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UniProtKB/Swiss-Prot O75197: Variant p.Ser356Leu

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

Variant position:  356
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 Serine (S) to Leucine (L) at position 356 (S356L, p.Ser356Leu).
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 polar (S) to medium size and hydrophobic (L)
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.

Variant description:  In idiopathic osteoporosis and OPPG; appears to traffic comparably than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable 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:  356
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:   CKAGAEEVLLLARRTDLRRI  S LDTPDFTDIVLQVDDIRHAI
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                         CKAGAEEVLLLARRTDLRRISLDTPDFTDIVLQVDDIRHAI

Mouse                         CKTGAEEVLLLARRTDLRRISLDTPDFTDIVLQVGDIRHAI

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
Region 341 – 602 Beta-propeller 2


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;

Missense mutations in LRP5 are not a common cause of idiopathic osteoporosis in adult men.
Crabbe P.; Balemans W.; Willaert A.; van Pottelbergh I.; Cleiren E.; Coucke P.J.; Ai M.; Goemaere S.; van Hul W.; de Paepe A.; Kaufman J.-M.;
J. Bone Miner. Res. 20:1951-1959(2005)
Cited for: VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455; VARIANT THR-1537; CHARACTERIZATION OF VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455; CHARACTERIZATION OF VARIANT THR-1537;

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.