PIGA
Chr XXLRphosphatidylinositol glycan anchor biosynthesis class A
Also known as: GPI3, MCAHS2, NEDEPH, PIG-A, PNH1
The protein is essential for the first step of GPI anchor biosynthesis, catalyzing the synthesis of N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI), which is required for anchoring proteins to cell surfaces. Germline mutations cause X-linked recessive multiple congenital anomalies-hypotonia-seizures syndrome and neurodevelopmental disorder with epilepsy and hemochromatosis, while somatic mutations lead to the acquired hematologic condition paroxysmal nocturnal hemoglobinuria. Disease predominantly results from loss-of-function mutations disrupting GPI anchor synthesis.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
PIGA · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
RACE 2: a Long Term Follow-up of Patients Participating in the RACE Trial
ENROLLING BY INVITATIONMolecular and Clinical Analysis of Bone Marrow Failure: A Secondary Research Study
ENROLLING BY INVITATIONPrecision Medicine in the Treatment of Epilepsy
RECRUITINGA Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202)
ACTIVE NOT RECRUITINGExternal Resources
Links to major genomics databases and tools