Encyclopedia
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
- genes
1. Introduction
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.
2. Health Conditions Related to Genetic Changes
2.1. Activated PI3K-delta syndrome
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.
3. Other Names for This Gene
- APDS
- IMD14
- p110D
- P110DELTA
- phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform
- 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
- 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
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/pik3cd
References
- Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C,Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J,Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G,Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL,Condliffe A, Nejentsev S. Phosphoinositide 3-kinase δ gene mutation predisposesto respiratory infection and airway damage. Science. 2013 Nov15;342(6160):866-71. doi: 10.1126/science.1243292.
- Crank MC, Grossman JK, Moir S, Pittaluga S, Buckner CM, Kardava L, Agharahimi A, Meuwissen H, Stoddard J, Niemela J, Kuehn H, Rosenzweig SD. Mutations inPIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancersusceptibility. J Clin Immunol. 2014 Apr;34(3):272-6. doi:10.1007/s10875-014-0012-9.
- Jou ST, Chien YH, Yang YH, Wang TC, Shyur SD, Chou CC, Chang ML, Lin DT, LinKH, Chiang BL. Identification of variations in the human phosphoinositide3-kinase p110delta gene in children with primary B-cell immunodeficiency ofunknown aetiology. Int J Immunogenet. 2006 Oct;33(5):361-9.
- Kracker S, Curtis J, Ibrahim MA, Sediva A, Salisbury J, Campr V, Debré M,Edgar JD, Imai K, Picard C, Casanova JL, Fischer A, Nejentsev S, Durandy A.Occurrence of B-cell lymphomas in patients with activated phosphoinositide3-kinase δ syndrome. J Allergy Clin Immunol. 2014 Jul;134(1):233-6. doi:10.1016/j.jaci.2014.02.020.
- Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, Avery DT,Moens L, Cannons JL, Biancalana M, Stoddard J, Ouyang W, Frucht DM, Rao VK,Atkinson TP, Agharahimi A, Hussey AA, Folio LR, Olivier KN, Fleisher TA,Pittaluga S, Holland SM, Cohen JI, Oliveira JB, Tangye SG, Schwartzberg PL,Lenardo MJ, Uzel G. Dominant-activating germline mutations in the gene encodingthe PI(3)K catalytic subunit p110δ result in T cell senescence and humanimmunodeficiency. Nat Immunol. 2014 Jan;15(1):88-97. doi: 10.1038/ni.2771.
- Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immunecells. Annu Rev Immunol. 2013;31:675-704. doi:10.1146/annurev-immunol-032712-095946.
