In the nucleus, NBEA binds to the NOTCH1 intracellular domain (NICD1). This interaction involves the DPBW module of NBEA, which consists of DUF1088, PH-like, and BEACH domains, and WD40 repeats. NBEA negatively regulates transcription of NOTCH1-target genes through an unknown mechanism (Tuand et al. 2016). The interaction between NBEA and NOTCH1 may be relevant for the etiology of the autism spectrum disorders (ASD), as NBEA is an ASD candidate gene (Nuytens et al. 2013) while NOTCH signaling plays an important role in neuronal development (reviewed by Cau and Blader 2009, Ables et al. 2011, Giniger 2012, Zhang et al. 2018).