The PGAP2 gene provides instructions for making a protein that modifies a molecule called a glycosylphosphosphatidylinositol (GPI) anchor. The GPI anchor attaches (binds) to various proteins and then binds them to the outer surface of the cell membrane, ensuring that they are available when needed. The GPI anchor is made up of many different pieces and is assembled in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The anchor is then transferred to a different cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, the PGAP2 protein assists in attaching a molecule called a saturated fatty acid to the anchor. This saturated fatty acid is likely needed to help transport and attach the anchor to the fat-rich cell membrane.
Health Conditions Related to Genetic Changes
At least five PGAP2 gene mutations have been found to cause Mabry syndrome. The features of Mabry syndrome include intellectual disability, distinctive facial features, increased levels of an enzyme called alkaline phosphatase in the blood (hyperphosphatasia), and other signs and symptoms. These mutations change single protein building blocks (amino acids) in the PGAP2 protein and probably reduce the activity of the protein. As a result, the PGAP2 protein cannot efficiently modify the GPI anchor, likely impairing the anchor's ability to attach itself and its associated protein to the cell membrane. GPI anchor-associated proteins that cannot attach to the cell membrane are released from the cell.
An enzyme called alkaline phosphatase is normally attached to the cell membrane by a GPI anchor. However, when the anchor is impaired, alkaline phosphatase is released from the cell. This abnormal release of alkaline phosphatase is responsible for the hyperphosphatasia in Mabry syndrome. It is unclear how PGAP2 gene mutations lead to the other features of Mabry syndrome, but these signs and symptoms are likely due to a lack of proper GPI anchoring of proteins to cell membranes.More About This Health Condition
Other Names for This Gene
- cell wall biogenesis 43 N-terminal homolog
- FGF receptor activating protein 1
- FGF receptor-activating protein 1
- post-GPI attachment to proteins factor 2
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Fujita M, Jigami Y. Lipid remodeling of GPI-anchored proteins and its function. Biochim Biophys Acta. 2008 Mar;1780(3):410-20. doi: 10.1016/j.bbagen.2007.08.009. Epub 2007 Aug 25. Citation on PubMed
- 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. Citation on PubMed
- Hansen L, Tawamie H, Murakami Y, Mang Y, ur Rehman S, Buchert R, Schaffer S, Muhammad S, Bak M, Nothen MM, Bennett EP, Maeda Y, Aigner M, Reis A, Kinoshita T, Tommerup N, Baig SM, Abou Jamra R. Hypomorphic mutations in PGAP2, encoding a GPI-anchor-remodeling protein, cause autosomal-recessive intellectual disability. Am J Hum Genet. 2013 Apr 4;92(4):575-83. doi: 10.1016/j.ajhg.2013.03.008. Citation on PubMed or Free article on PubMed Central
- Krawitz PM, Murakami Y, Riess A, Hietala M, Kruger U, Zhu N, Kinoshita T, Mundlos S, Hecht J, Robinson PN, Horn D. PGAP2 mutations, affecting the GPI-anchor-synthesis pathway, cause hyperphosphatasia with mental retardation syndrome. Am J Hum Genet. 2013 Apr 4;92(4):584-9. doi: 10.1016/j.ajhg.2013.03.011. Citation on PubMed or Free article on PubMed Central
- Yamashita M, Yamashita A, Shigematsu A, Kagami Y, Akiyoshi H, Wassersug RJ, Naitoh T. [Video image analysis of respiratory and cardiac activity of tadpoles dedicated to space experiment]. Biol Sci Space. 2000 Oct;14(3):150-1. No abstract available. Japanese. Citation on PubMed
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