SLC25A3 Gene – Phosphate Carrier, Mitochondrial | Function, Mutations & Disease

SLC25A3 encodes the mitochondrial phosphate carrier (PiC), a transmembrane protein located in the inner mitochondrial membrane. It mediates the import of inorganic phosphate (Pi) into the mitochondrial matrix, which is essential for oxidative phosphorylation and ATP synthesis. The gene produces two splice variants: isoform A (heart/muscle) and isoform B (ubiquitous). Mutations in SLC25A3 cause mitochondrial phosphate carrier deficiency, a rare autosomal recessive disorder characterized by hypertrophic cardiomyopathy, muscle weakness, and lactic acidosis.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Mitochondrial phosphate carrier (SLC25A3) – Reactome R-HSA-8949215

• Oxidative phosphorylation – KEGG hsa00190

• Mitochondrial transport – WikiPathways WP111

The SLC25A3 protein (mitochondrial phosphate carrier) is a 362-amino acid transmembrane protein with six alpha-helical domains. It forms a homodimer and functions as a phosphate/hydroxyl antiporter or phosphate/proton symporter. The protein is essential for providing inorganic phosphate for ATP synthesis via ATP synthase. Isoform A is predominantly expressed in heart and skeletal muscle, while isoform B is found in all tissues. Defects in this protein lead to impaired mitochondrial energy production.