Tetratricopeptide Repeat Domain Protein 19 (TTC19)

A homozygous nonsense mutation in the gene encoding tetratricopeptide 19 (TTC19) in individuals from two families affected by progressive encephalopathy associated with profound cIII deficiency and accumulation of cIII-specific assembly intermediates. A second homozygous nonsense mutation in a fourth affected individual. TTC19 is embedded in the inner mitochondrial membrane as part of two high–molecular‐weight complexes, one of which coincides with cIII. A physical interaction between TTC19 and cIII by coimmunoprecipitation. A Drosophila melanogaster knockout model for TTC19 that showed low fertility, adult-onset locomotor impairment and bang sensitivity, associated with cIII deficiency. TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies.