Sideroflexin-4 (SFXN4)

Sideroflexin-4 (SFXN4) is a mitochondrial inner membrane protein that acts as an assembly factor for complex I of the mitochondrial electron transport chain. It is evolutionarily distinct from other members of the sideroflexin family, which mostly function as serine or amino acid transporters[2][3]. SFXN4 is essential for the correct assembly of the ND2 module of complex I, and loss-of-function mutations lead to isolated complex I deficiency with clinical manifestations such as macrocytic anemia, lactic acidosis, and neurological impairment[2][3]. Additionally, SFXN4 affects mitochondrial iron homeostasis and iron-sulfur cluster biogenesis, which in turn impacts heme synthesis and cellular metabolism[1][2]. Although its name and several aliases suggest a role in cancer resistance, its primary, functionally-validated roles are in mitochondrial physiology rather than in direct oncogenic pathways[1][2][3]. No drugs are currently known to target SFXN4, but pathogenic variants are relevant as diagnostic biomarkers for certain mitochondrial diseases.

Other names

Breast cancer resistance marker 1BCRM1SLC56A4COXPD18sideroflexin-4

Not targeted by drugs; loss-of-function causes mitochondrial disease via complex I deficiency and secondary effects on Fe-S cluster biogenesis