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Protein / target

Voltage-gated potassium channel KCNC2

Encoded byKCNC2Q96PR1Homo 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

Genetic developmental and epileptic encephalopathy

Via encoding gene KCNC2 · Genetic literature evidence · score 0.61

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.

View complete UniProt function annotation

Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Contributes to the regulation of the fast action potential repolarization and in sustained high-frequency firing in neurons of the central nervous system. Homotetramer channels mediate delayed-rectifier voltage-dependent potassium currents that activate rapidly at high-threshold voltages and inactivate slowly. Forms tetrameric 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 (Probable) (PubMed:15709110, PubMed:35314505, PubMed:36090251). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNC1, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel. Channel properties may be modulated either by the association with ancillary subunits, such as KCNE1, KCNE2 or KCNE3 or indirectly by nitric oxide (NO) through a cGMP- and PKG-mediated signaling cascade, slowing channel activation and deactivation of delayed rectifier potassium channels (By similarity). Contributes to fire sustained trains of very brief action potentials at high frequency in retinal ganglion cells, thalamocortical and suprachiasmatic nucleus (SCN) neurons and in hippocampal and neocortical interneurons (PubMed:15709110). Sustained maximal action potential firing frequency in inhibitory hippocampal interneurons is negatively modulated by histamine H2 receptor activation in a cAMP- and protein kinase (PKA) phosphorylation-dependent manner. Plays a role in maintaining the fidelity of synaptic transmission in neocortical GABAergic interneurons by generating action potential (AP) repolarization at nerve terminals, thus reducing spike-evoked calcium influx and GABA neurotransmitter release. Required for long-range synchronization of gamma oscillations over distance in the neocortex. Contributes to the modulation of the circadian rhythm of spontaneous action potential firing in suprachiasmatic nucleus (SCN) neurons in a light-dependent manner (By similarity)

Subcellular location

Cell membraneMembranePerikaryonCell projection, axonCell projection, dendritePostsynaptic cell membranePresynaptic cell membraneSynapse, synaptosomeSynapseApical cell membraneBasolateral cell membrane
Domains and Gene Ontology detail (44)

Gene Ontology

  • Capical plasma membrane
  • Caxolemma
  • Caxon
  • Caxon terminus
  • Cbasolateral plasma membrane
  • Ccell body
  • Cdendrite
  • Cdendrite membrane
  • CGABA-ergic synapse
  • Cmembrane
  • Cneuronal cell body membrane
  • Cperikaryon

638 aa · 70 kDa · 6 isoforms

Biological roles

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

Inhibitory neurotransmissionUniProt · GOIon channel gatingGO
View supporting evidence

Inhibitory neurotransmission

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

Ion channel gating

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

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 KCNC2

Gene-level evidence surfaced through the gene KCNC2that 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
0.72Moderately supported

Genetic evidence dominant · Open Targets 0.39

Congenital myasthenic syndromes
0.65Moderately supported

Clinical evidence dominant · Open Targets 0.50

Genetic developmental and epileptic encephalopathy
0.64Moderately supported

Genetic literature evidence dominant · Open Targets 0.39

Infantile spasms
0.63Moderately supported

Genetic literature evidence dominant · Open Targets 0.39

View evidence synthesis (4)
Undetermined early-onset epileptic encephalopathyModerately supported
0.72
agreement 0.590.84
Genetic68%Animal model32%

Open Targets aggregate 0.39 · 2 independent evidence families

Congenital myasthenic syndromesModerately supported
0.65
agreement 0.510.79
Clinical84%Animal model16%

Open Targets aggregate 0.50 · 2 independent evidence families

Genetic developmental and epileptic encephalopathyModerately supported
0.64
agreement 0.520.77
Genetic literature61%Animal model38%Literature1%

Open Targets aggregate 0.39 · 3 independent evidence families

Infantile spasmsModerately supported
0.63
agreement 0.510.76
Genetic literature63%Animal model36%Literature1%

Open Targets aggregate 0.39 · 3 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
Congenital myasthenic syndromes0.50
Genetic developmental and epileptic encephalopathy0.39
Infantile spasms0.39
Undetermined early-onset epileptic encephalopathy0.39

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)
TEDISAMILApproval
AMIFAMPRIDINE PHOSPHATEApproval
GUANIDINE HYDROCHLORIDEApproval
AMIFAMPRIDINEApproval
DALFAMPRIDINEApproval
NERISPIRDINEPhase 2

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

View underlying tractability evidence (5)
SM · Approved DrugSM · Druggable FamilyAB · GO CC high confAB · UniProt loc med confAB · UniProt SigP or TMHMM

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.