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Symbol HCN2 contributors: mct/npt/pgu - updated : 18-03-2019
HGNC name hyperpolarization activated cyclic nucleotide-gated potassium channel 2
HGNC id 4846
Location 19p13.3      Physical location : 589.892 - 617.157
Synonym name brain cyclic nucleotide gated 2
Synonym symbol(s) BCNG2, BCNG-2, HAC-1
TYPE functioning gene
STRUCTURE 27.27 kb     8 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Physical map
LOC390871 19 similar to CXYorf1-related protein LOC390872 19 similar to Olfactory receptor 4F3 LOC388486 19 similar to bA476I15.3 (novel protein similar to septin) LOC390873 19 similar to capicua homolog LOC388487 19 LOC388487 PPAP2C 19p13 phosphatidic acid phosphatase type 2C KIAA1193 19p13.3 phosphatidic acid phosphatase type 2C THEG 19p13.3 Theg homolog (mouse) KIAA1957 19p13.3 KIAA1957 FLJ40059 19p13.3 hypothetical protein FLJ40059 MADCAM1 19p13.3 mucosal vascular addressin cell adhesion molecule 1 LOC91978 19p13.3 hypothetical gene supported by BC009520 CDC34 19p13.3 cell division cycle 34 GZMM 19p13.3 granzyme M (lymphocyte met-ase 1) BSG 19p13.3 basigin (OK blood group) HCN2 19p13.3 hyperpolarization activated cyclic nucleotide-gated potassium channel 2 POLRMT 19p13.3 polymerase (RNA) mitochondrial (DNA directed) FGF22 19p13.3 fibroblast growth factor 22 RNF126 19p13.3 ring finger protein 126 FSTL3 19p13 follistatin-like 3 (secreted glycoprotein) PALM 19p13.3 paralemmin LOC126353 19p13.3 hypothetical protein LOC126353 PTBP1 19p13.3 polypyrimidine tract binding protein 1 FLJ11535 19p13.3 hypothetical protein FLJ11535 AZU1 19p13.3 azurocidin 1 (cationic antimicrobial protein 37) PRTN3 19p13.3 proteinase 3 (serine proteinase, neutrophil, Wegener granulomatosis autoantigen) ELA2 19p13.3 elastase 2, neutrophil DF 19p13.3 D component of complement (adipsin) TRAP95 MGC16353 19p13.3 hypothetical protein MGC16353 GPR54 19p13.3 G protein-coupled receptor 54 DRIL1 19p13.3 dead ringer-like 1 (Drosophila) WDR18 19p13.3 WD repeat domain 18 GRIN3B 19p13.3 glutamate receptor, ionotropic, N-methyl-D-aspartate 3B C19orf6 19p13.3 chromosome 19 open reading frame 6 CNN2 21q11 calponin 2 ABCA7 19p13.3 ATP-binding cassette, sub-family A (ABC1), member 7 HA-1 19p13.3 ATP-binding cassette, sub-family A (ABC1), member 7 POLR2E 19p13.3 polymerase (RNA) II (DNA directed) polypeptide E, 25kDa GPX4 19p13.3 glutathione peroxidase 4 (phospholipid hydroperoxidase) KIAA0963 19p13.3 Homo sapiens KIAA0963 protein (KIAA0963), mRNA. STK11 19p13.3 serine/threonine kinase 11 (Peutz-Jeghers syndrome) MGC40084 19p13.3 hypothetical protein MGC40084 ATP5D 19p13.3 ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
8 - 3459 - 889 - 2008 17931874
Type restricted
   expressed in (based on citations)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Hearing/Equilibriumearinnercochlea   Homo sapiens
Nervousbrainhindbraincerebellum   Rattus norvegicus
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
SystemCellPubmedSpeciesStageRna symbol
Hearing / Equilibriumhair cell receptor Homo sapiens
Hearing / Equilibriumstereocilia Homo sapiens
NervousPurkinje cell Rattus norvegicus
cell lineage
cell lines
  • 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
  • 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
    a component
  • part of HCN channel ((HCN1 and HCN2 may coassemble to form heteromeric channels in some areas, similar to other K(+) channels)
    small molecule
  • neuropathic pain is initiated by HCN2-driven action potential firing in SCN10A-expressing nociceptors
  • cell & other
    activated by hyperpolarization-activated and cyclic nucleotide gated potassium
    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
    Variant & Polymorphism
    Candidate gene
    Therapy target
    HCN2-selective blockers may have value as analgesics to combat both inflammatory and neuropathic pain
    silencing or inhibition of HCN2 affects APP processing and thereby could serve as a potential treatment strategy
  • mutation in HCN2 likely leads to impaired gastrointestinal motility, causing the severe growth restriction seen in mice with mutations that eliminate HCN2 expression