Meyahealth
HomeGeneticsGenePIK3R2 gene
Back to Gene
PIK3R2 gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PIK3R2 gene

The PIK3R2 gene regulates the PI3K enzyme, and its mutations are linked to brain development disorders characterized by abnormal cell growth.

Normal Function

The PIK3R2 gene provides instructions for making the P85β subunit, which regulates the activity of the enzyme phosphatidylinositol 3-kinase (PI3K). PI3K is a kinase that phosphorylates signaling molecules, triggering the PI3K-AKT-mTOR pathway. This pathway is essential for critical cell functions, including protein synthesis, cell growth and division, and cell survival. It is particularly important for the normal development of the brain.

Health Conditions Related to Genetic Changes

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome

Mutations in the PIK3R2 gene cause MPPH syndrome, a rare condition affecting brain development. Symptoms include:

  • Megalencephaly (unusually large brain and head size)
  • Abnormalities of the brain's structure
  • Polydactyly (extra fingers or toes)

The mutations associated with this syndrome are "gain-of-function," meaning they increase the activity of PI3K. This enhanced activity increases signaling through the PI3K-AKT-mTOR pathway, leading to excessive cell growth and division. In the brain, this results in rapid and abnormal growth starting before birth. The extra digits observed in some patients are likely related to abnormal cell proliferation in the developing hands and feet.

Frequently Asked Questions

PIK3R2 mutation is confirmed by targeted next‑generation sequencing (NGS) panels that include the gene, or by whole‑exome sequencing if a panel is negative. The test is usually done on a blood sample; for prenatal diagnosis, a chorionic villus sampling or amniocentesis sample is used. The results are interpreted by a clinical geneticist who correlates them with the patient’s clinical features.
PIK3R2 mutations causing MPPH syndrome are typically autosomal dominant. If one parent carries a pathogenic variant, each pregnancy has a 50 % chance of inheriting the mutation. Prenatal testing or pre‑implantation genetic diagnosis can be discussed with a genetic counselor to assess risk and options.
In infants with PIK3R2 mutations, a rapidly increasing head circumference (measured at birth and then at regular intervals), abnormal brain imaging findings such as polymicrogyria, and early motor delays or seizures are common. Early referral to a pediatric neurologist and neuroimaging (MRI) can help identify these signs before significant disability develops.
Management is multidisciplinary: surgical intervention may be needed for hydrocephalus or refractory seizures; developmental therapies (physical, occupational, speech) are essential; regular ophthalmologic and audiologic evaluations are recommended; and genetic counseling should be offered to the family. There is no curative treatment, so the focus is on optimizing function and quality of life.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

Meyahealth

Ⓒ 2026. All rights reserved by MEYA

About UsTerms & PolicyFAQ