TBC1D20

This gene encodes a GTPase-activating protein that accelerates GTP hydrolysis for Rab1, Rab2, and RAB18 small GTPases and is involved in maintaining endoplasmic reticulum structure. Mutations cause Warburg micro syndrome 4, an autosomal recessive disorder characterized by congenital microcephaly, microphthalmia, congenital cataracts, and intellectual disability. The gene is highly constrained against loss-of-function variants (pLI 0.93, LOEUF 0.36), consistent with its role in this severe early-onset developmental syndrome.