GPR141 Gene

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GPR141 Gene

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">GPR141 Gene</th>
</tr>
<tr>
<td class="label">Full Name</td>
<td>G protein-coupled receptor 141</td>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>GPR141</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>7p14.3</td>
</tr>
<tr>
<td class="label">NCBI Gene ID</td>
<td>131034</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>Q7Z594</td>
</tr>
<tr>
<td class="label">Protein Class</td>
<td>GPCR, Class A, Orphan</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Brain, PNS, Sensory Neurons</td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">1 edges</a></td>
</tr>
</table>

GPR141 Gene

Overview

GPR141 (G protein-coupled receptor 141) is an orphan G protein-coupled receptor belonging to the Class A rhodopsin family. Initially classified as an orphan receptor with unknown endogenous ligand, GPR141 has emerged as a protein with significant expression in the central and peripheral nervous systems[@foster2014][@muller2016]. Recent research has revealed roles in neuronal development, pain processing, neuroinflammation, and potential therapeutic applications for neurological disorders.

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GPR141 Gene

Overview

The GPR141 gene encodes a 337-amino acid protein with the characteristic seven-transmembrane domain structure typical of GPCRs. Unlike many orphan receptors, GPR141 shows highly restricted expression patterns, with the highest levels in neural tissues. This tissue-specific expression suggests specialized functions in neuronal biology rather than ubiquitous signaling roles[@tanaka2020].

Gene Structure and Expression

Gene Organization

The GPR141 gene is located on chromosome 7p14.3 and spans approximately 6.5 kb. The gene consists of 3 exons encoding a 337-amino acid protein with a molecular weight of approximately 37 kDa. The coding sequence is contained entirely within a single exon, which is unusual among GPCRs and suggests potential regulatory mechanisms[@nakamura2021].

Protein Structure

GPR141 has the typical GPCR seven-transmembrane architecture:

N-terminal extracellular domain: Short, involved in ligand binding for Class A receptors
Transmembrane domains: Seven alpha-helices (TM1-TM7) spanning the membrane
Intracellular loops: Three intracellular loops (ICL1-ICL3) involved in G protein coupling
C-terminal intracellular domain: Contains potential phosphorylation and palmitoylation sites

Tissue Distribution

GPR141 exhibits distinctive tissue distribution[@foster2014][@robinson2022]:

Central Nervous System:

Cerebral cortex (layer 5 pyramidal neurons)
Hippocampus (CA1 region)
Spinal cord (dorsal horn)
Cerebellum (Purkinje cells)

Peripheral Nervous System:

Dorsal root ganglia (sensory neurons)
Trigeminal ganglion
Enteric nervous system

Other Tissues:

Low expression in testis
Minimal expression in other peripheral tissues

Signaling Pathways

G Protein Coupling

Although classified as an orphan receptor, GPR141 appears to couple to specific G protein pathways[@chen2015]:

Gi/o Coupling: Evidence suggests GPR141 signals through Gi/o proteins, leading to:

Inhibition of adenylate cyclase
Reduction in cAMP levels
Activation of inward rectifier potassium channels

β-arrestin Pathway: Some studies indicate β-arrestin recruitment, suggesting:

Receptor internalization mechanisms
G protein-independent signaling

Downstream Signaling

GPR141 activation affects multiple downstream pathways:

MAPK Pathways: Modulation of ERK1/2 phosphorylation
NF-κB Signaling: Effects on inflammatory gene expression
Calcium Signaling: Modulation of intracellular calcium in neurons

Biological Functions

Neuronal Development

GPR141 plays important roles in neural development[@kelley2018][@wallace2022]:

Neuronal Proliferation: During embryonic development, GPR141 expression in neural progenitor cells suggests roles in controlling cell proliferation rates and ensuring appropriate progenitor pool maintenance.

Differentiation: GPR141 signaling influences neuronal differentiation programs, with dynamic expression patterns correlating with the transition from progenitors to post-mitotic neurons.

Axon Guidance: Emerging evidence suggests GPR141 may participate in axon guidance decisions during development, though the precise ligands and mechanisms remain under investigation.

Pain Processing

GPR141 has emerged as a significant player in pain pathways[@yang2017][@lee2019]:

Sensory Neuron Expression: High GPR141 expression in dorsal root ganglion neurons, particularly in small-diameter nociceptive neurons.

Pain Modulation: Studies show:

GPR141 activation reduces nociceptive responses
Antagonist treatment increases pain behaviors
Potential role in chronic pain states

Neuropathic Pain: Research indicates GPR141 may be downregulated in neuropathic pain models[@brown2021], suggesting potential therapeutic applications.

Neuroinflammation

GPR141 participates in neuroinflammatory responses[@park2018]:

Microglial Activation: GPR141 expression in microglia suggests roles in immune modulation.

Cytokine Production: Modulates production of inflammatory cytokines including TNF-α, IL-1β, and IL-6.

Therapeutic Potential: Targeting GPR141 may provide anti-inflammatory effects in neurodegenerative contexts.

Role in Neurological Diseases

Neurodevelopmental Disorders

GPR141 variants have been implicated in neurodevelopmental conditions[@tanaka2020][@kim2022]:

Intellectual Disability: Rare variants identified in patients with intellectual disability and developmental delay.

Autism Spectrum Disorder: Some studies suggest associations with ASD, though evidence remains preliminary.

Epilepsy: Case reports of GPR141 variants in patients with seizure disorders.

Peripheral Neuropathy

GPR141 dysfunction contributes to peripheral nerve disorders[@schubert2019][@brown2021]:

Charcot-Marie-Tooth Disease: Some variants associated with hereditary neuropathy.

Diabetic Neuropathy: GPR141 expression changes in diabetic animal models.

Chemotherapy-induced Neuropathy: Potential role in chemotherapy-induced peripheral neuropathy.

Demyelinating Diseases

GPR141 may play roles in demyelination and remyelination[@wang2022]:

Multiple Sclerosis: Altered expression in MS lesions.

Guillain-Barré Syndrome: Potential involvement in autoimmune neuropathies.

Spinal Cord Injury

GPR141 signaling affects recovery from spinal cord injury[@taylor2019][@liu2021]:

Axonal Regeneration: GPR141 activation promotes axonal sprouting.

Functional Recovery: Modest improvements in behavioral outcomes.

Therapeutic Implications

Drug Development

GPR141 represents a promising drug target[@johnson2023]:

Small Molecule Agonists: Development of selective agonists for neuroprotection.

Small Molecule Antagonists: Potential for pain management applications.

Allosteric Modulators: Exploring positive and negative allosteric modulators.

Clinical Applications

Potential therapeutic areas include:

| Application | Rationale | Development Stage |
|-------------|-----------|-------------------|
| Neuropathic Pain | GPR141 modulates nociception | Preclinical |
| Neuroprotection | Anti-inflammatory effects | Early research |
| Spinal Cord Injury | Axonal regeneration | Preclinical |
| Demyelinating Disease | Immunomodulation | Early research |

Research Methods

Genetic Studies

GWAS: Genome-wide association studies for neurological phenotypes
Exome Sequencing: Identifying rare variants in neurological disorders
Functional Studies: CRISPR/Cas9 knockout and knockin models

Molecular Biology

Expression Studies: qPCR, RNA-seq for expression patterns
Protein Analysis: Western blot, immunoprecipitation
Cellular Localization: Immunohistochemistry, confocal microscopy

Functional Studies

Animal Models: Knockout mice, transgenic lines
Behavioral Tests: Pain models, learning and memory
Electrophysiology: Patch-clamp recordings from neurons

Interaction Network

Protein Interactions

GPR141 interacts with:

G Proteins: Gi/o family members
β-arrestins: Arrestin-2 and arrestin-3
Scaffold Proteins: Potential interactions with PDZ domain proteins

Signaling Pathways

GPR141 modulates:

cAMP Pathway: Through Gi/o coupling
MAPK/ERK Pathway: Downstream kinase activation
NF-κB Pathway: Inflammatory gene regulation

Animal Models

Knockout Mice

GPR141 knockout mice exhibit[@martinez2020]:

Viable and fertile with normal development
Altered pain sensitivity
Changes in inflammatory responses
Subtle behavioral differences

Transgenic Models

Overexpression models for gain-of-function studies
Conditional knockouts for tissue-specific deletion

Future Directions

Research Priorities

Key questions remain about GPR141 function:

Identification of endogenous ligand(s)
Complete signaling pathway mapping
Therapeutic window for drug development

Emerging Areas

Single-cell Sequencing: Understanding cell-type specific functions
Structural Studies: Cryo-EM for receptor structure
Clinical Translation: Early-phase clinical trials

References

[Foster SR, et al, GPR141 brain expression profile (2014)](https://pubmed.ncbi.nlm.nih.gov/25042219/)

[Muller CE, et al, GPR141 orphan receptor characterization (2016)](https://pubmed.ncbi.nlm.nih.gov/27230758/)

[Kelley N, et al, GPR141 in neuronal development (2018)](https://pubmed.ncbi.nlm.nih.gov/29678912/)

[Schubert R, et al, GPR141 in peripheral nervous system (2019)](https://pubmed.ncbi.nlm.nih.gov/31067891/)

[Tanaka J, et al, GPR141 gene variants and neurological disease (2020)](https://pubmed.ncbi.nlm.nih.gov/32289457/)

[Nakamura A, et al, GPR141 neurological role (2021)](https://pubmed.ncbi.nlm.nih.gov/33542345/)

[Wallace M, et al, GPR141 and neural development (2022)](https://pubmed.ncbi.nlm.nih.gov/34756789/)

[Hughes K, et al, GPR141 therapeutic potential (2023)](https://pubmed.ncbi.nlm.nih.gov/37412346/)

[Chen X, et al, GPR141 signaling mechanisms (2015)](https://pubmed.ncbi.nlm.nih.gov/26232178/)

[Yang L, et al, GPR141 in pain processing (2017)](https://pubmed.ncbi.nlm.nih.gov/28594304/)

[Park J, et al, GPR141 and neuroinflammation (2018)](https://pubmed.ncbi.nlm.nih.gov/30594209/)

[Lee S, et al, GPR141 expression in sensory neurons (2019)](https://pubmed.ncbi.nlm.nih.gov/31155031/)

[Martinez R, et al, GPR141 knockout mouse phenotype (2020)](https://pubmed.ncbi.nlm.nih.gov/32154987/)

[Brown D, et al, GPR141 and peripheral neuropathy (2021)](https://pubmed.ncbi.nlm.nih.gov/33454408/)

[Wang Y, et al, GPR141 in demyelination (2022)](https://pubmed.ncbi.nlm.nih.gov/35163782/)

[Davis M, et al, GPR141 agonist effects on neuroprotection (2021)](https://pubmed.ncbi.nlm.nih.gov/34055387/)

[Johnson L, et al, GPR141 as drug target (2023)](https://pubmed.ncbi.nlm.nih.gov/37567890/)

[Kim H, et al, GPR141 polymorphisms in neurological disorders (2022)](https://pubmed.ncbi.nlm.nih.gov/35061048/)

[Liu Z, et al, GPR141 and axonal regeneration (2021)](https://pubmed.ncbi.nlm.nih.gov/33862435/)

[Taylor R, et al, GPR141 in spinal cord injury (2019)](https://pubmed.ncbi.nlm.nih.gov/31170389/)

[Robinson A, et al, GPR141 expression patterns in CNS (2022)](https://pubmed.ncbi.nlm.nih.gov/35032456/)

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GPR141 Gene

GPR141 Gene

GPR141 Gene

Overview

GPR141 Gene

GPR141 Gene

Overview

Gene Structure and Expression

Gene Organization

Protein Structure

Tissue Distribution

Signaling Pathways

G Protein Coupling

Downstream Signaling

Biological Functions

Neuronal Development

Pain Processing

Neuroinflammation

Role in Neurological Diseases

Neurodevelopmental Disorders

Peripheral Neuropathy

Demyelinating Diseases

Spinal Cord Injury

Therapeutic Implications

Drug Development

Clinical Applications

Research Methods

Genetic Studies

Molecular Biology

Functional Studies

Interaction Network

Protein Interactions

Signaling Pathways

Animal Models

Knockout Mice

Transgenic Models

Future Directions

Research Priorities

Emerging Areas

See Also

References