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UniProtKB/Swiss-Prot Q16518: Variant p.Asn321Lys

Retinoid isomerohydrolase
Gene: RPE65
Variant information

Variant position:  321
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LB/B
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 Asparagine (N) to Lysine (K) at position 321 (N321K, p.Asn321Lys).
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 polar (N) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  No effect on retinol isomerase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  321
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:   NNKYRTSPFNLFHHINTYED  N GFLIVDLCCWKGFEFVYNYL
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                         NNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVYNYL

                              NNKYRTSSFNLFHHINTYEDNEFLIVDLCCWKGFEFVYNYL

Mouse                         NNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVYNYL

Rat                           NNKYRTSPFNLFHHINTYEDNGFLIVDLCCWKGFEFVYNYL

Bovine                        NNKYRTSPFNLFHHINTYEDHEFLIVDLCCWKGFEFVYNYS

Chicken                       NIKYRTSAFNLFHHINTFEDNGFLIVDLCTWKGFEFVYNYL

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
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

Mutation analysis of 3 genes in patients with Leber congenital amaurosis.
Lotery A.J.; Namperumalsamy P.; Jacobson S.G.; Weleber R.G.; Fishman G.A.; Musarella M.A.; Hoyt C.S.; Heon E.; Levin A.; Jan J.; Lam B.; Carr R.E.; Franklin A.; Radha S.; Andorf J.L.; Sheffield V.C.; Stone E.M.;
Arch. Ophthalmol. 118:538-543(2000)
Cited for: VARIANTS LCA2 PHE-287 AND GLY-393; VARIANT LYS-321;

Four novel mutations in the RPE65 gene in patients with Leber congenital amaurosis.
Simovich M.J.; Miller B.; Ezzeldin H.; Kirkland B.T.; McLeod G.; Fulmer C.; Nathans J.; Jacobson S.G.; Pittler S.J.;
Hum. Mutat. 18:164-164(2001)
Cited for: VARIANTS LCA2 SER-40; GLN-44; GLN-91; ASP-144; TYR-182 AND GLN-417; VARIANT LYS-321;

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;

Analysis of protein-coding genetic variation in 60,706 humans.
Lek M.; Karczewski K.J.; Minikel E.V.; Samocha K.E.; Banks E.; Fennell T.; O'Donnell-Luria A.H.; Ware J.S.; Hill A.J.; Cummings B.B.; Tukiainen T.; Birnbaum D.P.; Kosmicki J.A.; Duncan L.E.; Estrada K.; Zhao F.; Zou J.; Pierce-Hoffman E.; Berghout J.; Cooper D.N.; Deflaux N.; DePristo M.; Do R.; Flannick J.; Fromer M.; Gauthier L.; Goldstein J.; Gupta N.; Howrigan D.; Kiezun A.; Kurki M.I.; Moonshine A.L.; Natarajan P.; Orozco L.; Peloso G.M.; Poplin R.; Rivas M.A.; Ruano-Rubio V.; Rose S.A.; Ruderfer D.M.; Shakir K.; Stenson P.D.; Stevens C.; Thomas B.P.; Tiao G.; Tusie-Luna M.T.; Weisburd B.; Won H.H.; Yu D.; Altshuler D.M.; Ardissino D.; Boehnke M.; Danesh J.; Donnelly S.; Elosua R.; Florez J.C.; Gabriel S.B.; Getz G.; Glatt S.J.; Hultman C.M.; Kathiresan S.; Laakso M.; McCarroll S.; McCarthy M.I.; McGovern D.; McPherson R.; Neale B.M.; Palotie A.; Purcell S.M.; Saleheen D.; Scharf J.M.; Sklar P.; Sullivan P.F.; Tuomilehto J.; Tsuang M.T.; Watkins H.C.; Wilson J.G.; Daly M.J.; MacArthur D.G.;
Nature 536:285-291(2016)
Cited for: VARIANT LYS-321;

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.