UniProtKB/SwissProt variant VAR

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 Threonine (T) to Alanine (A) at position 458 (T458A, p.Thr458Ala).

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 polar (T) to small size and hydrophobic (A)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

0

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:

Retinitis pigmentosa 78 (RP78) [MIM:617433]: A form of retinitis pigmentosa, a retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP78 inheritance is autosomal recessive. {ECO:0000269|PubMed:28132693}. 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 RP78; decreased function in positive regulation of Rho protein signal transduction; loss of function in regulation of actomyosin structure organization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs987233144 [ dbSNP | Ensembl ]

Sequence information

Variant position:

458

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

Protein sequence length:

1361

The length of the canonical sequence.

Location on the sequence:

AKKQKREVVKRQDVLYELMQ T EVHHVRTLKIMLKVYSRALQ

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                         AKKQKREVVKRQDVLYELMQTEVHHVRTLKIMLKVYSRALQ

Mouse                         AKKQKKEVVKRQDVLYELMQTEAHHVRTLKIMLKVYSRALQ

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 – 1361	Rho guanine nucleotide exchange factor 18
Domain	447 – 644	DH

Literature citations

Biallelic mutation of ARHGEF18, involved in the determination of epithelial apicobasal polarity, causes adult-onset retinal degeneration.
Arno G.; Carss K.J.; Hull S.; Zihni C.; Robson A.G.; Fiorentino A.; Hardcastle A.J.; Holder G.E.; Cheetham M.E.; Plagnol V.; Moore A.T.; Raymond F.L.; Matter K.; Balda M.S.; Webster A.R.;
Am. J. Hum. Genet. 100:334-342(2017)
Cited for: FUNCTION; INVOLVEMENT IN RP78; VARIANTS RP78 ALA-458; 854-ARG--PHE-1361 DEL; 1066-GLU--PHE-1361 DEL AND 1101-ARG--GLU-1108 DEL; CHARACTERIZATION OF VARIANTS RP78 ALA-458 AND 1101-ARG--GLU-1108 DEL;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q6ZSZ5: Variant p.Thr458Ala