PGAP1 (Post-GPI Attachment to Proteins 1): Gene, Function, and Disease Associations
A comprehensive overview of the PGAP1 gene, its role in GPI anchor remodeling, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | PGAP1 |
|---|---|
| Full Name | post-GPI attachment to proteins 1 |
| Gene Type | protein coding |
| Chromosomal Location | 2q33.1 |
| NCBI Gene ID | 80055 ncbi.nlm.nih.gov/gene/80055 |
| Ensembl ID | ENSG00000157110 |
| UniProt ID | Q75T13 |
| OMIM ID | 611655 |
| HGNC ID | 25712 |
| Aliases | FLJ21820, GPI inositol-deacylase |
Description
PGAP1 (post-GPI attachment to proteins 1) encodes an enzyme involved in the remodeling of glycosylphosphatidylinositol (GPI) anchors. Specifically, it catalyzes the deacetylation of inositol, a step required for the proper maturation of GPI-anchored proteins. This gene is essential for the correct sorting and function of GPI-anchored proteins, which play roles in cell signaling, adhesion, and immunity. Mutations in PGAP1 are associated with intellectual disability and other neurodevelopmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive 42 | Loss-of-function mutations impair GPI anchor remodeling, leading to defective GPI-anchored protein expression on cell surfaces, affecting neuronal development. | OMIM #616589; ClinVar submissions |
| Hyperphosphatasia with intellectual disability syndrome (HPMRS) (in some cases) | Biallelic mutations in PGAP1 cause a phenotype overlapping with HPMRS, characterized by elevated serum alkaline phosphatase and intellectual disability. | OMIM #616589; case reports in PubMed |
| Developmental delay and seizures | PGAP1 mutations disrupt GPI anchor biosynthesis, affecting synaptic function and neuronal excitability. | ClinVar and literature (e.g., PMID 25356898) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.4 | Medium |
| Testis | 8.9 | Low |
| Kidney | 7.2 | Low |
| Liver | 5.1 | Low |
| Lung | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.5 | Embryonic kidney cells; moderate expression |
| HeLa | 8.2 | Cervical carcinoma; moderate expression |
| K562 | 6.7 | Leukemia; low expression |
| HepG2 | 5.9 | Liver carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Ter) | Nonsense | Rare | Loss of function; premature truncation |
| c.1576G>A (p.Gly526Arg) | Missense | Rare | Likely damaging; affects enzyme activity |
| c.2002delC (p.Leu668TrpfsTer3) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most PGAP1 mutations are loss-of-function, leading to reduced or absent deacylase activity, impairing GPI anchor remodeling and causing disease.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PGAP1.
Dominant Negative (DN)
No dominant-negative effects have been documented; PGAP1 mutations are typically recessive.
View complete mutation data：
Gene Ontology (GO)
| • GPI inositol-deacylase activity | • hydrolase activity |
| • membrane | • GPI-anchor biosynthetic process |
| • protein glycosylation |
Pathways
• GPI anchor biosynthesis
• Metabolism of proteins
• Post-translational protein modification
Protein Summary
The PGAP1 protein is a transmembrane enzyme localized to the endoplasmic reticulum (ER) and Golgi apparatus. It catalyzes the removal of an acetyl group from the inositol ring of GPI anchors, a critical step in GPI lipid remodeling. This remodeling is necessary for the efficient transport of GPI-anchored proteins to the plasma membrane and for their association with lipid rafts. Defects in PGAP1 lead to abnormal GPI-anchored protein expression, contributing to neurodevelopmental phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGAP1 Knockout HEK293 Cell Line | EDJ-KQ9440 | Human | 80055 | Details Get a Quote |
| PGAP1 Knockout A-549 Cell Line | EDJ-KQ36120 | Human | 80055 | Details Get a Quote |
| PGAP1 Knockout HCT 116 Cell Line | EDJ-KQ36121 | Human | 80055 | Details Get a Quote |
| PGAP1 Knockout HeLa Cell Line | EDJ-KQ36122 | Human | 80055 | Details Get a Quote |
