To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https

UniProtKB/Swiss-Prot P09486: Variant p.Arg166His

SPARC
Gene: SPARC
Chromosomal location: 5q31.3-q32
Variant information

Variant position:  166
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 Histidine (H) at position 166 (R166H, p.Arg166His).
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 (H)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 17 (OI17) [MIM:616507]: 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. {ECO:0000269|PubMed:26027498}. 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 OI17; decreased secretion of the protein; altered secretion of procollagen type I.
Any additional useful information about the variant.



Sequence information

Variant position:  166
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  303
The length of the canonical sequence.

Location on the sequence:   IGPCKYIPPCLDSELTEFPL  R MRDWLKNVLVTLYERDEDNN
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                         IGPCKYIPPCLDSELTEFPLRMRDWLKNVLVTLYERDEDNN

Mouse                         IGPCKYIAPCLDSELTEFPLRMRDWLKNVLVTLYERDEGNN

Rat                           IGPCKYIAPCLDSELTEFPLRMRDWLKNVLVTLYERDEGNN

Pig                           IGPCKYIPPCLDSELTEFPLRMRDWLKNVLVTLYERDENNN

Bovine                        IGPCKYIPPCLDSELTEFPLRMRDWLKNVLVTLYERDEDNN

Chicken                       IGPCKFIPACLDTELTEFPLRMRDWLKNVLITLYERDEDNN

Xenopus laevis                IGPCKYIAPCLDNELSEFPLRIGDWLKNVLVSLYERDENNN

Caenorhabditis elegans        LGECKKLDECTEEHMAQFPERMADWLFQVMKELKKRRELHK

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 18 – 303 SPARC
Disulfide bond 155 – 265
Mutagenesis 166 – 166 R -> ALK. Strongly reduced collagen binding.
Mutagenesis 173 – 173 N -> AQ. Strongly reduced collagen binding.
Helix 157 – 181


Literature citations

Recessive osteogenesis imperfecta caused by missense mutations in SPARC.
Mendoza-Londono R.; Fahiminiya S.; Majewski J.; Tetreault M.; Nadaf J.; Kannu P.; Sochett E.; Howard A.; Stimec J.; Dupuis L.; Roschger P.; Klaushofer K.; Palomo T.; Ouellet J.; Al-Jallad H.; Mort J.S.; Moffatt P.; Boudko S.; Baechinger H.P.; Rauch F.;
Am. J. Hum. Genet. 96:979-985(2015)
Cited for: INVOLVEMENT IN OI17; VARIANTS OI17 HIS-166 AND LYS-263; CHARACTERIZATION OF VARIANTS OI17 HIS-166 AND LYS-263;

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.