PIGT gene
The PIGT gene provides instructions for creating a protein essential for anchoring molecules to the cell surface, with variants linked to rare blood and developmental disorders.
Normal Function
The PIGT gene provides instructions for making a protein called GPI transamidase component PIG-T (shortened to PIG-T protein). This protein is important for the attachment of certain proteins to the cell surface. Specifically, the PIG-T protein attaches (binds) a molecule called a glycosylphosphatidylinositol (GPI) anchor to various proteins inside the cell. After the GPI anchor and protein are bound, the anchor is attached to the outer surface of the cell membrane. Anchored proteins have a variety of roles, including sticking cells to one another, relaying signals into cells, and protecting cells from destruction.
Health Conditions Related to Genetic Changes
Paroxysmal nocturnal hemoglobinuria
Variants (also known as mutations) in the PIGT gene cause a rare form of paroxysmal nocturnal hemoglobinuria (PNH), which is a condition that affects blood cells. People with PNH have episodes of blood in the urine (hemoglobinuria) that results from the breakdown of red blood cells. Other blood cell abnormalities also occur. In addition, individuals with PIGT-related PNH have abnormal inflammation, which can cause:
- Recurrent aseptic meningitis (inflammation of the membranes surrounding the brain and spinal cord not caused by infections)
- A red, itchy rash (known as hives or urticaria)
- Joint pain (arthralgia)
- Inflammatory bowel disease
Affected individuals are born with a germline variant in one copy of the PIGT gene. A second somatic variant, which deletes the other normal copy of the gene, is acquired during the person’s lifetime in a hematopoietic stem cell. Together, these variants severely reduce or eliminate the function of the PIG-T protein. This leads to a shortage of proteins that protect red blood cells, causing premature destruction of these cells (hemolytic anemia) and blood in the urine. Additionally, GPI anchors without attached proteins trigger inflammation in the body.
Other disorders
Variants in the PIGT gene also cause a rare condition called multiple congenital anomalies-hypotonia-seizures syndrome 3. Affected individuals inherit two altered copies of the gene, one from each parent. Symptoms include:
- Delayed development
- Seizures
- Low muscle tone (hypotonia)
- Distinct facial features
- Congenital abnormalities (typically involving the heart, bones, urinary system, or digestive system)
Researchers suspect that a shortage of proteins important for development on the surface of cells impairs the normal development of many body systems.