UniProtKB/SwissProt variant VAR

Variant information

Variant position:

2418

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 Valine (V) to Methionine (M) at position 2418 (V2418M, p.Val2418Met).

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:

Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans (SSOAOD) [MIM:165800]: An autosomal dominant disease characterized by short stature, advanced bone maturation, early-onset osteoarthritis, and mild dysmorphic features consisting of midface hypoplasia, brachydactyly, broad great toes, and lumbar lordosis. Other features include intervertebral disk disease and osteochondritis dissecans. Osteochondritis dissecans is defined as a separation of cartilage and subchondral bone from the surrounding tissue. {ECO:0000269|PubMed:20137779}. 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 SSOAOD.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs779794758 [ dbSNP | Ensembl ]

Sequence information

Variant position:

2418

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

Protein sequence length:

2530

The length of the canonical sequence.

Location on the sequence:

FENWRPNQPDNFFAAGEDCV V MIWHEKGEWNDVPCNYHLPF

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                         FENWRPNQPDNFFAAGEDCVVMIWHEKGEWNDVPCNYHLPF

                              FENWRPNQPDNFFVSGEDCVVMIWHEKGEWNDVPCNYYLPF

Mouse                         FEKWRPNQPDNFFATGEDCVVMIWHERGEWNDVPCNYQLPF

Rat                           FEKWRPNQPDNFFATGEDCVVMIWHERGEWNDVPCNYQLPF

Bovine                        FENWRPNQPDNFFATGEDCVVMIWHEKGEWNDVPCNYQLPF

Chicken                       FENWRPNQPDNFFFAGEDCVVMIWHEQGEWNDVPCNYHLPF

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	17 – 2530	Aggrecan core protein
Chain	393 – 2530	Aggrecan core protein 2
Domain	2327 – 2441	C-type lectin
Region	2278 – 2530	G3
Metal binding	2405 – 2405	Calcium 2
Metal binding	2407 – 2407	Calcium 2
Metal binding	2408 – 2408	Calcium 1
Metal binding	2414 – 2414	Calcium 1; via carbonyl oxygen
Metal binding	2414 – 2414	Calcium 2
Metal binding	2415 – 2415	Calcium 1
Metal binding	2415 – 2415	Calcium 3
Metal binding	2428 – 2428	Calcium 2
Metal binding	2429 – 2429	Calcium 2
Metal binding	2429 – 2429	Calcium 2; via carbonyl oxygen
Disulfide bond	2348 – 2440
Disulfide bond	2416 – 2432

Literature citations

A missense mutation in the aggrecan C-type lectin domain disrupts extracellular matrix interactions and causes dominant familial osteochondritis dissecans.
Stattin E.L.; Wiklund F.; Lindblom K.; Onnerfjord P.; Jonsson B.A.; Tegner Y.; Sasaki T.; Struglics A.; Lohmander S.; Dahl N.; Heinegard D.; Aspberg A.;
Am. J. Hum. Genet. 86:126-137(2010)
Cited for: VARIANT SSOAOD MET-2418; DETECTION OF VARIANT SSOAOD MET-2418 BY MASS SPECTROMETRY;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16112: Variant p.Val2418Met