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Genetics Home Reference: your guide to understanding genetic conditions
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PIK3CA

Reviewed February 2014

What is the official name of the PIK3CA gene?

The official name of this gene is “phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha.”

PIK3CA is the gene's official symbol. The PIK3CA gene is also known by other names, listed below.

What is the normal function of the PIK3CA gene?

The PIK3CA gene provides instructions for making the p110 alpha (p110α) protein, which is one piece (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 (produced by a different gene) regulates the enzyme's activity.

Like other kinases, PI3K adds a cluster of oxygen and phosphorus atoms (a phosphate group) to other proteins through a process called phosphorylation. PI3K phosphorylates certain signaling molecules, which triggers a series of additional reactions that transmit chemical signals within cells. PI3K signaling is important for many cell activities, including cell growth and division (proliferation), movement (migration) of cells, production of new proteins, transport of materials within cells, and cell survival. Studies suggest that PI3K signaling may be involved in the regulation of several hormones and may play a role in the maturation of fat cells (adipocytes).

How are changes in the PIK3CA gene related to health conditions?

megalencephaly-capillary malformation syndrome - caused by mutations in the PIK3CA gene

At least 15 mutations in the PIK3CA gene have been found to cause a condition known as megalencephaly-capillary malformation syndrome (MCAP), which is characterized by overgrowth of the brain (megalencephaly) and abnormalities caused by enlargement of small blood vessels in the skin (capillary malformations). Most PIK3CA gene mutations involved in MCAP change single protein building blocks (amino acids) in the p110α protein. The mutations involved in MCAP are not inherited from a parent; they arise randomly in one cell during the early stages of development before birth. As cells continue to divide, some cells will have the mutation and other cells will not. This mixture of cells with and without a genetic mutation is known as mosaicism.

The PIK3CA gene mutations involved in MCAP lead to production of an altered p110α subunit that makes PI3K abnormally active. The altered kinase triggers unregulated chemical signaling in cells, which allows cells to continuously grow and divide. Increased cell proliferation in the brain and other tissues and organs leads to the overgrowth characteristic of MCAP.

Despite involvement of the PIK3CA gene mutations in cancer (described below) and the overgrowth of cells caused by changes in this gene, individuals with MCAP do not appear to have an elevated risk of developing cancer.

cancers - associated with the PIK3CA gene

Mutations in the PIK3CA gene are involved in many types of cancer, including cancer of the ovary, breast, lung, brain, and stomach. These mutations are also involved in cancer of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. The PIK3CA gene mutations involved in cancer are somatic, which means they are acquired during a person's lifetime and are present only in the tumor cells. These mutations change single amino acids in the p110α protein. Two common mutations occur in the same region and change the amino acid glutamate at position 542 or at position 545 of the p110α protein to the amino acid lysine (written as Glu542Lys and Glu545Lys, respectively). Two other common mutations occur in another region, changing the amino acid histidine at position 1047 of p110α to the amino acid arginine or leucine (written as His1047Arg and His1047Leu, respectively).

Cancer-associated PIK3CA gene mutations result in production of an altered p110α subunit that allows PI3K to signal without regulation. The increased signaling leads to abnormal proliferation of cells, resulting in the development of cancer.

other disorders - caused by mutations in the PIK3CA gene

Mutations in the PIK3CA gene, including those associated with cancer, have been found to cause several other conditions related to overgrowth of tissues. These conditions include hemimegalencephaly; fibroadipose hyperplasia; and a condition called 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 (adipose) tissues in various regions of the body, which leads to 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. It is unknown if individuals with these disorders have an elevated risk of developing cancer.

As in MCAP (described above), the genetic changes involved in these disorders occur early in development and are found in only some of the body's cells. This mosaicism helps explain why different conditions can be caused by the same gene mutations.

Where is the PIK3CA gene located?

Cytogenetic Location: 3q26.3

Molecular Location on chromosome 3: base pairs 179,148,113 to 179,235,136

The PIK3CA gene is located on the long (q) arm of chromosome 3 at position 26.3.

The PIK3CA gene is located on the long (q) arm of chromosome 3 at position 26.3.

More precisely, the PIK3CA gene is located from base pair 179,148,113 to base pair 179,235,136 on chromosome 3.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about PIK3CA?

You and your healthcare professional may find the following resources about PIK3CA helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the PIK3CA gene or gene products?

  • p110-alpha
  • phosphatidylinositol 3-kinase, catalytic, 110-KD, alpha
  • phosphatidylinositol 3-kinase, catalytic, alpha polypeptide
  • phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha
  • phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
  • phosphoinositide-3-kinase, catalytic, alpha polypeptide
  • PI3K
  • PI3K-alpha
  • PI3-kinase p110 subunit alpha
  • PK3CA_HUMAN
  • ptdIns-3-kinase subunit p110-alpha
  • serine/threonine protein kinase PIK3CA

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding PIK3CA?

acids ; adipocytes ; adipose tissue ; amino acid ; arginine ; cancer ; catalytic ; cell ; cell proliferation ; colon ; colorectal ; congenital ; disability ; enzyme ; fat cells ; gene ; histidine ; hyperplasia ; inherited ; intestine ; kinase ; leucine ; lysine ; malformation ; megalencephaly ; mosaicism ; mutation ; ovary ; oxygen ; phosphate ; phosphorus ; phosphorylation ; proliferation ; protein ; rectum ; serine ; stomach ; subunit ; syndrome ; threonine ; tissue ; tumor ; vascular

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Gene Review: PIK3CA-Related Segmental Overgrowth (http://www.ncbi.nlm.nih.gov/books/NBK153722)
  • Graupera M, Guillermet-Guibert J, Foukas LC, Phng LK, Cain RJ, Salpekar A, Pearce W, Meek S, Millan J, Cutillas PR, Smith AJ, Ridley AJ, Ruhrberg C, Gerhardt H, Vanhaesebroeck B. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008 May 29;453(7195):662-6. doi: 10.1038/nature06892. Epub 2008 Apr 30. (http://www.ncbi.nlm.nih.gov/pubmed/18449193?dopt=Abstract)
  • Hawkins PT, Anderson KE, Davidson K, Stephens LR. Signalling through Class I PI3Ks in mammalian cells. Biochem Soc Trans. 2006 Nov;34(Pt 5):647-62. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17052169?dopt=Abstract)
  • Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML. Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet. 2012 Jun 8;90(6):1108-15. doi: 10.1016/j.ajhg.2012.05.006. Epub 2012 May 31. (http://www.ncbi.nlm.nih.gov/pubmed/22658544?dopt=Abstract)
  • Lee JH, Huynh M, Silhavy JL, Kim S, Dixon-Salazar T, Heiberg A, Scott E, Bafna V, Hill KJ, Collazo A, Funari V, Russ C, Gabriel SB, Mathern GW, Gleeson JG. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat Genet. 2012 Jun 24;44(8):941-5. doi: 10.1038/ng.2329. (http://www.ncbi.nlm.nih.gov/pubmed/22729223?dopt=Abstract)
  • Lindhurst MJ, Parker VE, Payne F, Sapp JC, Rudge S, Harris J, Witkowski AM, Zhang Q, Groeneveld MP, Scott CE, Daly A, Huson SM, Tosi LL, Cunningham ML, Darling TN, Geer J, Gucev Z, Sutton VR, Tziotzios C, Dixon AK, Helliwell T, O'Rahilly S, Savage DB, Wakelam MJ, Barroso I, Biesecker LG, Semple RK. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet. 2012 Jun 24;44(8):928-33. doi: 10.1038/ng.2332. (http://www.ncbi.nlm.nih.gov/pubmed/22729222?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5290)
  • OMIM: PHOSPHATIDYLINOSITOL 3-KINASE, CATALYTIC, ALPHA (http://omim.org/entry/171834)
  • Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL; Finding of Rare Disease Genes (FORGE) Canada Consortium, Majewski J, Bulman DE, O'Driscoll M, Shendure J, Graham JM Jr, Boycott KM, Dobyns WB. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012 Jun 24;44(8):934-40. doi: 10.1038/ng.2331. (http://www.ncbi.nlm.nih.gov/pubmed/22729224?dopt=Abstract)
  • Zhao L, Vogt PK. Class I PI3K in oncogenic cellular transformation. Oncogene. 2008 Sep 18;27(41):5486-96. doi: 10.1038/onc.2008.244. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18794883?dopt=Abstract)
  • Zhao L, Vogt PK. Hot-spot mutations in p110alpha of phosphatidylinositol 3-kinase (pI3K): differential interactions with the regulatory subunit p85 and with RAS. Cell Cycle. 2010 Feb 1;9(3):596-600. (http://www.ncbi.nlm.nih.gov/pubmed/20009532?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2014
Published: December 16, 2014