UniProtKB/SwissProt variant VAR

Variant information

Variant position:

113

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 113 (R113H, p.Arg113His).

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:

Geleophysic dysplasia 1 (GPHYSD1) [MIM:231050]: An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. {ECO:0000269|PubMed:18677313, ECO:0000269|PubMed:21415077}. 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 GPHYSD1; leads to the reduced secretion of the mutated protein.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs113994122 [ dbSNP | Ensembl ]

Sequence information

Variant position:

113

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

Protein sequence length:

951

The length of the canonical sequence.

Location on the sequence:

TSKRYQLCRVQECPPDGRSF R EEQCVSFNSHVYNGRTHQWK

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                         TSKRYQLCRVQECPPDGRSFREEQCVSFNSHVYNGRTHQWK

Mouse                         TSKRYQLCRVQECPPDGRSFREEQCVSFNSRVYDGRAYQWK

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.

Type	Positions	Description
Chain	23 – 951	ADAMTS-like protein 2

Literature citations

ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation.
Le Goff C.; Morice-Picard F.; Dagoneau N.; Wang L.W.; Perrot C.; Crow Y.J.; Bauer F.; Flori E.; Prost-Squarcioni C.; Krakow D.; Ge G.; Greenspan D.S.; Bonnet D.; Le Merrer M.; Munnich A.; Apte S.S.; Cormier-Daire V.;
Nat. Genet. 40:1119-1123(2008)
Cited for: VARIANTS GPHYSD1 HIS-113; LYS-114; LEU-147 AND ARG-811; CHARACTERIZATION OF VARIANTS HIS-113; LEU-147 AND ARG-811; INTERACTION WITH LTBP1;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q86TH1: Variant p.Arg113His