Disease relevance of GPR143

• Ocular albinism type 1 (OA1) is an X-linked disorder characterized by severe impairment of visual acuity, retinal hypopigmentation and the presence of macromelanosomes [1].
• We isolated a novel transcript from the OA1 critical region in Xp22.3-22.2 which is expressed at high levels in RNA samples from retina, including the retinal pigment epithelium, and from melanoma [1].
• OA1 mutations and deletions in X-linked ocular albinism [2].
• Ocular albinism type 1 (OA1) is an X-linked disorder mainly characterized by congenital nystagmus and photodysphoria, moderate to severe reduction of visual acuity, hypopigmentation of the retina, and the presence of macromelanosomes in the skin and eyes [3].
• Albinism ocular type 1 (OA1) is an X-linked type of albinism that mainly effects pigment production in the eye, resulting in hypopigmentation of the retina, nystagmus, strabismus, foveal hypoplasia, abnormal crossing of the optic fibers, and reduced visual acuity [4].

Psychiatry related information on GPR143

• Ocular albinism type 1 (OA1) is an X-linked disorder, mainly characterized by a severe reduction in visual acuity, foveal hypoplasia, nystagmus, hypopigmentation of the retina, the presence of macromelanosomes in the skin and eyes, and the misrouting of optic pathways, resulting in the loss of stereoscopic vision [5].
• In this paper, we describe a 14 7/12 year old Japanese boy with mental retardation and an interstitial deletion at Xp22.3 involving STS, KAL1, and OA1, and compare the deletion map with that of previously reported three familial male patients with low-normal intelligence and a similar interstitial deletion at Xp22 [6].

High impact information on GPR143

• We provide here structural evidence that the protein product of the ocular albinism type 1 gene (OA1), a pigment cell-specific integral membrane glycoprotein, represents a novel member of the GPCR superfamily and demonstrate that it binds heterotrimeric G proteins [7].
• Moreover, we show that OA1 is not found at the plasma membrane, being instead targeted to specialized intracellular organelles, the melanosomes [7].
• Our data suggest that OA1 represents the first example of an exclusively intracellular GPCR and support the hypothesis that GPCR-mediated signal transduction systems also operate at the internal membranes in mammalian cells [7].
• Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome [1].
• The gene contains 18 exons spanning approximately 150 kb of the genomic region adjacent to the ocular albinism gene (OA1) on the telomeric side [8].

Chemical compound and disease context of GPR143

• The mother has patchy fundal hypopigmentation consistent with random X inactivation in an OA1 carrier [9].

Biological context of GPR143

• Southern blot and RFLP analysis in the XI/OA1 family support the order tel-[STS-OA1-DXS278]-DXS9-DXS41-cen [9].
• If a contiguous gene deletion is responsible for the observed XI/OA1 phenotype, it localizes OA1 to the Xp22.3 region [9].
• We have characterized the genomic structure of the OA1 gene, which spans approximately 40 kb of genomic DNA and contains nine exons [10].
• Various types of mutation have been identified within the OA1 gene in patients with the disorder, including several missense mutations of unknown functional significance [11].
• All nine exons of the OA1 gene, as well as the 5' and 3' untranslated regions, were scanned for point mutations in PCR-amplified DNA from 60 OA1 patients [10].

Anatomical context of GPR143

• Eleven of the nineteen OA1 mutants (approximately 60%) were retained in the endoplasmic reticulum, showing defecNStive intracellular transport and glycosylation, consistent with protein misfolding [11].
• In order to shed light into the molecular pathogenesis of ocular albinism and possibly define critical functional domains within the OA1 protein, we characterized 19 independent missense mutations with respect to processing and subcellular distribution on expression in COS-7 cells [11].
• These data provide compelling evidence for T cell tolerance to OA1 in humans [12].
• The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes [13].
• Using polyclonal antibodies we have identified the endogenous OA1 protein in retinal pigment epithelial cells, in normal human melanocytes and in various melanoma cell lines [13].

Associations of GPR143 with chemical compounds

• The mutations identified include: two frameshifts and a splice site mutation leading to truncated OA1 proteins; a deletion of a threonine codon at position 290; and four missense mutations,two of which involve amino acids located within putative transmembrane domains [10].
• Upon subcellular fractionation and phase separation with the nonionic detergent Triton X-114, the OA1 protein segregated into the melanosome-rich fraction and behaved as an authentic integral membrane protein [13].
• Fluorescein angiography of the anterior ocular segment using the Topcon OA-1 ocular camera [14].

Other interactions of GPR143

• X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity [2].
• Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1 [12].
• We have previously isolated the gene for OA1 and characterized its protein product as melanosomal membrane glycoprotein displaying structural and functional features of G protein-coupled receptors [3].
• We have used cell lines from patients with deletions and translocations involving the Xp22 region to map the genes for two X-linked disorders, ocular albinism type 1 (OA1) and microphthalmia with linear skin defects (MLS) [15].
• Fluorescence in situ hybridization (FISH) study using probes for Kallmann (KAL), steroid sulfatase, and ocular albinism type 1 all showed nullisomy on Xp22.3 in this patient, and hemizygosity in his older sister, mother, and maternal grandmother [16].

Analytical, diagnostic and therapeutic context of GPR143

• Immunofluorescence and immunogold analyses on normal human melanocytes confirmed the melanosomal membrane localization of the endogenous OA1 protein, consistent with its possible involvement in melanosome biogenesis [13].
• DNA samples were subjected to PCR and subsequent analysis using SSCP for all exons of the OA1 gene [17].
• DNA from buccal swabs was obtained for use in denaturing high performance liquid chromatography (DHPLC) and chemical cleavage of mismatch (CCM) to scan several hotspots for X-linked ocular albinism (OA1) mutations [18].

References