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The official name of this gene is “phosphoinositide-3-kinase, regulatory subunit 1 (alpha).”
PIK3R1 is the gene's official symbol. The PIK3R1 gene is also known by other names, listed below.
The PIK3R1 gene provides instructions for making a part (subunit) of an enzyme called phosphatidylinositol 3-kinase (PI3K). The primary function of the subunit is to regulate the enzyme's activity. Several slightly different versions of this regulatory subunit are produced from the PIK3R1 gene; the most abundant of these is called p85α.
PI3K is a kinase, which means that it 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, 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, including insulin, which helps control blood sugar levels. PI3K signaling may also play a role in the maturation of fat cells (adipocytes).
The PIK3R1 gene belongs to a family of genes called SH2 domain containing (SH2 domain containing).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
At least seven mutations in the PIK3R1 gene have been reported to cause a condition known as short stature, hyperextensibility, hernia, ocular depression, Rieger anomaly, and teething delay (often called SHORT syndrome). This condition is characterized by signs and symptoms affecting many parts of the body, including the skin, eyes, teeth, and joints. The most common mutation, which has been identified in at least 10 affected families, changes a single protein building block (amino acid) in the regulatory subunit of PI3K. Specifically, the amino acid arginine is replaced with the amino acid tryptophan at protein position 649 (written as Arg649Trp or R649W). Mutations in the PIK3R1 gene alter the structure of the subunit, which reduces the ability of PI3K to participate in cell signaling. Because the mutations reduce the enzyme's activity, they are described as "loss-of-function" mutations.
Researchers are working to determine how PIK3R1 gene mutations lead to the specific features of SHORT syndrome. PI3K's role in insulin activity may be related to insulin resistance and diabetes, which are problems with blood sugar regulation that are found in some people with SHORT syndrome. Abnormal adipocyte maturation might contribute to a lack of fatty tissue under the skin (lipoatrophy), which is another common feature of the condition. It is unclear how reduced PI3K signaling is associated with the other signs and symptoms of SHORT syndrome.
Some gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic PIK3R1 gene mutations have been identified in some cancers of the uterine lining (endometrial cancers) and in a form of brain cancer called glioblastoma. Less commonly, somatic mutations in the PIK3R1 gene have been found in cancers of the colon, ovary, and breast.
Cancer-associated changes in the PIK3R1 gene alter the regulatory subunit such that it can no longer control the activity of PI3K, which increases PI3K signaling dramatically. Because the genetic changes enhance the activity of the enzyme, they are classified as "gain-of-function" mutations. Increased PI3K signaling appears to promote the uncontrolled cell growth and division that is characteristic of cancerous tumors. It is unclear why these mutations seem to be more common in some types of cancer than in others.
Cytogenetic Location: 5q13.1
Molecular Location on chromosome 5: base pairs 68,215,755 to 68,301,820
The PIK3R1 gene is located on the long (q) arm of chromosome 5 at position 13.1.
More precisely, the PIK3R1 gene is located from base pair 68,215,755 to base pair 68,301,820 on chromosome 5.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about PIK3R1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
adipocytes ; amino acid ; cancer ; cell ; colon ; depression ; diabetes ; endometrial ; enzyme ; fat cells ; fatty tissue ; gene ; glioblastoma ; hernia ; insulin ; insulin resistance ; kinase ; mutation ; oncogene ; ovary ; oxygen ; phosphate ; phosphorus ; phosphorylation ; protein ; short stature ; stature ; subunit ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
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.