Table 2.

Comparison of CHEK2 variants characteristics as determined by protein modeling

Mutation	Domain	Interaction(s)	Proposed impact	Functional data
S471F	Kinase/Dimer Interface	H-bonding	Abrogate interaction with residue R305 (intermolecular), and possibly residue Q476 (intramolecular) to destabilize the dimerization of CHEK2, reducing its efficacy of transphosphorylation and activation	Roeb et al, 2012
R160G	FHA-ligand interface	Cation-Pi	The loss of the positively charged guanidinium group likely abrogates the Cation-Pi interactions with His and Phe	Wu et al, 2006; Delimitsou et al, 2019; Roeb et al, 2012; Chrisanthar et al, 2008; Sodha et al, 2006
H186R	FHA domain	H-Bonding, Electrostatic	Introduction of bulky, constitutive charge within the core of the FHA domain, and removal of any potential for pH-dependent structural stability or ligand interaction. Similarly, H-bonding lost	Roeb et al, 2012; Walsh et al, 2011
R188W	FHA domain	Electrostatic, Cation-Pi, Salt Bridge	Loss of positive charge, trans-β-sheet salt bridge and Cation-Pi interactions	Wu et al, 2001; Li et al 2002; Delimitasou et al, 2019
I200T	FHA domain	Hydrophobic	Reduced hydrophobicity at a position proposed to be critical for hydrophobic driven dimerization and function	Falck et al, 2001a and 2001b; Kilpivaara et al, 2004; Li et al 2002; Roeb et al, 2012; Cai et al, 2009