The PIGA gene provides instructions for making a protein called phosphatidylinositol glycan class A. This protein takes part in a series of steps that produce a molecule called GPI anchor. Specifically, phosphatidylinositol glycan class A is involved in the first step of the sequence, which produces an intermediate molecule called N-acetylglucosaminyl phosphatidylinositol, or GlcNAc-PI. This step takes place in the endoplasmic reticulum of the cell, a structure involved in protein processing and transport. The PIGA protein forms a complex with several other proteins, and this complex helps to start the reaction that produces GlcNAc-PI.
The GPI anchor, the ultimate product of the sequence, attaches many different proteins to the cell membrane, thereby ensuring that these proteins are available when needed at the surface of the cell.
Health Conditions Related to Genetic Changes
Paroxysmal nocturnal hemoglobinuria
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. In people with paroxysmal nocturnal hemoglobinuria, somatic mutations of the PIGA gene occur in blood-forming cells called hematopoietic stem cells. Hematopoietic stem cells produce red blood cells (erythrocytes) that carry oxygen, white blood cells (leukocytes) that protect the body from infection, and platelets (thrombocytes) that are involved in blood clotting.
Individuals with paroxysmal nocturnal hemoglobinuria have one or more PIGA gene mutations in their hematopoietic stem cells, which leads to abnormal blood cells. As the abnormal hematopoietic stem cells multiply, populations of abnormal blood cells are formed, alongside normal blood cells produced by normal hematopoietic stem cells. The proportion of abnormal blood cells in the body affects the severity of the signs and symptoms of paroxysmal nocturnal hemoglobinuria.
Researchers have identified more than 100 somatic mutations in the PIGA gene. Some of these mutations alter the numbers or types of protein building blocks (amino acids) in phosphatidylinositol glycan class A, which impair its function. Other mutations result in the insertion of a premature stop signal in the instructions for making phosphatidylinositol glycan class A. As a result, an abnormally small protein, which is usually unstable, is produced.More About This Health Condition
MedlinePlus Genetics provides information about Simpson-Golabi-Behmel syndromeMore About This Health Condition
Other Names for This Gene
- GLCNAC-PI synthesis protein
- GPI anchor biosynthesis
- phosphatidylinositol glycan anchor biosynthesis, class A
- phosphatidylinositol glycan anchor biosynthesis, class A (paroxysmal nocturnal hemoglobinuria)
- phosphatidylinositol glycan, class A (paroxysmal nocturnal hemoglobinuria)
- phosphatidylinositol N-acetylglucosaminyltransferase subunit A
- phosphatidylinositol-glycan biosynthesis, class A protein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Brodsky RA, Hu R. PIG-A mutations in paroxysmal nocturnal hemoglobinuria and in normal hematopoiesis. Leuk Lymphoma. 2006 Jul;47(7):1215-21. Review. Citation on PubMed
- Inoue N, Murakami Y, Kinoshita T. Molecular genetics of paroxysmal nocturnal hemoglobinuria. Int J Hematol. 2003 Feb;77(2):107-12. Review. Citation on PubMed
- Mortazavi Y, Merk B, McIntosh J, Marsh JC, Schrezenmeier H, Rutherford TR; BIOMED II Pathophysiology and Treatment of Aplastic Anaemia Study Group. The spectrum of PIG-A gene mutations in aplastic anemia/paroxysmal nocturnal hemoglobinuria (AA/PNH): a high incidence of multiple mutations and evidence of a mutational hot spot. Blood. 2003 Apr 1;101(7):2833-41. Epub 2002 Nov 7. Citation on PubMed
- Rosti V. The molecular basis of paroxysmal nocturnal hemoglobinuria. Haematologica. 2000 Jan;85(1):82-7. Review. Citation on PubMed