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UniProtKB/Swiss-Prot O75695: Variant p.Arg118His

Protein XRP2
Gene: RP2
Variant information

Variant position:  118
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 Histidine (H) at position 118 (R118H, p.Arg118His).
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 (H)
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

Involvement in disease:  Retinitis pigmentosa 2 (RP2) [MIM:312600]: 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:10090907, ECO:0000269|PubMed:10520237, ECO:0000269|PubMed:10634633, ECO:0000269|PubMed:10937588, ECO:0000269|PubMed:10942419, ECO:0000269|PubMed:11462235, ECO:0000269|PubMed:11847227, ECO:0000269|PubMed:11992260, ECO:0000269|PubMed:12657579, ECO:0000269|PubMed:14564670, ECO:0000269|PubMed:16472755, ECO:0000269|PubMed:22334370, ECO:0000269|PubMed:9697692}. 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 RP2; reduces affinity for ARL3 800-fold; loss of stimulation of tubulin GTPase activity; no effect on subcellular location.
Any additional useful information about the variant.

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



Sequence information

Variant position:  118
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  350
The length of the canonical sequence.

Location on the sequence:   GSVFFRNCRDCKCTLACQQF  R VRDCRKLEVFLCCATQPIIE
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                         GSVFFRNCRDCKCTLACQQFRVRDCRKLEVFLCCATQPIIE

Mouse                         GSVFFRNCRDCKCTLACQQFRVRDCRKLEVFLCCATQPIIE

Chicken                       GSVFFRNCKDCKCIVACQQFRTRDCRRLEVFLCCATQPIIE

Xenopus laevis                GSVFFRDCKDCKCVVACQQFRTRDCRRMDVFLCCSTQPIIE

Zebrafish                     GSVFFRDCKDIKCVVACQQFRTRDCKKMDVFLCCATQPIIE

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 – 350 Protein XRP2
Domain 24 – 179 C-CAP/cofactor C-like
Nucleotide binding 115 – 118 GTP
Mutagenesis 101 – 101 F -> A. Reduces affinity for mouse ARL3.
Mutagenesis 115 – 115 Q -> A. Reduces affinity for mouse ARL3.
Mutagenesis 116 – 116 Q -> A. Reduces affinity and GTP-hydrolysis rate for mouse ARL3.
Mutagenesis 118 – 118 R -> A. Reduces affinity and GTP-hydrolysis rate for mouse ARL3.
Mutagenesis 120 – 120 R -> H. Reduces affinity for mouse ARL3; when associated with S-121.
Mutagenesis 121 – 121 D -> S. Reduces affinity for mouse ARL3; when associated with H-120.
Beta strand 106 – 121


Literature citations

Positional cloning of the gene for X-linked retinitis pigmentosa 2.
Schwahn U.; Lenzner S.; Dong J.; Feil S.; Hinzmann B.; van Duijnhoven G.; Kirschner R.; Hemberger M.; Bergen A.A.B.; Rosenberg T.; Pinckers A.J.L.G.; Fundele R.; Rosenthal A.; Cremers F.P.M.; Ropers H.-H.; Berger W.;
Nat. Genet. 19:327-332(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS RP2 SER-6 DEL AND HIS-118;

Mutations in the N-terminus of the X-linked retinitis pigmentosa protein RP2 interfere with the normal targeting of the protein to the plasma membrane.
Chapple J.P.; Hardcastle A.J.; Grayson C.; Spackman L.A.; Willison K.R.; Cheetham M.E.;
Hum. Mol. Genet. 9:1919-1926(2000)
Cited for: CHARACTERIZATION OF VARIANTS RP2 SER-6 DEL AND HIS-118; MYRISTOYLATION AT GLY-2; PALMITOYLATION AT CYS-3; MUTAGENESIS OF GLY-2 AND CYS-3; TISSUE SPECIFICITY; SUBCELLULAR LOCATION;

Functional overlap between retinitis pigmentosa 2 protein and the tubulin-specific chaperone cofactor C.
Bartolini F.; Bhamidipati A.; Thomas S.; Schwahn U.; Lewis S.A.; Cowan N.J.;
J. Biol. Chem. 277:14629-14634(2002)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANTS RP2 SER-6 DEL AND HIS-118; INTERACTION WITH ARL3;

Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3.
Kuehnel K.; Veltel S.; Schlichting I.; Wittinghofer A.;
Structure 14:367-378(2006)
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS); INTERACTION WITH ARL3; CHARACTERIZATION OF VARIANTS RP2 HIS-118 AND GLY-138; CHARACTERIZATION OF VARIANT TRP-282;

Mutations in the RP2 gene cause disease in 10% of families with familial X-Linked retinitis pigmentosa assessed in this study.
Hardcastle A.J.; Thiselton D.L.; Van Maldergem L.; Saha B.K.; Jay M.; Plant C.; Taylor R.; Bird A.C.; Bhattacharya S.;
Am. J. Hum. Genet. 64:1210-1215(1999)
Cited for: VARIANT RP2 HIS-118;

Genotype-phenotype correlation in X-linked retinitis pigmentosa 2 (RP2).
Rosenberg T.; Schwahn U.; Feil S.; Berger W.;
Ophthalmic Genet. 20:161-172(1999)
Cited for: VARIANTS RP2 SER-6 DEL AND HIS-118;

X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and correlation with visual function.
Sharon D.; Bruns G.A.P.; McGee T.L.; Sandberg M.A.; Berson E.L.; Dryja T.P.;
Invest. Ophthalmol. Vis. Sci. 41:2712-2721(2000)
Cited for: VARIANTS RP2 TYR-86; LEU-95; HIS-118 AND ILE-137 DEL; VARIANT TRP-282;

A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa.
Breuer D.K.; Yashar B.M.; Filippova E.; Hiriyanna S.; Lyons R.H.; Mears A.J.; Asaye B.; Acar C.; Vervoort R.; Wright A.F.; Musarella M.A.; Wheeler P.; MacDonald I.; Iannaccone A.; Birch D.; Hoffman D.R.; Fishman G.A.; Heckenlively J.R.; Jacobson S.G.; Sieving P.A.; Swaroop A.;
Am. J. Hum. Genet. 70:1545-1554(2002)
Cited for: VARIANTS RP2 TYR-67; HIS-118; ILE-137 DEL AND PRO-188; VARIANT TRP-282;

RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa.
Sharon D.; Sandberg M.A.; Rabe V.W.; Stillberger M.; Dryja T.P.; Berson E.L.;
Am. J. Hum. Genet. 73:1131-1146(2003)
Cited for: VARIANTS RP2 TYR-86; LEU-95; HIS-118 AND ILE-137 DEL; VARIANT TRP-282;

X-linked retinitis pigmentosa: RPGR mutations in most families with definite X linkage and clustering of mutations in a short sequence stretch of exon ORF15.
Bader I.; Brandau O.; Achatz H.; Apfelstedt-Sylla E.; Hergersberg M.; Lorenz B.; Wissinger B.; Wittwer B.; Rudolph G.; Meindl A.; Meitinger T.;
Invest. Ophthalmol. Vis. Sci. 44:1458-1463(2003)
Cited for: VARIANTS RP2 HIS-118 AND CYS-118;

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.