UniProtKB/SwissProt variant VAR

Variant information

Variant position:

454

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 Tyrosine (Y) to Serine (S) at position 454 (Y454S, p.Tyr454Ser).

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 large size and aromatic (Y) to small size and polar (S)

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:

Usher syndrome 3B (USH3B) [MIM:614504]: A syndrome characterized by progressive vision and hearing loss during early childhood. Some patients have the so-called 'Charles Bonnet syndrome,' involving decreased visual acuity and vivid visual hallucinations. USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH3 is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life. {ECO:0000269|PubMed:22279524}. 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 USH3B.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs387906639 [ dbSNP | Ensembl ]

Sequence information

Variant position:

454

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

Protein sequence length:

509

The length of the canonical sequence.

Location on the sequence:

AGIKAELLYKKNPKLLNQLQ Y CEEAGIPLVAIIGEQELKDG

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                         AGIKAELLYKKNPKLLNQLQYCEEAGIPLVAIIGEQELKDG

Mouse                         AGIKAELLYKKNPKLLNQLQYCEEAGIPLVAIIGEQELKDG

Bovine                        AGIKAELLYKKNPKLLNQLQYCEETGIPLVAIIGEQELKDG

Slime mold                    AGINAEFSYKVNPKLPAQLNTADESNIPLIIIIGKSEVETN

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 – 509	Histidine--tRNA ligase, cytoplasmic
Helix	448 – 458

Literature citations

Genetic mapping and exome sequencing identify variants associated with five novel diseases.
Puffenberger E.G.; Jinks R.N.; Sougnez C.; Cibulskis K.; Willert R.A.; Achilly N.P.; Cassidy R.P.; Fiorentini C.J.; Heiken K.F.; Lawrence J.J.; Mahoney M.H.; Miller C.J.; Nair D.T.; Politi K.A.; Worcester K.N.; Setton R.A.; Dipiazza R.; Sherman E.A.; Eastman J.T.; Francklyn C.; Robey-Bond S.; Rider N.L.; Gabriel S.; Morton D.H.; Strauss K.A.;
PLoS ONE 7:E28936-E28936(2012)
Cited for: VARIANT USH3B SER-454;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P12081: Variant p.Tyr454Ser