LONP1

This gene encodes an ATP-dependent serine protease in the mitochondrial matrix that degrades misfolded, damaged, or short-lived regulatory proteins and participates in mitochondrial gene expression regulation and genome maintenance. Biallelic mutations cause CODAS syndrome, an autosomal recessive disorder characterized by cerebral, ocular, dental, auricular, and skeletal abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.244), indicating that heterozygous loss-of-function mutations are likely not tolerated.