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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75096: Variant p.Glu1233Lys

Low-density lipoprotein receptor-related protein 4
Gene: LRP4
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Variant information Variant position: help 1233 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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: help From Glutamate (E) to Lysine (K) at position 1233 (E1233K, p.Glu1233Lys). 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: help Change from medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 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
Variant description: help In CMS17; decreases binding affinity for AGRN and MUSK proteins; does not enhance downstream activation of the MUSK signaling pathway thus impairing clustering of AChRs. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 1233 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 1905 The length of the canonical sequence.
Location on the sequence: help PNGLTVDKASSQLLWADAHT E RIEAADLNGANRHTLVSPVQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         PNGLTVDKASSQLLWADAHTERIEAADLNGANRHTLVSPVQ

Mouse                         PNGLTVDKTSSQLLWADAHTERIEVADLNGANRHTLVSPVQ

Rat                           PNGLTVDKTSSQLLWADAHTERIEVADLNGANRHTLVSPVQ
Sequence annotation in neighborhood: help 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 21 – 1905 Low-density lipoprotein receptor-related protein 4
Topological domain 21 – 1725 Extracellular
Repeat 1223 – 1263 LDL-receptor class B 14
Mutagenesis 1214 – 1214 N -> A. Compromises Wnt-suppressive activity.
Mutagenesis 1252 – 1252 V -> A. Compromises AGRN-mediated up-regulation of MUSK signaling.



Literature citations
LRP4 third beta-propeller domain mutations cause novel congenital myasthenia by compromising agrin-mediated MuSK signaling in a position-specific manner.
Ohkawara B.; Cabrera-Serrano M.; Nakata T.; Milone M.; Asai N.; Ito K.; Ito M.; Masuda A.; Ito Y.; Engel A.G.; Ohno K.;
Hum. Mol. Genet. 23:1856-1868(2014)
Cited for: INVOLVEMENT IN CMS17; VARIANTS SOST2 TRP-1170 AND SER-1186; VARIANTS CMS17 LYS-1233 AND HIS-1277; CHARACTERIZATION OF VARIANTS SOST2 TRP-1170 AND SER-1186; CHARACTERIZATION OF VARIANTS CMS17 LYS-1233 AND HIS-1277; MUTAGENESIS OF ASN-1214; VAL-1252; TYR-1256 AND ILE-1287;
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.