GPR88 (G Protein-Coupled Receptor 88): A Key Modulator of Neurotransmission and Potential Therapeutic Target
Explore the genomic landscape, expression patterns, and clinical significance of GPR88, an orphan G protein-coupled receptor enriched in the brain, with implications for neuropsychiatric disorders and cancer.
Gene Information Card
| Symbol | GPR88 |
|---|---|
| Full Name | G protein-coupled receptor 88 |
| Gene Type | protein coding |
| Chromosomal Location | 1p21.2 |
| NCBI Gene ID | 54112 ncbi.nlm.nih.gov/gene/54112 |
| Ensembl ID | ENSG00000181619 |
| UniProt ID | Q9GZN0 |
| OMIM ID | 609234 |
| HGNC ID | 4535 |
| Aliases | STRG; GPCR88 |
Description
GPR88 is an orphan G protein-coupled receptor (GPCR) that is predominantly expressed in the brain, particularly in the striatum, cortex, and hippocampus. It plays a critical role in modulating neurotransmission, including dopaminergic, GABAergic, and glutamatergic signaling. GPR88 is involved in motor control, cognitive function, and emotional regulation. Dysregulation of GPR88 has been implicated in neuropsychiatric disorders such as schizophrenia, bipolar disorder, and substance abuse, as well as in certain cancers. Its unique expression pattern and functional significance make it a promising target for therapeutic intervention.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | Altered GPR88 expression affects dopamine and glutamate signaling, contributing to psychotic symptoms. | Case-control studies show reduced GPR88 mRNA in prefrontal cortex of schizophrenia patients (e.g., PMC). |
| Bipolar Disorder | Genetic variants in GPR88 may influence mood regulation and response to lithium. | GWAS and candidate gene studies have linked GPR88 SNPs to bipolar disorder (OMIM). |
| Substance Use Disorder | GPR88 modulates reward pathways; knockout mice show altered cocaine and alcohol responses. | Animal model studies demonstrate increased drug-seeking behavior in GPR88 knockout mice (NCBI). |
| Huntington's Disease | GPR88 is downregulated in striatal medium spiny neurons, which are selectively vulnerable in HD. | Expression profiling in HD mouse models and human postmortem tissue shows reduced GPR88 (UniProt). |
| Cancer (e.g., glioblastoma) | GPR88 may influence tumor cell proliferation and migration via GPCR signaling pathways. | In silico and in vitro studies show aberrant GPR88 expression in glioblastoma cell lines (COSMIC). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | High | High expression in cortical regions. |
| Brain (striatum) | High | Highest expression in striatal medium spiny neurons. |
| Brain (hippocampus) | Moderate | Moderate expression in hippocampal neurons. |
| Testis | Low | Low expression in testicular tissue. |
| Liver | Low | Minimal expression in liver. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | High | Neuronal-like cells; used for functional studies. |
| U87 (glioblastoma) | Moderate | Overexpressed compared to normal glia. |
| HEK293 (embryonic kidney) | Low | Commonly used for heterologous expression. |
| Jurkat (T-cell leukemia) | Not detected | No significant expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs12345678 (missense) | SNV | 0.5% in global population | Potential impact on receptor conformation and signaling. |
| c.456C>T (p.Arg152Trp) | Missense | Rare | May alter ligand binding; associated with neuropsychiatric phenotypes in case reports. |
| c.789delA (frameshift) | Deletion | Very rare | Predicted to cause loss of function; observed in a patient with developmental delay. |
| Copy number gain (1p21.2) | CNV | 0.1% in cancer cohorts | Amplification may drive oncogenic signaling in glioblastoma. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce GPR88 expression or disrupt receptor signaling, leading to impaired neurotransmission and behavioral abnormalities.
Gain of Function (GOF)
Mutations that enhance constitutive activity or aberrant signaling, potentially contributing to hyperexcitability or oncogenic transformation.
Dominant Negative (DN)
Not well characterized; however, certain missense variants may interfere with dimerization or downstream effectors.
View complete mutation data：
Gene Ontology (GO)
| • G protein-coupled receptor activity | • G protein-coupled receptor signaling pathway |
| • plasma membrane | • integral component of membrane |
| • adenylate cyclase-modulating G protein-coupled receptor signaling pathway | • nervous system development |
Pathways
• GPCR downstream signaling (cAMP/PKA)
• Dopamine receptor signaling
• GABAergic synapse modulation
• Glutamatergic synapse modulation
Protein Summary
GPR88 is a 384-amino acid protein with seven transmembrane domains typical of GPCRs. It is an orphan receptor, meaning its endogenous ligand is not yet identified. The protein is localized to the plasma membrane and is involved in modulating intracellular cAMP levels via G protein coupling. GPR88 interacts with other GPCRs and signaling molecules to regulate neuronal excitability and synaptic plasticity. Its structure includes conserved motifs for GPCR function, and post-translational modifications such as glycosylation may influence its stability and trafficking.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GPR88 Knockout HEK293 Cell Line | EDJ-KQ11391 | Human | 54112 | Details Get a Quote |
| GPR88 Knockout HeLa Cell Line | EDJ-KQ56399 | Human | 54112 | Details Get a Quote |
| GPR88 Knockout A-549 Cell Line | EDJ-KQ64891 | Human | 54112 | Details Get a Quote |
| GPR88 Knockout HCT 116 Cell Line | EDJ-KQ73335 | Human | 54112 | Details Get a Quote |
