PIGV Gene - Phosphatidylinositol Glycan Anchor Biosynthesis Class V
Essential component in GPI anchor biosynthesis pathway; mutations cause inherited GPI deficiency (IGD) with hyperphosphatasia and intellectual disability.
Gene Information Card
| Symbol | PIGV |
|---|---|
| Full Name | Phosphatidylinositol glycan anchor biosynthesis class V |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.11 |
| NCBI Gene ID | 55650 ncbi.nlm.nih.gov/gene/55650 |
| Ensembl ID | ENSG00000142611 |
| UniProt ID | Q9NUD5 |
| OMIM ID | 610274 |
| HGNC ID | 26031 |
| Aliases | GPI7, MGC2650, PIG-V |
Description
The PIGV gene encodes phosphatidylinositol glycan anchor biosynthesis class V protein, a mannosyltransferase that catalyzes the transfer of the second mannose in the glycosylphosphatidylinositol (GPI) anchor precursor. GPI anchors are glycolipid structures that tether proteins to the cell surface. PIGV is essential for proper GPI anchor assembly; biallelic loss-of-function mutations cause inherited GPI deficiency (IGD) type 1, also known as hyperphosphatasia with intellectual disability syndrome (Mabry syndrome).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperphosphatasia with intellectual disability syndrome (Mabry syndrome) | Biallelic loss-of-function mutations in PIGV impair GPI anchor biosynthesis, leading to reduced cell surface GPI-anchored proteins, including alkaline phosphatase (causing elevated serum ALP). | OMIM #239300; multiple case reports (PMID: 20601953, 23967202) |
| Inherited GPI deficiency (IGD) | Defective PIGV mannosyltransferase activity disrupts the second mannose addition step in GPI anchor assembly, resulting in global deficiency of GPI-anchored proteins. | ClinVar; NCBI GeneReviews |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 15.2 | Medium |
| Testis | 20.1 | High |
| Lung | 6.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 18.4 | High expression |
| HeLa | 14.2 | Medium expression |
| K562 | 9.8 | Low expression |
| HepG2 | 11.5 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1022C>A (p.Ala341Glu) | Missense | Found in multiple families with Mabry syndrome | Loss of mannosyltransferase activity; reduced GPI anchor attachment |
| c.334C>T (p.Arg112*) | Nonsense | Rare | Premature truncation; complete loss of function |
| c.1465G>A (p.Gly489Arg) | Missense | Reported in IGD patients | Impaired protein stability and catalytic activity |
Mutation functional classification
Loss of Function (LOF)
Majority of PIGV mutations are loss-of-function (missense, nonsense, frameshift) leading to reduced or absent mannosyltransferase activity and GPI anchor deficiency.
Gain of Function (GOF)
No gain-of-function mutations reported for PIGV.
Dominant Negative (DN)
No dominant-negative effects described; disease is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex (GO:0000506) | • mannosyltransferase activity (GO:0000030) |
| • GPI anchor biosynthetic process (GO:0006506) | • membrane (GO:0016020) |
| • endoplasmic reticulum membrane (GO:0005789) |
Pathways
• GPI anchor biosynthesis (KEGG: hsa00563)
• Metabolism of GPI-anchored proteins (Reactome: R-HSA-162791)
Protein Summary
PIGV is a 493-amino acid transmembrane protein localized to the endoplasmic reticulum. It functions as a mannosyltransferase that adds the second mannose residue to the GPI anchor precursor. The protein contains a conserved DXD motif essential for catalytic activity. Mutations in PIGV disrupt GPI anchor assembly, leading to reduced cell surface expression of GPI-anchored proteins such as alkaline phosphatase, CD55, and CD59.
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