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Protein / target

Potassium voltage-gated channel subfamily A member 2

Encoded byKCNA2P16389Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Delayed rectifier potassium channel

Strongest disease association

Undetermined early-onset epileptic encephalopathy

Via encoding gene KCNA2 · Genetic evidence · score 0.87

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

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system.

View complete UniProt function annotation

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11211111, PubMed:19912772, PubMed:23769686, PubMed:8495559). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:20220134, PubMed:8495559). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:19912772, PubMed:23769686). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (PubMed:8495559). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity)

Subcellular location

Cell membraneMembraneCell projection, axonSynapseEndoplasmic reticulum membraneCell projection, lamellipodium membraneSynapse, synaptosomePresynaptic cell membraneCell projection, dendriteCell junction, paranodal septate junction
Domains and Gene Ontology detail (37)

Gene Ontology

  • Caxon
  • Caxon initial segment
  • Caxon terminus
  • Ccalyx of Held
  • Cdendrite
  • Cendoplasmic reticulum membrane
  • Cglutamatergic synapse
  • Cjuxtaparanode region of axon
  • Clamellipodium
  • Clamellipodium membrane
  • Cmembrane
  • Cneuronal cell body membrane

499 aa · 57 kDa · 2 isoforms

Biological roles

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

Ion channel gatingGOInhibitory neurotransmissionUniProt
View supporting evidence

Ion channel gating

  • ·voltage-gated monoatomic ion channel activity involved in regulation of postsynaptic mem…
  • ·voltage-gated monoatomic ion channel activity involved in regulation of presynaptic memb…
  • ·potassium ion transmembrane transport

Inhibitory neurotransmission

  • ·Voltage-gated potassium channel that mediates transmembrane potassium transport in excit…

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Approved medicines with mapped indications

2 medicines · 2 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.

Lambert-Eaton Myasthenic Syndrome1 medicine
Multiple Sclerosis1 medicine

5 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.

dalfampridine
ApprovedBlocker

Voltage-gated potassium channel blocker

Indicated for Multiple Sclerosis

Acts on a complex — shared with KCNC4, KCNC3, KCNB1 +36 more · 1 of 40 recorded protein targets — broad pharmacology

amifampridine
ApprovedBlocker

Voltage-gated potassium channel blocker

Indicated for Lambert-Eaton Myasthenic Syndrome

Acts on a complex — shared with KCNC4, KCNC3, KCNB1 +36 more · 1 of 40 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 KCNA2

Gene-level evidence surfaced through the gene KCNA2that 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.

Undetermined early-onset epileptic encephalopathy
0.94Well supported

Genetic evidence dominant · Open Targets 0.77

Genetic Diseases, Inborn
0.86Well supported

Genetic evidence dominant · Open Targets 0.52

Genetic developmental and epileptic encephalopathy
0.76Well supported

Genetic literature evidence dominant · Open Targets 0.64

Multiple Sclerosis
0.73Moderately supported

Clinical evidence dominant · Open Targets 0.59

Congenital myasthenic syndromes
0.66Moderately supported

Clinical evidence dominant · Open Targets 0.50

View evidence synthesis (5)
Undetermined early-onset epileptic encephalopathyWell supported
0.94
agreement 0.841.00
Genetic58%Somatic mutation25%Animal model17%Genetic literaturedup

Open Targets aggregate 0.77 · 3 independent evidence families · 1 not counted as duplicate

Genetic Diseases, InbornWell supported
0.86
agreement 0.721.00
Genetic100%Literature1%

Open Targets aggregate 0.52 · 2 independent evidence families

Genetic developmental and epileptic encephalopathyWell supported
0.76
agreement 0.640.89
Genetic literature68%Animal model30%Literature1%

Open Targets aggregate 0.64 · 3 independent evidence families

Multiple SclerosisModerately supported
0.73
agreement 0.570.88
Clinical99%Literature1%

Open Targets aggregate 0.59 · 2 independent evidence families

Congenital myasthenic syndromesModerately supported
0.66
agreement 0.530.80
Clinical81%Animal model19%

Open Targets aggregate 0.50 · 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 per-type scores above show the calculation.

Show all associations
Undetermined early-onset epileptic encephalopathy0.77
Genetic developmental and epileptic encephalopathy0.64
Multiple Sclerosis0.59
Genetic Diseases, Inborn0.52
Congenital myasthenic syndromes0.50

Drug development

6 compounds recorded · 5 approved · 1 in clinical development

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 (6)
NERISPIRDINEPhase 2
AMIFAMPRIDINEApproval
GUANIDINE HYDROCHLORIDEApproval
TEDISAMILApproval
AMIFAMPRIDINE PHOSPHATEApproval
DALFAMPRIDINEApproval

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

View underlying tractability evidence (9)
SM · Approved DrugSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMMPR · 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)

RECRUITING · via dalfampridine · NCT06333171

RECRUITING · via dalfampridine · NCT06853015

TERMINATED · via dalfampridine · NCT04026568

COMPLETED · via dalfampridine · NCT02006160

COMPLETED · via dalfampridine · NCT01444300

ClinicalTrials.gov via the drug-target graph.

What's happening now

6

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. Supplemental approval2026-08-10

    Supplemental approval: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  2. Label change2023-04-11

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  3. Label change2021-09-15

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  4. Label change2020-08-14

    Label change: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  5. Regulatory approval2019-03-11

    Approval: DALFAMPRIDINE (ANDA210158)

    fda · regulatory · fda · via dalfampridine

  6. Regulatory approval2009-12-23

    Approval: Firdapse (previously Zenas) (EMA)

    ema · regulatory · ema · via amifampridine

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.