Table 2. CHD4 mutations in cancer and Sifrim-Hitz-Weiss syndrome.

	Mutated Residue	Location	Predicted effect based on structure	Biochemical observations
Cancer
	Cys464Tyr	PHD finger 2	Disruption of Zn2+ binding in PHD finger 2	Reduction in ATPase activity (Kovač et al., 2018)
	Val558Phe	Double chromodomain		Reduced ATPase activity (Kovač et al., 2018)
	Arg572Gln	Double chromodomain	Disruption of contact with tracking strand	Reduced DNA binding affinity, Loss of full remodeling activity and ATPase activity (Kovač et al., 2018)
	Leu912Val	ATPase lobe 2	No prediction made	Reduction of ATPase activity (Kovač et al., 2018)
	His1151Arg	ATPase lobe 2	In close proximity to motif Va, might disrupt contact of Trp1148	Reduction of ATPase activity, abolishment of remodeling activity (Kovač et al., 2018)
	Arg1162Gln	ATPase lobe 2, motif VI	Located in ATPase motif VI (arginine finger), Disruption of interaction with ATP	Reduction of ATPase activity (Kovač et al., 2018)
	His1196Tyr	ATPase lobe 2	Located in the C-terminal bridge region, Removes negative regulation	Speed of chromatin remodeling is increased and better nucleosome centering capability (Kovač et al., 2018)
	Leu1215	ATPase lobe 2/C-terminal bridge	Not located in modeled region
Sifrim-Hitz-Weiss syndrome (Sifrim et al., 2016; Weiss et al., 2016)
	Cys467Tyr	PHD finger 2	Disruption of Zn2+ binding in PHD finger 2
	Ser851Tyr	ATPase lobe 1
	Gly1003Asp	ATPase lobe 2	Disruption of contact with H3
	Arg1068His	ATPase lobe 2	Disruption of structural integrity of RecA fold
	Arg1127Gln	ATPase lobe 2	Disruption of contact with DNA minor groove, equivalent arginine residue in SMARCA4 is implicated in ‘Coffin Siris syndrome’
	Trp1148Leu	ATPase lobe 2, motif Va	Disruption of contact with guide strand	Uncoupling of ATPase activity and chromatin remodeling (Liu et al., 2017)
	Arg1173Leu		Destabilization
	Val1608Ile		Not located in modeled region