On this page
PIGN
phosphatidylinositol glycan anchor biosynthesis class N
The PIGN gene provides instructions for an enzyme essential in the creation of glycophosphatidylinositol (GPI) anchors, which are crucial for attaching various proteins to cell surfaces. The PIGN gene encodes GPI ethanolamine phosphate transferase 1, an enzyme playing a key role in the biosynthesis of GPI anchors.
PIGN is located on the long (q) arm of chromosome 18, at band 18q21.33. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 18 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The PIGN gene, also known as phosphatidylinositol glycan anchor biosynthesis class N, is responsible for producing an enzyme called GPI ethanolamine phosphate transferase 1. This enzyme is a critical component in the multi-step process of creating glycophosphatidylinositol (GPI) anchors. GPI anchors are complex molecules that attach many different proteins to the cell surface, enabling them to perform their specific functions effectively.
What the gene does
The PIGN gene provides instructions for synthesising GPI ethanolamine phosphate transferase 1. This enzyme participates in the assembly pathway of a glycophosphatidylinositol (GPI) anchor, which is constructed within the endoplasmic reticulum. Once fully formed, a GPI anchor binds to specific proteins, known as GPI-anchored proteins. This attachment enables the GPI-anchored protein to then secure itself to the outer leaflet of the cell membrane. GPI-anchored proteins are diverse and perform a range of essential cellular functions, including mediating cell-to-cell adhesion, transmitting signals into cells, and contributing to cellular immunity against foreign substances.
Video: Genetics 101
Chromosome location
The PIGN gene is situated on chromosome 18. Its specific location is at band 18q21.33. This gene codes for a protein that is 931 amino acids in length.
Protein structure
The PIGN gene encodes a protein that is 931 amino acids long. 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, thereby disrupting the formation or function of GPI anchors. These genetic changes can range from single nucleotide changes to larger deletions or insertions, and their impact on protein function can vary.
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.2125C>T | p.Arg709Ter | 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 |
c.858G>A | p.Trp286Ter | Pathogenic/Likely pathogenic | ★★☆☆ | Multiple congenital anomalies-hypotonia-seizures syndrome 1 |
c.895C>T | p.Gln299Ter | 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 inherited conditions, primarily affecting development across multiple body systems. These include Fryns syndrome, characterised by a range of developmental abnormalities often including a defect in the diaphragm. PIGN variants can also cause multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1), which shares some features with Fryns syndrome but typically does not involve a congenital diaphragmatic hernia.
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 included on several panels within the NHS Genomic Medicine Service's PanelApp, indicating its clinical relevance in the UK. It is a 'green' gene for conditions such as Clefting, Congenital disorders of glycosylation, DDG2P, Early onset or syndromic epilepsy, Foetal anomalies (specifically within 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 the main role of the PIGN gene?
The PIGN gene provides instructions for creating an enzyme called GPI ethanolamine phosphate transferase 1, which is crucial for assembling glycophosphatidylinositol (GPI) anchors. These anchors are vital for attaching many proteins to the cell surface, enabling them to perform functions like cell adhesion and signalling.
What conditions are associated with PIGN gene variants?
Variants in the PIGN gene are primarily associated with Fryns syndrome, a condition affecting the development of multiple body parts, often including a defect in the diaphragm. They can also cause multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1), which presents with similar features but typically without a diaphragmatic hernia.
How does a GPI anchor work?
A GPI anchor is a molecule that acts like a tether, attaching specific proteins to the outer surface of a cell's membrane. This ensures the proteins are correctly positioned and available to carry out their various functions, such as helping cells interact or relaying signals.
References
- Adam MP, Bick S, Mirzaa GM. Fryns Syndrome. 1993. PMID: 20301632