PGAP2: Post-GPI Attachment to Proteins 2
Key regulator of GPI-anchor remodeling and neurodevelopmental disorders
Gene Information Card
| Symbol | PGAP2 |
|---|---|
| Full Name | Post-GPI Attachment to Proteins 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.4 |
| NCBI Gene ID | 27315 ncbi.nlm.nih.gov/gene/27315 |
| Ensembl ID | ENSG00000148925 |
| UniProt ID | Q9HCN3 |
| OMIM ID | 615787 |
| HGNC ID | 17893 |
| Aliases | PER1, GPI7, MRT17 |
Description
PGAP2 (Post-GPI Attachment to Proteins 2) encodes a protein that catalyzes the remodeling of the glycan core of glycosylphosphatidylinositol (GPI) anchors. This remodeling is essential for the stable attachment of GPI-anchored proteins to the cell surface. The protein is localized to the endoplasmic reticulum and is involved in the removal of an acyl chain from the inositol ring of the GPI anchor. Loss-of-function mutations in PGAP2 lead to impaired GPI-anchor remodeling and are associated with autosomal recessive intellectual disability and other neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 17 (MRT17) | Loss-of-function mutations impair GPI-anchor remodeling, reducing cell surface expression of GPI-anchored proteins | OMIM #615787; multiple case reports with homozygous or compound heterozygous mutations |
| Hyperphosphatasia with intellectual disability syndrome (HPMRS) | Defective GPI-anchor remodeling leads to elevated serum alkaline phosphatase and neurological symptoms | ClinVar; overlapping phenotype with PGAP2 mutations |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 7.1 | Low |
| Liver | 5.9 | Low |
| Heart | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | Embryonic kidney cells |
| HeLa | 8.5 | Cervical cancer cells |
| SH-SY5Y | 7.3 | Neuroblastoma cells |
| HepG2 | 6.1 | Hepatocellular carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of translation initiation, likely loss of function |
| c.337C>T (p.Arg113*) | Nonsense | Rare | Premature stop, loss of function |
| c.518G>A (p.Trp173*) | Nonsense | Rare | Premature stop, loss of function |
| c.649C>T (p.Arg217Trp) | Missense | Rare | Likely damaging to protein function |
Mutation functional classification
Loss of Function (LOF)
Homozygous or compound heterozygous loss-of-function mutations (nonsense, frameshift, start loss) cause autosomal recessive intellectual disability (MRT17) by impairing GPI-anchor remodeling.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • glycosylphosphatidylinositol anchor biosynthetic process (GO:0000506) | • endoplasmic reticulum (GO:0005783) |
| • integral component of membrane (GO:0016021) | • post-GPI attachment to proteins (GO:0043687) |
| • GPI anchor release (GO:0006506) |
Pathways
• GPI-anchor biosynthesis (Reactome: R-HSA-162791)
• Post-GPI attachment to proteins (Reactome: R-HSA-163125)
Protein Summary
PGAP2 is a 247-amino acid transmembrane protein localized to the endoplasmic reticulum. It functions as a deacylase that removes an acyl chain from the inositol ring of the GPI anchor, a critical step in GPI-anchor remodeling. This remodeling is required for the efficient transport and stable cell surface expression of GPI-anchored proteins. The protein contains a conserved domain of unknown function (DUF) and is widely expressed, with highest levels in brain and testis. Mutations in PGAP2 disrupt GPI-anchor remodeling, leading to reduced cell surface GPI-anchored protein levels and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGAP2 Knockout HEK293 Cell Line | EDJ-KQ8758 | Human | 27315 | Details Get a Quote |
| PGAP2 Knockout A-549 Cell Line | EDJ-KQ35014 | Human | 27315 | Details Get a Quote |
| PGAP2 Knockout HCT 116 Cell Line | EDJ-KQ35015 | Human | 27315 | Details Get a Quote |
| PGAP2 Knockout HeLa Cell Line | EDJ-KQ35016 | Human | 27315 | Details Get a Quote |
