DHCR7

DHCR7 encodes an oxidoreductase that catalyzes the final step of cholesterol biosynthesis, converting 7-dehydrocholesterol to cholesterol. Mutations cause Smith-Lemli-Opitz syndrome, an autosomal recessive disorder characterized by intellectual disability, distinctive facial features, syndactyly of the second and third toes, and in severe cases holoprosencephaly, with phenotypic severity ranging from minimal abnormalities with near-normal intelligence to profound developmental delays. The gene shows very low tolerance to loss-of-function variants (pLI near zero), reflecting the critical importance of cholesterol synthesis for normal development.