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UniProtKB/Swiss-Prot O75197: Variant p.Leu540Pro

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

Variant position:  540
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 Leucine (L) to Proline (P) at position 540 (L540P, p.Leu540Pro).
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:  -3
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:  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; the mutation results in significantly reduced Norrin signal transduction.
Any additional useful information about the variant.



Sequence information

Variant position:  540
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:   GDAKTDKIEVINVDGTKRRT  L LEDKLPHIFGFTLLGDFIYW
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                         GDAKTDKIEVINVDGTKRRTLLEDKLPHIFGFTLLGDFIYW

Mouse                         GDAKTDKIEVINIDGTKRKTLLEDKLPHIFGFTLLGDFIYW

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
Repeat 515 – 557 LDL-receptor class B 9
Region 341 – 602 Beta-propeller 2


Literature citations

Identification of two novel LRP5 mutations in families with familial exudative vitreoretinopathy.
Fei P.; Zhang Q.; Huang L.; Xu Y.; Zhu X.; Tai Z.; Gong B.; Ma S.; Yao Q.; Li J.; Zhao P.; Yang Z.;
Mol. Vis. 20:395-409(2014)
Cited for: VARIANT PRO-816; VARIANTS EVR4 THR-422; PRO-540 AND MET-852; CHARACTERIZATION OF VARIANTS EVR4 THR-422; PRO-540 AND MET-852; CHARACTERIZATION OF VARIANT PRO-816;

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.