Proprotein Convertase Subtilisin/Kexin Type 9: From the Discovery to the Development of New Therapies for Cardiovascular Diseases

Table 1

PCSK9 allelic variants with known functional property.

Functional domain	DNA allele	Mutation	Function	Ref.
5′UTR, 2.5-fold increase of transcriptional activity	C^−332A		Gain	[71]
Signal peptide	G^10A	Val^4Ile	Gain	[72, 73]
Prodomain	G^94A	Glu^32Lys	Gain	[73]
Prodomain	A^161C	Glu^54Ala	Gain	[73]
Generation of a truncated peptide (Ala^68fsLeu^82X)	^202del G	Ala^68ProfsX15	Loss	[74]
Prodomain	C^230T	Thr^77Ile	Loss	[74]
Prodomain	C^277T	Arg^93Cys	Loss	[73]
Prodomain	290-292del GCC	Arg^97del	Loss	[75]
Prodomain	C^310T	Arg^104Cys	Gain	[73]
Prodomain	G^316A	Gly^106Arg	Loss	[76]
Prodomain	T^341C	Val^114Ala	Loss	[74, 77]
Prodomain	T^381A	Ser^127Arg	Gain	[39, 78, 79]
Prodomain	G^385A	Asp^129Asn	Gain	[74]
Prodomain	A^386G	Asp^129Gly	Gain	[78]
Generation of a truncated peptide	C^426G	Tyr^142X	Loss	[80]
Catalytic	C^503A	Ala^168Glu	No effect	[78]
Catalytic	G^644A	Arg^215His	Gain	[79]
Catalytic	T^646C	Phe^216Leu	Gain	[39]
Catalytic	A^654T	Arg^218Ser	Gain	[81]
Catalytic	C^655G	Gln^219Glu	Loss	[73]
Catalytic	G^706A	Gly^236Ser	Loss	[79]
Catalytic	C^716A	Ala^239Asp	Loss	[73]
Catalytic	C^757T	Leu^253Phe	Loss	[82]
Catalytic	A^1061T	Asn^354Ile	Loss	[79]
Catalytic	G^1070A	Arg^357His	Gain	[81]
Catalytic	G^1120T	Asp^374Tyr	Gain	[40, 83, 84]
Catalytic	G^1120C	Asp^374His	Gain	[85]
Catalytic	C^1171A	His^391Asn	Loss	[82]
Catalytic	A^1274G	Asn^425Ser	Gain	[82, 86]
Catalytic	G^1284A	Trp^428X	Loss	[73]
C-terminal domain	C^1300T	Arg^434Trp	Loss	[87]
C-terminal domain	G^1355A	Gly^452Asp	Loss	[73]
Disrupts normal folding of the C-terminal domain	T^1384C	Ser^462Pro	Loss	[79]
C-terminal domain	C^1405T	Arg^469Trp	Gain	[81, 82]
C-terminal domain	C^1486T	Arg^496Trp	Gain	[86]
C-terminal domain	G^1540A	Ala^514Thr	Gain	[73]
C-terminal domain	G^1564A	Ala^522Thr	Gain	[74]
C-terminal domain	A^1658G	His^553Arg	Gain	[82]
C-terminal domain	C^1660G	Gln^554Glu	Loss	[82]
C-terminal domain	C^1847T	Pro^616Leu	Loss	[74]
C-terminal domain	G^1870A	Val^624Met	Gain	[73]
C-terminal domain	C^2004A	Ser^668Arg	Loss	[73]
Generation of a truncated peptide retained in the ER	C^2037A	Cys^679X	Loss	[80]