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UniProtKB/Swiss-Prot O75197: Variant p.Ala214Thr

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

Variant position:  214
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 Alanine (A) to Threonine (T) at position 214 (A214T, p.Ala214Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Endosteal hyperostosis, Worth type (WENHY) [MIM:144750]: An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus). Serum calcium, phosphorus and alkaline phosphatase levels are normal. Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible. With advancing age, the trabeculae of the metaphysis become thickened. WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture. Affected patients have normal height, proportion, intelligence and longevity. {ECO:0000269|PubMed:12579474}. 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 WENHY.
Any additional useful information about the variant.

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



Sequence information

Variant position:  214
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:   IYWPNGLTIDLEEQKLYWAD  A KLSFIHRANLDGSFRQKVVE
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                         IYWPNGLTIDLEEQKLYWADAKLSFIHRANLDGSFRQKVVE

Mouse                         IYWPNGLTIDLEEQKLYWADAKLSFIHRANLDGSFRQKVVE

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 207 – 247 LDL-receptor class B 4
Region 32 – 288 Beta-propeller 1


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;

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.