PHGDH gene
The PHGDH gene is responsible for the first step in the production of the amino acid serine, which is essential for central nervous system development.
Normal Function
The PHGDH gene provides instructions for making the subunits of the phosphoglycerate dehydrogenase enzyme. This enzyme converts 3-phosphoglycerate into 3-phosphohydroxypyruvate, the initial step in the synthesis of the amino acid serine.
Serine is vital for the development and function of the central nervous system. It is a component of neurotransmitters and is necessary for the formation of cell membranes and the fatty myelin layer that insulates nerves. Because dietary serine cannot cross the blood-brain barrier, brain cells must produce their own serine using this enzyme.
Health Conditions Related to Genetic Changes
Phosphoglycerate dehydrogenase deficiency
Mutations in the PHGDH gene cause phosphoglycerate dehydrogenase deficiency. This condition is characterized by:
- Microcephaly (unusually small head size)
- Severe developmental delay
- Intractable epilepsy (recurrent seizures that are difficult to treat)
These mutations result in an enzyme with decreased function, stalling serine production. The resulting lack of serine impairs the creation of neurotransmitters and proteins necessary for brain development and myelin formation, leading to the severe neurological symptoms observed in affected individuals.
Genomic Location
The PHGDH gene is located on chromosome 1.