PIGU Gene - Phosphatidylinositol Glycan Anchor Biosynthesis Class U
Essential Component of the GPI Transamidase Complex in Glycosylphosphatidylinositol (GPI) Anchor Synthesis
Gene Information Card
| Symbol | PIGU |
|---|---|
| Full Name | Phosphatidylinositol glycan anchor biosynthesis class U |
| Gene Type | Protein coding |
| Chromosomal Location | 20q11.22 |
| NCBI Gene ID | 128869 ncbi.nlm.nih.gov/gene/128869 |
| Ensembl ID | ENSG00000101464 |
| UniProt ID | Q9H490 |
| OMIM ID | 608528 |
| HGNC ID | 15791 |
| Aliases | GPI7, MGC2650, phosphatidylinositol glycan anchor biosynthesis class U protein |
Description
PIGU encodes a subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, which is essential for attaching GPI anchors to proteins. The GPI anchor is a glycolipid structure that tethers proteins to the cell membrane. PIGU is required for the recognition and cleavage of the GPI attachment signal peptide and the subsequent transfer of the GPI anchor to the protein. Mutations in PIGU cause inherited GPI deficiency, leading to neurological disorders including intellectual disability and seizures.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| GPI biosynthesis deficiency type 24 (GPIBD24) | Loss-of-function mutations in PIGU impair GPI transamidase activity, reducing cell surface GPI-anchored protein expression. | ClinVar, OMIM #617816 |
| Intellectual disability, autosomal recessive 73 (MRT73) | Biallelic PIGU variants disrupt GPI anchor synthesis, affecting neuronal development and function. | OMIM #618590 |
| Seizures, early-onset, with developmental delay | Reduced GPI-anchored protein levels due to PIGU deficiency lead to synaptic dysfunction and epileptic activity. | ClinVar, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 10.2 | Medium |
| Kidney | 8.9 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.0 | High expression |
| K562 | 9.5 | Medium expression |
| HeLa | 7.8 | Medium expression |
| HepG2 | 5.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, likely loss of function |
| c.370C>T (p.Arg124*) | Nonsense | Rare | Premature stop, loss of function |
| c.632G>A (p.Arg211Gln) | Missense | Rare | Impaired GPI transamidase activity |
| c.1000C>T (p.Arg334Trp) | Missense | Rare | Reduced protein stability and function |
Mutation functional classification
Loss of Function (LOF)
Most PIGU mutations are loss-of-function, leading to reduced GPI-anchored protein expression on the cell surface.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PIGU.
Dominant Negative (DN)
No dominant-negative mutations have been described for PIGU.
View complete mutation data：
Gene Ontology (GO)
| • GPI anchor biosynthetic process (GO:0006506) | • GPI-anchor transamidase activity (GO:0016255) |
| • membrane (GO:0016020) | • endoplasmic reticulum membrane (GO:0005789) |
| • integral component of membrane (GO:0016021) |
Pathways
• GPI anchor biosynthesis (Reactome: R-HSA-162791)
• Metabolism of proteins (Reactome: R-HSA-392499)
Protein Summary
PIGU is a 435-amino acid transmembrane protein localized to the endoplasmic reticulum membrane. It is a component of the GPI transamidase complex, which also includes PIGK, PIGS, PIGT, and GPAA1. PIGU is thought to be involved in substrate recognition and complex stability. The protein contains a conserved domain (DUF) of unknown function but is essential for GPI anchoring. Defects in PIGU lead to reduced cell surface expression of GPI-anchored proteins such as CD55 and CD59.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIGU Knockout HEK293 Cell Line | EDJ-KQ1978 | Human | 128869 | Details Get a Quote |
| PIGU Knockout A-549 Cell Line | EDJ-KQ23320 | Human | 128869 | Details Get a Quote |
| PIGU Knockout HCT 116 Cell Line | EDJ-KQ23322 | Human | 128869 | Details Get a Quote |
| PIGU Knockout HeLa Cell Line | EDJ-KQ23323 | Human | 128869 | Details Get a Quote |
