combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

Summary

combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 (MONDO:0030855) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 56

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2
Mondo ID	MONDO:0030855
OMIM	619120
UMLS	C5436847
MedGen	1751229
GARD	0018317
Is cancer (heuristic)	no

Also known as: combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 · OIEDS Syndrome 2 · OIEDS2

Data availability: 56 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Ehlers-Danlos syndrome › Ehlers-Danlos/osteogenesis imperfecta syndrome › combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2

Related 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

56 retrieved; paginated sample, class counts are floors:

14 uncertain significance, 13 pathogenic/likely pathogenic, 12 pathogenic, 5 likely pathogenic, 5 conflicting classifications of pathogenicity, 5 benign/likely benign, 1 likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
1498972	NM_000089.4(COL1A2):c.3583T>C (p.Cys1195Arg)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1694467	NM_000089.4(COL1A2):c.1531G>A (p.Gly511Ser)	COL1A2	Pathogenic	criteria provided, single submitter
17269	NM_000089.4(COL1A2):c.432+5G>A	COL1A2	Pathogenic	criteria provided, single submitter
17271	NC_000007.13:g.94035075_94047591dup	COL1A2	Pathogenic	no assertion criteria provided
17277	NM_000089.4(COL1A2):c.3105+2T>C	COL1A2	Pathogenic	no assertion criteria provided
265387	NM_000089.4(COL1A2):c.577G>A (p.Gly193Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
2682437	NM_000089.4(COL1A2):c.739G>A (p.Gly247Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2921400	NM_000089.4(COL1A2):c.432+1G>C	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3594954	NM_000089.4(COL1A2):c.1523G>T (p.Gly508Val)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
35957	NM_000089.4(COL1A2):c.838G>A (p.Gly280Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3767111	NM_000089.4(COL1A2):c.2774G>A (p.Gly925Asp)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425650	NM_000089.4(COL1A2):c.1937G>T (p.Gly646Val)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
425658	NM_000089.4(COL1A2):c.326G>A (p.Gly109Asp)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
426918	NM_000089.4(COL1A2):c.1136G>A (p.Gly379Glu)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
456802	NM_000089.4(COL1A2):c.1072G>A (p.Gly358Ser)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
496615	NM_000089.4(COL1A2):c.596G>A (p.Gly199Asp)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
503685	NM_000089.4(COL1A2):c.432+4_432+7del	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521008	NM_000089.4(COL1A2):c.1576G>A (p.Gly526Arg)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
579070	NM_000089.4(COL1A2):c.1127G>T (p.Gly376Val)	COL1A2	Pathogenic	criteria provided, multiple submitters, no conflicts
581099	NM_000089.4(COL1A2):c.433-2A>C	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
585504	NM_000089.4(COL1A2):c.389G>T (p.Gly130Val)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
618023	NM_000089.4(COL1A2):c.964G>A (p.Gly322Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
691333	NM_000089.4(COL1A2):c.892G>A (p.Gly298Ser)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
848804	NM_000089.4(COL1A2):c.3250G>T (p.Gly1084Cys)	COL1A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
988623	NM_000089.4(COL1A2):c.324+4del	COL1A2	Pathogenic	no assertion criteria provided
1398213	NM_000089.4(COL1A2):c.3971G>A (p.Trp1324Ter)	COL1A2	Likely pathogenic	criteria provided, single submitter
1683593	NM_000089.4(COL1A2):c.1018G>A (p.Gly340Ser)	COL1A2	Likely pathogenic	criteria provided, single submitter
3064106	NM_000089.4(COL1A2):c.299G>A (p.Gly100Asp)	COL1A2	Likely pathogenic	criteria provided, single submitter
3594955	NM_000089.4(COL1A2):c.2990G>T (p.Gly997Val)	COL1A2	Likely pathogenic	criteria provided, single submitter
4796610	NM_000089.4(COL1A2):c.1630G>C (p.Gly544Arg)	COL1A2	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 21 · Orphanet: 8 · 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
COL1A2	Definitive	Autosomal recessive	Ehlers-Danlos syndrome, cardiac valvular type	21

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

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

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
COL1A2	Other/Unknown	no		Fib_collagen_C, Collagen, Collagen_superfamily

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
COL1A2	295	ubiquitous	marker	periodontal ligament, stromal cell of endometrium, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL1A2	179

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL1A2	P08123	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. 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	COL1A2
Enhanced cleavage of VWF variant by ADAMTS13	1	2855.0×	0.003	COL1A2
Defective VWF cleavage by ADAMTS13 variant	1	2855.0×	0.003	COL1A2
Enhanced binding of GP1BA variant to VWF multimer:collagen	1	1631.4×	0.003	COL1A2
Defective binding of VWF variant to GPIb:IX:V	1	1631.4×	0.003	COL1A2
GP1b-IX-V activation signalling	1	951.7×	0.004	COL1A2
Anchoring fibril formation	1	761.3×	0.004	COL1A2
Platelet Adhesion to exposed collagen	1	671.8×	0.004	COL1A2
Scavenging by Class A Receptors	1	601.0×	0.004	COL1A2
Fibronectin matrix formation	1	571.0×	0.004	COL1A2
Crosslinking of collagen fibrils	1	571.0×	0.004	COL1A2
Platelet Aggregation (Plug Formation)	1	439.2×	0.005	COL1A2
Syndecan interactions	1	423.0×	0.005	COL1A2
MET activates PTK2 signaling	1	380.7×	0.005	COL1A2
GPVI-mediated activation cascade	1	308.6×	0.005	COL1A2
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	308.6×	0.005	COL1A2
Collagen chain trimerization	1	259.6×	0.006	COL1A2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.007	COL1A2
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL1A2
Collagen degradation	1	175.7×	0.008	COL1A2
Collagen biosynthesis and modifying enzymes	1	170.4×	0.008	COL1A2
Non-integrin membrane-ECM interactions	1	154.3×	0.008	COL1A2
ECM proteoglycans	1	150.3×	0.008	COL1A2
Integrin cell surface interactions	1	134.3×	0.008	COL1A2
Interleukin-4 and Interleukin-13 signaling	1	102.9×	0.010	COL1A2
Cell surface interactions at the vascular wall	1	95.2×	0.011	COL1A2
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	1	87.2×	0.011	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein heterotrimerization	1	16852.0×	8e-04	COL1A2
skin morphogenesis	1	1404.3×	0.003	COL1A2
collagen metabolic process	1	1053.2×	0.003	COL1A2
extracellular matrix assembly	1	936.2×	0.003	COL1A2
odontogenesis	1	526.6×	0.005	COL1A2
blood vessel development	1	374.5×	0.005	COL1A2
cellular response to amino acid stimulus	1	306.4×	0.005	COL1A2
bone mineralization	1	271.8×	0.005	COL1A2
Rho protein signal transduction	1	247.8×	0.005	COL1A2
collagen fibril organization	1	224.7×	0.005	COL1A2
regulation of blood pressure	1	221.7×	0.005	COL1A2
transforming growth factor beta receptor signaling pathway	1	159.0×	0.007	COL1A2
skeletal system development	1	125.8×	0.008	COL1A2

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
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
COL1A2	4	Functional:4

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	COL1A2

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)
COL1A2	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.