UniProtKB/SwissProt variant VAR

Variant information

Variant position:

781

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 Glutamate (E) to Lysine (K) at position 781 (E781K, p.Glu781Lys).

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 (E) to large size and basic (K)

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:

Night blindness, congenital stationary, 1B (CSNB1B) [MIM:257270]: A non-progressive retinal disorder characterized by impaired night vision. Congenital stationary night blindness type 1B is an autosomal recessive form associated with a negative electroretinogram waveform. Patients are night blind from an early age, and when maximally dark-adapted, they could perceive lights only with an intensity equal to or slightly dimmer than that normally detected by the cone system. ERGs in response to single brief flashes of light have clearly detectable a-waves, which are derived from photoreceptors, and greatly reduced b-waves, which are derived from the second-order inner retinal neurons. ERGs in response to sawtooth flickering light indicate a markedly reduced on response and a nearly normal OFF response. There is no subjective delay in the perception of suddenly appearing white vs black objects on a gray background. {ECO:0000269|PubMed:15781871, ECO:0000269|PubMed:17405131, ECO:0000269|PubMed:23714322}. 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 CSNB1B; abolishes expression at the cell membrane.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs62638625 [ dbSNP | Ensembl ]

Sequence information

Variant position:

781

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

Protein sequence length:

877

The length of the canonical sequence.

Location on the sequence:

LMVTCTVYAIKARGVPETFN E AKPIGFTMYTTCIIWLAFVP

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                         LMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVP

Mouse                         LMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVP

Rat                           LMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIIWLAFVP

Rabbit                        LMVTCTVYAIKARGVPETFNEAKPIGFTMYTTCIVWLAFVP

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	25 – 877	Metabotropic glutamate receptor 6
Topological domain	771 – 783	Cytoplasmic

Literature citations

Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6.
Dryja T.P.; McGee T.L.; Berson E.L.; Fishman G.A.; Sandberg M.A.; Alexander K.R.; Derlacki D.J.; Rajagopalan A.S.;
Proc. Natl. Acad. Sci. U.S.A. 102:4884-4889(2005)
Cited for: VARIANTS CSNB1B SER-150 AND LYS-781;

Night blindness-associated mutations in the ligand-binding, cysteine-rich, and intracellular domains of the metabotropic glutamate receptor 6 abolish protein trafficking.
Zeitz C.; Forster U.; Neidhardt J.; Feil S.; Kalin S.; Leifert D.; Flor P.J.; Berger W.;
Hum. Mutat. 28:771-780(2007)
Cited for: VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781; VARIANT PRO-59; CHARACTERIZATION OF VARIANT PRO-59; CHARACTERIZATION OF VARIANTS CSNB1B LEU-46; ARG-58; SER-150; THR-405; TYR-522 AND LYS-781; SUBUNIT; SUBCELLULAR LOCATION;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O15303: Variant p.Glu781Lys