PGAP2

Chr 11

post-GPI attachment to proteins 2

Also known as: CWH43-N, FRAG1, HPMRS3, MRT17, MRT21

NCBI Gene: 27315 ENSG00000148985 UniProt: Q9UHJ9

The protein catalyzes fatty acid remodeling of glycosylphosphatidylinositol (GPI) anchors by replacing unsaturated acyl chains with saturated stearoyl chains, which is critical for proper integration of GPI-anchored proteins into lipid rafts. Mutations cause autosomal recessive hyperphosphatasia with impaired intellectual development syndrome 3, characterized by elevated alkaline phosphatase levels and intellectual disability. The gene is highly constrained against loss-of-function variation (pLI 0.93, LOEUF 0.36), indicating that complete loss of protein function is poorly tolerated.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene plays a role in the maturation of glycosylphosphatidylinositol (GPI) anchors on GPI-anchored proteins. Mutations in this gene are associated with an autosomal recessive syndrome characterized by hyperphosphatasia and intellectual disability. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHyperphosphatasia with impaired intellectual development syndrome 3

Clinical highlights

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

0.36

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429