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UniProtKB/Swiss-Prot O75197: Variant p.Gly610Arg

Low-density lipoprotein receptor-related protein 5
Gene: LRP5
Chromosomal location: 11q13.4
Variant information

Variant position:  610
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Glycine (G) to Arginine (R) at position 610 (G610R, p.Gly610Arg).
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:  Change from glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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

Involvement in disease:  Osteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770]: A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures. Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, mental retardation and hypotonia. {ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16679074, ECO:0000269|PubMed:17437160, ECO:0000269|PubMed:18602879}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Involvement in disease:  Vitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:15024691, ECO:0000269|PubMed:15346351, ECO:0000269|PubMed:15981244, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16929062, ECO:0000269|PubMed:19324841, ECO:0000269|PubMed:20340138, ECO:0000269|PubMed:24715757}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 60% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  610
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:   GLKAVNVAKVVGTNPCADRN  G GCSHLCFFTPHATRCGCPIG
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                         GLKAVNVAKVVGTNPCADRNGGCSHLCFFTPHATRCGCPIG

Mouse                         GLKAVNVAKVVGTNPCADGNGGCSHLCFFTPRATKCGCPIG

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.

TypePositionsDescription
Chain 32 – 1615 Low-density lipoprotein receptor-related protein 5
Topological domain 32 – 1384 Extracellular
Domain 601 – 641 EGF-like 2
Disulfide bond 605 – 616


Literature citations

Clinical and molecular findings in osteoporosis-pseudoglioma syndrome.
Ai M.; Heeger S.; Bartels C.F.; Schelling D.K.;
Am. J. Hum. Genet. 77:741-753(2005)
Cited for: VARIANTS OPPG ASN-203; MET-244; PHE-307; TRP-348; GLN-353; LEU-356; LYS-390; GLU-400; ARG-404; ASN-434; LYS-460; GLN-494; VAL-520; TRP-570; ARG-610; ASN-683; HIS-733; TYR-1099; CYS-1113 AND ASP-1401; CHARACTERIZATION OF VARIANTS OPPG MET-244; LEU-356; LYS-390; ARG-404; ASN-434; VAL-520 AND ARG-610; CHARACTERIZATION OF VARIANTS EVR4 MET-173; GLN-570; HIS-1168; GLY-1361 AND LYS-1367; FUNCTION;

Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes.
Qin M.; Hayashi H.; Oshima K.; Tahira T.; Hayashi K.; Kondo H.;
Hum. Mutat. 26:104-112(2005)
Cited for: VARIANTS EVR4 PHE-145; CYS-444; THR-522; MET-535; ARG-610; CYS-617; ALA-798 AND ASP-1121; VARIANTS VAL-97 AND MET-1540;

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.