SLC25A36

SLC25A36 (mitochondrial pyrimidine nucleotide carrier; also called PNC2) is a member of the SLC25 mitochondrial carrier family: a ~34 kDa multi-pass protein of the mitochondrial inner membrane with three Solcar repeats and six transmembrane helices. Reconstituted in proteoliposomes it selectively transports cytosine and uracil (and, more weakly, guanine) (deoxy)nucleoside mono-, di-, and triphosphates across the inner membrane, chiefly by an antiport (nucleotide-for-nucleotide exchange) mechanism and, at a lower rate, by uniport; adenine nucleotides are not transported and CTP is the preferred substrate. By importing pyrimidine (deoxy)nucleotides into the matrix in exchange for the products of their catabolism, it supplies precursors for mitochondrial DNA and RNA synthesis and contributes to mitochondrial genome maintenance, membrane potential, and respiration. It is the human functional counterpart of the yeast RIM2 pyrimidine nucleotide carrier. Biallelic loss of function causes an autosomal recessive hyperinsulinism/hyperammonemia-type disorder (familial hyperinsulinemic hypoglycemia 8), with protein-provoked hypoglycemia, mild hyperammonemia, and seizures.