Genetics: Chromosome 1 RABGAP1L, GPR52, SERPINC1

I get the impression that GPR52 might be the relay receiving "erroneous" signals from another part of the brain.

The benefit for schizophrenia seems to lie in the possibility of avoiding hyperprolactinaemia whilst achieving the same effect as traditional antipsychotics. Among other things, cognitive improvements.

I think it could be interesting to take part in exploratory research (since this still seems to be the only stage at present) into GPR52 agonists and antagonists.
 
Haven't been able to keep up with all of these threads but just to note that there are a few entries in DGIdb, the drug-gene interaction database, for GPR52:

drug type direction conceptId COMP-43 inhibitor INHIBITORY iuphar.ligand:13995 COMPOUND 7A [PMID: 24884590] agonist ACTIVATING iuphar.ligand:8840 DERIVATIVE 17 [NAKAHATA ET AL., 2018] agonist ACTIVATING iuphar.ligand:9804 NXE0041178 agonist ACTIVATING iuphar.ligand:13909

Notably, PubMed ID 24884590 is this 2014 paper which explored the development of GPR52 agonists as a potentially new class of antipsychotics:
GPR52 inhibits dopamine D2 receptor signaling and activates dopamine D1/N-methyl-d-aspartate receptors via intracellular cAMP accumulation, and therefore, GPR52 agonists may have potential as a novel class of antipsychotics. A series of GPR52 agonists with a bicyclic core was designed to fix the conformation of the phenethyl ether moiety of compounds 2a and 2b.
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Sorry was just reviewing this, and maybe we have exhausted all options. Is there any methods left to try to get a more accurate pin on which gene this region is pointing too? I think this just came up as significant in the larger GWAS:

ME/CFS Science Blog

Post in thread 'PRIME International Symposium, September 28-29 2026'

I watched the presentation by Hanna M. Ollila titled "The Future of MECFS Genetics". She gave a good impression and presented findings from the big meta-analysis. Here's the direct link to the video:
EDIT: I've updated the images to versions with a better resolution.


The meta-analysis has 60,542 cases and 2,766,590 controls. Based on the slides, they included cases based on self-reported chronic fatigue and those with a diagnosis pos-viral fatigue syndrome. So a wider net than just ME/CFS.
1792227501907.webp

Here's the Manhhatten plot. Despite the large...
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This paper was interesting, "Gpr52 is located within an intron of Rabgap1".

A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity

Yao, Yuwei; Cui, Xiaotian; Al-Ramahi, Ismael; Sun, Xiaoli; Li, Bo; Hou, Jiapeng; Difiglia, Marian; Palacino, James; Wu, Zhi-Ying; Ma, Lixiang; Botas, Juan; Lu, Boxun

Abstract
Huntington's disease (HD) represents an important model for neurodegenerative disorders and proteinopathies. It is mainly caused by cytotoxicity of the mutant huntingtin protein (Htt) with an expanded polyQ stretch. While Htt is ubiquitously expressed, HD is characterized by selective neurodegeneration of the striatum. Here we report a striatal-enriched orphan G protein-coupled receptor(GPCR) Gpr52 as a stabilizer of Htt in vitro and in vivo. Gpr52 modulates Htt via cAMP-dependent but PKA independent mechanisms. Gpr52 is located within an intron of Rabgap1l , which exhibits epistatic effects on Gpr52-mediated modulation of Htt levels by inhibiting its substrate Rab39B , which co-localizes with Htt and translocates Htt to the endoplasmic reticulum. Finally, reducing Gpr52 suppresses HD phenotypes in both patient iPS-derived neurons and in vivo Drosophila HD models. Thus, our discovery reveals modulation of Htt levels by a striatal-enriched GPCR via its GPCR function, providing insights into the selective neurodegeneration and potential treatment strategies.

Web | DOI | PMC | PDF | eLife
 
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