. 2023 May 18;21(7):1504–1518. doi: 10.2174/1570159X21666221208091805

Table 3.

GOF Mutations in KCNN1-4 associated with human neurological diseases.

Clinical Phenotypes	Gene Type	Homo Variants	Location	Mutant Types	Function Test; Model	Results
ZLS, DD, ID, hypotonia [113]	KCNN1	G350D	S2-S3 domain	Missense mutation	Yes; pcDNA3.1 cloned by human KCNN3 cDNA	Increased Ca²⁺ sensitivity and faster channel activation in mutant SK channel.
DD, ID, ZLS [113]	KCNN1	S436K	S₄₅A domain	Missense mutation	Yes; subcloned CHO cell
ZLS, ID, DD, PDA [113]	KCNN2	K269E	N-terminus	Missense mutation	Yes; HEK293T cells
DD, Hypo-tonia [114]	KCNN3	V555F	NA	Missense mutation	Yes; NA
ID, DD [114]	KCNN3	V539del	NA	Nonsense mutation	Yes; NA
DD, Mild seizures [114]	KCNN3	A287S	NA	Missense mutation	Yes; NA
INCPH [115]	KCNN3	V450L	S₄₅B domain	Missense mutation	Yes; NA
HX [116]	KCNN4	R352H	CaMB domain	Missense mutation	Yes; HEK293T cells	Increased 10 folds Ca²⁺ sensitivity and current density in encoded mutant channel.
DHSt [117]	KCNN4	V282M	S6 domain	Missense mutation	Yes; CD34+ cells and K562 cells	Increased Ca²⁺ sensitivity in mutant channel.
DHSt [118]	KCNN4	V282E	S6 domain	Missense mutation	Yes; CD34+ cells and K562 cells	Increased Ca²⁺ sensitivity in mutant channel.

Abbreviations: DD, developmental delay; GOF, gain of functional mutation; ID, intellectual disability; INCPH, idiopathic non-cirrhotic portal hypertension; NA; not available. PDA, patent ductus arteriosus; ZLS, Zimmermann–Laband syndrome. CaMB, Calmodulin domain; HX, Hereditary xerocytosis; DHSt, Dehydrated hereditary stomatocytosis.