PTCH1

The PTCH1 gene provides instructions for producing the Patched-1 protein, which functions as a receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. A protein called Sonic Hedgehog is the ligand for the Patched-1 receptor. Together, ligands and their receptors trigger signals that affect cell development and function.

Patched-1 and Sonic Hedgehog function in a pathway that is essential for early development. This pathway plays a role in cell growth, cell specialization, and determining the shape (patterning) of many different parts of the developing body. If Sonic Hedgehog is absent, Patched-1 prevents cells from growing and dividing (proliferating). When Sonic Hedgehog is attached, Patched-1 stops suppressing cell proliferation. Because of its role in preventing cells from proliferating in an uncontrolled way, PTCH1 is called a tumor suppressor gene.

Gorlin syndrome - caused by mutations in the PTCH1 gene

At least 150 mutations in the PTCH1 gene have been found to cause Gorlin syndrome. Mutations in this gene prevent the production of Patched-1 or lead to the production of an abnormal version of the receptor. An altered or missing Patched-1 receptor cannot effectively suppress cell growth and division. As a result, cells proliferate uncontrollably to form the tumors that are characteristic of Gorlin syndrome.

cancers - associated with the PTCH1 gene

Some mutations are acquired during a person's lifetime and are present only in certain cells. These genetic changes, called somatic mutations, are not inherited. Somatic mutations in both copies of the PTCH1 gene are associated with a non-hereditary (sporadic) type of skin cancer called basal cell carcinoma. Other sporadic types of cancer may be associated with somatic mutations in the PTCH1 gene, including some forms of skin cancer, a childhood brain tumor called medulloblastoma, breast cancer, and colon cancer. A noncancerous (benign) jaw tumor called a keratocystic odontogenic tumor can also be associated with somatic PTCH1 gene mutations.

other disorders - caused by mutations in the PTCH1 gene

Mutations in the PTCH1 gene have been identified in a few individuals with a brain abnormality called holoprosencephaly. Holoprosencephaly occurs when the brain fails to divide into two halves during early development. The neurological symptoms associated with this condition can range from mild to severe depending on how well the brain has divided. Children born with this condition may also have abnormalities of the eyes, nose, and upper lip. Mutations in the PTCH1 gene that cause holoprosencephaly prevent the signaling that is necessary for normal brain cell patterning.