BPTF encodes a largest subunit of NURF (nucleosome remodeling factor), a family member of ISWI. Human BPTF contains two PHD finger domains followed proximally by a bromodomain (BRD). The second PHD finger of BPTF mediates binding of the NURF complex to chromatin with trimethylation of histone H3 lysine 4 (H3K4me3). In a combinatorial manner via multivalent interactions together with the PHD finger, the BRD binds to acetylated lysine 16 in histone H4 (H4K16ac), enabling the selective targeting of BPTF to chromatin that contains both histone marks, thereby increasing its selectivity.
Thus far, all identified genetic variants altering BPTF function are de novo. These are either truncating nonsense or missense mutations or CNV deletions of the entire BPTF gene and neighboring genes.
According to the preliminary functional investigations, the pathomechanism would be haploinsufficiency.