Skeletal dysplasia: genes and variants
Skeletal dysplasia is linked to 2 analyzed proteins (COL1A2 and LRP5). 2 DNA variants are known to cause it; 3 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to Skeletal dysplasia
COL1A2: Collagen alpha-2(I) chain
It contributes one of the three chains of type I collagen, providing tensile strength to bone, skin, tendon, blood vessels, and other connective tissues. Pathogenic variants can cause osteogenesis imperfecta, Ehlers-Danlos phenotypes, and related connective-tissue disorders.
1 disease-causing and 0 uncertain variants in COL1A2 are linked to Skeletal dysplasia.
LRP5: Low-density lipoprotein receptor-related protein 5
It transduces canonical Wnt signals that strongly regulate bone formation and also contributes to retinal vascular development. Loss-of-function variants cause osteoporosis-pseudoglioma syndrome, while activating variants cause high-bone-mass disorders.
1 disease-causing and 0 uncertain variants in LRP5 are linked to Skeletal dysplasia.
Weakly linked (only a few uncertain records): PTH1R, ACAN, ARID1A and FLNB.
Known disease-causing variants in Skeletal dysplasia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LRP5 A242T | 242 | LDL-receptor class B 4 | Disease-causing (★★) |
| COL1A2 G850E | 850 | Disease-causing (★) |
Same protein, different disease
- Exudative vitreoretinopathy 4 is also caused by LRP5 variants; they fall mostly in different places as the Skeletal dysplasia variants (17 disease-causing).
- Osteoporosis with pseudoglioma is also caused by LRP5 variants; they fall mostly in different places as the Skeletal dysplasia variants (9 disease-causing).
- Worth disease is also caused by LRP5 variants; they fall mostly in different places as the Skeletal dysplasia variants (9 disease-causing).
- Autosomal dominant osteopetrosis 1 is also caused by LRP5 variants; they fall mostly in different places as the Skeletal dysplasia variants (6 disease-causing).
- Polycystic liver disease 4 with or without kidney cysts is also caused by LRP5 variants; they fall mostly in different places as the Skeletal dysplasia variants (6 disease-causing).
- Osteogenesis imperfecta is also caused by COL1A2 variants; they fall mostly in different places as the Skeletal dysplasia variants (332 disease-causing).
- Ehlers-Danlos syndrome, classic type, 1 is also caused by COL1A2 variants; they fall mostly in different places as the Skeletal dysplasia variants (265 disease-causing).
- Osteogenesis imperfecta with normal sclerae, dominant form is also caused by COL1A2 variants; they fall mostly in different places as the Skeletal dysplasia variants (51 disease-causing).
- Osteogenesis imperfecta, perinatal lethal is also caused by COL1A2 variants; they fall mostly in different places as the Skeletal dysplasia variants (42 disease-causing).
- Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2 is also caused by COL1A2 variants; they fall mostly in different places as the Skeletal dysplasia variants (11 disease-causing).
Diseases related to Skeletal dysplasia
- Osteogenesis imperfecta, also linked to COL1A2 and LRP5
- Osteoporosis, also linked to COL1A2 and LRP5
- Postmenopausal osteoporosis, also linked to COL1A2 and LRP5
- Ehlers-Danlos syndrome, classic type, 1, also linked to COL1A2
- Ehlers-Danlos syndrome, also linked to COL1A2
- Osteogenesis imperfecta, perinatal lethal, also linked to COL1A2
- Osteogenesis imperfecta with normal sclerae, dominant form, also linked to COL1A2
- Connective tissue disorder, also linked to COL1A2
- Ehlers-Danlos syndrome, arthrochalasia type, also linked to COL1A2
- Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 2, also linked to COL1A2
- Exudative vitreoretinopathy 4, also linked to LRP5
- Worth disease, also linked to LRP5
Frequently asked questions
Which genes are linked to Skeletal dysplasia?
In CATVariant, Skeletal dysplasia is linked to 2 analyzed proteins: COL1A2 (Collagen alpha-2(I) chain) and LRP5 (Low-density lipoprotein receptor-related protein 5).
How many genetic variants are linked to Skeletal dysplasia?
7 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3 are of uncertain significance or have conflicting reports.
Which uncertain variants in Skeletal dysplasia look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
Download every variant as CSV · Browse all diseases · Methods · About the Center