AMER1

Mutations in the AMER1 gene have been found in Wilms tumor, a rare form of kidney cancer that occurs almost exclusively in children. These mutations are somatic, meaning that they are acquired during a person's lifetime and are present only in kidney cells that give rise to the tumor. AMER1 gene mutations result in a protein with a reduced ability to repress Wnt signaling. As a result, Wnt signaling is increased, which leads to the unchecked proliferation of kidney cells and tumor development.

Mutations in the AMER1 gene that are present in cells throughout the body (called germline mutations) cause a bone disorder called osteopathia striata with cranial sclerosis. This condition occurs almost exclusively in females because males with the disorder usually die before or soon after birth. Affected females have excessive bone growth (hyperostosis), which leads to multiple skeletal abnormalities including an unusually large head (macrocephaly) and abnormal facial features. Males who survive infancy have bone abnormalities and heart, gastrointestinal, and genitourinary malformations. AMER1 gene mutations that cause osteopathia striata with cranial sclerosis lead to a lack of functional AMER1 protein, disrupting its role in regulating the Wnt signaling pathway. It is unclear why these mutations primarily affect skeletal development.

In addition to Wilms tumor (described above), changes in the AMER1 gene have been reported to be associated with many other cancers. These mutations are somatic and are present only in cells that give rise to cancer. Studies have shown that AMER1 gene changes are associated with stomach (gastric), breast, and colorectal cancers. It is likely that these gene changes impair the protein's tumor suppressor function, allowing cells to proliferate without control or order, which leads to cancer development.