ROR2

The ROR2 gene provides instructions for making a protein whose function is not well understood. The ROR2 protein is part of a family of proteins known as receptor protein kinases (RTKs), which play a role in chemical signaling within cells. Receptor protein kinases are involved in many cell functions, including cell growth and division (proliferation), the process by which cells mature to carry out specific functions (differentiation), cell survival, and cell movement (motility).

Researchers believe that the ROR2 protein plays an essential role in development before birth. It is involved in a chemical signaling pathway called WNT signaling, which affects many aspects of embryonic development. This pathway controls the activity of genes needed at specific times during development, and it regulates the interactions between cells as organs and tissues are forming. Based on studies in animals, the ROR2 protein appears to be critical for the normal formation of the skeleton, heart, and genitals.

Robinow syndrome - caused by mutations in the ROR2 gene

At least 12 mutations in the ROR2 gene have been found to cause the autosomal recessive form of Robinow syndrome. Autosomal recessive inheritance means both copies of the gene in each cell have mutations. Some of these mutations change single protein building blocks (amino acids) in the ROR2 protein, while others lead to the production of an abnormally short, nonfunctional version of the protein. Because these genetic changes prevent any functional ROR2 protein from being made, they are described as "loss-of-function" mutations. A shortage of ROR2 protein disrupts embryonic development, particularly the formation of bones in the face, spine, and limbs, which leads to the skeletal abnormalities characteristic of Robinow syndrome. A lack of this protein during early development also underlies the other features of Robinow syndrome, including genital abnormalities and heart defects.

other disorders - caused by mutations in the ROR2 gene

Several mutations in the ROR2 gene have been identified in people with a disorder called brachydactyly type B1. This condition is characterized by abnormally short fingers and toes, particularly the fourth and fifth digits, and malformed or absent fingernails and toenails. Brachydactyly type B1 has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Unlike the mutations that cause Robinow syndrome, the ROR2 mutations responsible for brachydactyly type B1 are described as "gain-of-function" mutations. These genetic changes probably cause the ROR2 protein to be continuously active. It is unclear how the overactive protein disrupts the formation of bones in the hands and feet.