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Protein / target

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

Encoded byCACNA2D2Q9NY47Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
9
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Voltage-gated calcium channel

Strongest disease association

Genetic developmental and epileptic encephalopathy

Via encoding gene CACNA2D2 · Genetic evidence · score 0.91

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

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel.

View complete UniProt function annotation

The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis

Subcellular location

Membrane
Domains and Gene Ontology detail (9)

Domains & features

VWFACache

Gene Ontology

  • CGABA-ergic synapse
  • Cplasma membrane
  • Cpresynaptic active zone membrane
  • Cvoltage-gated calcium channel complex
  • Fmetal ion binding
  • Fvoltage-gated calcium channel activity
  • Pregulation of neurotransmitter receptor localization to postsynaptic specialization membrane

1150 aa · 130 kDa · 5 isoforms

Biological roles

Reactome v97

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

Synaptic signallingGO · Reactome
View supporting evidence

Synaptic signalling

  • ·GABA-ergic synapse
  • ·presynaptic active zone membrane
  • ·regulation of neurotransmitter receptor localization to postsynaptic specialization memb…
  • ·Presynaptic depolarization and calcium channel opening
View underlying pathways (6)

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.

CACNB2CACNA1CCACNA1ACACNG1CACNA1DCACNA1ECACNB4CACNB1CACNA1BCACNA1GCACNA2D2

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

2 medicines · 8 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

9 medicines meet Open Targets' target-level approved-medicine definition; the 2 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

2

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.

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 CACNA2D2

Gene-level evidence surfaced through the gene CACNA2D2that 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.

Genetic developmental and epileptic encephalopathy
0.94Well supported

Genetic evidence dominant · Open Targets 0.58

early-infantile DEE
0.93Well supported

Genetic evidence dominant · Open Targets 0.57

Cerebellar atrophy, developmental delay, and seizures
0.90Well supported

Genetic evidence dominant · Open Targets 0.74

Epilepsy
0.87Well supported

Clinical evidence dominant · Open Targets 0.70

Anxiety Disorders
0.76Well supported

Clinical evidence dominant · Open Targets 0.60

View evidence synthesis (5)
Genetic developmental and epileptic encephalopathyWell supported
0.94
agreement 0.821.00
Genetic73%Animal model27%Literature0%

Open Targets aggregate 0.58 · 3 independent evidence families

early-infantile DEEWell supported
0.93
agreement 0.811.00
Genetic80%Animal model20%

Open Targets aggregate 0.57 · 2 independent evidence families

Cerebellar atrophy, developmental delay, and seizuresWell supported
0.90
agreement 0.781.00
Genetic79%Animal model21%Genetic literaturedup

Open Targets aggregate 0.74 · 2 independent evidence families · 1 not counted as duplicate

EpilepsyWell supported
0.87
agreement 0.760.99
Clinical59%Genetic literature39%Literature2%

Open Targets aggregate 0.70 · 3 independent evidence families

Anxiety DisordersWell supported
0.76
agreement 0.660.86
Clinical79%Genetic21%

Open Targets aggregate 0.60 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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
Cerebellar atrophy, developmental delay, and seizures0.74
Epilepsy0.70
Anxiety Disorders0.60
Genetic developmental and epileptic encephalopathy0.58
early-infantile DEE0.57

Drug development

12 compounds recorded · 9 approved · 2 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 2 drugs that target this protein in Forefront's canonical graph (2 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ATAGABALINPhase 2
SULOCTIDILApproval
PHLOROGLUCINOLApproval
IMAGABALINPhase 3
MIROGABALINApproval
GABAPENTINApproval
PREGABALINApproval
GABAPENTIN ENACARBILApproval
TERODILINEApproval
BEPRIDILApproval

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 High-Quality Ligand support this modality.

AntibodiesEmerging

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

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (9)
SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confAB · UniProt SigP or TMHMMAB · Human Protein Atlas locPR · Database UbiquitinationPR · Half-life DataPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.

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 · NCT05076110

COMPLETED · via gabapentin · NCT05063656

COMPLETED · via gabapentin · NCT03472521

WITHDRAWN · via gabapentin · NCT03121963

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 2 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 publication2011-12-09
    Cerebrospinal fluid neurotransmitter changes during the perioperative period in patients undergoing total knee replacement: a randomized trial.

    Anesthesia and analgesia · 2012 · 22 citations · Europe PMC · via pregabalin

  12. New publication2010-11-03
    An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics.

    Advances in therapy · 2010 · 20 citations · Europe PMC · via pregabalin

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.