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Table 2 KCNK9 variants in this study assessed for TASK3 structure- and dynamics-based changes

From: Gain and loss of TASK3 channel function and its regulation by novel variation cause KCNK9 imprinting syndrome

Protein variant ΔΔGfold ΔFour-body Pot. ΔSRLF ΔPC a Transport events b ΔElec surface Selectivity Filter [K+] c Δ[K+] c Blinded prediction d
R131S 1.36 ± 0.17 − 2.63 1.13 PC2 (2.6σ) 8 + 0.39 ––– Occluded-permissive
R131H 1.05 ± 0.17 − 1.48 1.26 n.s. 4 + 1.42 Mixed-permissive
R131P 6.87 ± 0.65 4.34 − 0.71 PC2 (− 1.1σ)
PC3 (1.5σ)
10 -- 1.08 –– Mono-permissive
M132R 2.74 ± 0.10 14.77 − 1.21 PC3 (− 1.1σ) 14 n.s 2.30 + Mixed-permissive
F135del NA NA NA PC3 (− 2.4σ) 9 n.s 1.52 Mixed-permissive
M156V 2.54 ± 0.17 − 3.75 1.22 n.s. 6 + 0.62 ––– Permissive
M159I 8.01 ± 0.52 − 22.18 0.86 n.s. 8 + 1.93 n.s Permissive
F164C 3.48 ± 0.43 − 31.18 − 0.55 PC1 (1.2σ) 8 n.s 2.92 ++ Permissive
T199A 0.92 ± 0.14 1.83 0.08 PC2 (− 2.7σ)
PC3 (2.3 )
12 + 1.93 n.s Permissive
Y205C 4.01 ± 0.63 − 5.57 2.94 n.d. n.d. n.d. n.d. n.d. n.d.
G236R − 2.59 ± 0.54 − 3.41 − 0.46 PC2 (− 2.8σ)
PC3 (1.6σ)
0 ++ 0.25 ––– Occluded
G236R & A237T − 2.40 ± 0.54 0.32 NA PC1 (− 2.0σ)
PC3 (− 2.4σ)
10 ++ 0.81 –– Occluded-attenuated
A237D 5.36 ± 0.17 13.51 − 1.85 PC2 (− 1.3σ) 8 n.s 1.37 Permissive
A237T 0.13 ± 0.07 − 0.60 − 0.76 PC2 (− 2.9σ) 4 + 1.80 n.s Moderately permissive
M249T 6.41 ± 0.83 5.09 0.59 PC2 (− 3.1σ)
PC3 (1.2σ)
1 -- 2.00 n.s Permissive
  1. SRLF single residue level frustration, NA not applicable, n.d. not determined
  2. a PC alterations of at least 1 standard deviation (σ) away from WT are noted; others are labeled as not significant (n.s.); data used ignored the C-terminus (see Methods)
  3. b Compared to a WT value of 2 transport events
  4. c Defined based on the K+ radial distribution functions (Fig. S4 and S5) at 6.9 Å from residues 94 and 200. Comparisons are to the WT value of 1.8
  5. d Using only the computational simulation data, we predict if the variants will impair potassium transport or not