UniProtKB/SwissProt variant VAR

Variant information

Variant position:

263

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 Serine (S) to Proline (P) at position 263 (S263P, p.Ser263Pro).

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 polar (S) to medium size and hydrophobic (P)

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:

Achalasia-addisonianism-alacrima syndrome (AAAS) [MIM:231550]: An autosomal recessive disorder characterized by adreno-corticotropic hormone (ACTH)-resistant adrenal failure, achalasia of the esophageal cardia and alacrima. The syndrome is associated with variable and progressive neurological impairment involving the central, peripheral, and autonomic nervous system. Other features such as palmoplantar hyperkeratosis, short stature, facial dysmorphy and osteoporosis may also be present. {ECO:0000269|PubMed:11159947}. 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 AAAS.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121918550 [ dbSNP | Ensembl ]

Sequence information

Variant position:

263

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

Protein sequence length:

546

The length of the canonical sequence.

Location on the sequence:

GHTPVTSLAWAPSGGRLLSA S PVDAAIRVWDVSTETCVPLP

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                         GHTPVTSLAWAPSGGRLLSASPVDAAIRVWDVSTETCVPLP

Mouse                         GHTPVTSLAWAPNGGWLLSASPVDAVILVWDVSTETCVPLP

Drosophila                    NNLPITSMQWNKDGTQLATASIGDRSIIIWQPDTGMMQPLK

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 – 546	Aladin
Repeat	234 – 274	WD 3

Literature citations

Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene.
Handschug K.; Sperling S.; Yoon S.-J.K.; Hennig S.; Clark A.J.L.; Huebner A.;
Hum. Mol. Genet. 10:283-290(2001)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS AAAS LYS-15; 84-TRP--LEU-546 DEL; ARG-160; PRO-263; 286-ARG--LEU-546 DEL AND 342-ARG--LEU-546 DEL; FUNCTION; TISSUE SPECIFICITY;

UniProtKB/Swiss-Prot Q9NRG9: Variant p.Ser263Pro