PGAP3: Post-GPI Attachment to Proteins 3
A key enzyme in GPI anchor remodeling, linked to inherited glycosylphosphatidylinositol (GPI) biosynthesis defects and hyperphosphatasia with mental retardation syndrome (HPMRS).
Gene Information Card
| Symbol | PGAP3 |
|---|---|
| Full Name | Post-GPI Attachment to Proteins 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q12 |
| NCBI Gene ID | 57105 ncbi.nlm.nih.gov/gene/57105 |
| Ensembl ID | ENSG00000141510 |
| UniProt ID | Q96FM1 |
| OMIM ID | 611801 |
| HGNC ID | 25719 |
| Aliases | PERLD1, MGC26594, dJ1009E9.1 |
Description
PGAP3 encodes a Golgi-resident phospholipase A2 that catalyzes the remodeling of the glycosylphosphatidylinositol (GPI) anchor by removing an unsaturated fatty acid from the sn-2 position of the GPI lipid moiety. This remodeling step is essential for the stable attachment of GPI-anchored proteins (GPI-APs) to the cell surface. Loss-of-function mutations in PGAP3 cause hyperphosphatasia with mental retardation syndrome 4 (HPMRS4), also known as Mabry syndrome, characterized by elevated serum alkaline phosphatase, intellectual disability, seizures, and facial dysmorphism.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperphosphatasia with mental retardation syndrome 4 (HPMRS4) | Loss-of-function mutations impair GPI anchor remodeling, leading to reduced cell surface expression of GPI-APs and elevated serum alkaline phosphatase. | OMIM #616025; ClinVar; multiple case reports |
| Mabry syndrome (HPMRS) | Same mechanism as HPMRS4; PGAP3 is one of several genes (PIGV, PIGO, PIGW, PGAP2) causing this phenotype. | OMIM #239300; ClinVar |
| Intellectual disability, autosomal recessive 55 | PGAP3 mutations identified in consanguineous families with non-syndromic intellectual disability. | ClinVar; PMID: 27745837 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 9.8 | Medium |
| Kidney | 8.2 | Medium |
| Testis | 7.1 | Low |
| Lung | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HeLa | 11.2 | Medium expression |
| K562 | 8.9 | Medium expression |
| HepG2 | 7.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.200C>T (p.Pro67Leu) | Missense | Found in HPMRS4 families | Loss of function; reduced GPI-AP surface expression |
| c.314G>A (p.Arg105Gln) | Missense | Rare variant in intellectual disability | Likely loss of function |
| c.1A>G (p.Met1Val) | Start loss | Reported in HPMRS4 | Complete loss of function |
| c.544_545del (p.Leu182Valfs*5) | Frameshift | Homozygous in affected siblings | Loss of function; premature truncation |
Mutation functional classification
Loss of Function (LOF)
All reported pathogenic PGAP3 mutations are loss-of-function, leading to defective GPI anchor remodeling and reduced cell surface GPI-APs.
Gain of Function (GOF)
No gain-of-function mutations have been described for PGAP3.
Dominant Negative (DN)
No dominant-negative effects reported; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • lipid metabolic process (GO:0006629) | • GPI anchor biosynthetic process (GO:0006506) |
| • lipid catabolic process (GO:0016042) | • phospholipase A2 activity (GO:0004623) |
| • Golgi apparatus (GO:0005794) |
Pathways
• GPI anchor biosynthesis and remodeling (Reactome: R-HSA-163125)
• Post-translational modification: synthesis of GPI-anchored proteins (KEGG: hsa00563)
Protein Summary
PGAP3 is a 324-amino acid protein localized to the Golgi membrane. It functions as a phospholipase A2 that specifically removes an unsaturated fatty acid from the GPI anchor, a critical step for the stable association of GPI-APs with lipid rafts and their transport to the plasma membrane. The protein contains a conserved lipase motif (GXSXG) and is essential for proper GPI-AP function in development and neurobiology.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PGAP3 Knockout HEK293 Cell Line | EDJ-KQ11200 | Human | 93210 | Details Get a Quote |
| PGAP3 Knockout A-549 Cell Line | EDJ-KQ39261 | Human | 93210 | Details Get a Quote |
| PGAP3 Knockout HCT 116 Cell Line | EDJ-KQ39262 | Human | 93210 | Details Get a Quote |
| PGAP3 Knockout HeLa Cell Line | EDJ-KQ39263 | Human | 93210 | Details Get a Quote |
