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UniProtKB/Swiss-Prot Q8WVQ1: Variant p.Arg300Cys

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

Variant position:  300
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 Arginine (R) to Cysteine (C) at position 300 (R300C, p.Arg300Cys).
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 large size and basic (R) to medium size and polar (C)
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:  Desbuquois dysplasia 1 (DBQD1) [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 or absence of characteristic hand anomalies: an extra ossification center distal to the second metacarpal, delta phalanx, bifid distal thumb phalanx, and phalangeal dislocations. {ECO:0000269|PubMed:19853239, ECO:0000269|PubMed:20425819, ECO:0000269|PubMed:21037275, ECO:0000269|PubMed:21412251, ECO:0000269|PubMed:21654728, ECO:0000269|PubMed:22539336}. 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.

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

Sequence information

Variant position:  300
The position of the amino-acid change on the UniProtKB canonical protein sequence.

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

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.




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.

Chain 1 – 401 Soluble calcium-activated nucleotidase 1
Topological domain 63 – 401 Lumenal
Metal binding 284 – 284 Calcium; via carbonyl oxygen
Alternative sequence 246 – 401 Missing. In isoform 2.
Mutagenesis 287 – 287 C -> S. Reduces GDPase and ADPase activities 1.3-fold.
Mutagenesis 301 – 301 R -> A. Reduces activity by 99%.
Mutagenesis 308 – 308 S -> C. Reduces GDPase activity 1.3-fold and ADPase activity 2-fold. Severe loss of dimer formation; when associated with S-287.
Mutagenesis 317 – 317 A -> C. Reduces GDPase activity 1.7-fold and ADPase activity 1.5-fold. Severe loss of dimer formation; when associated with S-287.
Beta strand 300 – 305

Literature citations

Identification of CANT1 mutations in Desbuquois dysplasia.
Huber C.; Oules B.; Bertoli M.; Chami M.; Fradin M.; Alanay Y.; Al-Gazali L.I.; Ausems M.G.; Bitoun P.; Cavalcanti D.P.; Krebs A.; Le Merrer M.; Mortier G.; Shafeghati Y.; Superti-Furga A.; Robertson S.P.; Le Goff C.; Muda A.O.; Paterlini-Brechot P.; Munnich A.; Cormier-Daire V.;
Am. J. Hum. Genet. 85:706-710(2009)
Cited for: VARIANTS DBQD1 LEU-299; CYS-300 AND HIS-300;

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)

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.