UniProtKB/Swiss-Prot Q495M9: Variant p.Asp458Val

Usher syndrome type-1G protein
Gene: USH1G
Chromosomal location: 17q25.2
Variant information

Variant position:  458
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 Aspartate (D) to Valine (V) at position 458 (D458V, p.Asp458Val).
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 medium size and acidic (D) to medium size and hydrophobic (V)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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 1G (USH1G) [MIM:606943]: 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). USH1 is characterized by profound congenital sensorineural deafness, absent vestibular function and prepubertal onset of progressive retinitis pigmentosa leading to blindness. {ECO:0000269|PubMed:12588794, ECO:0000269|PubMed:16283141, ECO:0000269|PubMed:20142502}. 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 USH1G; atypical form with mild retinitis pigmentosa and normal vestibular function; also found in patients with autosomal recessive non-syndromic deafness; strongly reduced affinity for USH1C.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  458
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  461
The length of the canonical sequence.

Location on the sequence:   KILGAVRRRRQAMERPPALE  D TEL
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                         KILGAVRRRRQAMERPPALEDTEL

Mouse                         KILGAVRRRRQALERPLALEDTEL

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.

TypePositionsDescription
Chain 1 – 461 Usher syndrome type-1G protein


Literature citations

The structure of the harmonin/sans complex reveals an unexpected interaction mode of the two Usher syndrome proteins.
Yan J.; Pan L.; Chen X.; Wu L.; Zhang M.;
Proc. Natl. Acad. Sci. U.S.A. 107:4040-4045(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 388-461 IN COMPLEX WITH USH1C; INTERACTION WITH USH1C; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANT USH1G VAL-458;

A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome.
Kalay E.; de Brouwer A.P.M.; Caylan R.; Nabuurs S.B.; Wollnik B.; Karaguzel A.; Heister J.G.A.M.; Erdol H.; Cremers F.P.M.; Cremers C.W.R.J.; Brunner H.G.; Kremer H.;
J. Mol. Med. 83:1025-1032(2005)
Cited for: VARIANT USH1G VAL-458;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.