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UniProtKB/Swiss-Prot P04628: Variant p.Glu123Asp

Proto-oncogene Wnt-1
Gene: WNT1
Chromosomal location: 12q13
Variant information

Variant position:  123
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 Glutamate (E) to Aspartate (D) at position 123 (E123D, p.Glu123Asp).
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 acidic.
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:  Osteogenesis imperfecta 15 (OI15) [MIM:615220]: An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by low bone mass, bone fragility and susceptibility to fractures after minimal trauma. Disease severity ranges from very mild forms without fractures to intrauterine fractures and perinatal lethality. Extraskeletal manifestations, which affect a variable number of patients, are dentinogenesis imperfecta, hearing loss, and blue sclerae. OI15 is characterized by early-onset recurrent fractures, bone deformity, significant reduction of bone density, short stature, and, in some patients, blue sclerae. Tooth development and hearing are normal. Learning and developmental delays and brain anomalies have been observed in some patients. {ECO:0000269|PubMed:23434763, ECO:0000269|PubMed:23499309, ECO:0000269|PubMed:23499310, ECO:0000269|PubMed:23656646, ECO:0000269|PubMed:28528193}. 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 OI15; detected in a compound heterozygote also carrying G-153; reduced capacity to activate canonical Wnt signaling.
Any additional useful information about the variant.



Sequence information

Variant position:  123
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  370
The length of the canonical sequence.

Location on the sequence:   NCPTAPGPHLFGKIVNRGCR  E TAFIFAITSAGVTHSVARSC
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                         NC----PTAPG--PHLFGKIVNRGCRETAFIFAITSAGVTHSVARSC

Mouse                         NC----PTAPG--PHLFGKIVNRGCRETAFIFAITSAGVTH

Chicken                       NC----PTSQG--PNIFGKIVNRGCRETAFIFAITSAGVTH

Xenopus laevis                NC----PTGTG--NQVFGKIINRGCRETAFVFAITSAGVTH

Zebrafish                     NC----PTTHS--PNVFGKIVNRGCRETAFVFAITSAGVTH

Caenorhabditis elegans        NCTLIDPVTHEVIPDVF---LYENTRESAFVHAISSAAVAY

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 28 – 370 Proto-oncogene Wnt-1


Literature citations

Novel missense loss-of-function mutations of WNT1 in an autosomal recessive Osteogenesis imperfecta patient.
Won J.Y.; Jang W.Y.; Lee H.R.; Park S.Y.; Kim W.Y.; Park J.H.; Kim Y.; Cho T.J.;
Eur. J. Med. Genet. 60:411-415(2017)
Cited for: FUNCTION; INVOLVEMENT IN OI15; VARIANTS OI15 ASP-123 AND GLY-153; CHARACTERIZATION OF OI15 ASP-123 AND GLY-153;

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.