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GPR143
G protein-coupled receptor 143
The GPR143 gene provides instructions for a protein critical in developing eye and skin pigmentation, particularly controlling melanosome growth and melanin production. The GPR143 gene, also known as OA1, encodes a G protein-coupled receptor involved in the pigmentation of the eyes and skin.
GPR143 is located on the short (p) arm of chromosome X, at band Xp22.2. Arm ratio per GRCh38 - banding schematic.
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Clinical tests that include this
Overview
The GPR143 gene, or Ocular Albinism Type 1 (OA1), is involved in the process of pigmentation in humans, particularly within the eyes and skin. It provides the genetic blueprint for a protein that plays a significant role in a signalling pathway critical for the growth and development of melanosomes, the cellular organelles that produce and store melanin. Melanin is the primary pigment responsible for conferring colour to the skin, hair, and eyes. In the retina, this pigment is also vital for healthy vision.
What the gene does
The GPR143 protein functions as a G protein-coupled receptor, meaning it is involved in relaying signals from outside the cell to inside. This protein is primarily found in the retina, the light-sensitive tissue at the back of the eye, and in skin cells. Its main role is to regulate the growth and maturation of melanosomes, which are specialised structures responsible for synthesising and storing melanin. Melanin is the pigment that determines the colour of the skin, hair, and eyes. In the eye, this pigment is crucial for normal visual function. Disruptions to GPR143 protein function can lead to impaired melanosome development and melanin production.
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Chromosome location
The GPR143 gene is situated on the short arm of the X chromosome at position Xp22.2. The protein encoded by this gene consists of 404 amino acids.
Protein structure
The GPR143 protein contains several key functional regions. A specific region spanning amino acids 221-238 is necessary for its G protein-activation ability and normal distribution of melanosomes. It also features two lysosomal/melanosomal membrane localisation signals, one at amino acids 222-231 and another at amino acids 329-330. Additionally, a disordered region is found towards the C-terminus, from amino acids 338-404.
Key variants
Genetic variations within the GPR143 gene can alter the protein's structure or function, impacting its ability to regulate melanosome development and melanin production. Over 60 different genetic changes have been identified, with many affecting the protein's size or shape. Such alterations can prevent the GPR143 protein from reaching the melanosomes where it is required, leading to disrupted pigmentation.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.241G>C | p.Gly81Arg | Pathogenic/Likely pathogenic | ★★☆☆ | GPR143-related disorders |
c.360+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Nystagmus 6, congenital, X-linked |
c.360+2T>C | - | Pathogenic | ★★☆☆ | Ocular albinism, type I |
c.394T>C | p.Trp132Arg | Pathogenic | ★★☆☆ | not provided |
c.461del | p.Ile154fs | Pathogenic | ★★☆☆ | not provided |
c.548+2T>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | Ocular albinism, type I |
c.703G>A | p.Glu235Lys | Pathogenic/Likely pathogenic | ★★☆☆ | Ocular albinism, type I |
c.731del | p.Ile244fs | Pathogenic | ★★☆☆ | Nystagmus 6, congenital, X-linked |
c.733C>T | p.Arg245Ter | Pathogenic | ★★☆☆ | GPR143-related disorders |
c.73C>T | p.Gln25Ter | Pathogenic | ★★☆☆ | Ocular albinism, type I |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Pathogenic variants in the GPR143 gene are primarily associated with ocular albinism, specifically the Nettleship-Falls type, also known as type 1 ocular albinism. This condition is characterised by significantly reduced pigmentation in the eyes, which can lead to vision problems. These genetic changes impair the proper functioning of the GPR143 protein, affecting melanin production in the eyes.
No disease links recorded for this gene in our reference set.
UK clinical status
The GPR143 gene is included in several NHS England Genomic Medicine Service national test panels. It is listed on the 'Albinism or congenital nystagmus', 'Infantile nystagmus', 'Ocular and oculo-cutaneous albinism', and 'Retinal disorders' panels, all with a 'green' status, indicating that there is strong evidence for its association with these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the GPR143 gene?
The GPR143 gene provides instructions for a protein that is crucial for the pigmentation of the eyes and skin. It regulates the growth and maturation of melanosomes, which are cellular structures that produce and store melanin.
What condition is primarily associated with GPR143 gene variants?
Variants in the GPR143 gene are primarily associated with ocular albinism, specifically the Nettleship-Falls type (type 1). This condition is characterised by reduced pigmentation in the eyes, affecting vision.
Where is the GPR143 gene located?
The GPR143 gene is located on the X chromosome, specifically at position Xp22.2.
References
- Innamorati G, Piccirillo R, Bagnato P. The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor. Pigment cell research. 2006. PMID: 16524428
- Mayeur H, Roche O, Vêtu C. Eight previously unidentified mutations found in the OA1 ocular albinism gene. BMC medical genetics. 2006. PMID: 16646960
- Schiaffino MV, Tacchetti C. The ocular albinism type 1 (OA1) protein and the evidence for an intracellular signal transduction system involved in melanosome biogenesis. Pigment cell research. 2005. PMID: 16029416
- Cortese K, Giordano F, Surace EM. The ocular albinism type 1 (OA1) gene controls melanosome maturation and size. Investigative ophthalmology & visual science. 2005. PMID: 16303920
- Camand O, Boutboul S, Arbogast L. Mutational analysis of the OA1 gene in ocular albinism. Ophthalmic genetics. 2003. PMID: 12868035
- Oetting WS. New insights into ocular albinism type 1 (OA1): Mutations and polymorphisms of the OA1 gene. Human mutation. 2002. PMID: 11793467
- Shen B, Samaraweera P, Rosenberg B. Ocular albinism type 1: more than meets the eye. Pigment cell research. 2001. PMID: 11549106
- Adam MP, Bick S, Mirzaa GM. Ocular Albinism, X-Linked – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1993. PMID: 20301517