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UniProtKB/Swiss-Prot P04628: Variant p.Cys218Gly

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

Variant position:  218
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 Cysteine (C) to Glycine (G) at position 218 (C218G, p.Cys218Gly).
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 medium size and polar (C) to glycine (G)
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:  Osteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. {ECO:0000269|PubMed:23499309, ECO:0000269|PubMed:23656646}. Note=Disease susceptibility is associated with variations 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 OSTEOP; reduced capacity to activate canonical Wnt signaling.
Any additional useful information about the variant.

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



Sequence information

Variant position:  218
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:   MNLHNNEAGRTTVFSEMRQE  C KCHGMSGSCTVRTCWMRLPT
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                         MNLHNNEAGRTTVFSEMRQECKCHGMSGSCTVRTCWMRLPT

Mouse                         MNLHNNEAGRTTVFSEMRQECKCHGMSGSCTVRTCWMRLPT

Chicken                       MNLHNNEAGRMTVFSEMRQECKCHGMSGSCTVRTCWMRLPT

Xenopus laevis                VNLHNNQAGRLTVLTEMRQECKCHGMSGSCSLRTCWMRLPP

Zebrafish                     TNLHNNEAGRMTVASEMQQECKCHGMSGSCTVRTCWMRLPS

Caenorhabditis elegans        INLHNNQAGRQVLEKSLRRECKCHGMSGSCEMRTCWDSLPN

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
Lipidation 224 – 224 O-palmitoleoyl serine; by PORCN
Disulfide bond 218 – 232


Literature citations

WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta.
Laine C.M.; Joeng K.S.; Campeau P.M.; Kiviranta R.; Tarkkonen K.; Grover M.; Lu J.T.; Pekkinen M.; Wessman M.; Heino T.J.; Nieminen-Pihala V.; Aronen M.; Laine T.; Kroeger H.; Cole W.G.; Lehesjoki A.E.; Nevarez L.; Krakow D.; Curry C.J.; Cohn D.H.; Gibbs R.A.; Lee B.H.; Maekitie O.;
N. Engl. J. Med. 368:1809-1816(2013)
Cited for: INVOLVEMENT IN OI15; VARIANT OSTEOP GLY-218; FUNCTION; CHARACTERIZATION OF VARIANT OSTEOP GLY-218;

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.