Details for: GPR85

Gene ID: 54329

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: GPR85

Ensembl ID: ENSG00000164604

Description: G protein-coupled receptor 85

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • cerebral cortex endothelial cell CL1001602
    CSI 5.24
    rCSI 9.06%
    PRS 86.55
  • retinal blood vessel endothelial cell CL0002585
    CSI 4.75
    rCSI 7.59%
    PRS 93.5
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.52
    rCSI 4.21%
    PRS 79.55
  • ON-bipolar cell CL0000749
    CSI 3.33
    rCSI 4.95%
    PRS 90.34
  • interneuron CL0000099
    CSI 2.95
    rCSI 5.93%
    PRS 85.85
  • rod bipolar cell CL0000751
    CSI 2.78
    rCSI 5%
    PRS 86.92
  • H2 horizontal cell CL0004218
    CSI 2.74
    rCSI 13.62%
    PRS 86.53
  • retinal bipolar neuron CL0000748
    CSI 2.62
    rCSI 4.91%
    PRS 83.76
  • plasma cell CL0000786
    CSI 2.61
    rCSI 3.42%
    PRS 95.5
  • cerebellar granule cell CL0001031
    CSI 2.24
    rCSI 3.29%
    PRS 86.84
  • retina horizontal cell CL0000745
    CSI 2.03
    rCSI 3.1%
    PRS 88.48
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 1.91
    rCSI 3.38%
    PRS 78.94
  • pericyte CL0000669
    CSI 1.9
    rCSI 5.05%
    PRS 69.28
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.8
    rCSI 2.32%
    PRS 80.62
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 1.69
    rCSI 2.84%
    PRS 79.53
  • GABAergic amacrine cell CL4030027
    CSI 1.07
    rCSI 3.65%
    PRS 79.7
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.04
    rCSI 6.13%
    PRS 79.97
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 0.98
    rCSI 3.72%
    PRS 79.74
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.65
    rCSI 2.04%
    PRS 80.86
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.65
    rCSI 2.34%
    PRS 77.6

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

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • 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 [GPR85](/details-gene/54329), or G protein-coupled receptor 85, is a protein-coding gene located on human chromosome 7q31.1. As its name implies, it functions as a G protein-coupled receptor involved in signal transduction, primarily localized to the plasma membrane. Expression data indicates a highly specific role for [GPR85](/details-gene/54329) within the central nervous system. **Overall**, it exhibits its most significant expression in endothelial cells of the neurovasculature, such as [cerebral cortex endothelial cell](/details-cell/CL1001602) and [retinal blood vessel endothelial cell](/details-cell/CL0002585), as well as in specific neuronal subtypes including various [interneuron](/details-cell/CL0000099) populations and retinal neurons. This unique expression pattern suggests a dual role in both regulating the blood-brain/retina barrier and modulating neuronal signaling pathways. ## Cellular Roles and Expression Landscape The expression profile of [GPR85](/details-gene/54329) strongly points to a specialized function within the central nervous system. The gene's significance is highest in cells forming the neurovascular unit, with top scores in [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 5.24) and [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 4.75). This suggests a potential role in maintaining the integrity or specialized transport functions of the blood-brain and blood-retina barriers. Concurrently, [GPR85](/details-gene/54329) is a significant marker for several neuronal populations. It is highly expressed in inhibitory interneurons, including [VIP GABAergic cortical interneuron](/details-cell/CL4023016) and [sst GABAergic cortical interneuron](/details-cell/CL4023017). Furthermore, it shows prominent expression in the retina, specifically in [ON-bipolar cell](/details-cell/CL0000749), [rod bipolar cell](/details-cell/CL0000751), and [retina horizontal cell](/details-cell/CL0000745). This pattern implies a role in processing and transmitting neural signals, particularly within cortical inhibitory circuits and retinal pathways. Moderate significance is also noted in [plasma cell](/details-cell/CL0000786), which may suggest a yet-unexplored role in immune cell function, although its primary theater of action appears to be the nervous system. The specific expression in the brain has been previously documented [Link](https://doi.org/10.1016/s0167-4781(00)00182-2). ## Pathways and Molecular Function Functionally, [GPR85](/details-gene/54329) is annotated as a G protein-coupled receptor, placing it in one of the largest and most pharmacologically important protein families. Its molecular function is defined by [G protein-coupled receptor activity](/details-link/GO:0004930) and its involvement in the [G protein-coupled receptor signaling pathway](/details-link/GO:0007186). As a receptor, it is localized to the [plasma membrane](/details-link/GO:0005886), where it transduces extracellular signals into intracellular responses. The annotation for [protein binding](/details-link/GO:0005515) is supported by research showing its association with the postsynaptic density protein PSD-95 and the neuroligin complex, which are critical components of the synapse [Link](https://doi.org/10.1186/s13229-015-0012-5). This specific interaction is consistent with its high expression in neurons and strongly suggests a direct role in modulating synaptic structure or function. This finding also provides a molecular basis for its potential involvement in neurodevelopmental disorders like autism spectrum disorder, as highlighted in the same study. ## Research Directions The specific expression pattern of [GPR85](/details-gene/54329) in both the neurovasculature and distinct neuronal subtypes opens up several avenues for future investigation. ### Proposed Hypotheses 1. **[GPR85](/details-gene/54329) is a critical regulator of blood-brain barrier (BBB) integrity.** Given its high significance in [cerebral cortex endothelial cell](/details-cell/CL1001602), it may modulate tight junction protein expression or vesicular transport across the BBB in response to unknown endogenous ligands. 2. **[GPR85](/details-gene/54329) signaling modulates the excitability of cortical interneurons and contributes to the excitatory/inhibitory balance.** Based on its expression in GABAergic interneurons and its documented interaction with the PSD-95/neuroligin complex [Link](https://doi.org/10.1186/s13229-015-0012-5), dysregulation of [GPR85](/details-gene/54329) could lead to synaptic dysfunction implicated in neuropsychiatric or neurodevelopmental disorders. ### Experimental Approach To test the second hypothesis, a conditional knockout mouse model could be generated where *Gpr85* is specifically deleted in cortical interneuron subtypes (e.g., using Sst-Cre or VIP-Cre driver lines). Electrophysiological analysis, such as whole-cell patch-clamp recordings from pyramidal neurons in cortical slices, would be used to measure changes in the frequency and amplitude of spontaneous and miniature inhibitory postsynaptic currents (IPSCs). A significant alteration in these parameters in knockout animals compared to wild-type controls would provide direct evidence for the role of [GPR85](/details-gene/54329) in regulating inhibitory synaptic transmission. ### Therapeutic Potential As a G protein-coupled receptor, [GPR85](/details-gene/54329) is a classic 'druggable' target. Its highly restricted expression within the central nervous system makes it an attractive candidate for therapeutic intervention, as it could minimize the risk of peripheral off-target effects. If its dysregulation is causally linked to diseases characterized by excitatory/inhibitory imbalance, such as epilepsy or certain forms of autism, developing small molecule modulators (either agonists or antagonists, depending on the specific pathology) could be a viable strategy. Such compounds could be used to restore synaptic homeostasis, representing a targeted approach for treating complex neurological disorders.

Genular Protein ID: 2327455351

Symbol: GPR85_HUMAN

Name: Probable G-protein coupled receptor 85

UniProtKB Accession Codes:

P60893 Q9JHI6 Q9NPD1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 4 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 6 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 10978537

Title: The brain-specific G-protein coupled receptor GPR85 with identical protein sequence in man and mouse maps to human chromosome 7q31.

PubMed ID: 10978537

DOI: 10.1016/s0167-4781(00)00182-2

PubMed ID: 10833454

Title: An evolutionarily conserved G-protein coupled receptor family, SREB, expressed in the central nervous system.

PubMed ID: 10833454

DOI: 10.1006/bbrc.2000.2829

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

PubMed ID: 25780553

Title: The association of GPR85 with PSD-95-neuroligin complex and autism spectrum disorder: a molecular analysis.

PubMed ID: 25780553

DOI: 10.1186/s13229-015-0012-5

Sequence Information:

  • Length: 370
  • Mass: 41995
  • Checksum: 7B67A39F6166AAEB
  • Sequence:
    • MANYSHAADN ILQNLSPLTA FLKLTSLGFI IGVSVVGNLL ISILLVKDKT LHRAPYYFLL 
DLCCSDILRS AICFPFVFNS VKNGSTWTYG TLTCKVIAFL GVLSCFHTAF MLFCISVTRY 
LAIAHHRFYT KRLTFWTCLA VICMVWTLSV AMAFPPVLDV GTYSFIREED QCTFQHRSFR 
ANDSLGFMLL LALILLATQL VYLKLIFFVH DRRKMKPVQF VAAVSQNWTF HGPGASGQAA 
ANWLAGFGRG PTPPTLLGIR QNANTTGRRR LLVLDEFKME KRISRMFYIM TFLFLTLWGP 
YLVACYWRVF ARGPVVPGGF LTAAVWMSFA QAGINPFVCI FSNRELRRCF STTLLYCRKS 
RLPREPYCVI

Genular Protein ID: 3698437365

Symbol: Q8NEN2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8NEN2

Database IDs:

ARBA 12 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 2 Gene3D 1 InterPro 3 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PRINTS 1 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 4 SAM 1 SMR 1 SUPFAM 1

Citations:

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

Sequence Information:

  • Length: 370
  • Mass: 41965
  • Checksum: 20DD032E716BC797
  • Sequence:
    • MANYSHAADN ILQNLSPLTA FLKLTSLGFI IGVSVVGNLL ISILLVKDKT LHRAPYYFLL 
DLCCSDILRS AICFPFVFNS VKNGSTWTYG TLTCKVIAFL GVLSCFHTAF MLFCISVTRY 
LAIAHHRFYT KRLTFWTCLA VICMVWTLSV AMAFPPVLDV GTYSFIREED QCAFQHRSFR 
ANDSLGFMLL LALILLATQL VYLKLIFFVH DRRKMKPVQF VAAVSQNWTF HGPGASGQAA 
ANWLAGFGRG PTPPTLLGIR QNANTTGRRR LLVLDEFKME KRISRMFYIM TFLFLTLWGP 
YLVACYWRVF ARGPVVPGGF LTAAVWMSFA QAGINPFVCI FSNRELRRCF STTLLYCRKS 
RLPREPYCVI