GPAA1 Gene - Glycosylphosphatidylinositol Anchor Attachment 1
Essential Component of the GPI Transamidase Complex Involved in GPI Anchor Biosynthesis
Gene Information Card
| Symbol | GPAA1 |
|---|---|
| Full Name | Glycosylphosphatidylinositol Anchor Attachment 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 8q24.3 |
| NCBI Gene ID | 8733 ncbi.nlm.nih.gov/gene/8733 |
| Ensembl ID | ENSG00000120885 |
| UniProt ID | O43292 |
| OMIM ID | 603048 |
| HGNC ID | 4446 |
| Aliases | GAA1, GPI anchor attachment 1, hGAA1 |
Description
GPAA1 encodes a subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which is essential for attaching GPI anchors to proteins. The GPI anchor is a glycolipid that tethers proteins to the cell membrane. GPAA1 is the catalytic component that cleaves the GPI attachment signal peptide and transfers the GPI anchor to the protein. Mutations in GPAA1 cause inherited GPI deficiency (IGD) and are associated with congenital disorders of glycosylation (CDG).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inherited GPI deficiency (IGD) | Loss-of-function mutations in GPAA1 impair GPI anchor attachment, leading to reduced cell surface expression of GPI-anchored proteins. | ClinVar, OMIM |
| Congenital disorder of glycosylation (GPAA1-CDG) | Biallelic pathogenic variants disrupt GPI transamidase activity, causing multisystem developmental abnormalities. | OMIM #603048, NCBI Gene |
| Intellectual disability with seizures | GPAA1 mutations result in neurological phenotypes including developmental delay, epilepsy, and hypotonia. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 10.1 | Medium |
| Heart | 7.4 | Low |
| Lung | 9.6 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression |
| HeLa | 11.8 | Medium expression |
| K562 | 9.4 | Low expression |
| HepG2 | 10.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.404G>A (p.Arg135Gln) | Missense | Rare | Loss of function; reduced GPI transamidase activity |
| c.1075C>T (p.Arg359*) | Nonsense | Rare | Premature stop; loss of protein function |
| c.1486_1487del (p.Leu496Glufs*12) | Frameshift | Rare | Loss of function; truncated protein |
Mutation functional classification
Loss of Function (LOF)
Most reported GPAA1 mutations are loss-of-function, leading to reduced GPI anchor attachment and decreased surface expression of GPI-anchored proteins.
Gain of Function (GOF)
No gain-of-function mutations have been reported for GPAA1.
Dominant Negative (DN)
No dominant-negative mutations have been described for GPAA1.
View complete mutation data：
Gene Ontology (GO)
| • GPI anchor biosynthetic process (GO:0006506) | • GPI-anchor transamidase activity (GO:0015926) |
| • Endoplasmic reticulum membrane (GO:0005789) | • Integral component of membrane (GO:0016021) |
Pathways
• GPI anchor biosynthesis (Reactome: R-HSA-162791)
• Post-translational protein modification (Reactome: R-HSA-597592)
Protein Summary
GPAA1 is a 621-amino acid transmembrane protein localized to the endoplasmic reticulum. It forms the catalytic subunit of the GPI transamidase complex, which also includes PIGK, PIGS, PIGT, and PIGU. The protein cleaves the C-terminal GPI attachment signal peptide of nascent proteins and mediates the transfer of a preassembled GPI anchor. Defects in GPAA1 cause autosomal recessive GPI deficiency disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPAA1 Knockout HEK293 Cell Line | EDJ-KQ3429 | Human | 8733 | Details Get a Quote |
| GPAA1 Knockout HCT 116 Cell Line | EDJ-KQ25151 | Human | 8733 | Details Get a Quote |
| GPAA1 Knockout HeLa Cell Line | EDJ-KQ25152 | Human | 8733 | Details Get a Quote |
| GPAA1 Knockout A-549 Cell Line | EDJ-KQ23766 | Human | 8733 | Details Get a Quote |
