Property Summary

NCBI Gene PubMed Count 41
PubMed Score 10.60
PubTator Score 131.23

Knowledge Summary

Patent (14,841)

Expression

  Differential Expression (7)

Disease log2 FC p
ependymoma -1.700 6.0e-10
glioblastoma -1.100 1.2e-04
atypical teratoid/rhabdoid tumor -1.700 4.2e-07
medulloblastoma, large-cell -1.100 3.8e-03
adult high grade glioma -1.400 4.9e-06
sonic hedgehog group medulloblastoma -1.300 8.7e-04
aldosterone-producing adenoma -1.054 3.4e-02

Gene RIF (25)

PMID Text
26005035 Aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR1 and 133, compared with those of adult patients with sinus rhythm.
25423599 N-glycosylation is not required for HCN2 channels to function.
25197093 Data show that Rab8b-interacting protein TRIP8b does not compete with cyclic AMP for the same binding region of hyperpolarization activated cyclic nucleotide gated potassium channel 2 (HCN2).
24525276 Thermal hyperalgesia under chronic inflammatory conditions is mediated by HCN2 channels.
24324597 Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.
23907424 HCN2 polymorphism may play a role in chronic inflammatory periodontitis but not in peri-implantitis.
23395072 LBB-injected HCN2/SkM1 potentially provides a more clinically suitable biological pacemaker strategy than other reported constructs. This superiority is attributable to the more negative AP threshold and injection into the LBB
22131395 This is the first evidence in humans for a single-point, homozygous loss-of-function mutation in HCN2 potentially associated with generalized epilepsy with recessive inheritance.
22094222 HCN2 channels make an important contribution to the maintenance of spontaneous burst activity in embryonic cortical neuron cultures.
21615589 Genetic analysis in 48 Sudden unexpected death in epilepsy cases identified six novel and three previously reported nonsynonymous (amino acid changing) variants in HCN1 , HCN2, HCN3 and HCN4.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20437590 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
18768480 RPTPalpha plays a critical role in HCN channel function via tyrosine dephosphorylation
17931874 Several functional variants were identified including the amino acid substitution R527Q in HCN2 exon 5. HCN2 channels containing the R527Q variant demonstrated a trend towards a decreased slope of the conductance-voltage relation.
17931874 Observational study of gene-disease association. (HuGE Navigator)
17043149 Noise analysis on macroscopic currents revealed fluctuations whose magnitudes were systematically larger than predicted from the actual single channel current size, consistent with cooperativity between single HCN channels.
16777944 With computer modelling, we show that in channels with relatively slow opening kinetics and fast mode-shift transitions, such as HCN2 and HCN4 channels, the mode shift effects are not readily observable, except in the tail kinetics.
15980171 an intact F-actin cytoskeleton is a prerequisite for the swelling-induced HCN2 current
15961404 Mutations of a putative cyclic-nucleotide-binding domain (CNBD) can disrupt the function of the hyperpolarization-activated cyclic-nucleotide-gated channel (HCN2).
15932727 Observational study of gene-disease association. (HuGE Navigator)
15687126 Native I(f) channels in atrial myocardium are heteromeric complexes composed of HCN4 and/or HCN2.
12890777 HCN1 and HCN2 expression were measured using in situ hybridization and immunocytochemistry in hippocampi; the expression of HCN isoforms is dynamically regulated in human as well as in experimental hippocampal epilepsy
12813043 activation of the fast channel HCN2 is dependent on the S1 segment
12194012 HCN4 activates substantially slower than HCN2 and with a half-maximum activation voltage approximately equal 10 mV less negative, both isoforms activate more positively in myocytes suggesting cell-type specificity

AA Sequence

MDARGGGGRPGESPGATPAPGPPPPPPPAPPQQQPPPPPPPAPPPGPGPAPPQHPPRAEALPPEAADEGG      1 - 70
PRGRLRSRDSSCGRPGTPGAASTAKGSPNGECGRGEPQCSPAGPEGPARGPKVSFSCRGAASGPAPGPGP     71 - 140
AEEAGSEEAGPAGEPRGSQASFMQRQFGALLQPGVNKFSLRMFGSQKAVEREQERVKSAGAWIIHPYSDF    141 - 210
RFYWDFTMLLFMVGNLIIIPVGITFFKDETTAPWIVFNVVSDTFFLMDLVLNFRTGIVIEDNTEIILDPE    211 - 280
KIKKKYLRTWFVVDFVSSIPVDYIFLIVEKGIDSEVYKTARALRIVRFTKILSLLRLLRLSRLIRYIHQW    281 - 350
EEIFHMTYDLASAVMRICNLISMMLLLCHWDGCLQFLVPMLQDFPRNCWVSINGMVNHSWSELYSFALFK    351 - 420
AMSHMLCIGYGRQAPESMTDIWLTMLSMIVGATCYAMFIGHATALIQSLDSSRRQYQEKYKQVEQYMSFH    421 - 490
KLPADFRQKIHDYYEHRYQGKMFDEDSILGELNGPLREEIVNFNCRKLVASMPLFANADPNFVTAMLTKL    491 - 560
KFEVFQPGDYIIREGTIGKKMYFIQHGVVSVLTKGNKEMKLSDGSYFGEICLLTRGRRTASVRADTYCRL    561 - 630
YSLSVDNFNEVLEEYPMMRRAFETVAIDRLDRIGKKNSILLHKVQHDLNSGVFNNQENAIIQEIVKYDRE    631 - 700
MVQQAELGQRVGLFPPPPPPPQVTSAIATLQQAAAMSFCPQVARPLVGPLALGSPRLVRRPPPGPAPAAA    701 - 770
SPGPPPPASPPGAPASPRAPRTSPYGGLPAAPLAGPALPARRLSRASRPLSASQPSLPHGAPGPAASTRP    771 - 840
ASSSTPRLGPTPAARAAAPSPDRRDSASPGAAGGLDPQDSARSRLSSNL                         841 - 889
//

Text Mined References (42)

PMID Year Title
26005035 2015 Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.
25423599 2015 Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.
25197093 2014 Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
24525276 2014 HCN2 channels account for mechanical (but not heat) hyperalgesia during long-standing inflammation.
24324597 2013 Novel HCN2 mutation contributes to febrile seizures by shifting the channel's kinetics in a temperature-dependent manner.
23907424 2013 Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) polymorphism is associated with chronic inflammatory periodontitis. A cross-sectional study.
23395072 2013 HCN2/SkM1 gene transfer into canine left bundle branch induces stable, autonomically responsive biological pacing at physiological heart rates.
22748890 2012 Investigation of hyperpolarization-activated cyclic nucleotide-gated channels in interstitial cells of Cajal of human bladder.
22131395 2011 Recessive loss-of-function mutation in the pacemaker HCN2 channel causing increased neuronal excitability in a patient with idiopathic generalized epilepsy.
22094222 2012 Hyperpolarization-activated cation current contributes to spontaneous network activity in developing neocortical cultures.
22006928 2011 Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels.
21615589 2011 Genetic analysis of hyperpolarization-activated cyclic nucleotide-gated cation channels in sudden unexpected death in epilepsy cases.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20437590 2010 Augmented currents of an HCN2 variant in patients with febrile seizure syndromes.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19471099 2009 Transcriptional control of pacemaker channel genes HCN2 and HCN4 by Sp1 and implications in re-expression of these genes in hypertrophied myocytes.
18768480 2008 Novel mechanism for suppression of hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by receptor-like tyrosine phosphatase-alpha.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
17931874 2008 Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy.
17474147 2007 Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening.
17043149 2006 Cooperative gating between single HCN pacemaker channels.
16777944 2006 Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels.
16382102 2005 International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels.
15980171 2005 Hypoosmotic cell swelling as a novel mechanism for modulation of cloned HCN2 channels.
15961404 2005 Identification of the cyclic-nucleotide-binding domain as a conserved determinant of ion-channel cell-surface localization.
15932727 2005 [Association between familial febrile convulsions and HCN2 gene].
15687126 2005 Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias.
15057824 2004 The DNA sequence and biology of human chromosome 19.
12928435 2003 Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels.
12890777 2003 Enhanced expression of a specific hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN) in surviving dentate gyrus granule cells of human and experimental epileptic hippocampus.
12813043 2003 Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4.
12640457 2003 Hyperpolarization moves S4 sensors inward to open MVP, a methanococcal voltage-gated potassium channel.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12194012 2002 Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells.
12034718 2002 Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels.
11133998 2001 Functional heteromerization of HCN1 and HCN2 pacemaker channels.
11076863 2000 DNA cloning using in vitro site-specific recombination.
10524219 1999 The human gene coding for HCN2, a pacemaker channel of the heart.
10228147 1999 Two pacemaker channels from human heart with profoundly different activation kinetics.
9921901 1998 CCG repeats in cDNAs from human brain.
9630217 1998 Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain.
9405696 1997 Interactive cloning with the SH3 domain of N-src identifies a new brain specific ion channel protein, with homology to eag and cyclic nucleotide-gated channels.