LRP5

The LRP5 gene provides instructions for making a protein that is embedded in the outer membrane of many types of cells. It is known as a co-receptor because it works with another receptor protein, frizzled-4 (produced from the FZD4 gene), to transmit chemical signals from outside the cell to the cell's nucleus. Frizzled-4 and the LRP5 protein participate in the Wnt signaling pathway, a series of steps that affect the way cells and tissues develop. Wnt signaling is important for cell division (proliferation), attachment of cells to one another (adhesion), cell movement (migration), and many other cellular activities.

The LRP5 protein plays an important role in the development and maintenance of several tissues. During early development, it helps guide the specialization of cells in the retina, which is the light-sensitive tissue at the back of the eye. The LRP5 protein is also involved in establishing a blood supply to the retina and the inner ear. Additionally, this protein helps regulate bone mineral density, which is a measure of the amount of calcium and other minerals in bones.

familial exudative vitreoretinopathy - caused by mutations in the LRP5 gene

More than 15 mutations in the LRP5 gene have been identified in people with the eye disease familial exudative vitreoretinopathy. Some of these mutations change single protein building blocks (amino acids) in the LRP5 protein, while others insert or delete genetic material in the gene. Most of these mutations reduce the amount of functional LRP5 protein that is produced within cells.

A reduction in the amount of LRP5 protein disrupts chemical signaling in the developing eye, which interferes with the formation of blood vessels at the edges of the retina. The resulting abnormal blood supply to this tissue can lead to retinal damage and vision loss. Because the LRP5 protein plays a role in bone formation, LRP5 mutations also cause reduced bone mineral density in some people with familial exudative vitreoretinopathy.

other disorders - caused by mutations in the LRP5 gene

Mutations in the LRP5 gene cause several additional disorders characterized by altered bone mineral density. For example, more than 40 LRP5 mutations are responsible for a rare condition called osteoporosis-pseudoglioma syndrome. Beginning in childhood, people with this condition have extremely low bone mineral density (osteoporosis), which causes their bones to be brittle and to break easily. Affected individuals also experience vision loss from birth or early infancy. Most of the mutations that cause osteoporosis-pseudoglioma syndrome prevent cells from making any LRP5 protein. A lack of this protein disrupts chemical signaling pathways that are needed for normal retinal development and the formation of bone.

Studies suggest that changes in the LRP5 gene may influence the risk of developing osteoporosis, a disease that most often affects older women. This disease causes the bones to become thin, porous, and prone to fracture. The LRP5 gene is one of several genetic and environmental factors that likely contribute to this common disorder. LRP5 mutations have also been identified in several people with juvenile primary osteoporosis, a form of the disease that appears in childhood.

Other LRP5 mutations cause disorders associated with an increase in bone mineral density. These include autosomal dominant osteopetrosis type 1 and autosomal dominant osteosclerosis. In some cases, these conditions can cause abnormal bone growth and related skeletal abnormalities. Other people with increased bone mineral density do not have any associated medical problems. The mutations responsible for increased bone mineral density syndromes overactivate the LRP protein, which increases Wnt signaling within cells and enhances bone formation.