PIGK: GPI-Transamidase Component and Key Player in Glycosylphosphatidylinositol Anchor Biosynthesis
Comprehensive biomedical overview of PIGK (Phosphatidylinositol Glycan Anchor Biosynthesis Class K), including gene card, expression, mutations, and associated diseases.
Gene Information Card
| Symbol | PIGK |
|---|---|
| Full Name | Phosphatidylinositol Glycan Anchor Biosynthesis Class K |
| Gene Type | Protein-coding |
| Chromosomal Location | 1p31.1 |
| NCBI Gene ID | 10026 ncbi.nlm.nih.gov/gene/10026 |
| Ensembl ID | ENSG00000142892 |
| UniProt ID | Q92643 |
| OMIM ID | 605087 |
| HGNC ID | 8965 |
| Aliases | GPI8, PIG-K, hGPI8 |
Description
PIGK encodes the catalytic subunit of the glycosylphosphatidylinositol (GPI) transamidase complex. This complex is essential for cleaving the GPI signal peptide and attaching GPI anchors to proteins, tethering them to the cell membrane. PIGK is a cysteine protease that mediates the transamidation reaction. Defects in PIGK cause inherited GPI deficiency (IGD) and are associated with various developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inherited GPI Deficiency (IGD) | Loss-of-function mutations in PIGK impair GPI anchor attachment, leading to reduced cell surface GPI-anchored proteins and multisystem developmental abnormalities. | OMIM #605087; PMID: 23352259 |
| Developmental and Epileptic Encephalopathy | Biallelic PIGK variants disrupt GPI anchor synthesis, associated with seizures, intellectual disability, and brain malformations. | ClinVar; PMID: 31036916 |
| Hypophosphatasia-like Phenotype | PIGK deficiency may mimic hypophosphatasia due to defective GPI-anchored alkaline phosphatase. | OMIM; PMID: 23352259 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.2 | Low |
| Kidney | 10.1 | Medium |
| Heart | 9.8 | Medium |
| Testis | 15.3 | High |
| Lung | 7.6 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 14.2 | High expression |
| K562 | 11.5 | Medium expression |
| HeLa | 9.8 | Medium expression |
| HepG2 | 8.1 | Low 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 catalytic activity; associated with IGD |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe phenotype |
| c.649C>T (p.Arg217*) | Nonsense | Rare | Premature stop; loss of function |
| c.1019_1020del (p.Glu340Glyfs*12) | Frameshift | Rare | Truncated protein; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported PIGK mutations are loss-of-function, reducing or abolishing GPI transamidase activity, leading to GPI anchor deficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PIGK.
Dominant Negative (DN)
No dominant-negative mutations have been described; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:21369 - GPI anchor biosynthesis
• KEGG: hsa00563 - Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
• Reactome: R-HSA-162791 - GPI-anchor transamidase complex
Protein Summary
PIGK (GPI8) is a 395-amino-acid transmembrane protein localized to the endoplasmic reticulum. It functions as the catalytic subunit of the GPI transamidase complex, which cleaves the C-terminal GPI signal peptide and transfers the GPI anchor to the newly exposed C-terminus. The protein contains a cysteine protease active site (Cys199, His157, Asp174) essential for catalysis. Loss of PIGK function results in accumulation of unanchored precursor proteins and severe developmental phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIGK Knockout HEK293 Cell Line | EDJ-KQ13989 | Human | 10026 | Details Get a Quote |
| PIGK Knockout HeLa Cell Line | EDJ-KQ18020 | Human | 10026 | Details Get a Quote |
| PIGK Knockout A-549 Cell Line | EDJ-KQ45151 | Human | 10026 | Details Get a Quote |
| PIGK Knockout HCT 116 Cell Line | EDJ-KQ45153 | Human | 10026 | Details Get a Quote |
