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Protein / target

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

Encoded byCACNA1CQ13936Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
36
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

High voltage-gated calcium channel

Strongest disease association

long QT syndrome 8

Via encoding gene CACNA1C · Genetic literature evidence · score 0.95

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

Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents.

View complete UniProt function annotation

Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:12181424, PubMed:15454078, PubMed:15863612, PubMed:16299511, PubMed:17224476, PubMed:20953164, PubMed:23677916, PubMed:24728418, PubMed:26253506, PubMed:27218670, PubMed:29078335, PubMed:29742403, PubMed:30023270, PubMed:30172029, PubMed:34163037, PubMed:8099908). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation-contraction coupling in the heart. Required for normal heart development and normal regulation of heart rhythm (PubMed:15454078, PubMed:15863612, PubMed:17224476, PubMed:24728418, PubMed:26253506). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (PubMed:28119464). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable)

Subcellular location

Cell membraneCell membrane, sarcolemmaPerikaryonPostsynaptic density membraneCell projection, dendriteCell membrane, sarcolemma, T-tubule
Domains and Gene Ontology detail (37)

Gene Ontology

  • Ccytoplasm
  • Cdendrite
  • CL-type voltage-gated calcium channel complex
  • Cmembrane
  • Cperikaryon
  • Cplasma membrane
  • Cpostsynaptic density
  • Cpostsynaptic density membrane
  • Cvoltage-gated calcium channel complex
  • CZ disc
  • Falpha-actinin binding
  • Fcalmodulin binding

2221 aa · 249 kDa · 37 isoforms

Biological roles

Reactome v97

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

Ion channel gatingGOMuscle contractionGO
View supporting evidence

Ion channel gating

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

Muscle contraction

  • ·positive regulation of muscle contraction
  • ·regulation of cardiac muscle contraction by regulation of the release of sequestered cal…
View underlying pathways (5)

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.

CALML3CALML6CACNB2CALML5CALM3CALML4CACNA2…CACNB3CACNB1CACNA2…CACNA1C

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

3 medicines · 9 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.

Epilepsy2 medicines
Seizures2 medicines
Anxiety Disorders1 medicine
Fibromyalgia1 medicine
Neuralgia1 medicine
Neuralgia, Postherpetic1 medicine
Restless Legs Syndrome1 medicine
Spinal Cord Injuries1 medicine
Cardiovascular Diseases1 medicine

36 medicines meet Open Targets' target-level approved-medicine definition; the 3 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

3

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.

Nimodipine
ApprovedBlocker

Voltage-gated L-type calcium channel blocker

Indicated for Cardiovascular Diseases

Acts on a complex — shared with CACNA1S, CACNA1D, CACNA1F · 1 of 5 recorded protein targets

gabapentin
ApprovedModulator

Voltage-gated calcium channel modulator

Indicated for Epilepsy, Neuralgia, Postherpetic, Restless Legs Syndrome, Seizures

Acts on a complex — shared with CACNB4, CACNG4, CACNG3 +22 more · 1 of 26 recorded protein targets — broad pharmacology

pregabalin
ApprovedModulator

Voltage-gated calcium channel modulator

Indicated for Anxiety Disorders, Epilepsy, Fibromyalgia, Neuralgia

Acts on a complex — shared with CACNB4, CACNG4, CACNG3 +22 more · 1 of 26 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 CACNA1C

Gene-level evidence surfaced through the gene CACNA1Cthat 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.

Timothy syndrome
0.93Well supported

Genetic evidence dominant · Open Targets 0.82

long QT syndrome 8
0.93Well supported

Genetic evidence dominant · Open Targets 0.72

Hypertension
0.92Well supported

Clinical evidence dominant · Open Targets 0.72

acquired long QT syndrome
0.92Well supported

Genetic evidence dominant · Open Targets 0.65

Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
0.87Well supported

Genetic evidence dominant · Open Targets 0.70

View evidence synthesis (5)
Timothy syndromeWell supported
0.93
agreement 0.811.00
Genetic83%Animal model10%Literature7%Genetic literaturedup

Open Targets aggregate 0.82 · 3 independent evidence families · 1 not counted as duplicate

long QT syndrome 8Well supported
0.93
agreement 0.811.00
Genetic81%Animal model18%Literature2%Genetic literaturedup

Open Targets aggregate 0.72 · 3 independent evidence families · 1 not counted as duplicate

HypertensionWell supported
0.92
agreement 0.821.00
Clinical50%Genetic45%Literature5%

Open Targets aggregate 0.72 · 3 independent evidence families

acquired long QT syndromeWell supported
0.92
agreement 0.801.00
Genetic100%Genetic literaturedup

Open Targets aggregate 0.65 · 1 independent evidence family · 1 not counted as duplicate

Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizuresWell supported
0.87
agreement 0.750.99
Genetic100%Genetic literaturedup

Open Targets aggregate 0.70 · 1 independent evidence family · 1 not counted as duplicate

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
Timothy syndrome0.82
long QT syndrome 80.72
Hypertension0.72
Brugada syndrome 30.72
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures0.70
Brugada syndrome0.67
acquired long QT syndrome0.65
Epilepsy0.64
Diabetes Mellitus0.62

Drug development

41 compounds recorded · 36 approved · 4 in clinical development · 1 earlier-stage

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
NILVADIPINEApproval
MANIDIPINE 6300Approval
BARNIDIPINEApproval
NITRENDIPINEApproval
NICARDIPINE HYDROCHLORIDEApproval
IMAGABALINPhase 3
NICARDIPINEApproval
DRONEDARONEApproval
AMLODIPINE BESYLATEApproval
NIFEDIPINEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

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

View underlying tractability evidence (10)
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 · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

adverse eventsClinPGxincreased mortality of heart failure patientsUrban et al. (2012)fluid buildup in the legsUrban et al. (2012)dizzinessUrban et al. (2012)alcohol dependenceClinPGxhypotensionUrban et al. (2012)increased convulsionsLynch et al. (2017)induction of seizuresUrban et al. (2012)decreased/increased convulsionsLynch et al. (2017)increased PR intervalLynch et al. (2017)decreased blood pressureBowes et al. (2012)effect on heart rateUrban et al. (2012)

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.

View all trials (26)

ACTIVE_NOT_RECRUITING · via gabapentin · NCT05921604

RECRUITING · via gabapentin · NCT04724252

COMPLETED · via gabapentin · NCT05063656

COMPLETED · via gabapentin · NCT03472521

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 3 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. 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 change2026-07-17

    Label change: PREGABALIN (ANDA211687)

    fda · regulatory · fda · via pregabalin

  4. Regulatory approval2026-06-23

    Approval: GABAPENTIN (ANDA203611)

    fda · regulatory · fda · via gabapentin

  5. Regulatory approval2026-04-30

    Approval: PREGABALIN (ANDA219593)

    fda · regulatory · fda · via pregabalin

  6. Safety communication2022-04-19

    Drug Safety Update: Pregabalin (Lyrica): findings of safety study on risks during pregnancy

    mhra · safety · mhra · via pregabalin

  7. Safety communication2021-02-18

    Drug Safety Update: Pregabalin (Lyrica): reports of severe respiratory depression

    mhra · safety · mhra · via pregabalin

  8. Safety communication2017-10-26

    Drug Safety Update: Gabapentin (Neurontin): risk of severe respiratory depression

    mhra · safety · mhra · via gabapentin

  9. New publication2014-04-14
    Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2014 · 831 citations · Europe PMC · via gabapentin

  10. New publication2012-02-29
    A proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2012 · 132 citations · Europe PMC · via gabapentin

  11. New publication1998-12-01
    Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 1998 · 2,375 citations · Europe PMC · via Nimodipine

  12. New publication1995-04-01
    Pharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons.

    The Journal of neuroscience : the official journal of the Society for Neuroscience · 1995 · 586 citations · Europe PMC · via Nimodipine

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.