UniProtKB/Swiss-Prot Q16518: Variant p.Asp477Gly

Retinoid isomerohydrolase
Gene: RPE65
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Variant information Variant position:

477 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Aspartate (D) to Glycine (G) at position 477 (D477G, p.Asp477Gly). 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 glycine (G) 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
Variant description:

In RP87; uncertain significance; does not affect protein abundance; does not affect subcellular localization; does not affect isomerization activity; may cause abnormal splicing mRNAs thereby decreasing protein levels. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1571158279 [ dbSNP | Ensembl ]

Sequence information Variant position:

477 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:

TWVWQEPDSYPSEPIFVSHP D ALEEDDGVVLSVVVSPGAGQ 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                         TWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQ

                              TWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQ

Mouse                         IWMWQEPDSYPSEPIFVSQPDALEEDDGVVLSVVVSPGAGQ

Rat                           IWMWQEPDSYPSEPIFVSQPDALEEDDGVVLSVVVSPGAGQ

Bovine                        TWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSVVVSPGAGQ

Chicken                       TWVWQEPDSYPSEPIFVSHPDALEEDDGVVLSIVISPGSGP

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
Mutagenesis	469 – 469	E -> A. Decreasing protein levels. Loss of enzymatic activity.
Mutagenesis	469 – 469	E -> Q. Decreasing protein levels. Loss of enzymatic activity.
Mutagenesis	497 – 497	Q -> P. Does not affect isomerohydrolase activity.

Literature citations
A dominant mutation in RPE65 identified by whole-exome sequencing causes retinitis pigmentosa with choroidal involvement.
Bowne S.J.; Humphries M.M.; Sullivan L.S.; Kenna P.F.; Tam L.C.; Kiang A.S.; Campbell M.; Weinstock G.M.; Koboldt D.C.; Ding L.; Fulton R.S.; Sodergren E.J.; Allman D.; Millington-Ward S.; Palfi A.; McKee A.; Blanton S.H.; Slifer S.; Konidari I.; Farrar G.J.; Daiger S.P.; Humphries P.;
Eur. J. Hum. Genet. 19:1074-1081(2011)
Cited for: INVOLVEMENT IN RP87; VARIANT RP87 GLY-477; The clinical features of retinal disease due to a dominant mutation in RPE65.
Hull S.; Mukherjee R.; Holder G.E.; Moore A.T.; Webster A.R.;
Mol. Vis. 22:626-635(2016)
Cited for: INVOLVEMENT IN RP87; VARIANT RP87 GLY-477; Insights into the pathogenesis of dominant retinitis pigmentosa associated with a D477G mutation in RPE65.
Choi E.H.; Suh S.; Sander C.L.; Hernandez C.J.O.; Bulman E.R.; Khadka N.; Dong Z.; Shi W.; Palczewski K.; Kiser P.D.;
Hum. Mol. Genet. 27:2225-2243(2018)
Cited for: CHARACTERIZATION OF VARIANT RP87 GLY-477; SUBCELLULAR LOCATION; CATALYTIC ACTIVITY; Aberrant RNA splicing is the major pathogenic effect in a knock-in mouse model of the dominantly inherited c.1430A>G human RPE65 mutation.
Li Y.; Furhang R.; Ray A.; Duncan T.; Soucy J.; Mahdi R.; Chaitankar V.; Gieser L.; Poliakov E.; Qian H.; Liu P.; Dong L.; Rogozin I.B.; Redmond T.M.;
Hum. Mutat. 40:426-443(2019)
Cited for: CHARACTERIZATION OF VARIANT RP87 GLY-477;

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.