PIGZ: Phosphatidylinositol Glycan Anchor Biosynthesis Class Z
A key enzyme in GPI anchor biosynthesis, implicated in inherited GPI deficiency disorders and cancer.
Gene Information Card
| Symbol | PIGZ |
|---|---|
| Full Name | Phosphatidylinositol Glycan Anchor Biosynthesis Class Z |
| Gene Type | Protein coding |
| Chromosomal Location | 3q29 |
| NCBI Gene ID | 80223 ncbi.nlm.nih.gov/gene/80223 |
| Ensembl ID | ENSG00000127540 |
| UniProt ID | Q86VD9 |
| OMIM ID | 611209 |
| HGNC ID | 26013 |
| Aliases | SMP3, GPI-MT-III, PIG-Z |
Description
PIGZ encodes a mannosyltransferase (GPI-mannosyltransferase III) that catalyzes the transfer of the third mannose residue in the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. GPI anchors are glycolipid structures that attach proteins to the cell membrane. Defects in PIGZ cause inherited GPI deficiency (IGD) type 15, characterized by intellectual disability, seizures, and dysmorphic features. Somatic mutations in PIGZ have been reported in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Inherited GPI deficiency type 15 (IGD15) | Loss-of-function mutations in PIGZ impair GPI anchor biosynthesis, reducing cell surface expression of GPI-anchored proteins. | OMIM #617816; PMID: 28132693 |
| Colorectal cancer | Somatic mutations and copy number alterations in PIGZ may alter GPI anchor-dependent signaling. | COSMIC; PMID: 23535601 |
| Breast cancer | PIGZ overexpression associated with poor prognosis; potential role in tumor immune evasion. | PMID: 31570887 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.1 | Medium expression |
| HeLa | 11.3 | Medium expression |
| HepG2 | 7.8 | Low expression |
| K562 | 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; predicted loss of function |
| c.200C>T (p.Thr67Ile) | Missense | Rare | Reduced enzyme activity; associated with IGD15 |
| c.403C>T (p.Arg135*) | Nonsense | Rare | Premature stop; loss of function |
| c.614G>A (p.Arg205His) | Missense | Rare | Impaired mannosyltransferase activity |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations in PIGZ cause inherited GPI deficiency type 15, with reduced GPI anchor synthesis and cell surface GPI-AP expression.
Gain of Function (GOF)
Not reported in PIGZ.
Dominant Negative (DN)
Not reported in PIGZ.
View complete mutation data：
Gene Ontology (GO)
| • GPI anchor biosynthetic process (GO:0006506) | • mannosyltransferase activity (GO:0000030) |
| • membrane (GO:0016020) | • endoplasmic reticulum (GO:0005783) |
| • Golgi membrane (GO:0000139) |
Pathways
• KEGG: hsa00563 - Glycosylphosphatidylinositol (GPI)-anchor biosynthesis
• Reactome: R-HSA-162710 - GPI anchor biosynthesis
Protein Summary
PIGZ (GPI-mannosyltransferase III) is a 421-amino acid transmembrane protein localized to the endoplasmic reticulum. It catalyzes the addition of the third mannose to the GPI core structure. The protein contains a conserved mannosyltransferase domain and is essential for proper GPI anchor assembly. Mutations lead to incomplete GPI anchors and reduced surface expression of GPI-anchored proteins such as CD55 and CD59.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIGZ Knockout HEK293 Cell Line | EDJ-KQ9500 | Human | 80235 | Details Get a Quote |
| PIGZ Knockout A-549 Cell Line | EDJ-KQ36244 | Human | 80235 | Details Get a Quote |
| PIGZ Knockout HeLa Cell Line | EDJ-KQ57313 | Human | 80235 | Details Get a Quote |
| PIGZ Knockout HCT 116 Cell Line | EDJ-KQ74242 | Human | 80235 | Details Get a Quote |
