Table 1.

List of disease-causing CLCN7 mutations.

Mutation	Amino Acid Location	Disease	Current Amplitude	Current Activation	Lysosomal Localization
L90P (splice variant)	N-terminus	ARO	normal	normal	normal	[102]
Y99C	N-terminus	ADO II				[74]
R126H	Helix B	ARO (neurodegen.)	reduced	accelerated	strongly reduced	[102]
W127G	Helix B	ADO II				[106]
L132P (L227del)	Helix B	ARO				[72]
D145fs	Helix B	ARO				[52]
D145G	Helix B	ADO II		accelerated	normal	[107]
W179x	Helix C	ADO II				[52]
G203D	Loop helix C-D	IARO				[76]
L213F	Helix D	ADO II	normal	accelerated		[11,108]
N214S (R767P)	Helix D	ARO				[72]
G215R	Helix D	ADO II and ADO II + renal tubular acidosis			ER retention	[18,52,54,109,110]
L224R (K691fs)	Helix E	IARO				[71]
G240E (W127G)	Helix E	ARO				[111]
G240R (A299E)	Helix E	ARO (neurodegen.)	strongly reduced		reduced	[11,102]
G240R (R526W)	Helix E	ARO				[52]
G240R (L651P)	Helix E	ARO				[72]
P249L	Helix F	ADO II				[54,102]
P249R (S744F)	Helix F	ARO				[52]
I261F	Helix F	ARO				[112]
R271x	Loop helix F-G	ARO				[72]
R280C (splice variant)	Loop helix F-G	ARO				[113]
R286Q	Helix G	ADO II	normal	accelerated		[11,52]
R286W	Helix G	ADO II				[71,108]
V289L	Helix G	ADO II				[114]
S290F	Helix G	ADO II				[106]
S290Y	Helix G	ADO II				[71]
G292E (R403Q)	Helix G	ARO (neurodeg.)				[60]
V297M	Helix G	ARO	strongly reduced		normal (increased overall expression)	[52,115]
A299E	Helix G	ARO (neurodegen.)	strongly reduced		strongly reduced	[102,116]
A299V	Helix G	ADO II/ARO (neurodegen.)	strongly reduced		strongly reduced	[102]
E313K	Helix H	ADO II				[106]
A316G	Loop helix H-I	ADO II				[106]
F318L	Loop helix H-I	ADO II	reduced		normal	[52,72]
F318S	Loop helix H-I	ADO II				[111]
W319R	Loop helix H-I	ADO II				[71]
L323P	Helix I	ADO II	normal	accelerated	normal	[102]
R326G	Helix I	ADO II				[71]
M332V (R767W)	Helix I	ARO				[52]
G347R	Helix I	ADO II				[71]
E374x (in frame insertion G306)	Loop helix I-J	ARO				[52]
P376L	Helix J	ARO	reduced	accelerated	strongly reduced	[102]
R403Q (G512R)	Helix J	ARO				[72]
R409W	Loop helix J-K	ADO II				[117]
V418M	Helix K	ADO II				[70]
V418M (R674Q)	Helix K	IARO				[70]
V418fs	Helix K	ARO				[72]
P470L	Loop helix K-L	IARO				[77]
P470Q	Loop helix K-L	IARO				[76]
S473N	Helix L	ADO II				[71]
L490F	Helix M	ADO	reduced		Normal (reduced overall expression)	[11,52]
C502Y (V577M)	Helix M	IARO				[118]
A511T (G780W)	Loop helix M-N	ARO				[102]
G521R	Helix N	ARO (neurodegen.)	strongly reduced		reduced	[52]
R526Q	Helix N	ARO				[72]
R526T	Helix N	ARO				[72]
R526W	Helix N	ARO	strongly reduced		reduced ER retention	[52]
L549P	Helix O	ARO				[72]
Q555x (R762Q)	Helix O	ARO				[7]
R561Q	Loop Helix O-P	ARO				[119]
L564P	Helix P	ADO II				[71]
P582H	Helix Q	ARO (neurodegen.)			reduced	[102]
A590T	Helix Q	ARO			normal	[102]
L614P (Del exon 17)	Loop helix R–CBS1	ARO				[52]
P619L	Loop helix R–CBS1	ARO	reduced			[52,115]
P634fs	CBS1	ARO				[72]
L651P	CBS1	ARO	strongly reduced		normal	[52]
R674Q	CBS1	ADO II				[70]
G677V	CBS1	ADO II				[52,54]
K689E	Loop CBS1-CBS2	ADO II				[54]
K691E	Loop CBS1-CBS2	ADO II	reduced	slower	reduced	[102]
R712x (E730x)	Loop CBS1-CBS2	ARO				[72]
Y715C	Loop CBS1-CBS2	Lysosomal storage + albinism				[78]
G741R	Loop CBS1-CBS2	ADO II				[106]
R743W	Loop CBS1-CBS2	ADO II				[106]
S744F	Loop CBS1-CBS2	ARO	normal			[11,52]
Y746Q	CBS2	ADO bovine		accelerated	normal	[103]
S753W	CBS2	ADO II				[111]
F758L	CBS2	ADO II				[72]
R762L	CBS2	ADO II		accelerated		[11,108]
R762Q	CBS2	ARO		accelerated		[7,11]
R762W (splicing variant)	CBS2	ADO II				[72]
L766P	CBS2	ARO				[54]
R767P	CBS2	ARO	strongly reduced		normal (reduced overall expression)	[11]
R767Q	CBS2	ARO	normal	accelerated		[11,52]
R767W	CBS2	ADO II	Strongly reduced		Normal (reduced overall expression)	[11,54]
R767W (M332V)	CBS2	ARO				[52]
G780R (splice variant)	CBS2	ARO (neurodegen.)				[102]
A788D	CBS2	ADO II	normal			[11,73]
R791C	CBS2	ARO	normal	accelerated	strongly reduced	[102]
G796fs	CBS2	ADO II		accelerated		[11,54]

The table indicates the amino acid location, the specific type of osteopetrosis (ARO, ADO II and IARO), the effect of the mutation on the current amplitude and activation kinetics and on the lysosomal localization.