Table 2.

Compilation of naturally occurring and bioengineered mutations in human apoA-I^a.

Mutation	Effect on HDL structure and function	Mutation	Effect on HDL structure and function
P3R, von Eckardstein et al., 1989	Interferes with the formation of a β-turn in Nt	R149A, Koukos et al., 2007b	Reduces LCAT activity
P3H, von Eckardstein et al., 1989	(apoA-IMunster3C) interferes with the formation of a β-turn in Nt	R149V, Sviridov et al., 2000	Does not affect α-helical structure, reduces LCAT activity
P4R, von Eckardstein et al., 1989	(apoA-IMunster3B) has no known effect on RCT	R151C, Daum et al., 1999a	(apoA-IParis) inhibits LCAT activation, reduces HDL levels
R10L, Ladias et al., 1990	(apoA-IBaltimore) has no known effect on HDL phenotype	R153P, Esperoìn et al., 2008	(apoA-IMontevideo) lowers HDL levels and is associated with CAD
D13Y, Takada et al., 1991	(apoA-IYame) has no known effect on HDL phenotype	V156E, Huang et al., 1998	(apoA-IOita) decreases the levels of HDL in plasma and inhibits LCAT activation
Q17P+FScX26, Pisciotta et al., 2008	Frame shift (FS) and stop codon (X) lowers HDL plasma levels	A158E, Mahley et al., 1984	(apoA-IMunster2B) is associated with low levels of HDL in plasma
G26R, Nichols et al., 1988	Initiates deposition of mutant proteins or proteolytic cleaved fragments	L159R, Miettinen et al., 1997	(apoA-IFin) is associated with low levels of HDL in plasma
A37T, Matsunaga et al., 1991	Does not create apoA-I deficiency	L159P, Miller et al., 1998	(apoA-IZavalla) is associated with low levels of HDL in plasma and premature CAD
W50R, Booth et al., 1995	Causes hereditary amyloidosis	R160L, Daum et al., 1999b	(apoA-IOslo) is associated with low levels of HDL in plasma and LCAT inhibition
S52C, Zhu et al., 2005	Has no known effect on HDL phenotype	H162Q, Moriyama et al., 1996a; Hoang et al., 2003	(apoA-IKurume) does not produce accelerated atherosclerosis, reduces LCAT activity
L60R, Soutar et al., 1992	Causes autosomal dominant amyloidosis	H162–A207c; ΔK208–Q243, Moriyama et al., 1996b	Leads to low apoA-I and HDL levels and bilateral xanthomas of the Achilles tendon, elbow, knee joint, and corneal opacities
ΔL60–F71b; ins V,T, Booth et al., 1996	Causes hereditary hepatic and systemic amyloidosis	P165R, von Eckardstein et al., 1989	is associated with lower apoA-I and HDL levels
ΔE70–W72, Persey et al., 1998	Causes hereditary nephropathic systemic amyloidosis	ΔP165–A175, Martin-Campos et al., 2002	(ApoA-IMallorca) impairs LCAT activation and induces dominant familial hypoalphalipoproteinemia
N74C, Zhu et al., 2005	Slightly lowers cholesterol efflux	Y166F, Wu et al., 2007	Impairs LCAT activity
D89E, von Eckardstein et al., 1990	Mutation in less conserved domain of apoA-I, has no known effect on RCT	E169Q, von Eckardstein et al., 1990	Effect on HDL phenotype is unknown
L90P, Asl et al., 1999a	Causes hereditary amyloid cardiopathy	R173P, Asl et al., 1999b	Is associated with cardiac and cutaneous amyloidosis
A95D, Araki et al., 1994	(apoA-IHita) does not affect HDL phenotype	R173C, Weisgraber et al., 1980	(apoA-IMilano) is associated with reduced plasma levels of HDL and elevated TG levels
Y100H, Moriyama et al., 1996a	Does not accelerate atherosclerosis	R177H, Assmann et al., 1993	Effect on HDL phenotype is unknown
D103N, Menzel et al., 1982	(apoA-IMunster3A) effect on HDL phenotype is not known	L178H, Petrlova et al., 2012	Leads to altered conformation, decreased stability, reduced lipid binding capacity, forms fibrils
ΔK107, Amarzguioui et al., 1998	(apoA-IMunster2A) leads to extensive intimal amyloid deposits	L178P, Hovingh et al., 2004	Lowers HDL levels, leads to endothelial dysfunction, increased arterial wall thickness, CAD
ΔK107, Rall et al., 1984	(apoA-IMarburg) inhibits LCAT activation	ΔE191–P220, Nagao et al., 2014	Is associated with defective lipid binding and lower HDL levels
K107C, Zhu et al., 2005	Increases cholesterol efflux	K195C, Zhu et al., 2005	Reduces lipid binding capability and impaires cholesterol efflux
K107M, von Eckardstein et al., 1990	Effect on HDL phenotype not known	E198K, Assmann et al., 1993	(apoA-IMunster4) effect on HDL phenotype is unknown
W108R, Araki et al., 1994	(apoA-ITsushima) does not affect HDL phenotype	L203–F229c; ΔL230–Q243, Funke et al., 1991	Causes HDL deficiency, partial LCAT inhibition, and corneal opacity
E110K, Takada et al., 1990; Hoang et al., 2003	(apoA-IFukuoka) does not affect HDL phenotype, reduces LCAT activity	D213G, Mahley et al., 1984	(apoA-IMunster3D) effect on HDL phenotype is not know
G129C, Zhu et al., 2005	Increases structural stability, reduces lipid binding capability, slightly lowers cholesterol efflux	L218A, Fotakis et al., 2013b	Is associated with decrease in plasma cholesterol and apoA-I levels
E136K, Mahley et al., 1984	(apoA-INorway) effect on HDL phenotype is not known	L219A, Fotakis et al., 2013b	Is associated with decrease in plasma cholesterol and apoA-I levels
E136X, Dastani et al., 2006	Produces circulating HDL deficiency	V221A, Fotakis et al., 2013b	Is associated with decrease in plasma cholesterol and apoA-I levels
E139G, Assmann et al., 1993	Effect on HDL phenotype is not known	L222A, Fotakis et al., 2013b	Is associated with decrease in plasma cholesterol and apoA-I levels
ΔR140–D150, Sviridov et al., 2000	Affects α-helical structure, reduces LCAT activation	E223A, Fotakis et al., 2013b	Is associated with alterations in HDL phenotype
R140–D150 Q63–D73, Sviridov et al., 2000	Does not affect α-helical structure, reduces LCAT activation	ΔE223–Q243, Fotakis et al., 2013b	Leads to critical loss of lipid binding and low HDL levels
L141R, Miccoli et al., 1997	(apoA-IPisa) influences efflux of cholesterol into plasma and interferes with the formation of HDL	F225A, Fotakis et al., 2013a	Is associated with decrease in plasma cholesterol, HDL, and apoA-I levels
P143R, Assmann et al., 1993	(apoA-IGiessen) effect on HDL phenotype is not known	K226A, Fotakis et al., 2013b	Is associated with alterations in HDL phenotype
P143A, Sviridov et al., 2000	Affects α-helical structure, reduces LCAT activation	V227A, Fotakis et al., 2013a	Decreases plasma cholesterol, HDL and apoA-I levels
L144R, Recalde et al., 2001	apoA-IZaragoza decreases the levels of HDL in plasma, HDL has more TG and less CE	F229A, Fotakis et al., 2013a	Decreases plasma cholesterol, HDL and apoA-I levels
L144P, Recalde et al., 1998	Decreases the levels of HDL in plasma, has no effect on CVD	L230A, Fotakis et al., 2013a	Decreases plasma cholesterol, HDL and apoA-I levels
ΔE146–R160, Deeb et al., 1991	Leads to plasma apoA-I and HDL cholesterol below 15% of normal levels	ΔE235, Han et al., 1999	(apoA-INichinan) is associated with decreased protein stability and low plasma HDL levels
E147V, von Eckardstein et al., 1990	Effect on HDL phenotype is not known

^aApoA-I mutations associated with hereditary amyloidosis (underline font), mutations associated with low HDL plasma levels and LCAT deficiency (italic font) and mutations with unknown effect (normal font).

^bDeletion.

^cFrame shift.