UniProtKB/Swiss-Prot O75197: Variant p.Val667Met

Low-density lipoprotein receptor-related protein 5
Gene: LRP5
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Variant information Variant position:

667 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Valine (V) to Methionine (M) at position 667 (V667M, p.Val667Met). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Polymorphism:

Genetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population. Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs4988321 [ dbSNP | Ensembl ]

Sequence information Variant position:

667 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1615 The length of the canonical sequence.
Location on the sequence:

LVFTSRAAIHRISLETNNND V AIPLTGVKEASALDFDVSNN The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         LVFTSRAAIHRISLETNNNDVAIPLTGVKEASALDFDVSNN

Mouse                         LVFTSRATIHRISLETNNNDVAIPLTGVKEASALDFDVSNN

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	32 – 1615	Low-density lipoprotein receptor-related protein 5
Topological domain	32 – 1384	Extracellular
Region	644 – 903	Beta-propeller 3

Literature citations
Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density.
Van Wesenbeeck L.; Cleiren E.; Gram J.; Beals R.K.; Benichou O.; Scopelliti D.; Key L.; Renton T.; Bartels C.; Gong Y.; Warman M.L.; de Vernejoul M.-C.; Bollerslev J.; Van Hul W.;
Am. J. Hum. Genet. 72:763-771(2003)
Cited for: VARIANTS OPTA1 TYR-111; ARG-171; THR-242 AND ILE-253; VARIANTS WENHY THR-214; VAL-214 AND THR-242; VARIANT VBCH2 THR-242; VARIANTS 18-LEU--LEU-20 DEL; LEU-20 INS; ARG-89; MET-667 AND VAL-1330; Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites.
Ferrari S.L.; Deutsch S.; Choudhury U.; Chevalley T.; Bonjour J.-P.; Dermitzakis E.T.; Rizzoli R.; Antonarakis S.E.;
Am. J. Hum. Genet. 74:866-875(2004)
Cited for: VARIANTS MET-667 AND VAL-1330; LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.
Gong Y.; Slee R.B.; Fukai N.; Rawadi G.; Roman-Roman S.; Reginato A.M.; Wang H.; Cundy T.; Glorieux F.H.; Lev D.; Zacharin M.; Oexle K.; Marcelino J.; Suwairi W.; Heeger S.; Sabatakos G.; Apte S.; Adkins W.N.; Allgrove J.; Arslan-Kirchner M.; Batch J.A.; Beighton P.; Black G.C.; Boles R.G.; Boon L.M.; Borrone C.; Brunner H.G.; Carle G.F.; Dallapiccola B.; De Paepe A.; Floege B.; Halfhide M.L.; Hall B.; Hennekam R.C.M.; Hirose T.; Jans A.; Jueppner H.; Kim C.A.; Keppler-Noreuil K.; Kohlschuetter A.; LaCombe D.; Lambert M.; Lemyre E.; Letteboer T.; Peltonen L.; Ramesar R.S.; Romanengo M.; Somer H.; Steichen-Gersdorf E.; Steinmann B.; Sullivan B.; Superti-Furga A.; Swoboda W.; van den Boogaard M.-J.; Van Hul W.; Vikkula M.; Votruba M.; Zabel B.; Garcia T.; Baron R.; Olsen B.R.; Warman M.L.;
Cell 107:513-523(2001)
Cited for: VARIANTS OPPG GLN-494 AND TRP-570; VARIANT MET-667; FUNCTION;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.