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PIGV gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

PIGV gene

The PIGV gene encodes an enzyme critical for the production of GPI anchors, and its dysfunction is the primary cause of Mabry syndrome.

Normal Function

The PIGV gene provides instructions for making an enzyme called GPI mannosyltransferase 2. This enzyme takes part in a series of steps that produce a molecule called a glycosylphosphatidylinositol (GPI) anchor. Specifically, GPI mannosyltransferase 2 adds the second of three molecules of a complex sugar called mannose to the GPI anchor. This step takes place in the endoplasmic reticulum. The complete GPI anchor attaches to various proteins, which then bind to the outer surface of the cell membrane to ensure the protein is available when needed.

Health Conditions Related to Genetic Changes

Mabry syndrome

At least 14 mutations in the PIGV gene have been found to cause Mabry syndrome, a condition characterized by intellectual disability, distinctive facial features, and increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia). These mutations change single amino acids in the GPI mannosyltransferase 2 enzyme, making it less able to add mannose to the forming GPI anchor.

Because the incomplete GPI anchor cannot attach to proteins, those proteins cannot bind to the cell membrane and are released from the cell. Alkaline phosphatase is normally attached to a GPI anchor; when this anchoring is impaired, the enzyme is released into the blood, causing hyperphosphatasia. Other signs and symptoms of the syndrome are likely due to a general lack of proper GPI anchoring of proteins to cell membranes.

Frequently Asked Questions

Beyond intellectual disability and facial features, the lack of proper GPI anchoring can lead to various systemic issues. Patients may experience hearing loss, vision problems, and skeletal abnormalities. Because alkaline phosphatase is released into the blood instead of being anchored to cells, bone metabolism may be affected. Long-term monitoring is required to manage potential neurological decline, speech difficulties, and associated organ system involvement that arises from the general dysfunction of membrane-bound proteins.
Diagnosis typically begins with clinical evaluation for intellectual disability and distinctive facial features, followed by blood tests measuring alkaline phosphatase levels. Hyperphosphatasia, or significantly elevated alkaline phosphatase, is a hallmark sign. Definitive diagnosis is confirmed through genetic testing that identifies specific mutations in the PIGV gene, often involving sequencing to detect changes in the GPI mannosyltransferase 2 enzyme.
Currently, there is no cure that replaces the missing enzyme function. Treatment is supportive and focuses on managing symptoms. This includes speech and language therapy, occupational therapy, and special education services to address intellectual disabilities. Medical management may involve monitoring and treating specific complications such as hearing loss or bone health issues. Research into gene therapy or enzyme replacement strategies is ongoing, but no standard pharmacological intervention exists yet to restore GPI anchor production.
Mabry syndrome is usually caused by de novo mutations, meaning the genetic change occurs spontaneously in the egg or sperm cell or in the early embryo, so it is not typically inherited from a parent. However, if a parent has a mild or undiagnosed form of the condition or carries a balanced translocation, there is a small risk of recurrence. Genetic counseling is recommended for families to assess specific inheritance patterns and recurrence risks based on the family history and genetic test results.
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.

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