Table 2 Summary of the molecular consequences of neuropathic and structure-based mutants of MORC2

Mutation	Disease	Activity relative to wild-type MORC2		Position in structure	Proposed mechanism of MORC2 misregulation	References
Mutation	Disease	ATPase	HUSH	Position in structure	Proposed mechanism of MORC2 misregulation	References
Y18A	—	Higher	No activity	Dimer interface	Does not dimerize	This paper
N39A	—	No activity	No activity	Active site	Cannot bind ATP	This paper;⁴
S87L	CMT/SMA	Lower	Higher	ATP lid	Constitutive N-terminal dimerization	^16,21
R132L^a	CMT	nd	nd	ATPase core	Destabilize ATPase^a	²¹
E236G^a	CMT	nd	nd	ATPase core	Destabilize ATPase^a	¹⁷
R252W	CMT	Lower	Higher	ATPase–CW interface	Destabilize ATPase-CW module	^{16,17,20,21,4}
R266A	—	nd	Higher	ATPase–CW interface	Destabilize ATPase-CW module	This paper
R333E^b	—	nd	No activity	CC1	DNA binding & CC1 functional defect	This paper
Q400R^a	CMT	nd	nd	ATPase core	Destabilize ATPase^a	¹⁸
T424R	SMA	Higher	Lower	Dimer interface	Perturb dimerization dynamics	^19,22
D466N^a	CMT	nd	nd	ATPase surface	Destabilize ATPase^a	^18,23

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