Table 1. Summary of disease-associated LRP5 polymorphisms.

cDNA change*	Protein change	Associated diseases/phenotype	Effect on Wnt signaling	Biochemical phenotype	References
c266A>G	Q89R	FEVR; LBM; spinal osteoarthritis	Unknown	Unknown	[20,32]
c331G>T	D111Y	HBM	Increase	Decreases Dkk1 and SOST inhibition	[26,30]
c461G>T	R154M	HBM	Increase	Decreases SOST inhibition	[26]
c511G>C	G171R	HBM	Increase	Decreases Dkk1 and SOST inhibition	[30]
c512G>T	G171V	HBM	Increase	Decreases MESD binding; decreased cell surface presentation; decreased SOST inhibition/binding	[26,28]
c593A>G	N198S	HBM	Increase	Decreases SOST inhibition	[26]
c640G>A	A214T	HBM	Increase	Decreases Dkk1 and SOST inhibition/binding	[26,30]
c724G>A	A242T	HBM	Increase	Decreases Dkk1 and SOST inhibition/binding	[30]
c758C>T	T253I	HBM	Increase	Decreases Dkk1 and SOST inhibition/binding	[26,30]
c844A>G	M282V	HBM	Increase	Decreases Dkk1 and SOST inhibition/binding	[30]
c1330C>T	R444C	FEVR	Decrease	Inhibits Norrin-FZD4 mediated pathway activation	[20]
c1481G>A	R494Q	OPPG	Decrease	Increases Dkk1 inhibition	[8,22]
c1564G>A	A522T	FEVR	Decrease	Inhibits norrin-FZD4 mediated pathway activation	[20]
c1708C>T	R570W	OPPG	Decrease	Increases Dkk1 inhibition	[8,22]
c3989C>T	A1330V	FEVR	Decrease	Inhibits norrin-FZD4 mediated pathway activation	[20]
c4574T>C#	V1525A#	BMD#	Decrease	Unknown	[34]
c4619C>T	T1540M	FEVR	Decrease	Inhibits norrin-FZD4 mediated pathway activation	[20]
c4643G>T	C1548F	FEVR	Decrease	Inhibits norrin-FZD4 mediated pathway activation	[20]

*The number starts from the first nucleotide of the coding region. #The predominant allele is controversial [34]. The SNP database recorded c4574C (1525A) as the predominant type. However, c4574C (1525A) is less capable of signal transduction compared to c4574T (1525V). HBM: high bone mineral density; LBM: low bone mineral density; OPPG: Osteoporosis-pseudoglioma syndrome.