PIK3CA gene
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha.
The PIK3CA gene provides instructions for making the p110 alpha protein, which is one subunit of an enzyme called phosphatidylinositol 3-kinase (PI3K).
The p110α protein is called the catalytic subunit because it performs the action of PI3K, while the other subunit regulates the enzyme’s activity.
PI3K adds a cluster of oxygen and phosphorus atoms to other proteins through a process called phosphorylation.
PI3K phosphorylates certain signaling molecules, transmitting chemical signals within cells.
PI3K signaling is important for cell growth and division (proliferation), movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival.
PI3K signaling may be involved in the regulation of various hormones and may play a role in the maturation of adipocytes.
Somatic mutations in the PIK3CA gene have been found in some cases of bladder cancer.
Non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), based on where in the bladder the tumor is located.
A PIK3CA gene mutation has been found in about half of Non-muscle invasive bladder cancer (NMIBC) tumors.
A PIK3CA gene mutation changes single amino acids in the p110α protein, allowing PI3K to become overactive contributing to uncontrolled cell growth and division and the formation of bladder cancer.
Mutations in the PIK3CA gene have been found in up to a quarter of people with a certain type of epidermal nevus, an abnormal skin growth that are composed of keratinocytes.
Approximately 40% of hormone receptor positive and HER2 negative breast cancers harbor an activated mutation in PIK3CA.
The most common PIK3CA gene mutation found in epidermal nevi replaces glutamic acid with the amino acid glycine at position 545 of the p110α protein, causing cells to grow and divide more than normal.
The resulting overgrowth of skin cells leads to formation of epidermal nevi.
Individuals with an epidermal nevus do not appear to have an elevated risk of developing cancer.
At least five mutations in the PIK3CA gene have been found to cause Klippel-Trenaunay syndrome.
Klippel-Trenaunay syndrome is characterized by a a port-wine stain, abnormal overgrowth of soft tissues, such as, skin and muscles and bones, and vein malformations.
The PIK3CA gene mutations associated with this condition arise, and are called somatic mutations, which are not inherited.
The PIK3CA gene mutations associated with Klippel-Trenaunay syndrome change single protein building blocks, amino acids, in the p110α protein.
The altered p110α subunit that makes PI3K abnormally active triggering unregulated chemical signaling in cells, which allows cells to grow and divide continuously.
Increased cell proliferation leads to abnormal growth of the bones, soft tissues, and blood vessels.
Despite the involvement of PIK3CA gene mutations in cancer individuals with Klippel-Trenaunay syndrome do not appear to have an elevated risk of developing cancer.
At least 15 mutations in the PIK3CA gene have been found to cause a condition known as megalencephaly-capillary malformation syndrome ((MCAP), also known as PIK3CA-overgrowth spectrum (PROS), which is characterized by overgrowth of the brain (megalencephaly) and abnormalities caused by enlargement of small blood vessels in the skin (capillary malformations).
The mutations that cause MCAP overlap with those that cause Klippel-Trenaunay syndrome.
These mutations are not inherited from a parent,as arise randomly in one cell during the early stages of development before birth and lead to mosaicism.
Most PIK3CA gene mutations involved in MCAP change single amino acids in the p110α protein.
The altered p110α subunit makes PI3K abnormally active, resulting in unregulated signaling that allows cells to grow and divide continuously. Increased cell proliferation in the brain and other tissues and organs leads to the overgrowth characteristic of MCAP.
PI 3K is important in insulin signaling and glucose metabolism pathway and PIK3 inhibitors are associated with hyperglycemia.
Mutations in the PIK3CA gene, including those found in some cancers, have been found to cause several other conditions related to tissue overgrowth.
PIK3CA-Related Overgrowth Spectrum (PROS) conditions include hemimegalencephaly; fibroadipose hyperplasia; and a congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal or spinal abnormalities (CLOVES) syndrome.
Hemimegalencephaly is characterized by enlargement of one side of the brain and can cause seizures and intellectual disability.
Fibroadipose hyperplasia causes overgrowth of fibrous and fatty tissues: in various regions with enlargement of different portions of the body, such as the lower body, an individual arm or leg, or one or more fingers or toes.
CLOVES syndrome has multiple features, including an overgrowth of adipose tissue in the abdomen that is often associated with a reddish birthmark on the skin over it, in addition to blood vessel, skin, and bone abnormalities.
The overgrowth disorders caused by PIK3CA gene mutations are known as the PIK3CA-related overgrowth spectrum (PROS).