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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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GLRA3
glycine receptor alpha 3
Chromosome 4 · 4q34.1
NCBI Gene: 8001Ensembl: ENSG00000145451.13HGNC: HGNC:4328UniProt: O75311
24PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glycine-gated chloride channel complexextracellularly glycine-gated chloride channel activitychloride transmembrane transportplasma membranesmoking initiationneurodegenerative diseaseplacental retentionfrozen shoulder
✦AI Summary

GLRA3 encodes the alpha-3 subunit of glycine receptors, which function as ligand-gated chloride channels that regulate neuronal excitability 1. The gene produces two alternatively spliced variants (alpha3L and alpha3K) that differ in desensitization kinetics, with the cytoplasmic loop between transmembrane domains 3 and 4 serving as a critical determinant of channel inactivation 1. GLRA3 is widely expressed throughout the human central nervous system and contributes to inhibitory neurotransmission 1. Disease associations include diabetic complications, where genome-wide association studies have identified GLRA3 variants as significantly associated with diabetic albuminuria in Finnish type 1 diabetes patients, particularly in those with poor glycemic control 23. Additionally, GLRA3 variants show genome-wide significant association with chr4 postsurgical pain, potentially through prostaglandin E2-mediated pain processing pathways 4. A case report describes autism in a patient with a chr4 deletion including GLRA3, suggesting potential neurodevelopmental roles 5. However, population studies found no association between GLRA3 variants and idiopathic generalized epilepsies 6. The clinical significance lies in its potential as a therapeutic target for pain management and diabetic complications, though further validation across populations is needed.

Sources cited
1
GLRA3 encodes glycine receptor alpha-3 subunit forming ligand-gated chloride channels with two splice variants differing in desensitization kinetics
PMID: 9677400
2
GLRA3 variants show genome-wide significant association with diabetic albuminuria in Finnish type 1 diabetes patients
PMID: 30120300
3
GLRA3 variants associated with urinary albumin excretion in type 1 diabetes patients
PMID: 24595857
4
GLRA3 variants show genome-wide significant association with chronic postsurgical pain
PMID: 39863470
5
Chromosomal deletion including GLRA3 reported in autism case
PMID: 15090072
6
No association found between GLRA3 variants and idiopathic generalized epilepsies
PMID: 11496371
Disease Associationsⓘ20
smoking initiationOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.32Weak
placental retentionOpen Targets
0.31Weak
frozen shoulderOpen Targets
0.30Weak
diabetes mellitusOpen Targets
0.28Weak
hematopoietic and lymphoid cell neoplasmOpen Targets
0.27Weak
pyogenic granulomaOpen Targets
0.26Weak
intracranial hemorrhageOpen Targets
0.25Weak
edemaOpen Targets
0.24Weak
brain compressionOpen Targets
0.23Weak
breast carcinomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.06Suggestive
luminal A breast carcinomaOpen Targets
0.04Suggestive
breast neoplasmOpen Targets
0.04Suggestive
estrogen-receptor positive breast cancerOpen Targets
0.04Suggestive
ovarian carcinomaOpen Targets
0.04Suggestive
endometriosisOpen Targets
0.04Suggestive
cervical carcinomaOpen Targets
0.04Suggestive
glomerulonephritisOpen Targets
0.04Suggestive
AnisometropiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
GLRBProtein interaction75%GARS1Protein interaction72%GABREShared pathway44%CLCA4Shared pathway43%CLCA2Shared pathway43%CLCN4Shared pathway43%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
2%
Lung
1%
Liver
0%
Ovary
0%
Heart
0%
Gene Interaction Network
Click a node to explore
GLRA3GLRBGARS1GABRECLCA4CLCA2CLCN4
PROTEIN STRUCTURE
Preparing viewer…
PDB9BWC · 2.19 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.24LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.78 [0.51–1.24]
RankingsWhere GLRA3 stands among ~20K protein-coding genes
  • #13,197of 20,598
    Most Researched24
  • #13,113of 17,882
    Most Constrained (LOEUF)1.24
Genes detectedGLRA3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The human glycine receptor subunit alpha3. Glra3 gene structure, chromosomal localization, and functional characterization of alternative transcripts.
PMID: 9677400
J Biol Chem · 1998
1.00
2
Genetic variation of the human glycine receptor subunit genes GLRA3 and GLRB and susceptibility to idiopathic generalized epilepsies.
PMID: 11496371
Am J Med Genet · 2001
0.90
3
Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish patients with type 1 diabetes.
PMID: 30120300
Sci Rep · 2018
0.80
4
Genome-wide association study on chronic postsurgical pain in the UK Biobank.
PMID: 39863470
Br J Anaesth · 2025
0.70
5
A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R.
PMID: 15090072
BMC Med Genet · 2004
0.60