	1	468.1×	0.006	COL1A2
response to steroid hormone	1	421.3×	0.006	COL1A1
endochondral ossification	1	271.8×	0.008	COL1A1
cellular response to fibroblast growth factor stimulus	1	271.8×	0.008	COL1A1
odontogenesis	1	263.3×	0.008	COL1A2
response to cAMP	1	255.3×	0.008	COL1A1
face morphogenesis	1	247.8×	0.008	COL1A1
response to hydrogen peroxide	1	234.1×	0.008	COL1A1
embryonic skeletal system development	1	195.9×	0.009	COL1A1
protein localization to nucleus	1	175.5×	0.010	COL1A1
positive regulation of epithelial to mesenchymal transition	1	159.0×	0.010	COL1A1
cellular response to epidermal growth factor stimulus	1	159.0×	0.010	COL1A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 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
COL1A1	0	0
COL1A2	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
COL1A1	8	Binding:8
COL1A2	4	Functional:4

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	COL1A1, COL1A2

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)
COL1A1	8	—
COL1A2	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.