PIGA Gene - Phosphatidylinositol Glycan Anchor Biosynthesis Class A
Key regulator of GPI anchor synthesis, associated with PNH and inherited GPI deficiency
Gene Information Card
| Symbol | PIGA |
|---|---|
| Full Name | Phosphatidylinositol Glycan Anchor Biosynthesis Class A |
| Gene Type | Protein coding |
| Chromosomal Location | Xp22.2 |
| NCBI Gene ID | 5277 ncbi.nlm.nih.gov/gene/5277 |
| Ensembl ID | ENSG00000165209 |
| UniProt ID | P37287 |
| OMIM ID | 311770 |
| HGNC ID | 8957 |
| Aliases | GPI3, PIG-A, MGC88584 |
Description
The PIGA gene encodes the catalytic subunit of the phosphatidylinositol N-acetylglucosaminyltransferase (PIG-A) complex, which catalyzes the first step in glycosylphosphatidylinositol (GPI) anchor biosynthesis. GPI anchors are essential for tethering various proteins to the cell surface. Somatic mutations in PIGA cause paroxysmal nocturnal hemoglobinuria (PNH), while germline mutations lead to inherited GPI deficiency (IGD) with multiple congenital anomalies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Paroxysmal Nocturnal Hemoglobinuria (PNH) | Somatic mutation in PIGA in hematopoietic stem cells leads to loss of GPI-anchored proteins (e.g., CD55, CD59) on blood cells, resulting in complement-mediated hemolysis and thrombosis. | ClinVar, OMIM #300818 |
| Inherited GPI Deficiency (IGD) | Germline mutations in PIGA cause a severe multisystem disorder with intellectual disability, seizures, facial dysmorphism, and multiple congenital anomalies. | OMIM #300868, ClinVar |
| PIGA-Related Epilepsy | Hypomorphic mutations in PIGA are associated with early-onset epileptic encephalopathy and developmental delay. | ClinVar, NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 18.5 | Medium |
| Brain (cerebellum) | 12.3 | Medium |
| Lymph node | 10.1 | Medium |
| Liver | 8.7 | Low |
| Heart | 7.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 15.2 | High expression |
| HEK 293 (embryonic kidney) | 12.8 | Moderate expression |
| HeLa (cervical carcinoma) | 11.5 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 9.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | Somatic (PNH) | Loss of function; truncation of PIG-A protein |
| c.1475G>A (p.Trp492*) | Nonsense | Somatic (PNH) | Loss of function; premature stop codon |
| c.1A>G (p.Met1?) | Missense (initiator codon) | Germline (IGD) | Loss of function; no protein translation |
| c.548G>A (p.Arg183Gln) | Missense | Germline (epilepsy) | Hypomorphic; reduced GPI anchor synthesis |
Mutation functional classification
Loss of Function (LOF)
Most PIGA mutations (nonsense, frameshift, initiator codon) result in complete loss of PIG-A enzymatic activity, abolishing GPI anchor biosynthesis.
Gain of Function (GOF)
No gain-of-function mutations reported for PIGA.
Dominant Negative (DN)
No dominant-negative mutations reported; PIGA is X-linked and hemizygous in males, with somatic mutations causing clonal expansion in PNH.
View complete mutation data：
Gene Ontology (GO)
| • attachment of GPI anchor to protein (GO:0016255) | • glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex (GO:0000506) |
| • phosphatidylinositol N-acetylglucosaminyltransferase activity (GO:0017176) | • endoplasmic reticulum membrane (GO:0005789) |
| • plasma membrane (GO:0005886) |
Pathways
• Glycosylphosphatidylinositol (GPI)-anchor biosynthesis (KEGG hsa00563)
• Metabolism of proteins (Reactome R-HSA-392499)
Protein Summary
The PIG-A protein (UniProt P37287) is a 484-amino acid integral membrane protein localized to the endoplasmic reticulum. It functions as the catalytic subunit of the GPI-N-acetylglucosaminyltransferase complex, transferring N-acetylglucosamine to phosphatidylinositol. Loss of PIG-A function eliminates GPI anchor synthesis, leading to deficiency of all GPI-anchored proteins on the cell surface.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIGA Knockout HEK293 Cell Line | EDJ-KQ14759 | Human | 5277 | Details Get a Quote |
| PIGA Knockout HeLa Cell Line | EDJ-KQ43915 | Human | 5277 | Details Get a Quote |
| PIGA Knockout A-549 Cell Line | EDJ-KQ45142 | Human | 5277 | Details Get a Quote |
| PIGA Knockout HCT 116 Cell Line | EDJ-KQ45143 | Human | 5277 | Details Get a Quote |
| PIGA Knockout K-562 Cell Line | EDJ-KZ397 | Human | 5277 | Details Get a Quote |
