UniProtKB/SwissProt variant VAR

Variant information

Variant position:

90

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 Arginine (R) to Tryptophan (W) at position 90 (R90W, p.Arg90Trp).

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 basic (R) to large size and aromatic (W)

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

Variant description:

In LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs104894673 [ dbSNP | Ensembl ]

Sequence information

Variant position:

90

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

Protein sequence length:

299

The length of the canonical sequence.

Location on the sequence:

EEVALKINLPESRVQVWFKN R RAKCRQQRQQQKQQQQPPGG

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                         EEVALKINLPESRVQVWFKNRRAKCRQQRQQQKQQQQPPGG

                              EEVALKINLPESRVQVWFKNRRAKCRQQRQQQKEQPQPPGA

Mouse                         EEVALKINLPESRVQVWFKNRRAKCRQQRQQQKQQQQPPGA

Bovine                        EEVALKINLPESRVQVWFKNRRAKCRQQRQQQKQQQQPPGA

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 – 299	Cone-rod homeobox protein
DNA binding	39 – 98	Homeobox

Literature citations

The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation.
Mitton K.P.; Swain P.K.; Chen S.; Xu S.; Zack D.J.; Swaroop A.;
J. Biol. Chem. 275:29794-29799(2000)
Cited for: INTERACTION WITH NRL; CHARACTERIZATION OF VARIANT CORD2 TRP-41; CHARACTERIZATION OF VARIANT LCA7 TRP-90;

Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function.
Swaroop A.; Wang Q.-L.; Wu W.; Cook J.; Coats C.; Xu S.; Chen S.; Zack D.J.; Sieving P.A.;
Hum. Mol. Genet. 8:299-305(1999)
Cited for: VARIANT LCA7 TRP-90;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43186: Variant p.Arg90Trp