ADCYAP1

This gene encodes PACAP, a neuropeptide that stimulates adenylyl cyclase to increase cAMP levels and activate downstream gene transcription, serving as a key mediator of neuroendocrine stress responses with neuroprotective and neurodevelopmental functions. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, involving severe neurodevelopmental impairment and seizures with onset in infancy. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.752), consistent with recessive inheritance where biallelic mutations are required for disease manifestation.