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Protein / target

Gamma-aminobutyric acid receptor subunit alpha-6

Encoded byGABRA6Q16445Homo sapiensSwiss-Prot
UniProt: Q16445Ensembl: ENSG00000145863HGNC: HGNC:4080NCBI Gene: 2559
Clinically validated
Therapeutic maturity
58
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

GABA-gated chloride ion channel

Strongest disease association

Sleep Initiation and Maintenance Disorders

Via encoding gene GABRA6 · Genetic evidence · score 0.08

Therapeutic position

Established drug target

Small molecules

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 overview

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain.

View complete UniProt function annotation

Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:8632757). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interface(s) (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). Alpha-6/GABRA6 subunits are found at both synaptic and extrasynaptic sites (PubMed:8632757). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). Extrasynaptic alpha-6-containing receptors contribute to the tonic GABAergic inhibition. Alpha-6 subunits are also present on glutamatergic synapses (By similarity)

Subcellular location

Postsynaptic cell membraneCell membrane
Domains and Gene Ontology detail (17)

Gene Ontology

  • Ccerebellar Golgi cell to granule cell synapse
  • Cchloride channel complex
  • Cdendrite membrane
  • CGABA-A receptor complex
  • Cplasma membrane
  • Cpostsynapse
  • Cpostsynaptic specialization membrane
  • Fbenzodiazepine receptor activity
  • FGABA-A receptor activity
  • FGABA-gated chloride ion channel activity
  • Ftransmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
  • Pchloride transmembrane transport

453 aa · 51 kDa

Biological roles

Reactome v97

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

Inhibitory neurotransmissionUniProt · GOChloride transportUniProt · GOLigand-gated signallingUniProt · GOIon channel gatingGOExcitatory neurotransmissionUniProt
View supporting evidence

Inhibitory neurotransmission

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
  • ·inhibitory synapse assembly
  • ·synaptic transmission, GABAergic

Chloride transport

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
  • ·chloride channel complex
  • ·GABA-gated chloride ion channel activity

Ligand-gated signalling

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Ion channel gating

  • ·GABA-gated chloride ion channel activity
  • ·transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic…

Excitatory neurotransmission

  • ·Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-amino…
View underlying pathways (1)
GABA receptor activation

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.

PLCL1NSFHAP1TRAK2GABRA1GABRB3GABRDGABRB2GABARAPGABBR2GABRA6

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.

Approved medicines with mapped indications

9 medicines · 6 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Epilepsy5 medicines
cenobamateclonazepamganaxoloneMidazolamtopiramate
Seizures5 medicines
cenobamateclobazamclonazepamganaxolonetopiramate
Anxiety Disorders3 medicines
alprazolamlorazepammeprobamate
Status Epilepticus2 medicines
lorazepamMidazolam
Epileptic Syndromes1 medicine
ganaxolone
Migraine Disorders1 medicine
topiramate

58 medicines meet Open Targets' target-level approved-medicine definition; the 9 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

13

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Midazolam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

Isoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

Halothane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

sevoflurane
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 23 recorded protein targets — broad pharmacology

propofol
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

clobazam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

View all 13 targeting drugs
clonazepam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

lorazepam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders, Status Epilepticus

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

meprobamate
ApprovedAgonist

GABA-A receptor; anion channel agonist

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

topiramate
ApprovedPositive modulator

GABA-A receptor; anion channel positive modulator

Indicated for Epilepsy, Migraine Disorders, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 37 recorded protein targets — broad pharmacology

cenobamate
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 26 recorded protein targets — broad pharmacology

ganaxolone
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Epilepsy, Epileptic Syndromes, Seizures

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

alprazolam
ApprovedPositive allosteric modulator

GABA-A receptor; anion channel positive allosteric modulator

Indicated for Anxiety Disorders

Acts on a complex — shared with GABRG2, GABRB3, GABRG3 +12 more · 1 of 16 recorded protein targets — broad pharmacology

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GABRA6

Gene-level evidence surfaced through the gene GABRA6that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Sleep Initiation and Maintenance Disorders
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Epilepsy
0.76Well supported

Clinical evidence dominant · Open Targets 0.62

Major depressive disorder
0.76Well supported

Clinical evidence dominant · Open Targets 0.61

Panic disorder
0.75Moderately supported

Clinical evidence dominant · Open Targets 0.60

Anxiety Disorders
0.74Moderately supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Sleep Initiation and Maintenance DisordersWell supported
0.77
agreement 0.66–0.88
Clinical89%Genetic10%Literature1%

Open Targets aggregate 0.62 · 3 independent evidence families

EpilepsyWell supported
0.76
agreement 0.61–0.92
Clinical93%Literature7%

Open Targets aggregate 0.62 · 2 independent evidence families

Major depressive disorderWell supported
0.76
agreement 0.60–0.91
Clinical94%Literature6%

Open Targets aggregate 0.61 · 2 independent evidence families

Panic disorderModerately supported
0.75
agreement 0.59–0.90
Clinical99%Literature1%

Open Targets aggregate 0.60 · 2 independent evidence families

Anxiety DisordersModerately supported
0.74
agreement 0.59–0.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Sleep Initiation and Maintenance Disorders0.62
Epilepsy0.62
Major depressive disorder0.61
Panic disorder0.60
Anxiety Disorders0.60
Alcoholism0.59

Drug development

72 compounds recorded · 58 approved · 9 in clinical development · 5 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 13 drugs that target this protein in Forefront's canonical graph (9 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ZURANOLONEApproval
THIOPENTAL SODIUMPhase 1
CIPEPOFOLPhase 3
CHLORDIAZEPOXIDEApproval
FLUNITRAZEPAMApproval
MEPROBAMATEApproval
BUTABARBITALApproval
CLORAZEPATE DIPOTASSIUMApproval
ZOPICLONEApproval
SECOBARBITAL SODIUMUnknown

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Approved Drug and High-Quality Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (go cc high conf and uniprot loc med conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

decreased cardiac contractilityLynch et al. (2017)decreased memoryLynch et al. (2017)decreased convulsionsLynch et al. (2017)decreased locomotor activityLynch et al. (2017)increased sleepLynch et al. (2017)increased eatingLynch et al. (2017)increased respiratory rateLynch et al. (2017)decreased sleepLynch et al. (2017)muscle relaxationLynch et al. (2017)decreased body temperatureLynch et al. (2017)decreased painLynch et al. (2017)decreased blood pressureLynch et al. (2017)

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

Comparison of Hemodynamics and Respiratory Function Between Ciprofol and Propofol in Elderly Patients Undergoing Non-intubated General AnesthesiaPHASE4

NOT_YET_RECRUITING · via propofol · NCT07670923

Intravenous Acetaminophen and Ketorolac for Pain Management During Extracorporeal Shockwave Lithotripsy: A Quasi-Randomized Controlled TrialPHASE4

ENROLLING_BY_INVITATION · via Midazolam · NCT07368738

Management of Acute Tinnitus With Migraine Medications: A Randomized Clinical TrialPHASE4

ACTIVE_NOT_RECRUITING · via topiramate · NCT06799169

Effect of Volatile-based Versus Total Intravenous Anesthesia on Cerebral Homeostasis and Neucognitive Function in Patients Undergoing Elective Craniotomy for Brain Tumor Excision.PHASE4

RECRUITING · via sevoflurane · NCT06779890

View all trials (26)
Pain, Anxiety and Anesthetic Satisfaction for Patient With Different State Anxiety Underwent Cataract Surgery With Topical Anesthesia. An Extension Test of Whether to Use Oral Anti-anxiety Drugs (Alprazolam) When Patients Choose Second Eye Cataract Surgery After Unblinding, and Analyze Their Anxiety, Satisfaction and Pain Satisfaction.PHASE4

RECRUITING · via alprazolam · NCT06874452

A Phase 2, Multicenter Open-Label Extension Study to Evaluate the Long-term Safety of Cenobamate in Japanese Subjects With Partial Onset SeizuresPHASE2

RECRUITING · via cenobamate · NCT06590896

Leveraging Biomarkers for Personalized Treatment of Alcohol Use Disorder Comorbid With Post Traumatic Stress DisorderPHASE2

RECRUITING · via topiramate · NCT03667846

Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of BI 3031185 in Japanese Healthy Male Trial Participants (Single-blind, Randomised, Placebo-controlled, Parallel Group Design) and Effect of Multiple Doses of BI 3031185 on Pharmacokinetics of a Single Dose of a Combination of Drospirenone and Ethinylestradiol (Oral Contraceptive) in Japanese Healthy Female Trial Participants (Non-randomised, Open-label, Fixed Sequence Design)PHASE1

NOT_YET_RECRUITING · via Midazolam · NCT07656792

An Open-label, Single-arm, Fixed-sequence Phase I Clinical Trial to Evaluate the Effect of HRS-1301 Tablets on the Pharmacokinetics of Midazolam and Atorvastatin Calcium Tablets in Healthy ParticipantsPHASE1

RECRUITING · via Midazolam · NCT07608705

AN OPEN-LABEL PHASE 1 STUDY TO EVALUATE PF-07994525 IN PARTICIPANTS WITH ADVANCED MALIGNANCIESPHASE1

RECRUITING · via Midazolam · NCT07426757

A Multi-part, Phase 1, First-Time-in-Human Study to Investigate Safety, Tolerability, and PK of VH4770359 in Healthy ParticipantsPHASE1

NOT_YET_RECRUITING · via Midazolam · NCT07525544

A Phase I, Single-center, Open-Label, Single-Arm, Fixed-Sequence Study to Evaluate the Drug-Drug Interaction of HDM1002 and Metformin, Empagliflozin, Midazolam, Valsartan, and Warfarin in Overweight/Obese Adult Chinese SubjectsPHASE1

RECRUITING · via Midazolam · NCT07331389

A Randomized, Parallel, Open-label With Blinded Assessment Study Comparing Hemodynamic Profiles Between Remimazolam- and Propofol-based Total Intravenous Anesthesia in Patients Undergoing Robot-assisted Gynecologic SurgeryNA

NOT_YET_RECRUITING · via propofol · NCT07251101

Clinical and Molecular Mechanism Study of Remimazolam Regulating the N/OFQ-inflammation-immune Axis to Optimize the Effect of General Anesthesia in Gynecological SurgeryNA

NOT_YET_RECRUITING · via propofol · NCT06990763

Effects of an Opioid Sparing Care Pathway for Patients Undergoing Obesity SurgeryNA

RECRUITING · via propofol · NCT03756961

The Effect of Sevoflurane and Desflurane Anesthetic Agents Used in Elective Cholecystectomy Surgery on Heme Oxygenase-1 mRNA Expression and Heme Oxygenase-1 Protein Levels: A Comparative Prospective StudyPHASE4

WITHDRAWN · via sevoflurane · NCT06457958

A Multicenter Open Study of the Efficacy of Mianserin in Combination With SSRIs in Patients With Depression With Sleep ProblemsPHASE4

UNKNOWN · via lorazepam · NCT05599126

Comparison of the Use of Propofol and Nasal Dexmedetomidine in the Management of Agitation and Delirium in Patients Undergoing Dental ProceduresPHASE4

COMPLETED · via propofol · NCT06466915

Clinical Study on Sedative Effect and Safety of Remimazolam Besylate in ARDS Patients With Mechanical VentilationPHASE4

UNKNOWN · via Midazolam · NCT05758597

Cerebral Hemodynamic and Metabolic Responses to Anesthesia and Vasopressors in Adult Surgery: A 2x2 Factorial Design Randomized Controlled Trial With Light-based Neuromonitoring (CHEM-FACT Study)PHASE4

UNKNOWN · via propofol · NCT05941494

The Efficacy and Safety of First-Line Anti-Epileptic Drugs (AEDs) as Substitution Therapy in Children Who Are Resistant to Second-Line AEDsPHASE4

UNKNOWN · via clobazam · NCT05697614

Zolmitriptane as Prophylactic Therapy Childhood MigrainePHASE4

UNKNOWN · via topiramate · NCT06089356

Hemodynamic Effects of Ketamine Compared With Propofol as Continuous ICU Sedation in Mechanically Ventilated PatientsPHASE4

COMPLETED · via propofol · NCT06243822

The Effect Of Adding Ketamine to Propofol For Drug-induced Sleep Endoscopy in Adult Patients With Obstructive Sleep Apnea A Randomized Controlled StudyPHASE4

UNKNOWN · via propofol · NCT04452383

DExmEdetomidine Sedation Versus Propofol SEDATION FOR Catheter ABLATION of Atrial Fibrillation Under a Cardiologist Supervision: A Randomized Controlled Pilot STUDYPHASE4

COMPLETED · via propofol · NCT03844841

Comparison of Procedural Sedation With Propofol and Dexmedetomidine During Transcatheter Aortic Valve Implantation Using the Transfemoral Approach: Randomized Double Blind Prospective StudyPHASE4

COMPLETED · via propofol · NCT03747432

Delirium Reduction by Volatile Anesthesia in Cardiac Surgery: Prospective, Randomized, Single-blinded StudyPHASE4

COMPLETED · via propofol · NCT03729011

Ketamine Co-induction for Patients With Major Depressive Disorder; a Randomized Clinical TrialPHASE4

UNKNOWN · via propofol · NCT03666494

Determination of Dose-response Curves Between Propofol Concentration and Intraoperative Electroencephalographic Patterns Until Burst SuppressionPHASE4

COMPLETED · via propofol · NCT04345926

Evaluation of Automated Delivery of Propofol Using Closed-Loop Anaesthesia Delivery System in Patients Undergoing Thoracic Surgery: A Randomised Controlled StudyPHASE4

COMPLETED · via propofol · NCT03307551

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 7 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-08-13

    NMDAR Modulation As a Therapeutic Target and Probe of Neural Dysfunction in OCD

    Status changed to Completed · ClinicalTrials.gov · via Midazolam

  2. Regulatory approval2026-07-22

    Approval: TOPIRAMATE (ANDA220943)

    fda · regulatory · fda · via topiramate

  3. Trial status changed2026-07-22

    A Phase 1, 3-part, Open-label Study to Evaluate the Effects of KarXT Administration on the Pharmacokinetics of Midazolam, Fexofenadine, and Digoxin in Healthy Adult Participants

    Status changed to Completed · ClinicalTrials.gov · via Midazolam

  4. Trial status changed2026-07-20

    A Phase 1 Study to Evaluate the Effect of Multiple Doses of ABBV-722 on the Pharmacokinetics of Cocktail Probe Substrates of CYP3A and Select Transporters in Healthy Adult Subjects

    Status changed to Active, not recruiting · ClinicalTrials.gov · via Midazolam

  5. Regulatory approval2026-07-14

    Approval: PROPOFOL (ANDA220857)

    fda · regulatory · fda · via propofol

  6. Regulatory approval2026-07-13

    Approval: ALPRAZOLAM (ANDA213204)

    fda · regulatory · fda · via alprazolam

  7. Trial status changed2026-07-13

    Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder

    Status changed to Completed · ClinicalTrials.gov · via lorazepam

  8. Product recall2026-07-06

    Recall (Class III): TOPIRAMATE

    fda · safety · fda · via topiramate

  9. Supplemental approval2026-06-29

    Supplemental approval: PHENTERMINE AND TOPIRAMATE (NDA022580)

    fda · regulatory · fda · via topiramate

  10. 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

  11. Product recall2024-11-18

    Recall (Class I): CLONAZEPAM

    fda · safety · fda · via clonazepam

  12. Safety communication2024-06-20

    Drug Safety Update: Topiramate (Topamax): introduction of new safety measures, including a Pregnancy Prevention Programme

    mhra · safety · mhra · via topiramate

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.