LRP5

LRP5 is a 1,615-residue type-I single-pass membrane coreceptor of the low-density-lipoprotein-receptor-related family. Its large extracellular region contains four beta-propeller/EGF modules and three LDL-receptor class A repeats, while its cytoplasmic tail contains phosphorylatable PPPSP motifs that recruit AXIN during ligand-dependent signaling. At the plasma membrane, LRP5 cooperates with Frizzled receptors to transduce canonical Wnt signals; this activity is a major determinant of osteoblast differentiation and bone mass and is antagonized by extracellular inhibitors including sclerostin. LRP5 also serves with FZD4 in Norrin signaling required for retinal vascular morphogenesis, and damaging human variants cause familial exudative vitreoretinopathy. Loss- and gain-of-function variants produce opposing bone phenotypes, whereas proposed direct roles in glucose or lipid metabolism remain less firmly established.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• norrin_fzd4_retinal_vascular_development via Familial Exudative Vitreoretinopathy