SUPT16H encodes the SPT16 subunit of the FACT chromatin-remodelling complex and is highly constrained against protein-truncating and missense variation. Recently ported variants include missense, nonsense, frameshift, and in-frame indel alleles, mostly de novo, though a few are inherited, indicating variable expressivity. Recurrent substitutions cluster in the conserved mid-domain (aa 507–970). The likely mechanism is disruption of FACT-mediated chromatin remodelling. Diagnosis is achieved by exome or genome sequencing; functional assays are ongoing to clarify molecular effects.
SUPT16H