WWP1
WW domain containing E3 ubiquitin protein ligase 1
Normal Function
Health Conditions Related to Genetic Changes
Cowden syndrome
At least 7 variants in the WWP1 gene have been identified in people with Cowden syndrome or a similar disorder called Cowden-like syndrome. These conditions are characterized by multiple tumor-like growths called hamartomas and an increased risk of developing certain cancers, particularly breast cancer, thyroid cancer, colorectal cancer, and cancer of the uterine lining (endometrial cancer). Other features of Cowden syndrome can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. People with Cowden syndrome or Cowden-like syndrome and WWP1 gene variants are more likely to develop colorectal cancer than individuals with Cowden syndrome associated with other genes.
The WWP1 gene variants associated with Cowden syndrome and Cowden-like syndrome change single amino acids in the WWP1 protein. Researchers describe these variants as "gain-of-function" because they appear to enhance the activity of the WWP1 protein. Studies suggest that the altered protein binds to the PTEN enzyme more often than normal. Excessive binding impairs PTEN enzyme tumor suppressor activity, allowing cells to proliferate unchecked, leading to the formation of tumors.
More About This Health ConditionRelated Conditions
Cowden syndromeCancers
Health Conditions Related to Genetic Changes
At least 7 variants in the WWP1 gene have been identified in people with Cowden syndrome or a similar disorder called Cowden-like syndrome. These conditions are characterized by multiple tumor-like growths called hamartomas and an increased risk of developing certain cancers, particularly breast cancer, thyroid cancer, colorectal cancer, and cancer of the uterine lining (endometrial cancer). Other features of Cowden syndrome can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. People with Cowden syndrome or Cowden-like syndrome and WWP1 gene variants are more likely to develop colorectal cancer than individuals with Cowden syndrome associated with other genes.
The WWP1 gene variants associated with Cowden syndrome and Cowden-like syndrome change single amino acids in the WWP1 protein. Researchers describe these variants as "gain-of-function" because they appear to enhance the activity of the WWP1 protein. Studies suggest that the altered protein binds to the PTEN enzyme more often than normal. Excessive binding impairs PTEN enzyme tumor suppressor activity, allowing cells to proliferate unchecked, leading to the formation of tumors.
Mutations in the WWP1 gene are also associated with several types of cancers without the additional features of Cowden syndrome (described above). These include cancers of the prostate, breast, liver as well as other cancers that often occur in Cowden syndrome. Unlike the WWP1 gene changes in Cowden syndrome, these mutations are somatic, which means they arise during a person's lifetime and are not inherited. These mutations are found only in cells that give rise to cancer.
Similar to those in Cowden syndrome, the WWP1 gene changes are also known "gain-of-function" mutations as they enhance the activity of the WWP1 protein. As a result, the altered protein is thought to bind to the PTEN enzyme more often than normal. Excessive binding impairs PTEN enzyme tumor suppressor activity, allowing cells to proliferate unchecked, leading to cancer development in affected cells.