Skip to content
GenoLensGenoLens

KCNA2

Chr 1p13.3

potassium voltage-gated channel subfamily A member 2

Aliases:
Kv1.2, HK4
MANE:
ENST00000316361.10

Annotations refreshed 1 month ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Adult onset hereditary spastic paraplegia

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Ataxia and cerebellar anomalies - narrow panel

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Childhood onset hereditary spastic paraplegia

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • DDG2P

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Early onset or syndromic epilepsy

    MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
  • Hereditary ataxia with onset in adulthood

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Hereditary neuropathy

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
  • Intellectual disability

    MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

+2 more panels — install the extension to see the full list inline on any page.

Disease associations (Open Targets)

  • undetermined early-onset epileptic encephalopathy

    0.77
  • genetic developmental and epileptic encephalopathy

    0.64
  • multiple sclerosis

    0.59
  • Lambert-Eaton myasthenic syndrome

    0.56
  • myasthenia gravis

    0.56
  • hereditary disease

    0.52
  • Seizure

    0.52
  • Congenital myasthenic syndromes

    0.50
  • congenital myasthenic syndrome

    0.49
  • Epileptic encephalopathy

    0.46

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Potassium voltage-gated channel subfamily A member 2

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)

Curated MONDO disease pages that list KCNA2 among their top associated genes.

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.