UniProtKB/SwissProt variant VAR

Variant information

Variant position:

635

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 Proline (P) at position 635 (A635P, p.Ala635Pro).

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 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:

Childhood cancer retinoblastoma (RB) [MIM:180200]: Congenital malignant tumor that arises from the nuclear layers of the retina. It occurs in about 1:20'000 live births and represents about 2% of childhood malignancies. It is bilateral in about 30% of cases. Although most RB appear sporadically, about 20% are transmitted as an autosomal dominant trait with incomplete penetrance. The diagnosis is usually made before the age of 2 years when strabismus or a gray to yellow reflex from pupil ('cat eye') is investigated. {ECO:0000269|PubMed:10671068, ECO:0000269|PubMed:11524739, ECO:0000269|PubMed:1352883, ECO:0000269|PubMed:2594029, ECO:0000269|PubMed:7704558, ECO:0000269|PubMed:7795591, ECO:0000269|PubMed:7927327, ECO:0000269|PubMed:8346255, ECO:0000269|PubMed:8605116, ECO:0000269|PubMed:8776589, ECO:0000269|PubMed:9140452, ECO:0000269|PubMed:9311732, ECO:0000269|PubMed:9973307}. 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 RB.

Any additional useful information about the variant.

Sequence information

Variant position:

635

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

Protein sequence length:

928

The length of the canonical sequence.

Location on the sequence:

KKGSTTRVNSTANAETQATS A FQTQKPLKSTSLSLFYKKVY

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                         KKGSTTRVNSTANAETQATSAFQTQKPLKSTSLSLFYKKVY

Mouse                         KRTSTTRVNSAANTETQAASAFHTQKPLKSTSLALFYKKVY

Rat                           KRTSTTRVNSAANTETQAASAFHTQKPLKSTSLSLFYKKVY

Chicken                       KKASGHPQSGTSNPDAQPSATSQTQKPQKSTSLSLFYKKVF

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 – 928	Retinoblastoma-associated protein
Region	373 – 771	Pocket; binds T and E1A
Region	580 – 639	Spacer
Modified residue	624 – 624	Phosphoserine

Literature citations

Spectrum of germline mutations in the RB1 gene: a study of 232 patients with hereditary and non hereditary retinoblastoma.
Blanquet V.; Turleau C.; Gross-Morand M.S.; Senamaud-Beaufort C.; Doz F.; Besmond C.;
Hum. Mol. Genet. 4:383-388(1995)
Cited for: VARIANTS RB THR-185; PRO-635; GLU-654 AND PRO-685;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P06400: Variant p.Ala635Pro