COL1A1-related Ehlers-Danlos syndrome

Summary

COL1A1-related Ehlers-Danlos syndrome (MONDO:0100599) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	COL1A1-related Ehlers-Danlos syndrome
Mondo ID	MONDO:0100599
GARD	0027285
Is cancer (heuristic)	no

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › COL1A1-related Ehlers-Danlos 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/osteogenesis imperfecta syndrome, Ehlers-Danlos syndrome, vascular type, spondylodysplastic Ehlers-Danlos syndrome, Bethlem myopathy 2, Ehlers-Danlos syndrome, classic-like, 2, COL1A2-related Ehlers-Danlos syndrome, Ehlers-Danlos syndrome, classic-like, 3

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

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 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4075334	NM_000088.4(COL1A1):c.940G>A (p.Gly314Arg)	COL1A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 10 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

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
COL1A1	HGNC:2197	ENSG00000108821	P02452	Collagen alpha-1(I) chain	clinvar

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).

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)
COL1A1	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
periodontal ligament	1
skin of hip	1
stromal cell of endometrium	1

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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL1A1	5,341

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL1A1	P02452	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 26. 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
Defective VWF binding to collagen type I	1	3806.7×	0.003	COL1A1
Enhanced cleavage of VWF variant by ADAMTS13	1	2855.0×	0.003	COL1A1
Defective VWF cleavage by ADAMTS13 variant	1	2855.0×	0.003	COL1A1
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	1631.4×	0.003	COL1A1
Defective binding of VWF variant to GPIb:IX:V	1	1631.4×	0.003	COL1A1
GP1b-IX-V activation signalling	1	951.7×	0.004	COL1A1
Anchoring fibril formation	1	761.3×	0.004	COL1A1
Platelet Adhesion to exposed collagen	1	671.8×	0.004	COL1A1
Scavenging by Class A Receptors	1	601.0×	0.004	COL1A1
Fibronectin matrix formation	1	571.0×	0.004	COL1A1
Crosslinking of collagen fibrils	1	571.0×	0.004	COL1A1
RUNX2 regulates osteoblast differentiation	1	456.8×	0.004	COL1A1
Platelet Aggregation (Plug Formation)	1	439.2×	0.004	COL1A1
Syndecan interactions	1	423.0×	0.004	COL1A1
MET activates PTK2 signaling	1	380.7×	0.005	COL1A1
GPVI-mediated activation cascade	1	308.6×	0.005	COL1A1
Collagen chain trimerization	1	259.6×	0.006	COL1A1
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.006	COL1A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL1A1
Collagen degradation	1	175.7×	0.007	COL1A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL1A1
Non-integrin membrane-ECM interactions	1	154.3×	0.008	COL1A1
ECM proteoglycans	1	150.3×	0.008	COL1A1
Integrin cell surface interactions	1	134.3×	0.008	COL1A1
Cell surface interactions at the vascular wall	1	95.2×	0.011	COL1A1
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.011	COL1A1

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
cellular response to vitamin E	1	16852.0×	0.002	COL1A1
cellular response to fluoride	1	8426.0×	0.002	COL1A1
tooth mineralization	1	5617.3×	0.002	COL1A1
cellular response to acetaldehyde	1	3370.4×	0.003	COL1A1
intramembranous ossification	1	2808.7×	0.003	COL1A1
cartilage development involved in endochondral bone morphogenesis	1	2407.4×	0.003	COL1A1
bone trabecula formation	1	2106.5×	0.003	COL1A1
skin morphogenesis	1	1404.3×	0.003	COL1A1
collagen-activated tyrosine kinase receptor signaling pathway	1	1296.3×	0.003	COL1A1
response to hyperoxia	1	1123.5×	0.003	COL1A1
negative regulation of cell-substrate adhesion	1	1053.2×	0.003	COL1A1
collagen biosynthetic process	1	1053.2×	0.003	COL1A1
response to steroid hormone	1	842.6×	0.004	COL1A1
endochondral ossification	1	543.6×	0.005	COL1A1
cellular response to fibroblast growth factor stimulus	1	543.6×	0.005	COL1A1
response to cAMP	1	510.7×	0.005	COL1A1
face morphogenesis	1	495.6×	0.005	COL1A1
response to hydrogen peroxide	1	468.1×	0.005	COL1A1
embryonic skeletal system development	1	391.9×	0.005	COL1A1
blood vessel development	1	374.5×	0.005	COL1A1
protein localization to nucleus	1	351.1×	0.006	COL1A1
positive regulation of epithelial to mesenchymal transition	1	318.0×	0.006	COL1A1
cellular response to epidermal growth factor stimulus	1	318.0×	0.006	COL1A1
cellular response to amino acid stimulus	1	306.4×	0.006	COL1A1
cellular response to transforming growth factor beta stimulus	1	276.3×	0.006	COL1A1
cellular response to glucose stimulus	1	267.5×	0.006	COL1A1
cellular response to retinoic acid	1	234.1×	0.006	COL1A1
response to insulin	1	230.8×	0.006	COL1A1
collagen fibril organization	1	224.7×	0.006	COL1A1
cellular response to mechanical stimulus	1	216.1×	0.006	COL1A1

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
COL1A1	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

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	COL1A1

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)
COL1A1	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.