UniProtKB/Swiss-Prot Q8WVQ1: Variant p.Val226Met

Soluble calcium-activated nucleotidase 1
Gene: CANT1
Chromosomal location: 17q25.3
Variant information

Variant position:  226
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Valine (V) to Methionine (M) at position 226 (V226M, p.Val226Met).
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 hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  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

Involvement in disease:  Desbuquois dysplasia (DBQD) [MIM:251450]: A chondrodysplasia characterized by severe prenatal and postnatal growth retardation (less than -5 SD), joint laxity, short extremities, progressive scoliosis, round face, midface hypoplasia, prominent bulging eyes. The main radiologic features are short long bones with metaphyseal splay, a 'Swedish key' appearance of the proximal femur (exaggerated trochanter), and advance carpal and tarsal bone age. Two forms of Desbuquois dysplasia are distinguished on the basis of the presence (type 1) or absence (type 2) of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. 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 DBQD1; severely affects activity.
Any additional useful information about the variant.



Sequence information

Variant position:  226
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  401
The length of the canonical sequence.

Location on the sequence:   GTVEKGFKAEWLAVKDERLY  V GGLGKEWTTTTGDVVNENPE
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                         GTVEKGFKAEWLAVKDERLYVGGLGKEWTTTTGDVVNENPE

Mouse                         GTVEKGFKAEWLAVKDEHLYVGGLGKEWTTTTGEVMNENPE

Rat                           GAVEKGFKAEWLAVKDEHLYVGGLGKEWTTTTGEVVNENPE

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 1 – 401 Soluble calcium-activated nucleotidase 1
Topological domain 63 – 401 Lumenal
Metal binding 215 – 215 Calcium
Alternative sequence 220 – 245 KDERLYVGGLGKEWTTTTGDVVNENP -> REIVRKRWRLVKQVSHVGVLGQWIQR. In isoform 2.
Mutagenesis 215 – 215 E -> Q. Reduces activity by 99%.
Mutagenesis 246 – 246 E -> M. Increases activity 5-fold.
Beta strand 223 – 227


Literature citations

A founder mutation of CANT1 common in Korean and Japanese Desbuquois dysplasia.
Dai J.; Kim O.H.; Cho T.J.; Miyake N.; Song H.R.; Karasugi T.; Sakazume S.; Ikema M.; Matsui Y.; Nagai T.; Matsumoto N.; Ohashi H.; Kamatani N.; Nishimura G.; Furuichi T.; Takahashi A.; Ikegawa S.;
J. Hum. Genet. 56:398-400(2011)
Cited for: VARIANT DBQD1 MET-226;

CANT1 mutation is also responsible for Desbuquois dysplasia, type 2 and Kim variant.
Furuichi T.; Dai J.; Cho T.J.; Sakazume S.; Ikema M.; Matsui Y.; Baynam G.; Nagai T.; Miyake N.; Matsumoto N.; Ohashi H.; Unger S.; Superti-Furga A.; Kim O.H.; Nishimura G.; Ikegawa S.;
J. Med. Genet. 48:32-37(2011)
Cited for: VARIANTS DBQD1 CYS-125; THR-165; PRO-224; MET-226 AND ASP-360; CHARACTERIZATION OF VARIANTS DBQD1 CYS-125; THR-165; PRO-224; MET-226; CYS-300 AND ASP-360; CHARACTERIZATION OF VARIANTS THR-323 AND GLU-391;

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.