Overview of several genes related in the Wnt signaling pathway associated with diseases marked by bone overgrowth
| Protein activity | Gene | Chr | Protein function in Wnt signaling | Disease (manifestation) | References |
|---|---|---|---|---|---|
| Transmembrane co-receptors | LRP5 | 11 | Co-receptor that works with frizzled protein in the membrane | Endosteal hyperostosis (Worth disease; OMIM#144750) and steosclerosis (high bone mass) | [75, 102] |
| LRP4 | 11 | Related to LRP5/6 in modulation of Wnt/β-catenin pathway. Bind to SOSTDC1, also known as WISE, a family of Wnt antagonists [103] | Sclerosteosis type 2 (OMIM#614305) | [97] | |
| Inhibitors | DKK1 | 10 | Inhibitor of Wnt signaling pathway | DISH (OMIM#106400), OPLL (OMIM%602475), AS (OMIM#106300), and OYL (low levels of DKK1 in humans) | [104] |
| SOST | 17 | SOST by osteocytes is responsible for inhibiting bone formation | Sclerosteosis type 1 (OMIM#269500), Van Buchem disease (OMIM#239100), and Craniodiaphyseal dysplasia (OMIM#122860; high bone mass) | [94, 96, 105] | |
| SFRP4 | 7 | Secreted protein which binds to Wnt ligands and inhibits Wnt signaling | Pyle’s disease (OMIM#265900) | [106–108] | |
| WTX/AMER1 | X | Encodes an intracellular repressor of canonical Wnt signaling | Osteopathia striata (OMIM#300373; high bone mass) | [91] |
Chr: chromosome; SOSTDC1: SOST domain-containing protein 1; DISH: diffuse idiopathic skeletal hyperostosis; OPLL: ossification of the posterior longitudinal ligament; AS: ankylosing spondylitis; OYL: ossification of yellow ligament