The NMDA receptor is a subtype of ionotropic glutamate receptor that displays voltage-dependent block by Mg2+ and a high permeability to Ca2+; these receptors play important roles in synaptogenesis and synaptic plasticity. Recently, individuals with a range of neurodevelopmental disorders have been found to carry heterozygous missense and gene disrupting mutations in NMDAR genes. Mutations arising de novo are of particular interest as they are more likely than inherited mutations to be associated with a highly deleterious phenotype. We noted a number of de novo mutations affecting the M2 pore region of NMDAR subunits found in individuals with childhood onset epilepsies and intellectual disability1,2. Hypothesising that these mutations underlie their carrier’s severe neurodevelopmental disorders, we undertook functional evaluation of a mutation replacing an asparagine with a lysine in the GluN2A subunit’s M2 pore region (GluN2AN615K). We made observations of the mutation’s effect on NMDAR single channel properties and on triheteromeric NMDAR receptors generated using a recently developed technique3. Our findings show that the disease associated mutation GluN2AN615K has substantial effects on physiologically important NMDA receptor properties, consistent with a role in disease causation.