Protein / target

Voltage-dependent L-type calcium channel subunit alpha-1S

CACNA1SQ13698Homo sapiensSwiss-Prot
UniProt: Q13698Ensembl: ENSG00000081248HGNC: HGNC:1397NCBI Gene: 779
Clinically validated
Therapeutic maturity
36
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

High voltage-gated calcium channel activity

Primary system

Musculoskeletal system

Strongest disease association

hypokalemic periodic paralysis, type 1

Genetic evidence · score 0.93

Therapeutic maturity

Clinically validated target

36 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

36 approved · 4 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

Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group

Subcellular location

Cell membrane, sarcolemma, T-tubule
Domains and Gene Ontology detail (20)

Gene Ontology

  • Ccytoplasm
  • CI band
  • CL-type voltage-gated calcium channel complex
  • Cplasma membrane
  • Csarcoplasmic reticulum
  • CT-tubule
  • Cvoltage-gated calcium channel complex
  • Fcalmodulin binding
  • Fhigh voltage-gated calcium channel activity
  • Fmetal ion binding
  • Fmolecular function activator activity
  • Fsmall molecule binding

1873 aa · 212 kDa

Biological roles

Reactome v97

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

Muscle contractionUniProt · GOIon channel gatingGO
View supporting evidence

Muscle contraction

  • ·Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L…
  • ·muscle contraction
  • ·positive regulation of muscle contraction

Ion channel gating

  • ·calcium ion transmembrane transport
View underlying pathways (1)
NCAM1 interactions

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.

CACNA2…CACNG1RYR1CACNB1CALM3CACNA1FCACNB2CACNA1CCACNA1DSTAC3CACNA1S

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

2

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.

Nimodipine
ApprovedBlocker

Voltage-gated L-type calcium channel blocker

Appears in clinical studies involving cardiovascular disorder, subarachnoid hemorrhage, cocaine dependence, Mental deterioration

Acts on a complex — shared with CACNA1D, CACNA1F, CACNA1C · 1 of 5 recorded protein targets

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.

hypokalemic periodic paralysis, type 10.93

Genetic · overall 0.78

congenital myopathy 180.92

Genetic · overall 0.76

malignant hyperthermia of anesthesia0.72

Genetic literature · overall 0.62

Highest-confidence therapeutic associations

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

hypertensive disorder1.00

Clinical · overall 0.61

epilepsy1.00

Clinical · overall 0.61

coronary artery disorder0.99

Clinical · overall 0.60

Prinzmetal angina0.99

Clinical · overall 0.60

Hypertension0.99

Clinical · overall 0.60

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

neuropathic pain0.60

Clinical

fibromyalgia0.60

Clinical

Show all associations
hypokalemic periodic paralysis, type 10.78
congenital myopathy 180.76
malignant hyperthermia of anesthesia0.62
hypertensive disorder0.61
epilepsy0.61
Hypertension0.60
coronary artery disorder0.60
Prinzmetal angina0.60
neuropathic pain0.60
fibromyalgia0.60

Open Targets ranks 3,932 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 · 41 total

AMLODIPINE BENZOATEApproval

hypertensive disorder

MANIDIPINE 6300Approval

cardiovascular disorder · hypertensive disorder · aortic valve calcification

DILTIAZEMApproval

hemorrhoid · cardiovascular disorder · Hypertension

CLEVIDIPINEApproval

cardiovascular disorder · Hypertension · hypertensive disorder

LERCANIDIPINEApproval

cardiovascular disorder · Hypertension · essential hypertension

BEPRIDILApproval

cardiovascular disorder

IMAGABALINPhase 3

generalized anxiety disorder

LEVAMLODIPINEApproval

cardiovascular disorder · Hypertension · essential hypertension

AMLODIPINEApproval

cardiovascular disorder · Hypertension · Stroke

SULOCTIDILApproval

cardiovascular disorder

Tractability

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

Safety liabilities

Malignant Hyperthermiamalignant hyperthermia

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

A Randomized, Open-label, Single Dose, Two Formulation, Two Period, Double Cross Over Bioavailability Comparison Study of Two Types of Nimodipine Injections in Healthy VolunteersEARLY_PHASE1

UNKNOWN · via Nimodipine · NCT03794843

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

Show remaining trials (24)
Prevention of Persistent Pain and Opioid Use in Mothers - POMSPHASE4

COMPLETED · via gabapentin · NCT03472521

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

RCVS: The Rational Approach to Diagnosis and TreatmentPHASE4

WITHDRAWN · via Nimodipine · NCT03150524

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

High Dose Nimodipine Pharmacotherapy AdjunctPHASE2

COMPLETED · via Nimodipine · NCT00000332

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

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.

hypokalemic periodic paralysis, type 1Well supported
0.95
agreement 0.83–1.00
Genetic82%Animal model18%Literature1%Genetic literaturedup

Open Targets aggregate 0.78 · 3 independent evidence families · 1 not counted as duplicate

congenital myopathy 18Well supported
0.93
agreement 0.81–1.00
Genetic82%Animal model18%Genetic literaturedup

Open Targets aggregate 0.76 · 2 independent evidence families · 1 not counted as duplicate

hypertensive disorderWell supported
0.75
agreement 0.59–0.91
Clinical99%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

epilepsyModerately supported
0.75
agreement 0.59–0.90
Clinical99%Literature1%

Open Targets aggregate 0.61 · 2 independent evidence families

HypertensionModerately supported
0.75
agreement 0.59–0.90
Clinical99%Literature1%

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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

32

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target 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.