UniProtKB/SwissProt variant VAR

Variant information

Variant position:

2381

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 Aspartate (D) to Asparagine (N) at position 2381 (D2381N, p.Asp2381Asn).

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 medium size and acidic (D) to medium size and polar (N)

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:

Spondyloepimetaphyseal dysplasia, aggrecan type (SEMDAG) [MIM:612813]: A bone disease characterized by severe short stature, macrocephaly, severe midface hypoplasia, short neck, barrel chest and brachydactyly. The radiological findings comprise long bones with generalized irregular epiphyses with widened metaphyses, especially at the knees, platyspondyly, and multiple cervical-vertebral clefts. {ECO:0000269|PubMed:19110214}. 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 SEMDAG; creates a functional N-glycosylation site; does not adversely affect protein trafficking and secretion.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121913568 [ dbSNP | Ensembl ]

Sequence information

Variant position:

2381

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:

PEEQEFVNNNAQDYQWIGLN D RTIEGDFRWSDGHPMQFENW

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                         PEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHPMQFENW

                              PEEQEFVNNNAQDYQWIGLNDRTIEGDFRWSDGHSLQFENW

Mouse                         PEEQEFVNKNAQDYQWIGLNDRTIEGDFRWSDGHSLQFEKW

Rat                           PEEQEFVNKNAQDYQWIGLNDRTIEGDFRWSDGHSLQFEKW

Bovine                        PEEQEFVNNNAQDYQWIGLNDKTIEGDFRWSDGHSLQFENW

Chicken                       PEEQEFVNSHAQDYQWIGLSDRAVENDFRWSDGHSLQFENW

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	2381 – 2381	Calcium 1
Metal binding	2385 – 2385	Calcium 1
Metal binding	2385 – 2385	Calcium 3
Disulfide bond	2348 – 2440

Literature citations

A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan.
Tompson S.W.; Merriman B.; Funari V.A.; Fresquet M.; Lachman R.S.; Rimoin D.L.; Nelson S.F.; Briggs M.D.; Cohn D.H.; Krakow D.;
Am. J. Hum. Genet. 84:72-79(2009)
Cited for: VARIANT SEMDAG ASN-2381; CHARACTERIZATION OF VARIANT SEMDAG ASN-2381;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16112: Variant p.Asp2381Asn