Defective EXT1 causes exostoses 1, TRPS2 and CHDS

Heparan sulfate (HS) is involved in regulating various body functions functions during development, homeostasis and pathology including blood clotting, angiogenesis and metastasis of cancer cells. Exostosin 1 and 2 (EXT1 and 2) glycosyltransferases are required to form HS. They are able to transfer N-acetylglucosamine (GlcNAc) and glucuronate (GlcA) to HS during its synthesis. The functional form of these enzymes appears to be a complex of the two located on the Golgi membrane. Defects in either EXT1 or EXT2 can cause hereditary multiple exostoses 1 and 2 respectively (MIM:133700 and MIM:133701), autosomal dominant disorders characterized by multiple projections of bone capped by cartilage resulting in deformed legs, forearms and hands. Trichorhinophalangeal syndrome, type II (TRPS2 aka Langer-Giedion syndrome, LGS) is a disorder that combines the clinical features of trichorhinophalangeal syndrome type I (TRPS1, MIM:190350) and multiple exostoses type I, caused by mutations in the TRPS1 and EXT1 genes, respectively. Defects in EXT1 may also be responsible for chondrosarcoma (CHDS; MIM:215300).

Summary from Reactome (R-HSA-3656253), read 2026-09-23.