ZNF598

ZNF598 encodes an E3 ubiquitin ligase that functions as a ribosome collision sensor, detecting stalled ribosomes during translation and triggering ribosome quality control pathways that lead to degradation of aberrant nascent peptides. Mutations cause autosomal recessive neurodevelopmental disorder with or without anomalies of the brain, eye, or heart, typically presenting in early childhood with developmental delay, intellectual disability, and variable congenital malformations. The gene shows high constraint against loss-of-function variants (LOEUF 0.399), indicating that complete loss of protein function is likely not tolerated.