PGAP3

Chr 17AR

post-GPI attachment to proteins phospholipase 3

Also known as: AGLA546, CAB2, PERLD1, PP1498, hCOS16

NCBI Gene: 93210 ENSG00000161395 UniProt: Q96FM1 OMIM: 611801

This gene encodes a GPI-specific phospholipase that removes unsaturated fatty acids from GPI anchors in the Golgi apparatus, which is critical for proper integration of GPI-anchored proteins into lipid rafts. Mutations cause hyperphosphatasia with impaired intellectual development syndrome 4, an autosomal recessive disorder characterized by cognitive disability and elevated alkaline phosphatase levels. The gene shows tolerance to loss-of-function variants (pLI 0.002, LOEUF 0.83), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a glycosylphosphatidylinositol (GPI)-specific phospholipase that primarily localizes to the Golgi apparatus. This ubiquitously expressed gene is predicted to encode a seven-transmembrane protein that removes unsaturated fatty acids from the sn-2 position of GPI. The remodeling of the constituent fatty acids on GPI is thought to be important for the proper association between GPI-anchored proteins and lipid rafts. The tethering of proteins to plasma membranes via posttranslational GPI-anchoring is thought to play a role in protein sorting and trafficking. Mutations in this gene cause an autosomal recessive form of neurologic hyperphosphatasia with cognitive disability (HPMRS4). Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hyperphosphatasia with impaired intellectual development syndrome 4MIM #615716

Clinical highlights

Gene-disease validity (ClinGen)

hyperphosphatasia with intellectual disability syndrome 4 · 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

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P/LP missense

0.83

LOEUF

LOF

Mechanism· G2P