Protein / target

Voltage-dependent L-type calcium channel subunit beta-4

CACNB4O00305Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
7
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

Nervous system

Strongest disease association

episodic ataxia type 5

Genetic literature evidence · score 0.70

Therapeutic maturity

Clinically validated target

7 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

7 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 beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting

Domains and Gene Ontology detail (22)

Domains & features

SH3

Gene Ontology

  • Ccytoplasmic side of plasma membrane
  • Ccytosol
  • Cglutamatergic synapse
  • Cnuclear speck
  • Cplasma membrane
  • Cpresynapse
  • Csynapse
  • CT-tubule
  • Cvoltage-gated calcium channel complex
  • Fcalcium channel regulator activity
  • Fhigh voltage-gated calcium channel activity
  • Fprotein kinase binding

520 aa · 58 kDa · 4 isoforms

Biological roles

Reactome v97

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

Synaptic signallingGO · ReactomeExcitatory neurotransmissionGOIon channel gatingGOKinase signallingGOMuscle contractionGO
View supporting evidence

Synaptic signalling

  • ·glutamatergic synapse
  • ·presynapse
  • ·synapse
  • ·voltage-gated calcium channel activity involved in regulation of presynaptic cytosolic c…

Excitatory neurotransmission

  • ·glutamatergic synapse

Ion channel gating

  • ·calcium ion transmembrane transport

Kinase signalling

  • ·protein kinase binding

Muscle contraction

  • ·positive regulation of muscle contraction
View underlying pathways (2)

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.

CACNA1ACACNA2…CACNA1CCACNA1SCACNA1DCACNA1FCACNB3CACNA2…CACNA2…CACNG3CACNB4

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 CACNG4, CACNG3, CACNA1G +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.

episodic ataxia type 50.70

Genetic literature · overall 0.60

epilepsy0.19

Genetic · overall 0.64

Highest-confidence therapeutic associations

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

neuropathic pain0.99

Clinical · overall 0.60

fibromyalgia0.99

Clinical · overall 0.60

Seizure0.99

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.

anxiety disorder0.57

Clinical

neuralgia0.56

Clinical

Focal-onset seizure0.52

Clinical

Show all associations
epilepsy0.64
episodic ataxia type 50.60
neuropathic pain0.60
fibromyalgia0.60
Seizure0.60
restless legs syndrome0.59
postherpetic neuralgia0.57
anxiety disorder0.57
neuralgia0.56
Focal-onset seizure0.52

Open Targets ranks 1,656 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 · 10 total

TERODILINEApproval

Polyuria · Urinary incontinence

TERODILINE HYDROCHLORIDEUnknown
ATAGABALINPhase 2

insomnia

PHLOROGLUCINOLApproval

gastrointestinal disease · urinary system disorder · renal colic

IMAGABALINPhase 3

generalized anxiety disorder

BEPRIDILApproval

cardiovascular disorder

SULOCTIDILApproval

cardiovascular disorder

PREGABALINApproval

Seizure · neuropathic pain · fibromyalgia

GABAPENTINApproval

Seizure · epilepsy · Focal-onset seizure

GABAPENTIN ENACARBILApproval

restless legs syndrome · neuralgia · Sleep disturbance

Tractability

SM · Approved DrugSM · High-Quality LigandSM · Druggable FamilyAB · GO CC high confPR · Half-life Data

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.

Show remaining trials (24)

COMPLETED · via gabapentin · NCT02330094

COMPLETED · via gabapentin · NCT00279487

COMPLETED · via gabapentin · NCT00058890

RECRUITING · via gabapentin · NCT04724252

COMPLETED · via gabapentin · NCT00218374

UNKNOWN · via gabapentin · NCT00209872

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.

epilepsyWell supported
0.80
agreement 0.690.91
Clinical77%Genetic20%Literature3%Genetic literaturedup

Open Targets aggregate 0.64 · 3 independent evidence families · 1 not counted as duplicate

neuropathic painModerately supported
0.74
agreement 0.580.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

fibromyalgiaModerately supported
0.74
agreement 0.580.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

SeizureModerately supported
0.74
agreement 0.580.91
Clinical100%

Open Targets aggregate 0.60 · 1 independent evidence family

restless legs syndromeModerately supported
0.72
agreement 0.560.89
Clinical100%

Open Targets aggregate 0.59 · 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.