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RPH3A-related neurodevelopmental disorder is an ultra-rare, autosomal dominant condition caused by heterozygous missense variants in the RPH3Agene. The number of reports on this gene is still limited in 2025, thus the information below can evolve in the future.

The identified pathogenic variants have so far occurred de novo. The disorder has a variable clinical presentation. The main clinical features fall into two general phenotypes: 1) a severe form with drug-resistant epilepsy and moderate intellectual disability (ID), and 2) a milder form with high-functioning autism spectrum disorder (ASD) and learning disabilities. RPH3A encodes Rabphilin 3A, a synaptic protein crucial for the stabilization and function of GluN2A-containing N-methyl-D-aspartate (NMDA) receptors, which are essential for synaptic plasticity and cognition.