Structure-Function Correlation Analysis of Connexin50 Missense Mutations Causing Congenital Cataract: Electrostatic Potential Alteration Could Determine Intracellular Trafficking Fate of Mutants

Table 1

Summary of the functional parameters previously reported for 12 disease-causing Cx50 missense mutations.

Sl. number	Mutation	Functional study			Ref. number
		Trafficking (localization, if reported)	Gap junction channel	Inhibitory to WT Cx50
1	R23T	Impaired (cytoplasm)	N.F.	Yes	[20]
2	V44E	Proper	N.F.	Yes	[21]
3	W45S	Proper	N.F.	Yes	[27]
4	G46V	Proper	F. (conductance similar to WT)	No	[27, 28]
5	D47N	Impaired (cytoplasm) [proper trafficking at 27°C.]	N.F.	No	[22]
		Impaired	N.F.	No	[21]
6	E48K	[Not studied]; Predicted: impaired	N.F.	Yes	[30]
7	V79L	Proper	F. (lower conductance)	Yes	[21]
8	P88S	[Not studied]	N.F.	Yes	[23]
		Impaired (cytoplasm and appositional membranes)	N.F.	Yes	[24]
9	P88Q	Impaired (cytoplasm) [proper trafficking at 27°C.]	N.F.	Yes	[25]
10	R205G(Gja8)*; R198W/Q	Impaired; Predicted: Impaired	N.F.; Predicted: N.F.	Yes; —	[26]; —
11	E201K	Impaired (cytoplasm)	[Not studied]; Predicted: N.F.	[Not studied]	[29]
12	I247M	Proper	F. (conductance similar to WT)	[Not studied]	[38]

F.: functional; N.F.: nonfunctional; ER: endoplasmic reticulum.
*R205(Gja8) is functionally characterized in mouse model. R205(Gja8) corresponds to R198(GJA8) in human Cx50, bearing mutations R198Q and R198W, neither of which is functionally characterized.