A pathogenic role for HOMER1 variation in autism is supported by several observations: multiple rare, potentially deleterious variants were identified in the AGRE population but not in the control population; these autism-specific HOMER1 missense variants affect functionally significant protein motifs or regulatory sequences; these autism-specific variants also display tight co-segregation with autism in children of affected families, including in one case a de novo HOMER1 variant present in two affected children. Here, HOMER1 is linked to autism.