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FLASH GENE
Symbol HCN2 contributors: mct/npt/pgu - updated : 18-03-2019
HGNC name hyperpolarization activated cyclic nucleotide-gated potassium channel 2
HGNC id 4846
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Hearing/Equilibriumearinnercochlea   Homo sapiens
Nervousbrainhindbraincerebellum   Rattus norvegicus
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiac  
cells
SystemCellPubmedSpeciesStageRna symbol
Hearing / Equilibriumhair cell receptor Homo sapiens
Hearing / Equilibriumstereocilia Homo sapiens
Muscularmyocyte
NervousPurkinje cell Rattus norvegicus
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • six transmembrane segments
  • a leucine zipper of HCN channels that is a major determinant for hyperpolarization-activated channel gating
  • a pore helix and a selectivity filter between S5 and S6 and a cyclic nucleotide binding domain in the C terminus
  • HOMOLOGY
    Homologene
    FAMILY
  • potassium channel HCN family
  • superfamily of voltage-gated pore loop channels
  • CATEGORY transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
    basic FUNCTION
  • pace-maker channel of the heart
  • inward current activated by hyperpolarization from the resting potential and an important modulator of action potential firing frequency in many excitable cells
  • plays a key role in the control of cardiac and neuronal rhythmicity ("pacemaker current") and contributes to several other neuronal processes, including determination of resting membrane potential, dendritic integration and synaptic transmission
  • both the HCN1 and HCN2 isoforms are predominantly N-glycosylated in the embryonic heart, where they are found in significant amounts and where HCN-mediated currents are known to regulate beating frequency
  • HCN4 was confirmed as the predominant isoform of the primary pacemaker followed by a distinct expression of HCN1, but in contrast HCN2 shows only a confined expression to individual pacemaker cells
  • HCN2 channel activity reduces the repolarization reserve of the ventricular action potential and increases ectopic automaticity under pathological conditions such as excessive beta-adrenergic stimulation
  • HCN1, HCN2, and HCN4 subunits may have distinct physiological roles in the developing hippocampus
  • HCN1, HCN2, HCN4 channels are important regulators of excitability in neural, cardiac, and other pacemaking cells, which are often altered in disease
  • HCN2 channel may play an important role in regularizing firing patterns of subthalamic nucleus (STN) neurons, which is critical for basal ganglia motor functions
  • HCN2 channel may hold an essential position in normal rhythm patterns of STN neuronal firing activity and subsequent motor function of basal ganglia
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of HCN channel ((HCN1 and HCN2 may coassemble to form heteromeric channels in some areas, similar to other K(+) channels)
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • neuropathic pain is initiated by HCN2-driven action potential firing in SCN10A-expressing nociceptors
  • cell & other
    REGULATION
    activated by hyperpolarization-activated and cyclic nucleotide gated potassium
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation     gain of function
    in Genetic generalized epilepsy (GGE)
    constitutional     --over  
    in chronic inflammation resulting in an increased expression of HCN2 and causing sensitization in peripheral and spinal terminals of the pain transduction pathway
    constitutional germinal mutation      
    contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneouspain 
    HCN2-selective blockers may have value as analgesics to combat both inflammatory and neuropathic pain
    neurologyneurodegenerativealzheimer
    silencing or inhibition of HCN2 affects APP processing and thereby could serve as a potential treatment strategy
    ANIMAL & CELL MODELS
  • mutation in HCN2 likely leads to impaired gastrointestinal motility, causing the severe growth restriction seen in mice with mutations that eliminate HCN2 expression