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UniProtKB/Swiss-Prot Q16518: Variant p.Glu102Lys

Retinoid isomerohydrolase
Gene: RPE65
Chromosomal location: 1p31
Variant information

Variant position:  102
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 102 (E102K, p.Glu102Lys).
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:  Retinitis pigmentosa 20 (RP20) [MIM:613794]: 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. {ECO:0000269|PubMed:11095629, ECO:0000269|PubMed:12960219, ECO:0000269|PubMed:15557452, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:23878505, ECO:0000269|PubMed:9501220}. 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.

Involvement in disease:  Leber congenital amaurosis 2 (LCA2) [MIM:204100]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. {ECO:0000269|PubMed:10090910, ECO:0000269|PubMed:10766140, ECO:0000269|PubMed:11462243, ECO:0000269|PubMed:14611946, ECO:0000269|PubMed:14962443, ECO:0000269|PubMed:15024725, ECO:0000269|PubMed:16205573, ECO:0000269|PubMed:17297704, ECO:0000269|PubMed:17724218, ECO:0000269|PubMed:18682808, ECO:0000269|PubMed:28418496, ECO:0000269|PubMed:9326927, ECO:0000269|PubMed:9326941, ECO:0000269|PubMed:9801879}. 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 RP20 and LCA2.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  102
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:   RFIRTDAYVRAMTEKRIVIT  E FGTCAFPDPCKNIFSRFFSY
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                         RFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSY

                              RFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSY

Mouse                         RFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSY

Rat                           RFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSY

Bovine                        RFIRTDAYVRAMTEKRIVITEFGTCAFPDPCKNIFSRFFSY

Chicken                       RFVRTDAYVRAMTEKRIVITEFGTYAYPDPCKNIFSRFFSY

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.

TypePositionsDescription
Chain 2 – 533 Retinoid isomerohydrolase
Modified residue 101 – 101 Phosphothreonine
Modified residue 105 – 105 Phosphothreonine
Modified residue 113 – 113 N6-acetyllysine
Modified residue 117 – 117 Phosphoserine
Lipidation 112 – 112 S-palmitoyl cysteine; in membrane form
Mutagenesis 106 – 106 C -> A. No loss of enzymatic activity. No effect on palmitoylation. No loss of membrane association.
Mutagenesis 106 – 106 C -> Y. Does not affect isomerohydrolase activity.
Mutagenesis 112 – 112 C -> A. Loss of enzymatic activity. No palmitoylation. Loss of membrane association.


Literature citations

Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis.
Morimura H.; Fishman G.A.; Grover S.A.; Fulton A.B.; Berson E.L.; Dryja T.P.;
Proc. Natl. Acad. Sci. U.S.A. 95:3088-3093(1998)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS RP20 TRP-91; LYS-102; THR-132; SER-341; GLY-452 AND ASP-473;

Clinical and molecular genetics of Leber's congenital amaurosis: a multicenter study of Italian patients.
Simonelli F.; Ziviello C.; Testa F.; Rossi S.; Fazzi E.; Bianchi P.E.; Fossarello M.; Signorini S.; Bertone C.; Galantuomo S.; Brancati F.; Valente E.M.; Ciccodicola A.; Rinaldi E.; Auricchio A.; Banfi S.;
Invest. Ophthalmol. Vis. Sci. 48:4284-4290(2007)
Cited for: VARIANTS LCA2 PRO-22; VAL-70; PRO-91; LYS-102; ASP-144; TYR-167 AND ARG-313;

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.