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UniProtKB/Swiss-Prot O75445: Variant p.Cys759Phe

Usherin
Gene: USH2A
Variant information

Variant position:  759
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 Cysteine (C) to Phenylalanine (F) at position 759 (C759F, p.Cys759Phe).
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 (C) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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 RP39 and USH2A.
Any additional useful information about the variant.

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



Sequence information

Variant position:  759
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:   FNDVGCEPCQCNLHGSVNKF  C NPHSGQCECKKEAKGLQCDT
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                         FNDVGCEPCQCNLHGSVNKFCNPHSGQCECKKEAKGLQCDT

Mouse                         FNGDGCEPCQCNLHGSVNQLCDPLSGQCACKKEAKGLKCDS

Rat                           LNADGCEPCHCNLHGSVNQLCDPLSGQCVCKKEAKGLRCDV

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 747 – 794 Laminin EGF-like 5
Disulfide bond 747 – 759
Disulfide bond 749 – 766


Literature citations

Missense mutation in the USH2A gene: association with recessive retinitis pigmentosa without hearing loss.
Rivolta C.; Sweklo E.A.; Berson E.L.; Dryja T.P.;
Am. J. Hum. Genet. 66:1975-1978(2000)
Cited for: INVOLVEMENT IN RP39; VARIANT RP39 PHE-759;

Paternal uniparental heterodisomy with partial isodisomy of chromosome 1 in a patient with retinitis pigmentosa without hearing loss and a missense mutation in the Usher syndrome type II gene USH2A.
Rivolta C.; Berson E.L.; Dryja T.P.;
Arch. Ophthalmol. 120:1566-1571(2002)
Cited for: VARIANT RP39 PHE-759;

Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively.
Najera C.; Beneyto M.; Blanca J.; Aller E.; Fontcuberta A.; Millan J.M.; Ayuso C.;
Hum. Mutat. 20:76-77(2002)
Cited for: VARIANT ARG-713; VARIANT RP39 PHE-759;

Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments.
Aller E.; Najera C.; Millan J.M.; Oltra J.S.; Perez-Garrigues H.; Vilela C.; Navea A.; Beneyto M.;
Eur. J. Hum. Genet. 12:407-410(2004)
Cited for: VARIANT USH2A SER-303; VARIANT RP PHE-759;

Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa.
Seyedahmadi B.J.; Rivolta C.; Keene J.A.; Berson E.L.; Dryja T.P.;
Exp. Eye Res. 79:167-173(2004)
Cited for: VARIANTS USH2A ILE-307; ILE-391; PHE-419; CYS-464; VAL-516 THR-517; SER-575; ASN-587 DEL AND LEU-1059; VARIANTS RP39/USH2A ASP-478 AND PHE-759; VARIANTS RP39 LEU-739; ASN-911 AND ARG-1470; VARIANTS THR-125; MET-230; ARG-268; PHE-365; VAL-644; ARG-713; VAL-1047 AND LYS-1486;

Clinical and genetic studies in Spanish patients with Usher syndrome type II: description of new mutations and evidence for a lack of genotype-phenotype correlation.
Bernal S.; Meda C.; Solans T.; Ayuso C.; Garcia-Sandoval B.; Valverde D.; Del Rio E.; Baiget M.;
Clin. Genet. 68:204-214(2005)
Cited for: VARIANT RP39 PHE-759; VARIANTS THR-125; ASP-478; VAL-644; GLU-703; TYR-841 AND LYS-1486;

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.