UniProtKB/SwissProt variant VAR

Variant information

Variant position:

318

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

Type of variant:

LP/P [Disclaimer]

The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Tyrosine (Y) to Asparagine (N) at position 318 (Y318N, p.Tyr318Asn).

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 medium size and polar (N)

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

Variant description:

In LCA2; severely decreased retinol isomerase activity.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs61752905 [ dbSNP | Ensembl ]

Sequence information

Variant position:

318

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

Protein sequence length:

533

The length of the canonical sequence.

Location on the sequence:

KYLNNKYRTSPFNLFHHINT Y EDNGFLIVDLCCWKGFEFVY

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                         KYLNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVY

                              KYLNNKYRTSSFNLFHHINTYEDNEFLIVDLCCWKGFEFVY

Mouse                         KYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVY

Rat                           KYFNNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVY

Bovine                        KYINNKYRTSPFNLFHHINTYEDHEFLIVDLCCWKGFEFVY

Chicken                       RLLNIKYRTSAFNLFHHINTFEDNGFLIVDLCTWKGFEFVY

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 – 533	Retinoid isomerohydrolase
Metal binding	313 – 313	Iron; catalytic
Lipidation	329 – 329	S-palmitoyl cysteine; in membrane form
Lipidation	330 – 330	S-palmitoyl cysteine; in membrane form
Mutagenesis	313 – 313	H -> A. Decreasing protein levels. Loss of enzymatic activity. Significantly decreased protein stability.
Mutagenesis	330 – 330	C -> T. Does not affect isomerohydrolase activity.

Literature citations

Leber congenital amaurosis - a model for efficient genetic testing of heterogeneous disorders: LXIV Edward Jackson Memorial Lecture.
Stone E.M.;
Am. J. Ophthalmol. 144:791-811(2007)
Cited for: VARIANTS LCA2 ILE-101; SER-118; PRO-162; ASN-318; 402-TRP--SER-533 DEL; PRO-408; ALA-443; 460-TRP--SER-533 DEL AND THR-533;

Predicting the pathogenicity of RPE65 mutations.
Philp A.R.; Jin M.; Li S.; Schindler E.I.; Iannaccone A.; Lam B.L.; Weleber R.G.; Fishman G.A.; Jacobson S.G.; Mullins R.F.; Travis G.H.; Stone E.M.;
Hum. Mutat. 30:1183-1188(2009)
Cited for: CHARACTERIZATION OF VARIANTS LCA2 SER-40; GLN-44; GLN-91; TRP-91; ILE-101; ASP-239; ASN-318; PRO-408 AND VAL-434; CHARACTERIZATION OF VARIANT LYS-321; CHARACTERIZATION OF VARIANT RP20 THR-294;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q16518: Variant p.Tyr318Asn