UniProtKB/Swiss-Prot Q92834: Variant p.Cys250Arg

X-linked retinitis pigmentosa GTPase regulator
Gene: RPGR
Chromosomal location: Xp21.1
Variant information

Variant position:  250
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Cysteine (C) to Arginine (R) at position 250 (C250R, p.Cys250Arg).
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 basic (R)
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:  Retinitis pigmentosa 3 (RP3) [MIM:300029]: A X-linked 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. In RP3, affected males have a severe phenotype, and carrier females show a wide spectrum of clinical features ranging from completely asymptomatic to severe retinitis pigmentosa. Heterozygous women can manifest a form of choroidoretinal degeneration which is distinguished from other types by the absence of visual defects in the presence of a brilliant, scintillating, golden-hued, patchy appearance most striking around the macula, called a tapetal-like retinal reflex. 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 RP3; reduces interaction with PDE6D.
Any additional useful information about the variant.



Sequence information

Variant position:  250
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1020
The length of the canonical sequence.

Location on the sequence:   GNHRTPQLVSEIPEKVIQVA  C GGEHTVVLTENAVYTFGLGQ
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                         GNHRTPQLVSEIPEKVIQVACGGEHTVVLTENAVYTFGLGQ

Mouse                         MNHRSPQRVLGIPERVIQVACGGGHTVVLTEKVVYAFGLGQ

Dog                           VNHRMPQPVPGIPGKVVQVACGGGHTVVLTEKAVYTFGLGQ

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 1 – 1017 X-linked retinitis pigmentosa GTPase regulator
Repeat 209 – 261 RCC1 4
Beta strand 245 – 250


Literature citations

A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3).
Meindl A.; Dry K.L.; Herrmann K.; Manson F.D.; Ciccodicola A.; Edgar A.J.; Carvalho M.R.S.; Achatz H.; Hellebrand H.; Lennon A.A.; Migliaccio C.; Porter K.; Zrenner E.; Bird A.C.; Jay M.; Lorenz B.; Wittwer B.; D'Urso M.; Meitinger T.; Wright A.F.;
Nat. Genet. 13:35-42(1996)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4); VARIANTS RP3 GLN-98; VAL-215; ARG-250 AND 296-THR--ILE-300 DEL;

Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa.
Vervoort R.; Lennon A.A.; Bird A.C.; Tulloch B.; Axton R.; Miano M.G.; Meindl A.; Meitinger T.; Ciccodicola A.; Wright A.F.;
Nat. Genet. 25:462-466(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 525-840 (ISOFORM 1); VARIANTS RP3 GLN-98 AND ARG-250;

The retinitis pigmentosa GTPase regulator, RPGR, interacts with the delta subunit of rod cyclic GMP phosphodiesterase.
Linari M.; Ueffing M.; Manson F.; Wright A.; Meitinger T.; Becker J.;
Proc. Natl. Acad. Sci. U.S.A. 96:1315-1320(1999)
Cited for: INTERACTION WITH PDE6D; CHARACTERIZATION OF RP3 VARIANTS GLN-98; CYS-130; VAL-215; SER-235; ARG-250 AND SER-275; MUTAGENESIS OF VAL-36;

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.