PIK3CD gene

phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta

The PIK3CD gene provides instructions for making the p110 delta (p110δ) protein, which is one piece (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). The version of PI3K containing the p110δ subunit, called PI3K-delta, is specifically found in white blood cells, including immune system cells (lymphocytes) called B cells and T cells. These cells recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection.

Like other kinases, PI3K-delta adds a cluster of oxygen and phosphorus atoms (a phosphate group) to other proteins through a process called phosphorylation. PI3K-delta phosphorylates certain signaling molecules, which triggers a series of additional reactions that transmit chemical signals within cells. In lymphocytes, PI3K-delta signaling is important for many cell activities, including cell growth and division (proliferation) and maturation (differentiation). PI3K-delta helps direct B cells and T cells to differentiate into different types, each of which has a distinct function in the immune system.

At least four mutations in the PIK3CD gene have been found to cause a form of immunodeficiency called activated PI3K-delta syndrome. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with activated PI3K-delta syndrome typically have recurrent bacterial infections of the respiratory tract and chronic viral infections.

The PIK3CD gene mutations involved in activated PI3K-delta syndrome change single protein building blocks (amino acids) in the p110δ protein; the most common mutation replaces the amino acid glutamic acid with the amino acid lysine at position 1021 of the protein (written as Glu1021Lys or E1021K). A PI3K-delta enzyme containing the altered p110δ subunit is abnormally turned on (activated). Studies indicate that this overactive signaling causes T cells to mature and die too quickly. The excess signaling also blocks maturation of B cells at an early stage; the immature B cells cannot respond to foreign invaders and likely self-destruct. Lack of T cells and B cells makes it difficult for people with this disorder to fight off bacterial and viral infections. Overactivation of PI3K-delta signaling can also stimulate abnormal proliferation of lymphocytes, and accumulation of these cells can lead to enlarged lymph nodes (lymphadenopathy). Activated PI3K-delta syndrome also increases the risk of developing a form of cancer called B-cell lymphoma.

Genetics Home Reference provides information about autoimmune lymphoproliferative syndrome.

Cytogenetic Location: 1p36.22, which is the short (p) arm of chromosome 1 at position 36.22

Molecular Location: base pairs 9,629,889 to 9,729,114 on chromosome 1 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 1p36.22, which is the short (p) arm of chromosome 1 at position 36.22
  • APDS
  • IMD14
  • p110D
  • P110DELTA
  • phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta
  • phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform
  • phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
  • phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta
  • phosphoinositide-3-kinase C
  • phosphoinositide-3-kinase, catalytic, delta polypeptide variant p37delta
  • PI3-kinase p110 subunit delta
  • PI3K
  • PI3Kdelta
  • ptdIns-3-kinase subunit p110-delta