Human Gene HCN2 (uc002lpe.3)
  Description: Homo sapiens hyperpolarization activated cyclic nucleotide-gated potassium channel 2 (HCN2), mRNA.
RefSeq Summary (NM_001194): The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017].
Transcript (Including UTRs)
   Position: hg19 chr19:589,893-617,159 Size: 27,267 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr19:589,946-616,474 Size: 26,529 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:589,893-617,159)mRNA (may differ from genome)Protein (889 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HCN2_HUMAN
DESCRIPTION: RecName: Full=Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2; AltName: Full=Brain cyclic nucleotide-gated channel 2; Short=BCNG-2;
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). Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).
SUBUNIT: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits. Heteromultimer with HCN1. Interacts with KCNE2 (By similarity).
SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Highly expressed throughout the brain. Detected at low levels in heart.
DOMAIN: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
MISCELLANEOUS: Inhibited by extracellular cesium ions.
SIMILARITY: Belongs to the potassium channel HCN family.
SIMILARITY: Contains 1 cyclic nucleotide-binding domain.

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): HCN2
CDC HuGE Published Literature: HCN2
Positive Disease Associations: seizures, febrile
Related Studies:
  1. seizures, febrile
    Ma, Y. N. et al. 2005, [Association between familial febrile convulsions and HCN2 gene], Zhonghua yi xue za zhi. 2005 Mar;85(10):663-6. [PubMed 15932727]
    HCN2 may not be a susceptibility gene for FC in Chinese population.

-  MalaCards Disease Associations
  MalaCards Gene Search: HCN2
Diseases sorted by gene-association score: sinoatrial node disease (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 61.51 RPKM in Brain - Putamen (basal ganglia)
Total median expression: 582.22 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -32.5053-0.613 Picture PostScript Text
3' UTR -321.95685-0.470 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR018490 - cNMP-bd-like
IPR018488 - cNMP-bd_CS
IPR000595 - cNMP-bd_dom
IPR005821 - Ion_trans_dom
IPR013621 - Ion_trans_N
IPR003938 - K_chnl_volt-dep_EAG/ELK/ERG
IPR014710 - RmlC-like_jellyroll

Pfam Domains:
PF00027 - Cyclic nucleotide-binding domain
PF00520 - Ion transport protein
PF08412 - Ion transport protein N-terminal

SCOP Domains:
51206 - cAMP-binding domain-like
81324 - Voltage-gated potassium channels

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3U10 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9UL51
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserNo orthologNo ortholog
Gene DetailsGene Details Gene Details  
Gene SorterGene Sorter Gene Sorter  
 RGDEnsemblFlyBase  
 Protein SequenceProtein SequenceProtein Sequence  
 AlignmentAlignmentAlignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005216 ion channel activity
GO:0005222 intracellular cAMP activated cation channel activity
GO:0005244 voltage-gated ion channel activity
GO:0005248 voltage-gated sodium channel activity
GO:0005249 voltage-gated potassium channel activity
GO:0005267 potassium channel activity
GO:0005272 sodium channel activity
GO:0005515 protein binding
GO:0030552 cAMP binding
GO:0042802 identical protein binding

Biological Process:
GO:0006811 ion transport
GO:0006813 potassium ion transport
GO:0006814 sodium ion transport
GO:0007267 cell-cell signaling
GO:0034765 regulation of ion transmembrane transport
GO:0035725 sodium ion transmembrane transport
GO:0042391 regulation of membrane potential
GO:0055085 transmembrane transport
GO:0071320 cellular response to cAMP
GO:0071321 cellular response to cGMP
GO:0071805 potassium ion transmembrane transport
GO:0086012 membrane depolarization during cardiac muscle cell action potential
GO:0098719 sodium ion import across plasma membrane
GO:1990573 potassium ion import across plasma membrane

Cellular Component:
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0008076 voltage-gated potassium channel complex
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0098855 HCN channel complex


-  Descriptions from all associated GenBank mRNAs
  AJ012582 - Homo sapiens mRNA for hyperpolarization-activated cation channel HCN2.
AF065164 - Homo sapiens hyperpolarization-activated, cyclic nucleotide-gated channel 2 (HCN2) mRNA, complete cds.
DQ854815 - Homo sapiens hyperpolarization-activated cyclic nucleotide-gated potassium channel 2 mRNA, partial cds.
AB527443 - Synthetic construct DNA, clone: pF1KB7295, Homo sapiens HCN2 gene for hyperpolarization activated cyclic nucleotide-gated potassium channel 2, without stop codon, in Flexi system.
BC118001 - Synthetic construct Homo sapiens clone IMAGE:40080842, MGC:133396 HCN2 protein (HCN2) mRNA, encodes complete protein.
BC039619 - Homo sapiens hyperpolarization activated cyclic nucleotide-gated potassium channel 2, mRNA (cDNA clone IMAGE:5730201).
AF064877 - Homo sapiens ion channel BCNG-2 mRNA, partial cds.
DQ574370 - Homo sapiens piRNA piR-42482, complete sequence.
JD419299 - Sequence 400323 from Patent EP1572962.
JD470031 - Sequence 451055 from Patent EP1572962.
JD111539 - Sequence 92563 from Patent EP1572962.
JD416360 - Sequence 397384 from Patent EP1572962.
JD475191 - Sequence 456215 from Patent EP1572962.
JD076689 - Sequence 57713 from Patent EP1572962.
JD405741 - Sequence 386765 from Patent EP1572962.
JD395255 - Sequence 376279 from Patent EP1572962.
JD399386 - Sequence 380410 from Patent EP1572962.
JD128058 - Sequence 109082 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9UL51 (Reactome details) participates in the following event(s):

R-HSA-1297444 Binding of cAMP to HCN channels
R-HSA-1296043 Activation of HCN channels
R-HSA-1296061 HCN channels
R-HSA-1296071 Potassium Channels
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: BCNG2, HCN2_HUMAN, NM_001194, NP_001185, O60742, O60743, O75267, Q9UBS2, Q9UL51
UCSC ID: uc002lpe.3
RefSeq Accession: NM_001194
Protein: Q9UL51 (aka HCN2_HUMAN)
CCDS: CCDS12035.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001194.3
exon count: 8CDS single in 3' UTR: no RNA size: 3459
ORF size: 2670CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3826.00frame shift in genome: no % Coverage: 98.53
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.