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UniProtKB/Swiss-Prot Q00604: Variant p.Arg121Trp

Norrin
Gene: NDP
Variant information

Variant position:  121
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 Arginine (R) to Tryptophan (W) at position 121 (R121W, p.Arg121Trp).
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

Involvement in disease:  Norrie disease (ND) [MIM:310600]: Recessive disorder characterized by very early childhood blindness due to degenerative and proliferative changes of the neuroretina. Approximately 50% of patients show some form of progressive mental disorder, often with psychotic features, and about one-third of patients develop sensorineural deafness in the second decade. In addition, some patients have more complex phenotypes, including growth failure and seizure. {ECO:0000269|PubMed:10484772, ECO:0000269|PubMed:10544980, ECO:0000269|PubMed:11337749, ECO:0000269|PubMed:1303264, ECO:0000269|PubMed:1307245, ECO:0000269|PubMed:14635119, ECO:0000269|PubMed:15609522, ECO:0000269|PubMed:15776010, ECO:0000269|PubMed:16970763, ECO:0000269|PubMed:17128466, ECO:0000269|PubMed:17296899, ECO:0000269|PubMed:17325173, ECO:0000269|PubMed:17334993, ECO:0000269|PubMed:20340138, ECO:0000269|PubMed:7627181, ECO:0000269|PubMed:7662640, ECO:0000269|PubMed:7795608, ECO:0000269|PubMed:7993212, ECO:0000269|PubMed:8069314, ECO:0000269|PubMed:8268931, ECO:0000269|PubMed:8281159, ECO:0000269|PubMed:8589700, ECO:0000269|PubMed:8741107, ECO:0000269|PubMed:8807344, ECO:0000269|PubMed:8990009, ECO:0000269|PubMed:9143918, ECO:0000269|PubMed:9382152, ECO:0000269|PubMed:9407136}. 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:  Vitreoretinopathy, exudative 2 (EVR2) [MIM:305390]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:16163268, ECO:0000269|PubMed:16970763, ECO:0000269|PubMed:17296899, ECO:0000269|PubMed:17325173, ECO:0000269|PubMed:8252044, ECO:0000269|PubMed:8946107, ECO:0000269|PubMed:9143917}. 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 ND and EVR2.
Any additional useful information about the variant.

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



Sequence information

Variant position:  121
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  133
The length of the canonical sequence.

Location on the sequence:   SKLKALRLRCSGGMRLTATY  R YILSCHCEECNS
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                         SKLKALRLRCSGGMRLTATYRYILSCHCEECNS

Mouse                         SKLKALRLRCSGGMRLTATYRYILSCHCEECSS

Bovine                        SKLKALRLRCSGGMRLTATYRYILSCHCEECSS

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 25 – 133 Norrin
Domain 39 – 132 CTCK
Disulfide bond 65 – 126
Disulfide bond 69 – 128
Disulfide bond 131 – 131 Interchain
Beta strand 115 – 133


Literature citations

Missense mutations in the NDP gene in patients with a less severe course of Norrie disease.
Meindl A.; Lorenz B.; Achatz H.; Hellebrand H.; Schmitz-Valckenberg P.; Meitinger T.;
Hum. Mol. Genet. 4:489-490(1995)
Cited for: VARIANTS ND GLN-104; TRP-121 AND GLN-121;

Retinal phenotype-genotype correlation of pediatric patients expressing mutations in the Norrie disease gene.
Wu W.-C.; Drenser K.; Trese M.; Capone A. Jr.; Dailey W.;
Arch. Ophthalmol. 125:225-230(2007)
Cited for: VARIANTS EVR2 ARG-42; ILE-61 AND TRP-121; VARIANTS ND ARG-39 AND TYR-65; VARIANT PERSISTENT FETAL VASCULATURE SYNDROME SER-41;

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.