PDZRN3

This gene encodes a RING-type E3 ubiquitin ligase that regulates muscle-specific kinase (MUSK) levels on muscle cells by mediating its ubiquitination and degradation, contributing to terminal muscle differentiation. Mutations cause autosomal recessive congenital myasthenic syndrome, a neuromuscular junction disorder presenting in infancy or early childhood with muscle weakness, fatigue, and respiratory difficulties. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.