Protein / target

Voltage-dependent calcium channel subunit alpha-2/delta-1

CACNA2D1P54289Homo sapiensSwiss-Prot
UniProt: P54289Ensembl: ENSG00000153956HGNC: HGNC:1399NCBI Gene: 781
Clinically validated
Therapeutic maturity
9
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Voltage-gated calcium channel activity

Primary system

Nervous system

Strongest disease association

developmental and epileptic encephalopathy 110

Genetic evidence · score 0.79

Therapeutic maturity

Clinically validated target

9 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

9 approved · 2 in clinical development

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

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (PubMed:35293990). Plays an important role in excitation-contraction coupling (By similarity)

Subcellular location

MembraneCell membrane
Domains and Gene Ontology detail (25)

Domains & features

VWFACache

Gene Ontology

  • Cextracellular exosome
  • CGABA-ergic synapse
  • CL-type voltage-gated calcium channel complex
  • Cneuronal dense core vesicle
  • Cplasma membrane
  • Cpresynaptic active zone membrane
  • Csarcoplasmic reticulum
  • Cvoltage-gated calcium channel complex
  • Fmetal ion binding
  • Fvoltage-gated calcium channel activity
  • Pcalcium ion import across plasma membrane
  • Pcalcium ion transmembrane transport via high voltage-gated calcium channel

1103 aa · 125 kDa · 5 isoforms

Biological roles

Reactome v97

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

Synaptic signallingGOIon channel gatingGOInhibitory neurotransmissionGO
View supporting evidence

Synaptic signalling

  • ·GABA-ergic synapse
  • ·presynaptic active zone membrane

Ion channel gating

  • ·calcium ion transmembrane transport via high voltage-gated calcium channel
  • ·regulation of calcium ion transmembrane transport via high voltage-gated calcium channel

Inhibitory neurotransmission

  • ·GABA-ergic synapse
View underlying pathways (1)
Mechanical load activates signaling by PIEZO1 and integrins in osteocytes

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.

CACNB1CACNA1SCACNA1DCACNG1CACNA1CCACNB2CACNB3CACNA1BCACNA1ECACNA1FCACNA2D1

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

1

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.

gabapentin
ApprovedModulator

Voltage-gated calcium channel modulator

Appears in clinical studies involving Seizure, epilepsy, Focal-onset seizure, restless legs syndrome

Acts on a complex — shared with CACNB4, CACNG4, CACNG3 +22 more · 1 of 26 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.

developmental and epileptic encephalopathy 1100.79

Genetic · overall 0.49

Seizure0.61

Genetic literature · overall 0.69

anxiety disorder0.04

Genetic · overall 0.58

Highest-confidence therapeutic associations

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

epilepsy1.00

Clinical · overall 0.61

neuropathic pain0.99

Clinical · overall 0.60

fibromyalgia0.99

Clinical · overall 0.60

restless legs syndrome0.97

Clinical · overall 0.59

postherpetic neuralgia0.94

Clinical · overall 0.57

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neuralgia0.56

Clinical

Focal-onset seizure0.52

Clinical

Show all associations
Seizure0.69
epilepsy0.61
neuropathic pain0.60
fibromyalgia0.60
restless legs syndrome0.59
anxiety disorder0.58
postherpetic neuralgia0.57
neuralgia0.56
Focal-onset seizure0.52
developmental and epileptic encephalopathy 1100.49

Open Targets ranks 344 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 · 12 total

ATAGABALINPhase 2

insomnia

BEPRIDILApproval

cardiovascular disorder

PHLOROGLUCINOLApproval

gastrointestinal disease · urinary system disorder · renal colic

MIROGABALIN BESYLATEApproval

neuropathic pain · diabetic neuropathy

TERODILINEApproval

Polyuria · Urinary incontinence

GABAPENTIN ENACARBILApproval

restless legs syndrome · neuralgia · Sleep disturbance

TERODILINE HYDROCHLORIDEUnknown
GABAPENTINApproval

Seizure · epilepsy · Focal-onset seizure

PREGABALINApproval

Seizure · neuropathic pain · fibromyalgia

MIROGABALINApproval

peripheral neuropathy · cancer pain · cardiovascular disorder

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Half-life DataPR · 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.

Randomized Phase III, Double-Blind, Placebo Controlled Study of Prophylactic Gabapentin for the Reduction of Radiation Therapy Induced Pain During the Treatment of Oropharyngeal Squamous Cell CarcinomaPHASE3

COMPLETED · via gabapentin · NCT03269344

Randomized, Open-Label Quality of Life Study Using Gabapentin Versus Venlafaxine in Treating Hot Flashes in Patients With Prostate CancerPHASE2

TERMINATED · via gabapentin · NCT01533753

A Comparison Between Safety and Efficacy of Theophylline, Versus Sumatriptan and Gabapentin in The Treatment of Post-Dural Puncture Headache: A Prospective Randomized Double Blinded StudyNA

RECRUITING · via gabapentin · NCT07515456

The Impact of Pre-emptive Large Doses of Methylprednisolone Combined With Gabapentin on Pain Treatment and Convalescence After Total Knee Arthroplasty in Elderly: A Double-blind Randomized StudyPHASE4

COMPLETED · via gabapentin · NCT04653415

Oral Gabapentin and Median Nerve Neural Mobilization Versus Control in the Treatment of Carpal Tunnel SyndromePHASE4

COMPLETED · via gabapentin · NCT04285281

Prevention of Persistent Pain and Opioid Use in Mothers - POMSPHASE4

COMPLETED · via gabapentin · NCT03472521

Show remaining trials (24)
A Single Preoperative Dose of Gabapentin to Decreases Postoperative Pain in Ambulatory Anal SurgeriesEARLY_PHASE1

COMPLETED · via gabapentin · NCT05533684

Pain Control With Total Knee Replacement: Does Gabapentin Affect Narcotic Usage and Functional Outcome? A Randomized Controlled Trial.PHASE4

COMPLETED · via gabapentin · NCT01680549

Gabapentin Following Arthroscopic Rotator Cuff Repair: Evaluation of Postoperative Opioid Use and Sleep QualityPHASE4

UNKNOWN · via gabapentin · NCT05800847

Gabapentin for Headache in Aneurysmal Subarachnoid HemorrhagePHASE4

COMPLETED · via gabapentin · NCT02330094

Efficacy of Gabapentin in Alcohol Dependency Treatment: a Double-blinded Randomized Placebo-controlled TrialPHASE3

COMPLETED · via gabapentin · NCT03274167

Perioperative Analgesia Using Gabapentin in Head and Neck Cancer Surgery: A Randomized Controlled TrialPHASE3

TERMINATED · via gabapentin · NCT03682367

A 4 Week, Parallel-Design, Double-Blind, Placebo-Controlled Trial of Gabapentin in the Treatment of Neuroleptic-Induced Tremor: Clinical and Instrumental Ratings of Outcome.PHASE3

TERMINATED · via gabapentin · NCT00533455

Preanalgesic Effect of Gabapentin in Total Knee RepairNA

COMPLETED · via gabapentin · NCT00279487

Study of Gabapentin for the Pruritus of CholestasisPHASE3

COMPLETED · via gabapentin · NCT00058890

Primary Prophylactic Gabapentin for Taxane-Induced Arthralgia and Myalgia Syndrome in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled TrialPHASE2/PHASE3

UNKNOWN · via gabapentin · NCT03566394

Perioperative Use of Gabapentin To Decrease Opioid Requirements in Pediatric Spinal Fusion PatientsNA

COMPLETED · via gabapentin · NCT00726999

Gabapentin to Reduce Opioid Use Postoperatively (GROUP) in ChildrenPHASE2/PHASE3

RECRUITING · via gabapentin · NCT04724252

Efficacy and Safety of Fixed-Dose Combination (FDC) Products Containing Trazodone and Gabapentin in Patients Affected by Painful Diabetic Neuropathy: Randomized, Controlled, Dose Finding Study.PHASE2

COMPLETED · via gabapentin · NCT03749642

The Use of Gabapentin for Post-Operative Pain Control and Narcotic Reduction in Scrotal SurgeryPHASE3

COMPLETED · via gabapentin · NCT04230980

Evaluation of Initiation Time on the Efficacy of Gabapentin in Treating Neuropathic Pain in Spinal Cord Injury (SCI)PHASE4

COMPLETED · via gabapentin · NCT04256603

A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study of the Pharmacokinetics (PK) and Pharmacodynamics (PD) of Gabapentin Extended Release (G-ER) Tablets in the Treatment of Vasomotor Symptoms in Postmenopausal WomenPHASE2

COMPLETED · via gabapentin · NCT00511953

Gabapentin as a Pre-emptive Analgesic in Oral and Maxillofacial Surgical ProceduresPHASE4

WITHDRAWN · via gabapentin · NCT02957097

Oral Amantadine Versus Gabapentin to Attenuate the Hemodynamic Response to Laryngoscopy and Tracheal Intubation and Their Effect on β-endorphinPHASE2/PHASE3

COMPLETED · via gabapentin · NCT03172234

Gabapentin for Perioperative Pain Relief in Surgical Abortion: a Double-blind Randomized Controlled TrialEARLY_PHASE1

COMPLETED · via gabapentin · NCT04292171

A Prospective Randomized Double Blind Trial to Assess the Effect of a Single Preoperative Dose of Gabapentin on Postoperative Opioid Consumption in Patients Undergoing RhinoplastyPHASE1

ACTIVE_NOT_RECRUITING · via gabapentin · NCT03498261

Hyperalgesia in Methadone Patients: Can it be Treated?NA

COMPLETED · via gabapentin · NCT00218374

A Phase 4, Double-Blind, Placebo-Controlled, Crossover Study Comparing Simulated Driving Performance, Daytime Sedation, and Cognition in Healthy Volunteers Taking Therapeutic Doses of Gralise®, Neurontin®, or Lyrica®PHASE4

COMPLETED · via gabapentin · NCT03179345

Optimal Multimodal Analgesia in Abdominal HysterectomyPHASE4

UNKNOWN · via gabapentin · NCT00209872

Effect of a Multimodal Pain Regimen on Pain Control, Patient Satisfaction and Narcotic Use in Orthopaedic Trauma PatientsPHASE4

WITHDRAWN · via gabapentin · NCT02160301

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.

SeizureWell supported
0.87
agreement 0.76–0.98
Clinical60%Genetic literature40%

Open Targets aggregate 0.69 · 2 independent evidence families

developmental and epileptic encephalopathy 110Well supported
0.82
agreement 0.69–0.94
Genetic89%Animal model11%Genetic literaturedup

Open Targets aggregate 0.49 · 2 independent evidence families · 1 not counted as duplicate

epilepsyWell supported
0.75
agreement 0.60–0.91
Clinical98%Literature2%

Open Targets aggregate 0.61 · 2 independent evidence families

neuropathic painModerately supported
0.74
agreement 0.59–0.90
Clinical100%Literature0%

Open Targets aggregate 0.60 · 2 independent evidence families

fibromyalgiaModerately supported
0.74
agreement 0.58–0.91
Clinical100%

Open Targets aggregate 0.60 · 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

30

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

  1. Label change2026-07-22

    Label change: GABAPENTIN (ANDA217995)

    fda · regulatory · fda · via gabapentin

  2. Label change2026-07-17

    Label change: GABAPENTIN (ANDA203934)

    fda · regulatory · fda · via gabapentin

  3. Label change2026-07-16

    Label change: GABAPENTIN (ANDA075428)

    fda · regulatory · fda · via gabapentin

  4. Label change2026-06-25

    Label change: GABAPENTIN (ANDA077661)

    fda · regulatory · fda · via gabapentin

  5. Regulatory approval2026-06-23

    Approval: GABAPENTIN (ANDA203611)

    fda · regulatory · fda · via gabapentin

  6. Label change2024-12-27

    Label change: GABAPENTIN (ANDA217995)

    fda · regulatory · fda · via gabapentin

  7. Label change2024-12-16

    Label change: GABAPENTIN (ANDA075428)

    fda · regulatory · fda · via gabapentin

  8. Label change2024-07-08

    Label change: GABAPENTIN (ANDA075428)

    fda · regulatory · fda · via gabapentin

  9. Label change2024-07-08

    Label change: GABAPENTIN (ANDA075428)

    fda · regulatory · fda · via gabapentin

  10. Regulatory approval2024-01-24

    Approval: GABAPENTIN (ANDA203934)

    fda · regulatory · fda · via gabapentin

  11. Label change2023-09-21

    Label change: GABAPENTIN (ANDA077661)

    fda · regulatory · fda · via gabapentin

  12. Label change2023-09-21

    Label change: GABAPENTIN (ANDA077661)

    fda · regulatory · fda · via gabapentin

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.