SLC25A1 gene

solute carrier family 25 member 1

The SLC25A1 gene provides instructions for making a protein that is found in mitochondria, which are the energy-producing centers in cells. The SLC25A1 protein transports a molecule called citrate out of mitochondria in exchange for another molecule called malate, which is transported in. Within mitochondria, both citrate and malate participate in reactions that produce energy for cell activities. Citrate is transported out of mitochondria because it also has important functions in other parts of the cell. In particular, citrate is involved in the production of fats (lipids) and the regulation of glycolysis, which is another critical energy-producing process within cells.

At least 12 mutations in the SLC25A1 gene have been found to cause a form of 2-hydroxyglutaric aciduria called combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA). This condition causes severe brain abnormalities that become apparent in early infancy.

Each of the known SLC25A1 gene mutations greatly reduces the function of the SLC25A1 protein. As a result, citrate and malate cannot be transported into and out of mitochondria, which disrupts energy production within cells. Through processes that are not fully understood, the lack of citrate and malate transport allows other compounds to build up abnormally within cells. These compounds include D-2-hydroxyglutarate and L-2-hydroxyglutarate, which at high levels can damage cells and lead to cell death. Brain cells appear to be the most vulnerable to the toxic effects of these compounds, which may explain why the signs and symptoms of D,L-2-HGA primarily involve the brain. Researchers suspect that an imbalance of other molecules, particularly citrate, also contributes to the severe signs and symptoms of combined D,L-2-HGA

Cytogenetic Location: 22q11.21, which is the long (q) arm of chromosome 22 at position 11.21

Molecular Location: base pairs 19,175,575 to 19,178,863 on chromosome 22 (Homo sapiens Updated Annotation Release 109.20200522, GRCh38.p13) (NCBI)

Cytogenetic Location: 22q11.21, which is the long (q) arm of chromosome 22 at position 11.21
  • citrate transport protein
  • CTP
  • D2L2AD
  • SEA
  • SLC20A3
  • solute carrier family 20 (mitochondrial citrate transporter), member 3
  • solute carrier family 25 (mitochondrial carrier; citrate transporter), member 1
  • tricarboxylate carrier protein
  • tricarboxylate transport protein, mitochondrial