Sclerosteosis: genes and variants
Sclerosteosis is linked to 2 analyzed proteins (LRP4 and SOST). 4 DNA variants are known to cause it; 474 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: sclerosteosis 1; sclerosteosis 2
Genes linked to Sclerosteosis
LRP4: Low-density lipoprotein receptor-related protein 4
It coordinates Wnt-related developmental signaling and serves as the agrin coreceptor that activates MuSK at the neuromuscular junction. Biallelic or dominant pathogenic variants can cause syndactyly, Cenani-Lenz syndactyly syndrome, or congenital myasthenic syndrome depending on the mechanism.
4 disease-causing and 468 uncertain variants in LRP4 are linked to Sclerosteosis.
SOST: Sclerostin
It restrains bone formation by inhibiting canonical Wnt signaling in osteoblast-lineage cells. Loss-of-function variants cause sclerosteosis or van Buchem disease with very high bone mass, while therapeutic neutralization increases bone formation in osteoporosis.
0 disease-causing and 6 uncertain variants in SOST are linked to Sclerosteosis.
Known disease-causing variants in Sclerosteosis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| LRP4 E1233A | 1233 | LDL-receptor class B 14 | Disease-causing (★★) |
| LRP4 D137N | 137 | LDL-receptor class A 3 | Disease-causing (★) |
| LRP4 D300N | 300 | LDL-receptor class A 7 | Disease-causing (★) |
| LRP4 D99H | 99 | LDL-receptor class A 2 | Disease-causing (★) |
Same protein, different disease
- Cenani-Lenz syndactyly syndrome is also caused by LRP4 variants; they fall mostly in different places as the Sclerosteosis variants (9 disease-causing).
Diseases related to Sclerosteosis
- Congenital myasthenic syndrome 17, also linked to LRP4
- Cenani-Lenz syndactyly syndrome, also linked to LRP4
- Osteoporosis, also linked to SOST
Frequently asked questions
Which genes are linked to Sclerosteosis?
In CATVariant, Sclerosteosis is linked to 2 analyzed proteins: LRP4 (Low-density lipoprotein receptor-related protein 4) and SOST (Sclerostin).
How many genetic variants are linked to Sclerosteosis?
509 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 474 are of uncertain significance or have conflicting reports.
Which uncertain variants in Sclerosteosis 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.
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