For instance, heterozygous CUL3 variants have been associated with pseudohypoaldosteronism type IIIE (MIM # 614496) due to an in-frame deletion of exon 9, and only recently have loss-of-function (LoF) variants been found to be involved in overall developmental delay (Nakashima et al., 2020). Here, CUL3 is linked to Global developmental delay.