Autosomal dominant osteopetrosis 1: genes and variants
Autosomal dominant osteopetrosis 1 is linked to 1 analyzed protein (LRP5). 6 DNA variants are known to cause it; 97 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Autosomal dominant osteopetrosis type 1
Genes linked to Autosomal dominant osteopetrosis 1
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.
6 disease-causing and 97 uncertain variants in LRP5 are linked to Autosomal dominant osteopetrosis 1.
Weakly linked (only a few uncertain records): CLCNKB.
Where Autosomal dominant osteopetrosis 1 variants cluster
- LRP5 Beta-propeller 1 (positions 32–288): 3 of 6 disease-causing changes, 3.1× more than its size predicts.
Known disease-causing variants in Autosomal dominant osteopetrosis 1
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LRP5 G404R | 404 | LDL-receptor class B 6 | Disease-causing (★★) |
| LRP5 T1041M | 1041 | LDL-receptor class B 17 | Disease-causing (★★) |
| LRP5 T852M | 852 | LDL-receptor class B 14 | Disease-causing (★★) |
| LRP5 N198S | 198 | LDL-receptor class B 3 | Disease-causing (★★) |
| LRP5 G171R | 171 | LDL-receptor class B 3 | Disease-causing |
| LRP5 T253I | 253 | YWTD 4 | Disease-causing |
Uncertain variants in Autosomal dominant osteopetrosis 1 that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| LRP5 G404A | 404 | LDL-receptor class B 6 | Uncertain (★) | +7: G404R at the same position is pathogenic; seen in 6.6e-06 of gnomAD DNA copies; REVEL 0.944 |
Same protein, different disease
- Exudative vitreoretinopathy 4 is also caused by LRP5 variants; they fall mostly in different places as the Autosomal dominant osteopetrosis 1 variants (17 disease-causing).
- Osteoporosis with pseudoglioma is also caused by LRP5 variants; they fall mostly in different places as the Autosomal dominant osteopetrosis 1 variants (9 disease-causing).
- Worth disease is also caused by LRP5 variants; they fall mostly in different places as the Autosomal dominant osteopetrosis 1 variants (9 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 Autosomal dominant osteopetrosis 1 variants (6 disease-causing).
- Bone mineral density quantitative trait locus 1 is also caused by LRP5 variants; they fall mostly in different places as the Autosomal dominant osteopetrosis 1 variants (5 disease-causing).
Diseases related to Autosomal dominant osteopetrosis 1
- Osteogenesis imperfecta, also linked to LRP5
- Exudative vitreoretinopathy 4, also linked to LRP5
- Worth disease, also linked to LRP5
- Osteoporosis with pseudoglioma, also linked to LRP5
- Osteoporosis, also linked to LRP5
- Polycystic liver disease 4 with or without kidney cysts, also linked to LRP5
- Bone mineral density quantitative trait locus 1, also linked to LRP5
- Postmenopausal osteoporosis, also linked to LRP5
- Skeletal dysplasia, also linked to LRP5
- Autosomal dominant polycystic liver disease, also linked to LRP5
- Familial exudative vitreoretinopathy, also linked to LRP5
Frequently asked questions
Which genes are linked to Autosomal dominant osteopetrosis 1?
In CATVariant, Autosomal dominant osteopetrosis 1 is linked to 1 analyzed protein: LRP5 (Low-density lipoprotein receptor-related protein 5).
How many genetic variants are linked to Autosomal dominant osteopetrosis 1?
118 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 97 are of uncertain significance or have conflicting reports.
Which uncertain variants in Autosomal dominant osteopetrosis 1 look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example LRP5 G404A. These are leads for expert review, not diagnoses.
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.
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