Protein / target
Voltage-dependent L-type calcium channel subunit alpha-1S
Protein at a glance
Biological role
High voltage-gated calcium channel
Strongest disease association
Hypokalemic periodic paralysis, type 1
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle.
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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
Domains and Gene Ontology detail (20)Hide
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
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Ion channel gating
- ·calcium ion transmembrane transport
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
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Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
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.
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
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.
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
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.
Voltage-gated L-type calcium channel blocker
Indicated for Cardiovascular Diseases
Voltage-gated calcium channel modulator
Indicated for Epilepsy, Neuralgia, Postherpetic, Restless Legs Syndrome, Seizures
Voltage-gated calcium channel modulator
Indicated for Anxiety Disorders, Epilepsy, Fibromyalgia, Neuralgia
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
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 CACNA1S
Gene-level evidence surfaced through the gene CACNA1Sthat 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.
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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.
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Drug development
41 compounds recorded · 36 approved · 4 in clinical development · 1 earlier-stage
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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 molecules — Strong
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (7)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
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
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)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
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.
- Label change
Label change: GABAPENTIN (ANDA217995)
- Label change
Label change: GABAPENTIN (ANDA203934)
- Label change
Label change: PREGABALIN (ANDA211687)
- Regulatory approval
Approval: GABAPENTIN (ANDA203611)
- Regulatory approval
Approval: PREGABALIN (ANDA219593)
- Safety communication
Drug Safety Update: Pregabalin (Lyrica): findings of safety study on risks during pregnancy
- Safety communication
Drug Safety Update: Pregabalin (Lyrica): reports of severe respiratory depression
- Safety communication
Drug Safety Update: Gabapentin (Neurontin): risk of severe respiratory depression
- New publicationPrevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline.
- New publicationA proof-of-concept randomized controlled study of gabapentin: effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults.
- New publicationSynaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type.
- New publicationPharmacological dissection of multiple types of Ca2+ channel currents in rat cerebellar granule neurons.
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.