PMM2 gene
The PMM2 gene provides instructions for creating an enzyme critical to glycosylation, a process that modifies proteins to enable their proper function in the body.
Normal Function
The PMM2 gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). This enzyme is involved in glycosylation, a process that attaches groups of sugar molecules (oligosaccharides) to proteins, allowing them to perform a wider variety of functions.
In an early step of glycosylation, the PMM2 enzyme converts a molecule called mannose-6-phosphate to mannose-1-phosphate. This is subsequently converted into GDP-mannose, which transfers mannose to the growing oligosaccharide chain. Once the correct number of sugar molecules are linked, the oligosaccharide is attached to a protein.
Health Conditions Related to Genetic Changes
PMM2-congenital disorder of glycosylation
More than 115 mutations in the PMM2 gene cause PMM2-congenital disorder of glycosylation (PMM2-CDG, also known as congenital disorder of glycosylation type Ia). This is a severe condition characterized by:
- Developmental delay
- Weak muscle tone (hypotonia)
- Abnormal distribution of fat
- Various other signs and symptoms
All known mutations appear to result in reduced enzyme activity. This leads to a shortage of GDP-mannose within cells, meaning there is not enough activated mannose to form oligosaccharides. Consequently, glycosylation cannot proceed normally, and the production of abnormally glycosylated proteins in many organs and tissues leads to the signs and symptoms of the disorder.
Genomic Location
The PMM2 gene is found on chromosome 16.