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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GLRA1
glycine receptor alpha 1
Chromosome 5 Β· 5q33.1
NCBI Gene: 2741Ensembl: ENSG00000145888.11HGNC: HGNC:4326UniProt: P23415
145PubMed Papers
21Diseases
6Drugs
79Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
regulation of membrane potentialcellular response to amino acid stimulusintracellular membrane-bounded organelleplasma membranehereditary hyperekplexiaPaingenetic disorderFever
✦AI Summary

GLRA1 encodes the alpha-1 subunit of glycine-gated chloride channels, which play a crucial role in inhibitory neurotransmission by down-regulating neuronal excitability 1. The protein functions as a subunit of heteromeric glycine receptors that mediate chloride influx in response to glycine binding, contributing to the generation of inhibitory postsynaptic currents in the central nervous system 1. GLRA1 is most clinically significant as the primary cause of hereditary hyperekplexia, a rare neurogenetic disorder characterized by excessive startle responses, neonatal hypertonia, and generalized stiffness 12. Mutations in GLRA1 account for the majority of hyperekplexia cases, with both autosomal dominant and recessive inheritance patterns observed 13. The disorder can present as 'major' hyperekplexia with severe neonatal symptoms or 'minor' forms with milder startle phenotypes 2. Importantly, GLRA1-related hyperekplexia is not always benign, as neurodevelopmental issues including intellectual disability occur in approximately one-third of patients, with more severe outcomes observed in homozygous individuals 13. Early diagnosis is crucial as the condition can be misdiagnosed as epilepsy but requires different therapeutic approaches 3.

Sources cited
1
GLRA1 mutations cause hereditary hyperekplexia with both dominant and recessive inheritance, and neurodevelopmental issues occur in one-third of patients
PMID: 35636282
2
GLRA1 mutations cause major form hyperekplexia with excessive startle reflexes, falls, and neonatal stiffness
PMID: 16713923
3
Hyperekplexia patients show intellectual disability in 43.75% of cases and are often misdiagnosed with epilepsy
PMID: 39051604
⚠Limited data available β€” This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
hereditary hyperekplexiaOpen Targets
0.82Strong
PainOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.41Moderate
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
type 2 diabetes mellitusOpen Targets
0.32Weak
placenta praeviaOpen Targets
0.31Weak
adolescent idiopathic scoliosisOpen Targets
0.31Weak
cervical carcinomaOpen Targets
0.28Weak
ischemia reperfusion injuryOpen Targets
0.27Weak
SeizureOpen Targets
0.27Weak
skin diseaseOpen Targets
0.26Weak
brain aneurysmOpen Targets
0.26Weak
esophageal cancerOpen Targets
0.26Weak
fluoride poisoningOpen Targets
0.26Weak
Hyperekplexia 1UniProt
Pathogenic Variants79
NM_000171.4(GLRA1):c.1259G>A (p.Arg420His)Pathogenic
not provided|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2026β†’ Residue 420
NM_000171.4(GLRA1):c.839G>A (p.Arg280His)Pathogenic
Hereditary hyperekplexia|Hyperekplexia 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 280
NM_000171.4(GLRA1):c.569C>T (p.Thr190Met)Pathogenic
Hereditary hyperekplexia|not provided|Hyperekplexia 1
β˜…β˜…β˜†β˜†2025β†’ Residue 190
NM_000171.4(GLRA1):c.736C>T (p.Arg246Trp)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 246
NM_000171.4(GLRA1):c.896G>A (p.Arg299Gln)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 299
NM_000171.4(GLRA1):c.920A>G (p.Tyr307Cys)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 307
NM_000171.4(GLRA1):c.403del (p.His135fs)Pathogenic
Hyperekplexia 1|not provided|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2025β†’ Residue 135
NM_000171.4(GLRA1):c.298del (p.Arg100fs)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2024β†’ Residue 100
NM_000171.4(GLRA1):c.277C>T (p.Arg93Trp)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2024β†’ Residue 93
NM_000171.4(GLRA1):c.896G>T (p.Arg299Leu)Pathogenic
Hyperekplexia 1|Hereditary hyperekplexia|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 299
NM_000171.4(GLRA1):c.186dup (p.Pro63fs)Pathogenic
Hereditary hyperekplexia|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 63
NM_000171.4(GLRA1):c.913-1G>ALikely pathogenic
not provided|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2023
NM_000171.4(GLRA1):c.971C>A (p.Ser324Ter)Pathogenic
Hyperekplexia 1|not provided|Hereditary hyperekplexia
β˜…β˜…β˜†β˜†2022β†’ Residue 324
NM_000171.4(GLRA1):c.675C>A (p.Tyr225Ter)Pathogenic
Hyperekplexia 1
β˜…β˜…β˜†β˜†2021β†’ Residue 225
NM_000171.4(GLRA1):c.286T>A (p.Trp96Arg)Likely pathogenic
Hyperekplexia 1
β˜…β˜†β˜†β˜†2026β†’ Residue 96
NM_000171.4(GLRA1):c.338T>C (p.Leu113Pro)Likely pathogenic
Hyperekplexia 1
β˜…β˜†β˜†β˜†2026β†’ Residue 113
NM_000171.4(GLRA1):c.56+1G>TLikely pathogenic
Hereditary hyperekplexia
β˜…β˜†β˜†β˜†2025
NM_000171.4(GLRA1):c.365G>A (p.Trp122Ter)Pathogenic
Hereditary hyperekplexia
β˜…β˜†β˜†β˜†2025β†’ Residue 122
NM_000171.4(GLRA1):c.698-2delLikely pathogenic
Hereditary hyperekplexia
β˜…β˜†β˜†β˜†2025
NM_000171.4(GLRA1):c.801G>A (p.Trp267Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 267
View on ClinVar β†—
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%DPYSL5Protein interaction79%SLC6A5Protein interaction74%GARS1Protein interaction73%GLRBProtein interaction61%
Tissue Expression6 tissues
Brain
100%
Lung
29%
Ovary
29%
Liver
14%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
GLRA1GPHNARHGEF9DPYSL5SLC6A5GARS1GLRB
PROTEIN STRUCTURE
Preparing viewer…
PDB4X5T Β· 3.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.97LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.53–0.97]
RankingsWhere GLRA1 stands among ~20K protein-coding genes
  • #3,135of 20,598
    Most Researched145 Β· top quartile
  • #268of 1,025
    FDA-Approved Drug Targets6
  • #936of 5,498
    Most Pathogenic Variants79 Β· top quartile
  • #9,275of 17,882
    Most Constrained (LOEUF)0.97
Genes detectedGLRA1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Hereditary Hyperekplexia: A New Family and a Systematic Review of GLRA1 Gene-Related Phenotypes.
PMID: 35636282
Pediatr Neurol Β· 2022
1.00
2
Myoclonus.
PMID: 24092290
Continuum (Minneap Minn) Β· 2013
0.90
3
Startle syndromes.
PMID: 16713923
Lancet Neurol Β· 2006
0.80
4
Four Turkish families with hyperekplexia: A missense mutation and the exon 1-7 deletion in the GLRA1 gene.
PMID: 36434917
Parkinsonism Relat Disord Β· 2022
0.70
5
Hyperekplexia: A Single-Center Experience.
PMID: 39051604
J Child Neurol Β· 2024
0.60