SOST (Sclerostin) variants and mutations

SOST (also known as Sclerostin) is a human protein-coding gene encoding a sclerostin protein. 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. This analysis covers 707 SOST variants and mutations. Of these, 95% have computational variant effect predictions. Disease context includes sclerosteosis 1, craniodiaphyseal dysplasia, and hyperostosis corticalis generalisata. Example SOST variants include Q2*, L3F, and P4L.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SOST variants

Examples include Q2*, L3F, P4L, L5V, A6V, C8G, L9F, V10I. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.