MTIF3

This gene encodes a translation initiation factor that binds to the 28S ribosomal subunit and regulates the equilibrium between assembled 55S ribosomes and their free subunits to facilitate mitochondrial protein synthesis initiation. Mutations cause Combined Oxidative Phosphorylation Deficiency 4, an autosomal recessive mitochondrial disorder with infantile onset characterized by severe neurodegeneration and cardiomyopathy. The gene is extremely intolerant to loss-of-function variants, reflecting its critical role in mitochondrial function.