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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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GLRB
glycine receptor beta
Chromosome 4 · 4q32.1
NCBI Gene: 2743Ensembl: ENSG00000109738.12HGNC: HGNC:4329UniProt: P48167
55PubMed Papers
21Diseases
6Drugs
22Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
glycine bindingchemical synaptic transmissionnervous system developmentglycine-gated chloride channel complexhyperekplexia 2hereditary hyperekplexiaPainFever
✦AI Summary

GLRB encodes the β-subunit of heteromeric glycine-gated chloride channels 1, forming the predominant glycine receptor (GlyR) population in postnatal and adult brain, brainstem, and spinal cord 1. These 2α1:3β pentameric channels mediate inhibitory neurotransmission by generating glycine-activated chloride currents that suppress neuronal excitability 1. GLRB plays a critical role in downregulating neuronal excitability and contributing to inhibitory postsynaptic current generation 2. Pathologically, GLRB mutations are the third major genetic cause of hyperekplexia, a neonatal/pediatric startle disorder characterized by excessive startle reflexes, hypertonia, and generalized stiffness 1. Recessive null mutations (nonsense, frameshifts, large deletions) and dominant missense variants cause severe phenotypes including apnea attacks, learning difficulties, and developmental delay 1. Additionally, non-coding GLRB polymorphisms (rs78726293, rs191260602, rs17035816, rs7688285) are associated with panic disorder and agoraphobia through increased startle response and fear network activation 3. Partial Glrb knockout mice exhibit agoraphobic phenotypes, supporting a mechanistic link between GLRB dysfunction and anxiety disorders 3. These variants regulate GLRB and nearby gene expression in brain tissues 4, providing a potential neurogenetic pathway linking glycinergic signaling deficits to psychiatric disease.

Sources cited
1
GLRB encodes β-subunit of heteromeric glycine receptors in 2α1:3β configuration; GLRB is third major gene for hyperekplexia with recessive and dominant mutations causing startle disorder and developmental complications
PMID: 23184146
2
GLRB contributes to generation of inhibitory postsynaptic currents
PMID: 25445488
3
GLRB non-coding polymorphisms associated with panic disorder/agoraphobia through increased startle response and fear network activation; partial Glrb knockout mice exhibit agoraphobic phenotype
PMID: 28167838
4
GLRB variants regulate GLRB gene expression and nearby genes in human brain tissues
PMID: 29042589
5
GLRB mutations identified in 14.28% of genetically confirmed neonatal hyperekplexia cases
PMID: 39223854
Disease Associationsⓘ21
hyperekplexia 2Open Targets
0.75Strong
hereditary hyperekplexiaOpen Targets
0.66Moderate
PainOpen Targets
0.55Moderate
FeverOpen Targets
0.37Weak
acute respiratory distress syndromeOpen Targets
0.35Weak
injuryOpen Targets
0.35Weak
COVID-19Open Targets
0.35Weak
cancerOpen Targets
0.35Weak
coronary artery diseaseOpen Targets
0.33Weak
respiratory failureOpen Targets
0.32Weak
placental retentionOpen Targets
0.31Weak
ischemia reperfusion injuryOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
brain aneurysmOpen Targets
0.26Weak
cerebral arterial diseaseOpen Targets
0.26Weak
esophageal cancerOpen Targets
0.26Weak
fluoride poisoningOpen Targets
0.26Weak
severe acute respiratory syndromeOpen Targets
0.26Weak
genetic disorderOpen Targets
0.19Weak
morbid obesityOpen Targets
0.18Weak
Hyperekplexia 2UniProt
Pathogenic Variants22
NM_000824.5(GLRB):c.298-1G>APathogenic
Hyperekplexia 2
★★☆☆2025
NM_000824.5(GLRB):c.610+5G>APathogenic
Hyperekplexia 2|not provided
★★☆☆2025
NM_000824.5(GLRB):c.122+1G>CLikely pathogenic
Hyperekplexia 2
★☆☆☆2025
NM_000824.5(GLRB):c.297+1G>TLikely pathogenic
Hyperekplexia 2|Gastric cancer
★☆☆☆2025
NM_000824.5(GLRB):c.1221dup (p.Val408fs)Pathogenic
Hyperekplexia 2
★☆☆☆2025→ Residue 408
NM_000824.5(GLRB):c.472del (p.Gln158fs)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 158
NM_000824.5(GLRB):c.762del (p.Cys255fs)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 255
NM_000824.5(GLRB):c.634C>T (p.Arg212Ter)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 212
NM_000824.5(GLRB):c.756C>G (p.Tyr252Ter)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 252
NM_000824.5(GLRB):c.24del (p.Phe9_Leu10insTer)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 9
NM_000824.5(GLRB):c.704del (p.Lys235fs)Pathogenic
Hyperekplexia 2
★☆☆☆2024→ Residue 235
NM_000824.5(GLRB):c.790A>T (p.Arg264Trp)Likely pathogenic
Seizure
★☆☆☆2023→ Residue 264
NM_000824.5(GLRB):c.449del (p.Ser150fs)Pathogenic
Hyperekplexia 2
★☆☆☆2023→ Residue 150
NM_000824.5(GLRB):c.84del (p.Lys31fs)Pathogenic
Hyperekplexia 2
★☆☆☆2023→ Residue 31
NM_000824.5(GLRB):c.371del (p.Gly124fs)Pathogenic
Hyperekplexia 2
★☆☆☆2022→ Residue 124
NM_000824.5(GLRB):c.618C>G (p.Tyr206Ter)Pathogenic
Hyperekplexia 2
★☆☆☆2022→ Residue 206
NM_000824.5(GLRB):c.1114C>T (p.Gln372Ter)Pathogenic
Hyperekplexia 2
★☆☆☆2020→ Residue 372
NM_000824.5(GLRB):c.122+1G>APathogenic
Hyperekplexia 2
★☆☆☆2019
NC_000004.12:g.(?_157170412)_(157170748_?)delLikely pathogenic
Hyperekplexia 2
★☆☆☆2018
NM_000824.5(GLRB):c.123-2A>GPathogenic
Hyperekplexia 2
★☆☆☆2018
View on ClinVar ↗
Drug Targets6
DESFLURANEApproved
Potassium channel subfamily K member 10 opener
ENFLURANEApproved
Potassium channel subfamily K member 10 opener
HALOTHANEApproved
Potassium channel subfamily K member 10 opener
ISOFLURANEApproved
Potassium channel subfamily K member 2 opener
METHOXYFLURANEApproved
GABA-A receptor; anion channel positive modulator
SEVOFLURANEApproved
Glycine receptor (alpha-1/beta) positive modulator
Related Genes
GPHNProtein interaction100%ARHGEF9Protein interaction90%NBEAProtein interaction78%GLRA3Protein interaction75%SLC6A5Protein interaction74%GLRA1Protein interaction61%
Tissue Expression6 tissues
Brain
100%
Heart
61%
Lung
5%
Ovary
4%
Bone Marrow
3%
Liver
3%
Gene Interaction Network
Click a node to explore
GLRBGPHNARHGEF9NBEAGLRA3SLC6A5GLRA1
PROTEIN STRUCTURE
Preparing viewer…
PDB8DN3 · 3.55 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.75LoF Tolerant
pLIⓘ
0.46Tolerant
Observed/Expected LoF0.38 [0.21–0.75]
RankingsWhere GLRB stands among ~20K protein-coding genes
  • #8,202of 20,598
    Most Researched55
  • #275of 1,025
    FDA-Approved Drug Targets6
  • #2,106of 5,498
    Most Pathogenic Variants22
  • #5,888of 17,882
    Most Constrained (LOEUF)0.75
Genes detectedGLRB
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GLRB variants regulate nearby gene expression in human brain tissues.
PMID: 29042589
Sci Rep · 2017
1.00
2
Myoclonus.
PMID: 24092290
Continuum (Minneap Minn) · 2013
0.90
3
The human glycine receptor beta subunit gene (GLRB): structure, refined chromosomal localization, and population polymorphism.
PMID: 9676428
Genomics · 1998
0.80
4
Anxiety and Startle Phenotypes in
PMID: 32848605
Front Mol Neurosci · 2020
0.70
5
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
0.60