Osteoporosis with pseudoglioma: genes and variants
Osteoporosis with pseudoglioma is linked to 1 analyzed protein (LRP5). 9 DNA variants are known to cause it; 61 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 Osteoporosis with pseudoglioma
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.
9 disease-causing and 61 uncertain variants in LRP5 are linked to Osteoporosis with pseudoglioma.
Where Osteoporosis with pseudoglioma variants cluster
- LRP5 Beta-propeller 2 (positions 341–602): 4 of 9 disease-causing changes, 2.7× more than its size predicts.
- LRP5 Beta-propeller 1 (positions 32–288): 3 of 9 disease-causing changes, 2.1× more than its size predicts.
Known disease-causing variants in Osteoporosis with pseudoglioma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LRP5 R494Q | 494 | LDL-receptor class B 8 | Disease-causing (★★) |
| LRP5 R494W | 494 | LDL-receptor class B 8 | Disease-causing (★★) |
| LRP5 R353Q | 353 | Beta-propeller 2 | Disease-causing (★★) |
| LRP5 M791V | 791 | LDL-receptor class B 13 | Disease-causing (★) |
| LRP5 Y776S | 776 | LDL-receptor class B 13 | Disease-causing (★) |
| LRP5 D381G | 381 | Beta-propeller 2 | Disease-causing (★) |
| LRP5 T244M | 244 | LDL-receptor class B 4 | Disease-causing |
| LRP5 L145F | 145 | LDL-receptor class B 2 | Disease-causing |
| LRP5 D69Y | 69 | Beta-propeller 1 | Disease-causing |
Which prediction tools work for Osteoporosis with pseudoglioma
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 93 out of 100
Same protein, different disease
- Exudative vitreoretinopathy 4 is also caused by LRP5 variants; they fall mostly in different places as the Osteoporosis with pseudoglioma variants (17 disease-causing).
- Worth disease is also caused by LRP5 variants; they fall mostly in different places as the Osteoporosis with pseudoglioma variants (9 disease-causing).
- Autosomal dominant osteopetrosis 1 is also caused by LRP5 variants; they fall mostly in different places as the Osteoporosis with pseudoglioma 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 Osteoporosis with pseudoglioma 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 Osteoporosis with pseudoglioma variants (5 disease-causing).
Diseases related to Osteoporosis with pseudoglioma
- Osteogenesis imperfecta, also linked to LRP5
- Exudative vitreoretinopathy 4, also linked to LRP5
- Worth disease, also linked to LRP5
- Osteoporosis, also linked to LRP5
- Autosomal dominant osteopetrosis 1, 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 Osteoporosis with pseudoglioma?
In CATVariant, Osteoporosis with pseudoglioma is linked to 1 analyzed protein: LRP5 (Low-density lipoprotein receptor-related protein 5).
How many genetic variants are linked to Osteoporosis with pseudoglioma?
70 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 61 are of uncertain significance or have conflicting reports.
Which uncertain variants in Osteoporosis with pseudoglioma look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
Which variant effect predictor works best for Osteoporosis with pseudoglioma?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.93, based on 9 disease-causing and 14 harmless variants).
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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