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Last update 08 May 2025

GLRA3

Last update 08 May 2025

Basic Info

Synonyms

GLRA3, glycine receptor alpha 3, Glycine receptor subunit alpha-3

Introduction

Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:26416729, PubMed:9677400). Channel characteristics depend on the subunit composition; heteropentameric channels display faster channel closure (By similarity). Plays an important role in the down-regulation of neuronal excitability (By similarity). Contributes to the generation of inhibitory postsynaptic currents (By similarity). Contributes to increased pain perception in response to increased prostaglandin E2 levels (By similarity). Plays a role in cellular responses to ethanol (By similarity).

Drugs associated with GLRA3

CMB-C28-H01

Target

GLRA3

Mechanism

GLRA3 modulators

Active Org.-

Originator Org.

The University of Queensland

Active Indication-

Inactive Indication

Inflammation [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with GLRA3

100 Translational Medicine associated with GLRA3

0 Patents (Medical) associated with GLRA3

Literatures (Medical) associated with GLRA3

01 Mar 2025·British Journal of Anaesthesia

Genome-wide association study on chronic postsurgical pain in the UK Biobank

Article

Author: Parisien, Marc ; van Boekel, Regina L M ; Vissers, Kris C P ; Li, Song ; Diatchenko, Luda ; Ten Broek, Richard P G ; Toneman, Masja K ; Coenen, Marieke J H

BACKGROUNDChronic postsurgical pain (CPSP) persists beyond the expected healing period after surgery, imposing a substantial burden on overall patient well-being. Unfortunately, CPSP often remains underdiagnosed and undertreated. To better understand the mechanism of CPSP development, we aimed to identify genetic variants associated with CPSP.METHODSA genome-wide association study was conducted in a cohort of 95,931 individuals from the UK Biobank who had undergone different surgical procedures. Three analyses were performed: (1) case-control analysis (2923 cases with CPSP and 93,008 controls), (2) ordinal analysis in three groups based on time of analgesics use (n=95,931), and (3) a meta-analysis combining our dataset with a recent publication (n=97,281).RESULTSIn the case-control analysis, one genetic locus within GLRA3 displayed a genome-wide significant (P<2.5×10^-8) association with CPSP, and nine loci displayed suggestively significant associations (P<1×10^-6). The ordinal analysis aligned with the case-control analysis, with an additional locus (rs140330443) reaching genome-wide significance. In the meta-analysis with the recently published dataset, the single nucleotide polymorphism (SNP) rs17298280 in the GLRA3 gene remained significant (P=2.19×10^-9).CONCLUSIONSThis study contributes new insights into the genetic factors associated with CPSP. The top hit GLRA3 is known for involvement in prostaglandin E2-induced pain processing pathways. Our study provides a foundation for future investigations into the function of these risk variants and the mechanisms underlying CPSP by offering summary statistics. However, further validation in other cohorts is required to confirm these findings.

01 Feb 2025·Addictive Behaviors

A novel smoking cessation behavior based on quit attempts may identify new genes associated with long-term abstinence

Article

Author: Diver, W Ryan ; Lee Westmaas, J. ; Westmaas, J. Lee ; Westmaas, J Lee ; Diver, W. Ryan ; Ryan Diver, W. ; Patel, Alpa V. ; Lori, Adriana ; Patel, Alpa V

BACKGROUNDSmoking cessation at any age has been shown to improve quality of life, decrease illness, and reduce mortality. About half of smokers attempt to quit each year, but only ∼ 7 % maintain long-term abstinence unaided. Few genetic factors have been consistently associated with smoking cessation, possibly due to poor phenotype definition.METHODSWe performed a genome-wide association study (GWAS) with an alternative phenotype based on the difficulty of quitting smoking (DQS) in the Cancer Prevention Study-3 cohort. Difficult quitters were defined as having made at least ten quit attempts, whether successful or not, and easy quitters as having quit after only one attempt. Only individuals of European ancestry were selected for the study. Among 10,004 smokers (5,071 difficult quitters, 4,933 easy quitters), we assessed the genetic heritability of DQS and evaluated associations between DQS and each genome-wide variant using logistic regression while adjusting for confounders, including smoking intensity (cigarettes per day).RESULTSThe genetic heritability of the DQS phenotype was 13 %, comparable to, or higher than, the reported heritability of other smoking behaviors (e.g., smoking intensity, cessation). Although no variants were genome-wide significant, several genes were identified at a subthreshold level (p < 10^-4). A variant in MEGF9 (rs149760032), a transmembrane protein largely expressed in the central nervous system, showed the strongest association with DQS (OR = 0.60, p = 1.3x10^-7). Additional variants associated with DQS independently by smoking intensity were also detected in GLRA3 (rs73006492, OR = 0.77, p = 5.6x10^-7) and FOCAD (rs112251973, OR = 1.96, p = 1.8x10^-6) and are plausibly related to smoking cessation through pathways in the brain and respiratory system.CONCLUSIONSThe use of an alternative cessation phenotype based on difficulty quitting smoking facilitated the identification of new pathways that could lead to unique smoking treatments.

01 Nov 2024·Journal of Diabetes and its Complications

“Predicting diabetic kidney disease in youth with type 1 diabetes: Insights from genetic risk assessment”

Article

Author: Darcan, Şükran ; Özkan, Behzat ; Özen, Samim ; Kabasakal, Caner ; Gökşen, Damla ; Köse, Timur ; Ak, Güneş ; Atik, Tahir ; Evin, Ferda ; Kırkgöz, Tarık

OBJECTIVEDiabetic kidney disease (DKD) is influenced by multiple factors, yet its precise progression mechanisms remain largely unclear. This study aimed to create a clinical risk-scoring system based on genetic polymorphisms in the AFF3, CARS, CERS2, ERBB4, GLRA3, RAET1L, TMPO, and ZMIZ1 genes.METHODSThe study included a DKD group diagnosed with diabetic kidney disease before age 18 and a WDC group matched by age, gender, and age at diabetes diagnosis. Genetic data and clinical data from diabetes diagnosis to moderately increased albuminuria (MIA) detection were compared between the groups.RESULTSAmong 43 DKD cases, 22 were girls and 21 were boys. At MIA diagnosis, mean body weight SDS was -0.24 ± 0.94, height SDS was 0.34 ± 1.15, and BMI SDS was -0.26 ± 0.94. Systolic blood pressure was at the 72nd percentile (2-99), and diastolic blood pressure was at the 74th percentile (33-99). Significant differences in rs267734, rs267738, and rs942263 polymorphisms were found between DKD and non-complication diabetic groups (13[30.2 %] vs 5[11.6 %], p = 0.034; 14[32.6 %] vs 5[11.6 %], p = 0.019; 26[60.5 %] vs 40[93 %], p < 0.001).CONCLUSIONSeveral factors were identified as significant in DKD onset, including low follow-up weight SDS, elevated diastolic blood pressure, presence of rs267734, and absence of rs942263 polymorphisms. The model demonstrated a specificity of 81.4 % and a sensitivity of 74.4 %.

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GLRA3

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