rs4988321

plus

Geno	Mag	Summary
(A;A)	1.3	slightly increased (~1.3x) risk for osteoporosis
(A;G)	1.1	very slightly increased risk for osteoporosis
(G;G)	0	normal

Reference

GRCh38 38.1/141

Chromosome

11

Position

68406721

Gene

LRP5

is a	snp
is	mentioned by
dbSNP	rs4988321
dbSNP (classic)	rs4988321
ClinGen	rs4988321
ebi	rs4988321
HLI	rs4988321
Exac	rs4988321
Gnomad	rs4988321
Varsome	rs4988321
LitVar	rs4988321
Map	rs4988321
PheGenI	rs4988321
Biobank	rs4988321
1000 genomes	rs4988321
hgdp	rs4988321
ensembl	rs4988321
geneview	rs4988321
scholar	rs4988321
google	rs4988321
pharmgkb	rs4988321
gwascentral	rs4988321
openSNP	rs4988321
23andMe	rs4988321
SNPshot	rs4988321
SNPdbe	rs4988321
MSV3d	rs4988321
GWAS Ctlg	rs4988321

GMAF

0.02204

Max Magnitude

1.3

?

(A;A) (A;G) (G;G)

28

rs4988321 is a SNP in the LRP5 gene that is also known as Val667Met or V667M; the more common (G) allele encodes the Val (valine), while the rarer (A) allele encodes the Met (methionine), which is the risk allele.

rs4988321(A) is associated with vertebral fractures and reduced bone mineral density (BMD), with an overall odds ratio for vertebral fractures of 1.26 per allele (CI: 1.08-1.47; 2001 fractures among 20,488 individuals studied). More specifically, the rs4988321(A) allele was associated with reduced lumbar spine BMD density (p = 3.3 x 10^-8), and femoral neck BMD (p = 3.8 x 10^-5).[PMID 18349089 ]

Note that rs3736228, another LRP5 SNP (also known as Ala1330Val), was independently associated with BMD in this same study.[PMID 18349089 ]

[PMID 19148563] No association was found between rs4988321 and either hip or spine BMD in a study of 249 Caucasian osteoporotic or osteopenic men.

OMIM	603506
Desc	OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME
Variant	0009
Related	also

triallelic and on a chip

ClinVar
Risk	Rs4988321(A;A) rs4988321(C;C)
Alt	Rs4988321(A;A) rs4988321(C;C)
Reference	Rs4988321(G;G)
Significance	Pathogenic
Disease	Osteoporosis with pseudoglioma not provided not specified
Variation	info
Gene	LRP5
CLNDBN	Osteoporosis with pseudoglioma not provided not specified
Reversed	0
HGVS	NC_000011.9:g.68174189G>A
CLNSRC	OMIM Allelic Variant UniProtKB (protein)
CLNACC	RCV000006654.7, RCV000086953.1, RCV000250939.1,

[PMID 17137849 ] Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men.

[PMID 17903296 ] Genome-wide association with bone mass and geometry in the Framingham Heart Study.

[PMID 18058054 ] Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study.

[PMID 18588671 ] Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

[PMID 19629617 ] Replication study of candidate genes/loci associated with osteoporosis based on genome-wide screening.

[PMID 15767] The conjugation of benzoic acid in the African bat, Epomops franqueti.

[PMID 12579474 ] Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.

[PMID 15777745] LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women.

[PMID 15824861] Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation.

[PMID 15850991] LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders.

[PMID 17307038] LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women.

[PMID 23242660] Association of LRP5 haplotypes with osteoporosis in Mexican women.

[PMID 29963786] The importance of the Wnt/β-catenin pathway and LRP5 protein in bone metabolism of postmenopausal women.