Disease relevance of RP2

• Genotype-phenotype correlation in X-linked retinitis pigmentosa 2 (RP2) [1].
• Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR [2].
• Our data provide evidence that mutations in this gene, designated RP2, are responsible for progressive retinal degeneration [3].
• In a patient with congenital adrenal hyperplasia, we discovered a TNXB-TNXA recombinant with the deletion of RP2-C4B-CYP21B [4].
• Novel mutation in RP2 gene in two brothers with X-linked retinitis pigmentosa and mtDNA mutation of leber hereditary optic neuropathy who showed marked differences in clinical severity [5].

Psychiatry related information on RP2

• We conclude that this family is segregating a contiguous gene deletion and that the absence of a functional RP2 accounts, at least in part, for the retinal degeneration while deletion of one or more of the other genes is likely responsible for the mental retardation phenotype [6].

High impact information on RP2

• The RP3 gene was recently isolated by positional cloning, whereas the RP2 locus was mapped genetically to a 5-cM interval [3].
• Mutation screening was performed by single-strand conformation analysis and by sequencing of all RP2 exons and RPGR exons 1-14, ORF15, and 15a [7].
• Protein-truncation mutations in the RP2 gene in a North American cohort of families with X-linked retinitis pigmentosa [8].
• Two genetic loci, RP2 and RP3, for X-linked retinitis pigmentosa (XLRP) have been localized to Xp11.3-11.23 and Xp21.1, respectively [9].
• The location of the RP3 locus was found to be 0.4 cM distal to OTC in the Xp21.1 region, and that of the RP2 locus was 6.5 cM proximal to DXS7 in Xp11.2-p11 [10].

Chemical compound and disease context of RP2

• Our data imply that this residue acts as an "arginine finger" to trigger the tubulin GTPase activity and suggest that loss of this function in RP2 contributes to retinal degeneration [11].

Biological context of RP2

• In agreement with the previous studies, we show that mutations in the RP2 gene and in the original 19 RPGR exons are detected in <10% and approximately 20% of XLRP probands, respectively [12].
• RESULTS: Screening of 58 xlRP families revealed RP2 mutations in 8% and RPGR mutations in 71% of families with definite X-linked inheritance [13].
• METHODS: Fifty-eight apparently unrelated index-patients were screened for mutations in all coding exons of the RP2 and the RPGR genes, including splice-sites, by single-strand conformation polymorphism (SSCP) analysis, except for RPGR exon ORF15 [13].
• CONCLUSIONS: Interfamilial differences in RP2 phenotype might be related to the type and location of the mutational event [1].
• Evidence that such mutations are different from the 21 RP2 mutations described thus far suggests that a high mutation rate occurs at the RP2 locus, and that most mutations arise independently, without a founder effect [14].

Anatomical context of RP2

• We also show that in Saccharomyces cerevisiae, both cofactor C and RP2 partially complement the microtubule phenotype resulting from deletion of the cofactor C homolog, demonstrating their functional overlap in vivo [11].
• C-terminal protein truncation mutations, which account for 2/3 of the pathogenic RP2 variants, lead to scattered fluorescent foci in the cytoplasm of COS-7 and HeLa cells [15].
• Thus, loss of the protein and/or aberrant intracellular distribution might be the basis for the photoreceptor cell degeneration in most RP2 cases [15].
• The results suggest that the phenotype of this RP2 genotype of X-linked retinitis pigmentosa, unlike other forms of retinitis pigmentosa, is first expressed as a cone photoreceptor system dysfunction, and as the disease progresses, both rod and cone systems are involved [16].
• Arg120stop nonsense mutation in the RP2 gene: mutational hotspot and germ line mosaicism [17]?

Associations of RP2 with chemical compounds

• We find that this function is abolished by mutation in an arginine residue that is conserved in both cofactor C and RP2 [11].
• It contains the functional gene steroid CYP21A, long stretches of repetitive DNA elements, and three partially duplicated gene segments TNXA, SKI2W2 and RP2 [18].
• (1)H, (13)C and (15)N Resonance Assignments of the C-terminal Domain of RP2 [19].
• NP TLC and RP2 TLC plates (silica gel NP 60F(254) and silica gel RP2 60F(254) silanized precoated), impregnated with a solution of aspartic acid (l-Asp) and a solution of an analogue of aspartic acid (propionic acid), were used in two developing solvents as H(1)-, H(2)- and H(3)-antihistaminic interaction models [20].

Physical interactions of RP2

• It has been shown that RP2 can interact directly with Arl3 [21].

Other interactions of RP2

• A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa [12].
• RP2 is a specific effector protein of Arl3 [22].
• The maximum likelihood location of this locus shows a multipoint lod score of 7.17 close to DXS255 (in Xp11.22) and TIMP (in Xp11.3-p11.23), neither of which show recombination with RP2, in an area extending from 2 cM proximal to DXS7 to 1 cM distal to DXS14 (approximate 95% confidence limits) [23].
• So far, diagnostic services have been offered only to those families in which linkage to one RP locus (RP2 or RP3) has been clearly established [24].
• Using STS-content and YAC end-clone mapping, an approximately 1.2 Mb YAC contig has been established encompassing the proximal RP2 boundary and extending from T1MP1 to DXS1240 in Xp11.23 [25].

Analytical, diagnostic and therapeutic context of RP2

• In addition to novel mutations, we report here that a deeper sequence analysis of the RP2 product predicts, in addition to cofactor C homology domain, further putative functional domains, and that some novel mutations identify RP2 amino acid residues which are evolutionary conserved, hence possibly crucial to the RP2 function [14].
• DXS426 is therefore an important highly informative marker for the purposes of carrier detection and early diagnosis of RP2 and for the localization of the disease gene [26].
• Protein sequence alignments show that RP2 and cofactor C represent members of two distinct orthologous groups [15].
• Rod- and cone-mediated function was studied with psychophysics and electroretinography in members of an X-linked retinitis pigmentosa pedigree with the RP2 genotype [16].
• Pneumonectomy 2 (RP2) was a group of extralobar N1 and nonskip metastasis involvement (N1-N2) [27].

References