Table 1.

Summary of mutations identified by the scientific literature, detailing the domain affected, the in vitro and in vivo phenotypes detected by various studies, as well as the studies that have investigated and/or reported the corresponding mutations. Mutations are represented as the corresponding amino acid change at the reported amino acid sequence position. OAD, oocyte activation deficiency

Mutation	Domain affected	In vitro phenotype	In vivo phenotype	Associated studies
I120M	EF-X linker	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Torra-Massana et al. [158]
C196X	X	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Dai et al. [157]
C196*	X	No recombinant protein produced by mammalian cells; reduced activation success following cRNA injection in mouse oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Mu et al. [160]; Yan et al. [161]
R197H	X	Predicted alteration of local protein fold	OAD; low fertilization success	Ferrer-Vaquer et al. [153]; Torra-Massana et al. [158]
L224P	X	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Torra-Massana et al. [158]
H233L	X	Reduced expression in mammalian cells; reduced/absent oscillations following cRNA injections in mouse oocytes; reduced embryogenesis in mouse; predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Kashir et al. [142, 151, 152]; Ferrer-Vaquer et al. [153]; Torra-Massana et al. [158]
L246F	X	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Dai et al. [157]
L277P	X	Predicted alteration of local protein fold; reduced activation success following cRNA injection in human oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Yan et al. [161]
T324fs	X-Y linker	Truncated recombinant protein produced by mammalian cells; reduced activation success following cRNA injection in mouse oocytes	OAD; low fertilization success	Mu et al. [160]
V326K fs*25	X-Y linker	Predicted frameshift truncation of protein	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Torra-Massana et al. [158]
S350P	Y	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Dai et al. [157]
N377del	Y	Predicted alteration of local protein fold; no activation success following cRNA injection in human oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Yan et al. [161]
A384V	Y	Predicted alteration of local protein fold; no activation success following cRNA injection in human oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Yan et al. [161]
H398P	Y	Reduced expression in mammalian cells; reduced/absent oscillations following cRNA injections in mouse oocytes; predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Heytens et al. 2009; Kashir et al. [143, 152, 153]
R412fs	Y	Truncated recombinant protein produced by mammalian cells; reduced activation success following cRNA injection in mouse oocytes	OAD; low fertilization success	Mu et al. [160]
P420L	Y	Reduced recombinant protein produced by mammalian cells; reduced activation success following cRNA injection in mouse oocytes	OAD; low fertilization success	Mu et al. [160]
K448N	Y	Predicted alteration of local protein fold; reduced activation success following cRNA injection in human oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Yan et al. [161]
I489F	C2	Reduced/absent oscillations following cRNA injections in mouse oocytes; reduced embryogenesis in mouse; predicted alteration of local protein fold; similar enzymatic properties, but dramatically reduced substrate binding	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Escoffier et al. [154]; Nomikos et al. [156]
S500L	C2	Predicted alteration of local protein fold	OAD; reduced/absent PLCζ in patient sperm; abnormal PLCζ localization	Torra-Massana et al. [158]
R553P	C2	Reduced/absent fertilization following cRNA injections in mouse oocytes; predicted alteration of local protein fold; mouse fertilization and embryogenesis comparable following injection of higher levels of mutant cRNA	Comparable levels of PLCζ in patient sperm	Yuan et al. [168]
M578T	After C2	Predicted alteration of local protein fold; No activation success following cRNA injection in human oocytes	OAD; reduced/absent PLCζ in patient sperm; low fertilization success	Yan et al. [161]