PIGA
Function
Catalytic subunit of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.
Involvement in disease
Paroxysmal nocturnal hemoglobinuria 1
PNH1
A disorder characterized by hemolytic anemia with hemoglobinuria, thromboses in large vessels, and a deficiency in hematopoiesis. Red blood cell breakdown with release of hemoglobin into the urine is manifested most prominently by dark-colored urine in the morning.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Multiple congenital anomalies-hypotonia-seizures syndrome 2
MCAHS2
An X-linked recessive developmental disorder characterized by dysmorphic features, neonatal hypotonia, myoclonic seizures, and variable congenital anomalies involving the central nervous, cardiac, and urinary systems. Most affected individuals die in infancy.
None
The disease is caused by variants affecting the gene represented in this entry.
Neurodevelopmental disorder with epilepsy and hemochromatosis
NEDEPH
An X-liked recessive disorder characterized by severe developmental delay, intellectual disability, early-onset epilepsy, and early systemic iron overload resulting in juvenile-onset hemochromatosis. Variable additional features may include joint contractures, visual or hearing impairment, and skin abnormalities.
None
The disease is caused by variants affecting the gene represented in this entry. PIGA deficiency causes disruption of iron homeostasis, due to failure to attach GPI anchors to hemojuvelin (HJV), a BMP coreceptor that regulates hepcidin (HAMP) expression. HAMP is an essential regulator of iron absorption and distribution across tissues. PIGA-deficient cells lack hemojuvelin surface expression and show significantly lower HAMP mRNA levels compared to control cells.
Pathway
Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor biosynthesis.
Sequence Similarities
Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass membrane protein
Alternative names
Phosphatidylinositol N-acetylglucosaminyltransferase subunit A, GlcNAc-PI synthesis protein, Phosphatidylinositol-glycan biosynthesis class A protein, PIG-A, PIGA