UniProtKB/SwissProt variant VAR

Variant information

Variant position:

279

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 Lysine (K) at position 279 (R279K, p.Arg279Lys).

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 large size and basic.

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

2

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:

Loeys-Dietz syndrome 3 (LDS3) [MIM:613795]: An aortic aneurysm syndrome with widespread systemic involvement. The disorder is characterized by the triad of arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Patients with LDS3 also manifest early-onset osteoarthritis. They lack craniosynostosis and mental retardation. {ECO:0000269|PubMed:21217753, ECO:0000269|PubMed:21778426}. Note=The disease is caused by mutations affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (PubMed:21778426), they have been classified as LDS3 by the OMIM resource. {ECO:0000269|PubMed:21778426}.

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 LDS3.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387906852 [ dbSNP | Ensembl ]

Sequence information

Variant position:

279

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

Protein sequence length:

425

The length of the canonical sequence.

Location on the sequence:

GFTDPSNSERFCLGLLSNVN R NAAVELTRRHIGRGVRLYYI

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                         GFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYI

Mouse                         GFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYI

Rat                           GFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYI

Pig                           GFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYI

Chicken                       GFTDPSNSERFCLGLLSNVNRNAAVELTRRHIGRGVRLYYI

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	2 – 425	Mothers against decapentaplegic homolog 3
Domain	232 – 425	MH2
Region	271 – 324	Sufficient for interaction with XPO4

Literature citations

Exome sequencing identifies SMAD3 mutations as a cause of familial thoracic aortic aneurysm and dissection with intracranial and other arterial aneurysms.
Regalado E.S.; Guo D.C.; Villamizar C.; Avidan N.; Gilchrist D.; McGillivray B.; Clarke L.; Bernier F.; Santos-Cortez R.L.; Leal S.M.; Bertoli-Avella A.M.; Shendure J.; Rieder M.J.; Nickerson D.A.; Milewicz D.M.;
Circ. Res. 109:680-686(2011)
Cited for: VARIANTS LDS3 VAL-112; LYS-239 AND LYS-279;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P84022: Variant p.Arg279Lys