UniProtKB/SwissProt variant VAR

Variant information

Variant position:

436

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 Alanine (A) to Aspartate (D) at position 436 (A436D, p.Ala436Asp).

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 small size and hydrophobic (A) to medium size and acidic (D)

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:

GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms. {ECO:0000269|PubMed:11583302, ECO:0000269|PubMed:12719376}. 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 GNASHYP.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs61749698 [ dbSNP | Ensembl ]

Sequence information

Variant position:

436

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

Protein sequence length:

1037

The length of the canonical sequence.

Location on the sequence:

APADPDSGAFAADPDSGAAP A APADPDSGAAPDAPADPDSG

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                         APADPDSGAFAADPDSGAAP------------AAPADPDSGAAPDAPADPDSG

Mouse                         EPASEAVPATTAESASGAAPVTQVEPAAAAVSATLAEPAAR

Rat                           EPAAEAVPDTEAESASGAVPDTQEEPAAAAASATPAEPAAR

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	1 – 1037	Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
Compositional bias	358 – 522	Ala-rich

Literature citations

Genetic variation of the extra-large stimulatory G protein alpha-subunit leads to Gs hyperfunction in platelets and is a risk factor for bleeding.
Freson K.; Hoylaerts M.F.; Jaeken J.; Eyssen M.; Arnout J.; Vermylen J.; Van Geet C.;
Thromb. Haemost. 86:733-738(2001)
Cited for: VARIANTS GNASHYP ASP-436; PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459;

Functional polymorphisms in the paternally expressed XLalphas and its cofactor ALEX decrease their mutual interaction and enhance receptor-mediated cAMP formation.
Freson K.; Jaeken J.; Van Helvoirt M.; de Zegher F.; Wittevrongel C.; Thys C.; Hoylaerts M.F.; Vermylen J.; Van Geet C.;
Hum. Mol. Genet. 12:1121-1130(2003)
Cited for: VARIANTS GNASHYP ASP-436; PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459;

UniProtKB/Swiss-Prot Q5JWF2: Variant p.Ala436Asp