Protein / target

Glycine receptor subunit alpha-1

GLRA1P23415Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
6
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Glycine-gated chloride channel activity

Primary system

Nervous system

Strongest disease association

hereditary hyperekplexia

Genetic evidence · score 0.93

Therapeutic maturity

Clinically validated target

6 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

6 approved

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Subunit of heteromeric glycine-gated chloride channels (PubMed:14551753, PubMed:23994010, PubMed:25730860, PubMed:37821459). Plays an important role in the down-regulation of neuronal excitability (PubMed:8298642, PubMed:9009272). Contributes to the generation of inhibitory postsynaptic currents (PubMed:25445488). Channel activity is potentiated by ethanol (PubMed:25973519). Potentiation of channel activity by intoxicating levels of ethanol contribute to the sedative effects of ethanol (By similarity)

Subcellular location

Postsynaptic cell membraneSynapsePerikaryonCell projection, dendriteCell membrane
Domains and Gene Ontology detail (37)

Gene Ontology

  • Cchloride channel complex
  • Cdendrite
  • Cexternal side of plasma membrane
  • Cglycinergic synapse
  • Cinhibitory synapse
  • Cintracellular membrane-bounded organelle
  • Cmembrane
  • Cneuron projection
  • Cneuronal cell body
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic membrane

457 aa · 53 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Synaptic signallingUniProt · GO · ReactomeInhibitory neurotransmissionUniProt · GOChloride transportUniProt · GOIon channel gatingGOLigand-gated signallingGOMuscle contractionGO
View supporting evidence

Synaptic signalling

  • ·Subunit of heteromeric glycine-gated chloride channels (PubMed:14551753, PubMed:23994010…
  • ·Postsynaptic cell membrane
  • ·Synapse
  • ·glycinergic synapse

Inhibitory neurotransmission

  • ·Subunit of heteromeric glycine-gated chloride channels (PubMed:14551753, PubMed:23994010…
  • ·glycinergic synapse
  • ·inhibitory synapse
  • ·inhibitory postsynaptic potential

Chloride transport

  • ·Subunit of heteromeric glycine-gated chloride channels (PubMed:14551753, PubMed:23994010…
  • ·chloride channel complex
  • ·extracellularly glycine-gated chloride channel activity
  • ·chloride transport

Ion channel gating

  • ·excitatory extracellular ligand-gated monoatomic ion channel activity
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ligand-gated signalling

  • ·excitatory extracellular ligand-gated monoatomic ion channel activity
  • ·ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membr…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Muscle contraction

  • ·muscle contraction
View underlying pathways (1)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

SLC6A5GPHNARHGEF9GLRBGLRA4DPYSL5GARS1AMPHGAD2IL12AGLRA1

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

3

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

Isoflurane
ApprovedPositive modulator

Glycine receptor (alpha-1/beta) positive modulator

Appears in clinical studies involving kidney injury, Hydrocephalus, delirium, sedation

Acts on a complex — shared with GLRB · 1 of 23 recorded protein targets — broad pharmacology

Halothane
ApprovedPositive modulator

Glycine receptor (alpha-1/beta) positive modulator

Appears in clinical studies involving septic shock, Sepsis

Acts on a complex — shared with GLRB · 1 of 23 recorded protein targets — broad pharmacology

sevoflurane
ApprovedPositive modulator

Glycine receptor (alpha-1/beta) positive modulator

Appears in clinical studies involving endometrial cancer, myocardial infarction, sedation, delirium

Acts on a complex — shared with GLRB · 1 of 23 recorded protein targets — broad pharmacology

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

hereditary hyperekplexia0.93

Genetic · overall 0.83

hereditary disease0.68

Genetic · overall 0.41

type 2 diabetes mellitus0.50

Genetic · overall 0.31

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

Pain0.90

Clinical · overall 0.55

sedation0.62

Clinical · overall 0.38

acute respiratory distress syndrome0.62

Clinical · overall 0.38

Fever0.61

Clinical · overall 0.37

delirium0.61

Clinical · overall 0.37

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

aortic valve disorder0.32

Clinical

mitral valve disorder0.32

Clinical

Show all associations
hereditary hyperekplexia0.83
Pain0.55
hereditary disease0.41
sedation0.38
acute respiratory distress syndrome0.38
Fever0.37
delirium0.37
aortic valve disorder0.32
mitral valve disorder0.32
type 2 diabetes mellitus0.31

Open Targets ranks 2,235 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 6 total

ISOFLURANEApproval

kidney injury · Hydrocephalus · delirium

METHOXYFLURANEApproval

Fever · Pain · Pain

ENFLURANEApproval

septic shock · Sepsis

DESFLURANEApproval

Intellectual disability · cognitive disorder · delirium

SEVOFLURANEApproval

endometrial cancer · myocardial infarction · sedation

HALOTHANEApproval

septic shock · Sepsis

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

WITHDRAWN · via sevoflurane · NCT00531349

COMPLETED · via sevoflurane · NCT01851005

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

hereditary hyperekplexiaWell supported
0.95
agreement 0.831.00
Genetic78%Animal model20%Literature2%Genetic literaturedup

Open Targets aggregate 0.83 · 3 independent evidence families · 1 not counted as duplicate

hereditary diseaseModerately supported
0.68
agreement 0.540.82
Genetic99%Literature1%

Open Targets aggregate 0.41 · 2 independent evidence families

PainModerately supported
0.67
agreement 0.510.84
Clinical100%

Open Targets aggregate 0.55 · 1 independent evidence family

type 2 diabetes mellitusModerately supported
0.51
agreement 0.370.65
Genetic97%Literature3%

Open Targets aggregate 0.31 · 2 independent evidence families

sedationLimited support
0.47
agreement 0.300.63
Clinical100%

Open Targets aggregate 0.38 · 1 independent evidence family

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

3

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2025-02-08
    Neonatal sevoflurane exposures inhibits DHHC5-mediated palmitoylation of TfR1 in oligodendrocytes, leading to hypomyelination and neurological impairments.

    Journal of advanced research · 2025 · 9 citations · Europe PMC · via sevoflurane

  2. New publication2003-02-01
    Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 2003 · 1,387 citations · Europe PMC · via Isoflurane

  3. New publication1995-01-01
    Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 1995 · 798 citations · Europe PMC · via Halothane

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.