PIGA

Chr XXLR

phosphatidylinositol glycan anchor biosynthesis class A

Also known as: GPI3, MCAHS2, NEDEPH, PIG-A, PNH1

NCBI Gene: 5277 ENSG00000165195 UniProt: P37287 OMIM: 311770

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a protein required for synthesis of N-acetylglucosaminyl phosphatidylinositol (GlcNAc-PI), the first intermediate in the biosynthetic pathway of GPI anchor. The GPI anchor is a glycolipid found on many blood cells and which serves to anchor proteins to the cell surface. Paroxysmal nocturnal hemoglobinuria, an acquired hematologic disorder, has been shown to result from mutations in this gene. Alternate splice variants have been characterized. A related pseudogene is located on chromosome 12. [provided by RefSeq, Jun 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Multiple congenital anomalies-hypotonia-seizures syndrome 2MIM #300868

XLR

Neurodevelopmental disorder with epilepsy and hemochromatosisMIM #301072

XLR

Paroxysmal nocturnal hemoglobinuria, somaticMIM #300818

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· G2P