Details for: GPR143

Gene ID: 4935

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: GPR143

Ensembl ID: ENSG00000101850

Description: G protein-coupled receptor 143

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • melanocyte CL0000148
    CSI 7.64
    rCSI 5.66%
    PRS 98.38
  • retinal pigment epithelial cell CL0002586
    CSI 4.23
    rCSI 8.4%
    PRS 98.05
  • epithelial cell CL0000066
    CSI 3.49
    rCSI 5.36%
    PRS 95.3
  • choroid plexus epithelial cell CL0000706
    CSI 3.42
    rCSI 5.61%
    PRS 97.76
  • placental villous trophoblast CL2000060
    CSI 2.32
    rCSI 3.58%
    PRS 98.45
  • astrocyte of the cerebral cortex CL0002605
    CSI 1.79
    rCSI 4.02%
    PRS 96.74

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [GPR143](/details-gene/4935) (G protein-coupled receptor 143), also known as OA1, is an intracellular G protein-coupled receptor (GPCR) encoded by a gene on the X chromosome. Its primary function is centered on the biogenesis, transport, and organization of melanosomes, the organelles responsible for pigment synthesis and storage. Consistent with this role, **Overall** expression analysis reveals that [GPR143](/details-gene/4935) is most significantly and specifically expressed in pigmented cells, particularly [melanocyte](/details-cell/CL0000148)s and [retinal pigment epithelial cell](/details-cell/CL0002586)s. Mutations in the [GPR143](/details-gene/4935) gene are the primary cause of X-linked ocular albinism type 1 ([300500](https://omim.org/entry/300500)), a condition characterized by severely impaired visual acuity and abnormal development of optic pathways, underscoring the gene's critical role in visual system development. Research has identified L-DOPA as an endogenous ligand for this receptor ([Link](https://doi.org/10.1371/journal.pbio.0060236)), linking its signaling activity directly to the melanin synthesis pathway. ## Cellular Roles and Expression Landscape The expression profile of [GPR143](/details-gene/4935) highlights its specialized function in pigmented tissues. **Overall**, the gene exhibits its highest significance in [melanocyte](/details-cell/CL0000148) (CSI: 7.64), the primary pigment-producing cells in the skin and hair, and in [retinal pigment epithelial cell](/details-cell/CL0002586) (CSI: 4.23), which are crucial for the health and function of photoreceptors in the eye. This dual-specificity firmly establishes [GPR143](/details-gene/4935) as a key regulator of pigmentation in both cutaneous and ocular systems. Lesser but still significant expression is noted in other cell types, including [epithelial cell](/details-cell/CL0000066) (CSI: 3.49), [choroid plexus epithelial cell](/details-cell/CL0000706) (CSI: 3.42), and [placental villous trophoblast](/details-cell/CL2000060) (CSI: 2.32). Its expression in the [choroid plexus epithelial cell](/details-cell/CL0000706) and [astrocyte of the cerebral cortex](/details-cell/CL0002605) (CSI: 1.79) may suggest an uncharacterized role in the central nervous system, which could be relevant to the nystagmus and foveal hypoplasia seen in ocular albinism. However, its profound enrichment in pigmented cells suggests its principal biological role is the regulation of melanosome biology. ## Pathways and Molecular Function The functional annotations for [GPR143](/details-gene/4935) are highly consistent with its expression profile and clinical significance. Biologically, it is integral to multiple aspects of melanosome life cycle, including [melanosome organization](/details-cell/GO:0032438), [melanosome localization](/details-cell/GO:0032400), and [melanosome transport](/details-cell/GO:0032402). These processes are crucial for proper skin and eye pigmentation. Studies have confirmed that [GPR143](/details-gene/4935) functions to regulate melanosome transport within pigment cells ([Link](https://doi.org/10.1093/hmg/ddn241)). At the molecular level, [GPR143](/details-gene/4935) functions as a [G protein-coupled receptor activity](/details-cell/GO:0004930) that engages the [G alpha (q) signalling events](/details-pathway/R-HSA-416476) pathway. It has been shown to bind L-DOPA ([L-dopa binding](/details-cell/GO:0072544)), a precursor in melanin synthesis, thereby acting as a sensor for the melanin production cascade ([Link](https://doi.org/10.1371/journal.pbio.0060236)). Its activity is tied to signaling pathways governed by the Microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte development, as evidenced by its inclusion in Reactome pathways such as [Mitf-m-regulated melanocyte development](/details-pathway/R-HSA-9730414) and [Regulation of mitf-m-dependent genes involved in pigmentation](/details-pathway/R-HSA-9824585). Cellularly, the protein is localized to the [melanosome membrane](/details-cell/GO:0033162) and [lysosomal membrane](/details-cell/GO:0005765), where it controls organelle identity and transport ([Link](https://doi.org/10.1093/hmg/9.20.3011)). ## Research Directions The highly specific expression and well-defined role of [GPR143](/details-gene/4935) in melanosome biology present several avenues for future research, particularly concerning pigmentation disorders and neuronal development. **Proposed Hypotheses:** 1. Given its expression in [astrocyte of the cerebral cortex](/details-cell/CL0002605) and the severe neuro-visual defects associated with its mutation (e.g., misrouting of optic nerves), the dysregulation of [GPR143](/details-gene/4935) signaling in glial cells may directly contribute to the abnormal development of the visual pathway, independent of its role in retinal pigment epithelium. It may function in a non-canonical, L-DOPA-related signaling pathway in these cells that influences axonal guidance. 2. As a GPCR that binds L-DOPA, [GPR143](/details-gene/4935) activity could be a key checkpoint that couples melanin synthesis rates with melanosome maturation and size. Pathological conditions of hyper- or hypo-pigmentation may be associated with altered receptor sensitivity or downstream signaling efficiency, rather than just mutations in the gene itself. **Experimental Approach:** To test the hypothesis that [GPR143](/details-gene/4935) is a druggable node for controlling pigmentation, a pharmacological approach could be employed. First, a high-throughput screening platform could be developed using a human melanoma cell line (e.g., MNT-1) stably expressing a Gq-pathway reporter (e.g., a fluorescent calcium indicator). This system would be used to screen small molecule libraries for novel agonists and antagonists of [GPR143](/details-gene/4935). Hits would then be validated in primary human [melanocyte](/details-cell/CL0000148) cultures. The effect of lead compounds on pigmentation would be quantified by measuring total melanin content, and their impact on melanosome biology would be assessed by transmission electron microscopy to analyze melanosome size, number, and maturation stage. **Therapeutic Potential:** [GPR143](/details-gene/4935) represents a promising therapeutic target for pigmentation disorders. For X-linked ocular albinism, a loss-of-function disease, strategies would focus on activation or restoration of function. This could include gene therapy to deliver a functional copy of the gene to retinal pigment epithelial cells or the development of small-molecule agonists that can bypass the genetic defect and stimulate the downstream signaling pathway. Conversely, for hyperpigmentation disorders like melasma, potent and specific antagonists of [GPR143](/details-gene/4935) could be developed as topical agents to reduce melanin production. Its high cell-type specificity suggests that systemic side effects of such modulators might be limited.

Genular Protein ID: 72543013

Symbol: GP143_HUMAN

Name: G-protein coupled receptor 143

UniProtKB Accession Codes:

P51810 Q6NTI7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 24 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 3 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 7647783

Title: Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome.

PubMed ID: 7647783

DOI: 10.1038/ng0595-13

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 10094567

Title: Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism.

PubMed ID: 10094567

DOI: 10.1002/(sici)1098-1004(1999)13:2<99::aid-humu2>3.0.co;2-c

PubMed ID: 10471510

Title: Ocular albinism: evidence for a defect in an intracellular signal transduction system.

PubMed ID: 10471510

DOI: 10.1038/12715

PubMed ID: 11115845

Title: Defective intracellular transport and processing of OA1 is a major cause of ocular albinism type 1.

PubMed ID: 11115845

DOI: 10.1093/hmg/9.20.3011

PubMed ID: 11793467

Title: New insights into ocular albinism type 1 (OA1): mutations and polymorphisms of the OA1 gene.

PubMed ID: 11793467

DOI: 10.1002/humu.10034

PubMed ID: 12643545

Title: Proteomic analysis of early melanosomes: identification of novel melanosomal proteins.

PubMed ID: 12643545

DOI: 10.1021/pr025562r

PubMed ID: 16621890

Title: An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1.

PubMed ID: 16621890

DOI: 10.1242/jcs.02930

PubMed ID: 17081065

Title: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.

PubMed ID: 17081065

DOI: 10.1021/pr060363j

PubMed ID: 16524428

Title: The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor.

PubMed ID: 16524428

DOI: 10.1111/j.1600-0749.2006.00292.x

PubMed ID: 18697795

Title: The ocular albinism type 1 protein, an intracellular G protein-coupled receptor, regulates melanosome transport in pigment cells.

PubMed ID: 18697795

DOI: 10.1093/hmg/ddn241

PubMed ID: 18828673

Title: L-DOPA is an endogenous ligand for OA1.

PubMed ID: 18828673

DOI: 10.1371/journal.pbio.0060236

PubMed ID: 19717472

Title: The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.

PubMed ID: 19717472

DOI: 10.1093/hmg/ddp415

PubMed ID: 8634705

Title: Analysis of the OA1 gene reveals mutations in only one-third of patients with X-linked ocular albinism.

PubMed ID: 8634705

DOI: 10.1093/hmg/4.12.2319

PubMed ID: 9529334

Title: OA1 mutations and deletions in X-linked ocular albinism.

PubMed ID: 9529334

DOI: 10.1086/301776

PubMed ID: 9887374

Title: X-linked ocular albinism: prevalence and mutations -- a national study.

PubMed ID: 9887374

DOI: 10.1038/sj.ejhg.5200226

PubMed ID: 11214907

Title: Diverse prevalence of large deletions within the OA1 gene in ocular albinism type 1 patients from Europe and North America.

PubMed ID: 11214907

DOI: 10.1007/s004390000440

PubMed ID: 16646960

Title: Eight previously unidentified mutations found in the OA1 ocular albinism gene.

PubMed ID: 16646960

DOI: 10.1186/1471-2350-7-41

PubMed ID: 17822861

Title: New mutations identified in the ocular albinism type 1 gene.

PubMed ID: 17822861

DOI: 10.1016/j.gene.2007.07.020

PubMed ID: 17516023

Title: Identification of a novel GPR143 mutation in a large Chinese family with congenital nystagmus as the most prominent and consistent manifestation.

PubMed ID: 17516023

DOI: 10.1007/s10038-007-0152-3

PubMed ID: 17960122

Title: Identification of two novel mutations in families with X-linked ocular albinism.

PubMed ID: 17960122

PubMed ID: 18978956

Title: Novel GPR143 mutations and clinical characteristics in six Chinese families with X-linked ocular albinism.

PubMed ID: 18978956

Sequence Information:

  • Length: 404
  • Mass: 43878
  • Checksum: 20DEB20E80CC0E1D
  • Sequence:
    • MASPRLGTFC CPTRDAATQL VLSFQPRAFH ALCLGSGGLR LALGLLQLLP GRRPAGPGSP 
ATSPPASVRI LRAAAACDLL GCLGMVIRST VWLGFPNFVD SVSDMNHTEI WPAAFCVGSA 
MWIQLLYSAC FWWLFCYAVD AYLVIRRSAG LSTILLYHIM AWGLATLLCV EGAAMLYYPS 
VSRCERGLDH AIPHYVTMYL PLLLVLVANP ILFQKTVTAV ASLLKGRQGI YTENERRMGA 
VIKIRFFKIM LVLIICWLSN IINESLLFYL EMQTDINGGS LKPVRTAAKT TWFIMGILNP 
AQGFLLSLAF YGWTGCSLGF QSPRKEIQWE SLTTSAAEGA HPSPLMPHEN PASGKVSQVG 
GQTSDEALSM LSEGSDASTI EIHTASESCN KNEGDPALPT HGDL