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Genetics Home Reference: your guide to understanding genetic conditions
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PIG gene family

Reviewed August 2013

What are the PIG genes?

The genes in this family provide instructions for making proteins that are involved in the production (biosynthesis) of molecules called phosphatidylinositol glycan anchors (commonly called GPI anchors). GPI anchors attach (bind) to various proteins and anchor them to the outer surface of cell membranes. This anchoring is necessary for the functioning of most cells and to ensure the availability of the proteins at the cell surface, but the specific purpose of the anchoring is largely unknown.

The biosynthesis of GPI anchors occurs in a series of steps that take place in the endoplasmic reticulum, which is a structure involved in protein processing and transport within cells. The first step occurs when a group of phosphatidylinositol glycan (PIG) proteins come together to form an enzyme complex and create the basic structure of a GPI anchor. In subsequent steps, PIG proteins add various molecules, including sugars and fats, to the growing GPI anchor. Lastly, PIG proteins form an enzyme complex called GPI transamidase that brings together complete GPI anchors with the proteins that bind to them. The GPI-anchor associated protein is transferred to a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins, for further refining. From the Golgi apparatus, the protein is transported, then anchored, to the surface of the cell membrane.

Mutations in several PIG genes in the phosphatidylinositol glycan anchor biosynthesis pathway can cause genetic disorders. An error in anchor biosynthesis results in an incomplete GPI anchor that cannot attach to proteins. A lack of GPI anchoring prevents certain proteins from being attached to the cell membrane and results in their abnormal release from the cell, leading to unusually high amounts of that protein in the blood. For example, mutations in the PIGO or PIGV gene cause Mabry syndrome, a condition characterized by intellectual disability, distinctive facial features, and increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia).

Which genes are included in the PIG gene family?

The HUGO Gene Nomenclature Committee (HGNC) provides a list of genes in the PIG family (http://www.genenames.org/genefamilies/PIG).

Genetics Home Reference summarizes the normal function and health implications of these members of the PIG gene family: PIGA, PIGO, and PIGV.

What conditions are related to genes in the PIG gene family?

Genetics Home Reference includes these conditions related to genes in the PIG gene family:

  • Mabry syndrome
  • paroxysmal nocturnal hemoglobinuria

Where can I find additional information about the PIG gene family?

You may find the following resources about the PIG gene family helpful.

  • Essentials of Glycobiology (second edition, 2009): Components of the Mammalian GPI-Biosynthetic Machinery (http://www.ncbi.nlm.nih.gov/books/NBK1966/table/ch11.t2/)
  • Molecular Biology of the Cell (fourth edition, 2002): The Attachment of a GPI Anchor to a Protein in the ER (figure) (http://www.ncbi.nlm.nih.gov/books/NBK26841/figure/A2241/?report=objectonly)
  • Basic Neurochemistry (sixth edition, 1999): Glycosylphosphatidylinositol-Anchored Proteins (figure) (http://www.ncbi.nlm.nih.gov/books/NBK28131/box/A206/)
  • Essentials of Glycobiology (second edition, 2009): Glycosylphosphatidylinositol Anchors (http://www.ncbi.nlm.nih.gov/books/NBK1966/)

What glossary definitions help with understanding the PIG gene family?

cell ; cell membrane ; class ; disability ; endoplasmic reticulum ; enzyme ; gene ; glycan ; Golgi apparatus ; phosphatase ; protein ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

These sources were used to develop the Genetics Home Reference summary for the PIG gene family.

  • Tsai YH, Liu X, Seeberger PH. Chemical biology of glycosylphosphatidylinositol anchors. Angew Chem Int Ed Engl. 2012 Nov 12;51(46):11438-56. doi: 10.1002/anie.201203912. Epub 2012 Oct 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23086912?dopt=Abstract)
  • Paulick MG, Bertozzi CR. The glycosylphosphatidylinositol anchor: a complex membrane-anchoring structure for proteins. Biochemistry. 2008 Jul 8;47(27):6991-7000. doi: 10.1021/bi8006324. Epub 2008 Jun 17. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18557633?dopt=Abstract)
  • Fujita M, Kinoshita T. Structural remodeling of GPI anchors during biosynthesis and after attachment to proteins. FEBS Lett. 2010 May 3;584(9):1670-7. doi: 10.1016/j.febslet.2009.10.079. Epub 2009 Oct 31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19883648?dopt=Abstract)
  • Fujita M, Kinoshita T. GPI-anchor remodeling: potential functions of GPI-anchors in intracellular trafficking and membrane dynamics. Biochim Biophys Acta. 2012 Aug;1821(8):1050-8. doi: 10.1016/j.bbalip.2012.01.004. Epub 2012 Jan 11. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22265715?dopt=Abstract)
  • Almeida A, Layton M, Karadimitris A. Inherited glycosylphosphatidyl inositol deficiency: a treatable CDG. Biochim Biophys Acta. 2009 Sep;1792(9):874-80. doi: 10.1016/j.bbadis.2008.12.010. Epub 2009 Jan 9. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19168132?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2013
Published: December 22, 2014