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Aliases for HCN2 Gene

Aliases for HCN2 Gene

  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 2 2 3
  • BCNG2 3 4 6
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 2 2 3
  • Brain Cyclic Nucleotide-Gated Channel 2 3 4
  • BCNG-2 3 4
  • Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 3
  • Brain Cyclic Nucleotide Gated Channel 2 3
  • HAC-1 3

External Ids for HCN2 Gene

Previous HGNC Symbols for HCN2 Gene

  • BCNG2

Previous GeneCards Identifiers for HCN2 Gene

  • GC19P000641
  • GC19P000529
  • GC19P000540
  • GC19P000359

Summaries for HCN2 Gene

Entrez Gene Summary for HCN2 Gene

  • Hyperpolarization-activated cation channels of the HCN gene family, such as HCN2, contribute to spontaneous rhythmic activity in both heart and brain.[supplied by OMIM, Jul 2010]

GeneCards Summary for HCN2 Gene

HCN2 (Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 2) is a Protein Coding gene. Diseases associated with HCN2 include sick sinus syndrome and thyrotoxicosis. Among its related pathways are Transmission across Chemical Synapses and Antiarrhythmic Pathway, Pharmacodynamics. GO annotations related to this gene include voltage-gated potassium channel activity and cation channel activity. An important paralog of this gene is KCNH1.

UniProtKB/Swiss-Prot for HCN2 Gene

  • Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).

Gene Wiki entry for HCN2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HCN2 Gene

Genomics for HCN2 Gene

Regulatory Elements for HCN2 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for HCN2 Gene

589,893 bp from pter
617,159 bp from pter
27,267 bases
Plus strand

Genomic View for HCN2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for HCN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCN2 Gene

Proteins for HCN2 Gene

  • Protein details for HCN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
    Protein Accession:
    Secondary Accessions:
    • O60742
    • O60743
    • O75267
    • Q9UBS2

    Protein attributes for HCN2 Gene

    889 amino acids
    Molecular mass:
    96950 Da
    Quaternary structure:
    • The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Heterotetramer with HCN1. Forms an obligate 4:4 complex with accessory subunit PEX5L. Interacts with KCNE2 (By similarity). Homotetramer.
    • Inhibited by extracellular cesium ions

    Three dimensional structures from OCA and Proteopedia for HCN2 Gene

neXtProt entry for HCN2 Gene

Proteomics data for HCN2 Gene at MOPED

Post-translational modifications for HCN2 Gene

  • Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.
  • Ubiquitination at Lys177
  • Glycosylation at Asn407
  • Modification sites at PhosphoSitePlus

Other Protein References for HCN2 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for HCN2 Gene

Domains for HCN2 Gene

Gene Families for HCN2 Gene

  • CNG :Voltage-gated ion channels / Cyclic nucleotide-regulated channels

Suggested Antigen Peptide Sequences for HCN2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Q9UL51
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position
  • Contains 1 cyclic nucleotide-binding domain.
  • Belongs to the potassium channel HCN family.
genes like me logo Genes that share domains with HCN2: view

Function for HCN2 Gene

Molecular function for HCN2 Gene

GENATLAS Biochemistry: hyperpolarization-activated and cyclic nucleotide gated potassium channel 2,expressed in brain and heart (conduction tissues and contractile myocytes),pace-maker channel of the heart
UniProtKB/Swiss-Prot EnzymeRegulation: Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.
UniProtKB/Swiss-Prot Function: Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).

Gene Ontology (GO) - Molecular Function for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity --
GO:0005222 intracellular cAMP activated cation channel activity IDA 10228147
GO:0005248 voltage-gated sodium channel activity IMP 22748890
GO:0005249 voltage-gated potassium channel activity IMP 22748890
GO:0005515 protein binding --
genes like me logo Genes that share ontologies with HCN2: view
genes like me logo Genes that share phenotypes with HCN2: view

Animal Models for HCN2 Gene

MGI Knock Outs for HCN2:

Animal Model Products

CRISPR Products

miRNA for HCN2 Gene

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for HCN2 Gene

Localization for HCN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCN2 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

Jensen Localization Image for HCN2 Gene COMPARTMENTS Subcellular localization image for HCN2 gene
Compartment Confidence
plasma membrane 4
cytosol 2
cytoskeleton 1
extracellular 1
nucleus 1

Gene Ontology (GO) - Cellular Components for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 10228147
GO:0008076 voltage-gated potassium channel complex TAS 9630217
GO:0016020 membrane --
genes like me logo Genes that share ontologies with HCN2: view

Pathways for HCN2 Gene

genes like me logo Genes that share pathways with HCN2: view

Pathways by source for HCN2 Gene

1 Qiagen pathway for HCN2 Gene
3 Reactome pathways for HCN2 Gene
1 PharmGKB pathway for HCN2 Gene

PCR Array Products

  • Pathway & Disease-focused RT² Profiler PCR Arrays

Gene Ontology (GO) - Biological Process for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport --
GO:0007267 cell-cell signaling TAS 9630217
GO:0007268 synaptic transmission TAS --
GO:0034765 regulation of ion transmembrane transport IEA --
GO:0035725 sodium ion transmembrane transport IMP 22748890
genes like me logo Genes that share ontologies with HCN2: view

Compounds for HCN2 Gene

(3) HMDB Compounds for HCN2 Gene

Compound Synonyms Cas Number PubMed IDs
  • Cl2
Cyclic AMP
  • Cyclic AMP
  • Sodium

(2) Drugbank Compounds for HCN2 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
Cyclic Adenosine Monophosphate
  • 3'-5'-cyclic adenosine monophosphate
60-92-4 target
Cyclic Guanosine Monophosphate
7665-99-8 target

(5) IUPHAR Ligand for HCN2 Gene

Ligand Type Action Affinity Pubmed IDs
cilobradine Pore Blocker Antagonist 6
zatebradine Pore Blocker Antagonist 5.7
ivabradine Pore Blocker Antagonist 5.7
ZD7288 Pore Blocker Antagonist 4.7
Cs+ Pore Blocker Antagonist 3.8

(2) Novoseek inferred chemical compound relationships for HCN2 Gene

Compound -log(P) Hits PubMed IDs
potassium 33.9 2
cysteine 9.79 1
genes like me logo Genes that share compounds with HCN2: view

Transcripts for HCN2 Gene

mRNA/cDNA for HCN2 Gene

(1) REFSEQ mRNAs :
(5) Additional mRNA sequences :
(38) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HCN2 Gene

Hyperpolarization activated cyclic nucleotide-gated potassium channel 2:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HCN2

Primer Products

  • OriGene qSTAR qPCR primer pairs in human,mouse,rat for HCN2

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HCN2 Gene

No ASD Table

Relevant External Links for HCN2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for HCN2 Gene

mRNA expression in normal human tissues for HCN2 Gene

mRNA differential expression in normal tissues according to GTEx for HCN2 Gene

This gene is overexpressed in Brain - Putamen (basal ganglia) (6.2), Brain - Spinal cord (cervical c-1) (5.3), Brain - Caudate (basal ganglia) (5.0), Brain - Substantia nigra (4.8), Brain - Cortex (4.7), and Brain - Nucleus accumbens (basal ganglia) (4.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for HCN2 Gene

SOURCE GeneReport for Unigene cluster for HCN2 Gene Hs.124161

mRNA Expression by UniProt/SwissProt for HCN2 Gene

Tissue specificity: Highly expressed throughout the brain. Detected at low levels in heart.
genes like me logo Genes that share expressions with HCN2: view

In Situ Assay Products

Orthologs for HCN2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HCN2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia HCN2 36
  • 78 (a)
LOC467640 35
  • 94.4 (n)
  • 91.66 (a)
(Bos Taurus)
Mammalia HCN2 35
  • 91.4 (n)
  • 96.73 (a)
HCN2 36
  • 96 (a)
(Canis familiaris)
Mammalia HCN2 35
  • 93.03 (n)
  • 96.29 (a)
HCN2 36
  • 96 (a)
(Mus musculus)
Mammalia Hcn2 35
  • 87.39 (n)
  • 93.6 (a)
Hcn2 16
Hcn2 36
  • 94 (a)
(Monodelphis domestica)
Mammalia HCN2 36
  • 88 (a)
(Ornithorhynchus anatinus)
Mammalia HCN2 36
  • 67 (a)
(Rattus norvegicus)
Mammalia Hcn2 35
  • 87.93 (n)
  • 93.83 (a)
(Gallus gallus)
Aves HCN2 35
  • 84.59 (n)
  • 89.97 (a)
HCN2 36
  • 78 (a)
(Anolis carolinensis)
Reptilia HCN2 36
  • 63 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia hcn2 35
  • 76.49 (n)
  • 88.24 (a)
(Danio rerio)
Actinopterygii HCN2 (2 of 2) 36
  • 65 (a)
hcn2b 35
  • 71.32 (n)
  • 78.59 (a)
hcn2b 36
  • 69 (a)
fruit fly
(Drosophila melanogaster)
Insecta Ih 36
  • 27 (a)
Ih 37
  • 53 (a)
(Triticum aestivum)
Liliopsida Ta.20011 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 53 (a)
Species with no ortholog for HCN2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • worm (Caenorhabditis elegans)

Evolution for HCN2 Gene

Gene Tree for HCN2 (if available)
Gene Tree for HCN2 (if available)

Paralogs for HCN2 Gene

Selected SIMAP similar genes for HCN2 Gene using alignment to 1 proteins: Pseudogenes for HCN2 Gene

genes like me logo Genes that share paralogs with HCN2: view

Variants for HCN2 Gene

Sequence variations from dbSNP and Humsavar for HCN2 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs873634 -- 588,305(-) GCCCA(G/T)GCCTG upstream-variant-2KB
rs1054786 -- 613,898(+) CGGGC(C/T)GACAC synonymous-codon, reference
rs2301778 -- 613,307(+) AACGC(C/T)GACCC reference, synonymous-codon
rs2392750 -- 593,382(-) GCCTC(A/G)GCCTC intron-variant
rs3752158 -- 607,984(-) GAGTA(C/G/T)AGTTC synonymous-codon, reference

Structural Variations from Database of Genomic Variants (DGV) for HCN2 Gene

Variant ID Type Subtype PubMed ID
nsv428360 CNV Gain 18775914
nsv910102 CNV Loss 21882294
nsv910109 CNV Loss 21882294
nsv470101 CNV Loss 18288195
nsv910119 CNV Gain 21882294
dgv3508n71 CNV Loss 21882294
dgv3510n71 CNV Loss 21882294
dgv3511n71 CNV Loss 21882294
dgv3512n71 CNV Loss 21882294
dgv3513n71 CNV Loss 21882294
dgv3514n71 CNV Gain 21882294
dgv3515n71 CNV Loss 21882294
dgv3516n71 CNV Loss 21882294
dgv3518n71 CNV Loss 21882294
dgv3519n71 CNV Gain+Loss 21882294
nsv910175 CNV Loss 21882294
dgv3525n71 CNV Loss 21882294
dgv3526n71 CNV Loss 21882294
dgv3527n71 CNV Loss 21882294
dgv3528n71 CNV Loss 21882294
nsv910211 CNV Loss 21882294
dgv3529n71 CNV Loss 21882294
esv2658944 CNV Deletion 23128226
dgv3530n71 CNV Gain 21882294
dgv3531n71 CNV Loss 21882294
nsv910224 CNV Loss 21882294
nsv828350 CNV Loss 20364138
dgv523e201 CNV Deletion 23290073
esv2717746 CNV Deletion 23290073
esv1739089 CNV Insertion 17803354
esv2717748 CNV Deletion 23290073
esv2717749 CNV Deletion 23290073
dgv3532n71 CNV Gain 21882294
dgv524e201 CNV Deletion 23290073
esv3037 CNV Deletion 18987735
dgv525e201 CNV Deletion 23290073
dgv3533n71 CNV Gain+Loss 21882294
dgv3534n71 CNV Loss 21882294
nsv910233 CNV Loss 21882294
nsv910235 CNV Loss 21882294
esv27631 CNV Gain 19812545
nsv910238 CNV Loss 21882294
dgv3535n71 CNV Loss 21882294
dgv3536n71 CNV Gain 21882294
dgv3537n71 CNV Loss 21882294

Relevant External Links for HCN2 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCN2 Gene

Disorders for HCN2 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (2) Diseases for HCN2 Gene including...

Search for HCN2 Gene in MalaCards »

(2) University of Copenhagen DISEASES for HCN2 Gene

(1) Novoseek inferred disease relationships for HCN2 Gene

Disease -log(P) Hits PubMed IDs
epilepsy 24.8 2

Relevant External Links for HCN2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with HCN2: view

No data available for UniProtKB/Swiss-Prot for HCN2 Gene

Publications for HCN2 Gene

  1. Two pacemaker channels from human heart with profoundly different activation kinetics. (PMID: 10228147) Ludwig A. … Biel M. (EMBO J. 1999) 3 4 23
  2. Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy. (PMID: 17931874) Tang B. … Escayg A. (Neurobiol. Dis. 2008) 3 23 48
  3. Augmented currents of an HCN2 variant in patients with febrile seizure syndromes. (PMID: 20437590) Dibbens L.M. … Petrou S. (Ann. Neurol. 2010) 3 23 48
  4. Identification of a gene encoding a hyperpolarization-activated 'pacemaker' channel of brain. (PMID: 9630217) Santoro B. … Tibbs G.R. (Cell 1998) 2 3 4
  5. 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. (PMID: 9405696) Santoro B. … Kandel E.R. (Proc. Natl. Acad. Sci. U.S.A. 1997) 2 3

Products for HCN2 Gene

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