Table 2.

Summary of the phenotypes resulting from genetic alterations of NCS proteins

NCS protein	Organism	Phenotypes
NCS-1 (frequenin)	S. cerevisiae	Knockout is lethal owing to requirement in Pik1 activation 21
	S. pombe	Growth defect at high Ca2+, decreased sporulation 147
	D. discoideum	Development accelerated 76
	C. elegans	Knockout impairs learning 77
	D. melangaster	Overexpression increases facilitation of neurotransmission16
	D. rerio	Knockdown of NCS-1a impairs development of inner ear 22
Hippocalcin	Mouse	Knockout causes impaired spatial learning and reduced neurodegeneration 138, 148
Recoverin	Mouse	Knockout results in shorter responses to bright flasher in dark-adapted state and decreased sensitivity to dim light in retinal rod cells44. 58 Signal transmission downstream of phototransduction reduced 58
GCAP1/2	Mouse	Rod and cone photoreceptors with knockout of both GCAP1 and 2 show increased light sensitivity and a slower recovery following flash response 59, 60, 149, 150
		Expression of GCAP1 in GCAP1/2-knockout mice restores normal function 59, 60
		Expression of GCAP2 in GCAP1/2-knock-out mice is not effective in recovering normal kinetics of flash response 150
GCAP1	Human	Various mutations result in cone or rod/cone degeneration 151
KChIP2	Mouse	Knockout is highly susceptible to cardiac arrhythmias 93
KChIP3	Mouse	One study showed reduced responses to pain and elevated dynorphin levels in knockout 70
		Another study showed reduced levels of Aβ peptides, enhanced long-term potentiation and downregulation of Kv4 channels in hippocampus 70, 71

GCAP, guanylyl cyclase-activating protein; KChIP, Kv channel-interacting protein; NCS, neuronal Ca²⁺ sensor; Pik1, phosphatidylinositol kinase.