SLC25A19

The SLC25A19 gene provides instructions for producing a protein that is a member of the solute carrier (SLC) family of proteins. Proteins in the SLC family transport various compounds across the membranes surrounding the cell and its component parts. The protein produced from the SLC25A19 gene transports a molecule called thiamine pyrophosphate into the mitochondria, the energy-producing centers of cells. Thiamine pyrophosphate is involved in the functioning of a group of mitochondrial enzymes called the alpha-ketoglutarate dehydrogenase complex. This complex acts on a compound called alpha-ketoglutaric acid as part of an important series of reactions known as the citric acid cycle or Krebs cycle. The transport of thiamine pyrophosphate into the mitochondria is believed to be important in brain development.

Amish lethal microcephaly - caused by mutations in the SLC25A19 gene

All known individuals with Amish lethal microcephaly have a mutation in which the protein building block (amino acid) alanine is substituted for the amino acid glycine at position 177 of the SLC25A19 protein, written as Gly177Ala or G177A. Researchers believe that this mutation interferes with the transport of thiamine pyrophosphate into the mitochondria and the activity of the alpha-ketoglutarate dehydrogenase complex, resulting in the abnormal brain development and the excess of alpha-ketoglutaric acid in the urine characteristic of Amish lethal microcephaly.