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rs4988321

From SNPedia

Orientationplus
Stabilizedplus
Geno Mag Summary
(A;A) increased risk for osteoporosis
(A;G) increased risk for osteoporosis
(G;G) 0 normal
ReferenceGRCh38 38.1/141
Chromosome11
Position68406721
GeneLRP5
is asnp
is mentioned by
dbSNPrs4988321
ebirs4988321
HLIrs4988321
Exacrs4988321
Varsomers4988321
Maprs4988321
PheGenIrs4988321
hapmaprs4988321
1000 genomesrs4988321
hgdprs4988321
ensemblrs4988321
gopubmedrs4988321
geneviewrs4988321
scholarrs4988321
googlers4988321
pharmgkbrs4988321
gwascentralrs4988321
openSNPrs4988321
23andMers4988321
23andMe allrs4988321
SNP Nexus

SNPshotrs4988321
SNPdbers4988321
MSV3drs4988321
GWAS Ctlgrs4988321
GMAF0.02204
Max Magnitude0
? (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 18349089OA-icon.png]

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

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

OMIM603506
DescOSTEOPOROSIS-PSEUDOGLIOMA SYNDROME
Variant0009
Relatedalso
triallelic and on a chip


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



[PMID 17137849OA-icon.png] 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 17903296OA-icon.png] Genome-wide association with bone mass and geometry in the Framingham Heart Study.

[PMID 18058054OA-icon.png] 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 18588671OA-icon.png] Association between LRP5 polymorphism and bone mineral density: a Bayesian meta-analysis.

[PMID 19629617OA-icon.png] 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 12579474OA-icon.png] 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.


GET Evidence
LRP5-V667M
aa_change Val667Met
aa_change_short V667M
impact pathogenic
qualified_impact High clinical importance, Uncertain pathogenic
overall_frequency 0.0413646
summary This variant has been implicated in causing osteoporosis-pseudoglioma syndrome in a recessive manner. The gene is strongly implicated in causing the disease, but an insufficient number of controls means this variant's observation lacks statistical significance. The condition manifests in childhood with early onset osteoporosis and eye problems.



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