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PIGS
phosphatidylinositol glycan anchor biosynthesis class S
PIGS is located on the long (q) arm of chromosome 17, at band 17q11.2. Arm ratio per GRCh38 - banding schematic.
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Overview
PIGS is located on chromosome 17 and belongs to a family of genes that orchestrate the biosynthesis of glycosylphosphatidylinositol (GPI) anchors. These molecular structures tether more than 150 different proteins to the exterior face of cell membranes across nearly all human tissues. The protein encoded by PIGS contributes to the early stages of GPI anchor assembly within the endoplasmic reticulum. Disruption of this pathway can impair the surface expression of many functionally diverse proteins, with consequences that vary depending on which tissues are most affected and the severity of the underlying genetic change.
What the gene does
The PIGS protein operates as part of a stepwise enzymatic cascade that constructs GPI anchors from phosphatidylinositol and several sugar moieties. Specifically, PIGS participates in adding N-acetylglucosamine to phosphatidylinositol, one of the earliest reactions in the pathway. This modification is a prerequisite for subsequent enzymatic steps that complete the mature GPI structure. Once assembled, GPI anchors are transferred onto target proteins in the endoplasmic reticulum, after which the modified proteins travel to the cell surface. Proteins that rely on GPI anchors include receptors involved in immune recognition, enzymes that regulate complement activation, and adhesion molecules that mediate cell-cell interactions. Consequently, adequate PIGS function is necessary to maintain proper membrane protein composition and support normal cellular communication.
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Chromosome location
PIGS resides at chromosomal band 17q11.2 on the long arm of chromosome 17. The genomic structure and total number of exons have not been comprehensively detailed in public databases. The region 17q11.2 also harbours several other genes, and structural variation in this area has been associated with diverse phenotypes in clinical genetics literature.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. Sequence analysis places PIGS within the GPI anchor biosynthesis enzyme family, but individual functional modules have not been mapped to specific amino acid ranges in publicly available structural databases.
Key variants
Genetic variants in PIGS span the spectrum from benign polymorphisms common in the general population to rare changes that disrupt protein function. Pathogenic variants typically arise de novo or follow recessive inheritance, meaning both gene copies must carry a deleterious change for clinical features to manifest. The variant landscape includes missense substitutions, small deletions, and splicing alterations, though large-scale population sequencing has not yet established definitive prevalence estimates for most alleles.
Sample of pathogenic variants
8 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.662_663del | p.Leu221fs | Pathogenic | ★☆☆☆ | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.734G>A | p.Trp245Ter | Pathogenic | ★☆☆☆ | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.1070G>A | p.Gly357Asp | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.1141_1164dup | p.Asp381_Val388dup | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.1316_1352delinsGGTTGCT | p.Thr439_Lys451delinsArgLeuLeu | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.174G>C | p.Gln58His | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.468+1G>C | - | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
c.986C>G | p.Pro329Arg | Pathogenic | - | Glycosylphosphatidylinositol biosynthesis defect 18 |
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
Functional loss of PIGS has been linked to a rare congenital disorder characterised by intellectual disability, seizures, and multiple organ system involvement. The clinical presentation reflects the widespread reliance of tissues on GPI-anchored proteins. Because the disorder is exceptionally rare, most knowledge comes from case reports and small case series rather than large cohort studies. The severity and specific features observed in affected individuals can vary, likely influenced by the exact nature of the genetic change and potential modifying factors elsewhere in the genome.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the PIGS gene do?
PIGS encodes an enzyme that helps build GPI anchors, molecular tags that attach many different proteins to the outer surface of cells. These anchored proteins support immune function, cell signalling, and development.
How are variants in PIGS inherited?
Inheritance patterns can vary. Pathogenic changes often follow autosomal recessive inheritance, meaning both gene copies must carry a variant for clinical features to appear, though de novo changes have also been reported.
Is PIGS included in NHS genetic testing panels?
PIGS is not currently listed on routine NHS Genomic Medicine Service panels. Testing may be available through specialist referral when clinical features suggest a disorder of GPI anchor biosynthesis.