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UniProtKB/Swiss-Prot O75445: Variant p.Arg4115Cys

Usherin
Gene: USH2A
Chromosomal location: 1q41
Variant information

Variant position:  4115
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 Cysteine (C) at position 4115 (R4115C, p.Arg4115Cys).
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 medium size and polar (C)
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:  Usher syndrome 2A (USH2A) [MIM:276901]: USH is a genetically heterogeneous condition characterized by the association of retinitis pigmentosa with sensorineural deafness. Age at onset and differences in auditory and vestibular function distinguish Usher syndrome type 1 (USH1), Usher syndrome type 2 (USH2) and Usher syndrome type 3 (USH3). USH2 is characterized by congenital mild hearing impairment with normal vestibular responses. {ECO:0000269|PubMed:10729113, ECO:0000269|PubMed:10738000, ECO:0000269|PubMed:10909849, ECO:0000269|PubMed:11311042, ECO:0000269|PubMed:12112664, ECO:0000269|PubMed:12525556, ECO:0000269|PubMed:14970843, ECO:0000269|PubMed:15015129, ECO:0000269|PubMed:15025721, ECO:0000269|PubMed:15241801, ECO:0000269|PubMed:15325563, ECO:0000269|PubMed:17085681, ECO:0000269|PubMed:17405132, ECO:0000269|PubMed:18273898, ECO:0000269|PubMed:18452394, ECO:0000269|PubMed:19683999, ECO:0000269|PubMed:19737284, ECO:0000269|PubMed:20309401, ECO:0000269|PubMed:20440071, ECO:0000269|PubMed:20507924, ECO:0000269|PubMed:21593743, ECO:0000269|PubMed:21686329, ECO:0000269|PubMed:22004887, ECO:0000269|PubMed:23737954, ECO:0000269|PubMed:26377068, ECO:0000269|PubMed:9624053}. 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:  Retinitis pigmentosa 39 (RP39) [MIM:613809]: 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:10775529, ECO:0000269|PubMed:12112664, ECO:0000269|PubMed:12427073, ECO:0000269|PubMed:15325563, ECO:0000269|PubMed:16098008, ECO:0000269|PubMed:17296898, ECO:0000269|PubMed:20507924, ECO:0000269|PubMed:21686329, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:24227914}. 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 USH2A and RP39; associated with M-4425.
Any additional useful information about the variant.

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



Sequence information

Variant position:  4115
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  5202
The length of the canonical sequence.

Location on the sequence:   GVIKTYNIFSDGFLEYSGLN  R QFLFRRLDPFTLYTLTLEAC
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                         GVIKTYNIFSDGFLEYSGLNRQFLFRRLDPFTLYTLTLEAC

Mouse                         GVIKAYNIFNDGVLEYSGLGRQFLFRRLAPFTLYTLILEAC

Rat                           GVIKAYNVFSDGLPEYSGLGRQFLFRRLAPFTLYILTLEAC

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 32 – 5202 Usherin
Topological domain 32 – 5042 Extracellular
Domain 4068 – 4153 Fibronectin type-III 26
Alternative sequence 1547 – 5202 Missing. In isoform 2.


Literature citations

Identification of 51 novel exons of the Usher syndrome type 2A (USH2A) gene that encode multiple conserved functional domains and that are mutated in patients with Usher syndrome type II.
Van Wijk E.; Pennings R.J.E.; Te Brinke H.; Claassen A.; Yntema H.G.; Hoefsloot L.H.; Cremers F.P.M.; Cremers C.W.R.J.; Kremer H.;
Am. J. Hum. Genet. 74:738-744(2004)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); TISSUE SPECIFICITY; VARIANTS USH2A CYS-4115 AND MET-4425;

Molecular and in silico analyses of the full-length isoform of usherin identify new pathogenic alleles in Usher type II patients.
Baux D.; Larrieu L.; Blanchet C.; Hamel C.; Ben Salah S.; Vielle A.; Gilbert-Dussardier B.; Holder M.; Calvas P.; Philip N.; Edery P.; Bonneau D.; Claustres M.; Malcolm S.; Roux A.-F.;
Hum. Mutat. 28:781-789(2007)
Cited for: VARIANTS USH2A GLU-218; PHE-280; LYS-284; TRP-334; GLN-334; HIS-346; ILE-352; PHE-759; GLU-1833; SER-2795; ARG-3282; MET-3571; GLU-3895; MET-3976; CYS-4115 AND MET-4425; VARIANT PHE-1572;

Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II.
Dreyer B.; Brox V.; Tranebjaerg L.; Rosenberg T.; Sadeghi A.M.; Moeller C.; Nilssen O.;
Hum. Mutat. 29:451-451(2008)
Cited for: VARIANTS USH2A TYR-163; ARG-268; CYS-303; TRP-334; HIS-346; ILE-352; ARG-536; PHE-759; LEU-1212; ASP-2265-ASP-TYR-2266 DELINS ASP; GLY-3124; THR-3504; ARG-3521; ILE-4054; ARG-4232; ILE-4439; CYS-4487; HIS-4592 AND ARG-4795; VARIANTS THR-125; MET-230; ASP-478; SER-595; VAL-644; ARG-713; PRO-1349; LYS-1486; PHE-1572; THR-1665; CYS-1757; ASN-2080; ASN-2086; THR-2106; THR-2169; ALA-2238; HIS-2292; ALA-2562; GLN-2875; PHE-2886; LYS-3088; SER-3099; ALA-3115; ASN-3144; ASP-3199; ALA-3411; LEU-3590; ILE-3835; VAL-3868; THR-3893; CYS-4115; LEU-4433; VAL-4624 AND TRP-5031;

Next-generation genetic testing for retinitis pigmentosa.
Neveling K.; Collin R.W.; Gilissen C.; van Huet R.A.; Visser L.; Kwint M.P.; Gijsen S.J.; Zonneveld M.N.; Wieskamp N.; de Ligt J.; Siemiatkowska A.M.; Hoefsloot L.H.; Buckley M.F.; Kellner U.; Branham K.E.; den Hollander A.I.; Hoischen A.; Hoyng C.; Klevering B.J.; van den Born L.I.; Veltman J.A.; Cremers F.P.; Scheffer H.;
Hum. Mutat. 33:963-972(2012)
Cited for: VARIANTS RP39 PHE-419; PHE-759; CYS-1859; HIS-2460; TYR-3358; ARG-3669; CYS-4115; HIS-4192 AND MET-4425;

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.