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PIGN
phosphatidylinositol glycan anchor biosynthesis class N
The PIGN gene encodes an enzyme crucial for the biosynthesis of glycophosphatidylinositol (GPI) anchors, which are essential for attaching various proteins to the cell surface. The PIGN gene provides instructions for making GPI ethanolamine phosphate transferase 1, an enzyme that plays a key role in creating glycophosphatidylinositol (GPI) anchors.
PIGN is located on the long (q) arm of chromosome 18, at band 18q21.33. Arm ratio per GRCh38 - banding schematic.
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Overview
The PIGN gene, also known as phosphatidylinositol glycan anchor biosynthesis class N, is involved in a fundamental cellular process: the synthesis of glycophosphatidylinositol (GPI) anchors. These anchors are complex molecules that enable many different proteins to attach to the outer surface of cell membranes. The accurate production and attachment of GPI anchors are essential for a wide range of cellular activities.
Inherited variants in the PIGN gene are associated with several rare genetic conditions that can affect multiple bodily systems.
What the gene does
The PIGN gene provides instructions for producing an enzyme called GPI ethanolamine phosphate transferase 1. This enzyme is a critical component in the multi-step pathway of glycophosphatidylinositol (GPI) anchor biosynthesis, which occurs within the endoplasmic reticulum, a cell structure involved in protein processing. The GPI anchor itself is composed of various smaller molecules.
Once a GPI anchor is fully assembled, it binds to specific proteins, known as GPI-anchored proteins. This attachment then facilitates the anchoring of these proteins to the outer leaflet of the cell membrane. GPI-anchored proteins are involved in a diverse array of cellular processes, including cell adhesion (how cells stick together), cell signalling (how cells communicate), and cellular immunity (protecting against foreign invaders). Their proper function relies on the correct synthesis and attachment of the GPI anchor.
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Chromosome location
The PIGN gene is located on chromosome 18 at position 18q21.33. This specific genomic address helps to identify its precise location within the human genome. The PIGN gene codes for a protein that is 931 amino acids in length.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Variants within the PIGN gene can alter the function of the GPI ethanolamine phosphate transferase 1 enzyme, potentially disrupting the normal biosynthesis of GPI anchors. These genetic changes are typically inherited in an autosomal recessive pattern.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1556G>A | p.Trp519Ter | Pathogenic/Likely pathogenic | ★★☆☆ | PIGN-related disorder |
c.2125C>T | p.Arg709Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.2237_2238del | p.Ile746fs | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.2329C>T | p.Arg777Ter | Pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.2399G>A | p.Gly800Glu | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.465T>A | p.Tyr155Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.601_602insT | p.Glu201fs | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.629T>G | p.Leu210Ter | Pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.718G>T | p.Glu240Ter | Pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.817dup | p.Ala273fs | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the PIGN gene are associated with several rare genetic conditions, including Fryns syndrome and multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). These conditions often present with a range of developmental and neurological symptoms, reflecting the broad importance of GPI-anchored proteins in cellular function.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic PIGN variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The PIGN gene is assessed by the UK's National Health Service (NHS) Genomic Medicine Service. It is currently featured on several Green RAG status panels within NHS Genomic Medicine Service laboratories, indicating that there is strong evidence for its association with specific conditions. These panels include Clefting, Congenital disorders of glycosylation, DDG2P, Early onset or syndromic epilepsy, Foetal anomalies (R21), Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is a GPI anchor?
A GPI anchor is a special molecule that helps attach certain proteins to the outer surface of cell membranes. These anchored proteins are crucial for various cellular activities, such as cell communication and immunity.
What is the function of the PIGN gene?
The PIGN gene provides instructions for making an enzyme called GPI ethanolamine phosphate transferase 1. This enzyme is essential for one of the steps in building the glycophosphatidylinositol (GPI) anchor.
How are PIGN gene variants inherited?
Variants in the PIGN gene are typically inherited in an autosomal recessive manner. This means an individual must inherit two copies of the altered gene (one from each parent) to develop a condition associated with PIGN.
References
- Adam MP, Bick S, Mirzaa GM. Fryns Syndrome. 1993. PMID: 20301632