GPAA1

Chr 8AR

glycosylphosphatidylinositol anchor attachment 1

Also known as: GAA1, GPIBD15, hGAA1

NCBI Gene: 8733 ENSG00000197858 UniProt: O43292 OMIM: 603048

The protein is a component of the GPI-anchor transamidase complex that catalyzes the linkage between proteins and GPI anchors, enabling proteins to attach to cell surface membranes. Mutations cause glycosylphosphatidylinositol biosynthesis defect 15, which follows autosomal recessive inheritance. This gene is highly intolerant to loss-of-function variants (pLI near 1), indicating that complete loss of function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Posttranslational glycosylphosphatidylinositol (GPI) anchor attachment serves as a general mechanism for linking proteins to the cell surface membrane. The protein encoded by this gene presumably functions in GPI anchoring at the GPI transfer step. The mRNA transcript is ubiquitously expressed in both fetal and adult tissues. The anchor attachment protein 1 contains an N-terminal signal sequence, 1 cAMP- and cGMP-dependent protein kinase phosphorylation site, 1 leucine zipper pattern, 2 potential N-glycosylation sites, and 8 putative transmembrane domains. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Glycosylphosphatidylinositol biosynthesis defect 15MIM #617810

Clinical highlights

Gene-disease validity (ClinGen)

glycosylphosphatidylinositol biosynthesis defect 15 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

LOF

Mechanism· G2P