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Aliases for HCN2 Gene

Aliases for HCN2 Gene

  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 2 2 3 5
  • Brain Cyclic Nucleotide-Gated Channel 2 3 4
  • BCNG-2 3 4
  • BCNG2 3 4
  • Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 3
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 2 2
  • 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 Sinoatrial Node Disease. Among its related pathways are Potassium Channels and Transmission across Chemical Synapses. GO annotations related to this gene include identical protein binding and voltage-gated potassium channel activity. An important paralog of this gene is HCN4.

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).

Tocris Summary for HCN2 Gene

  • HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. They are cationic channels that open under hyperpolarization.

Gene Wiki entry for HCN2 Gene

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

Genomics for HCN2 Gene

Regulatory Elements for HCN2 Gene

Enhancers for HCN2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19F000718 1.5 FANTOM5 Ensembl ENCODE 14.1 +129.8 129802 3.1 TBP ELF3 ARID4B BMI1 DNMT3B THRB ZNF48 RARA EGR1 SCRT2 HCN2 PALM FGF22 SHC2 C2CD4C GC19M000724
GH19F000615 1.1 Ensembl ENCODE 13.3 +30.4 30360 9.7 BCOR CTCF KLF1 ZNF792 INSM2 ZMYM3 KLF17 RAD21 BCL11B ZIC2 POLRMT HCN2 SHC2 GC19P000611
GH19F000485 1.5 FANTOM5 Ensembl ENCODE 7.9 -104.0 -104034 1.3 ELF3 TBP MLX ARID4B ZNF48 THAP11 SP5 KAT8 SMARCA4 KLF16 SHC2 FGF22 HCN2 MADCAM1 PALM C2CD4C ODF3L2
GH19F000631 1.1 ENCODE 10.3 +43.4 43365 2.6 HDGF PKNOX1 ARNT CREB3L1 SIN3A ARID4B DMAP1 YY1 ZNF766 ZNF207 POLRMT FSTL3 HCN2 ENSG00000261204 GC19P000611
GH19F000603 1.5 FANTOM5 Ensembl ENCODE 5 +15.2 15164 2.6 HDGF ATF1 PKNOX1 ARNT CREB3L1 GATA2 ZNF143 NCOA1 MEF2D SMARCA4 FSTL3 HCN2 THEG GC19P000606 LOC100420586
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around HCN2 on UCSC Golden Path with GeneCards custom track

Promoters for HCN2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001815047 307 1201 ESRRA SUZ12 SP2 REST BCL11B ZBTB7A SCRT2 ID3 ZBTB26 E2F6

Genomic Location for HCN2 Gene

Chromosome:
19
Start:
589,893 bp from pter
End:
617,159 bp from pter
Size:
27,267 bases
Orientation:
Plus strand

Genomic View for HCN2 Gene

Genes around HCN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    Q9UL51-HCN2_HUMAN
    Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
    Protein Accession:
    Q9UL51
    Secondary Accessions:
    • O60742
    • O60743
    • O75267
    • Q9UBS2

    Protein attributes for HCN2 Gene

    Size:
    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.
    Miscellaneous:
    • Inhibited by extracellular cesium ions.

    Three dimensional structures from OCA and Proteopedia for HCN2 Gene

neXtProt entry for HCN2 Gene

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 Lys 177
  • Glycosylation at Asn 407
  • Modification sites at PhosphoSitePlus

Other Protein References for HCN2 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for HCN2 (HCN2)
  • Abcam antibodies for HCN2

No data available for DME Specific Peptides for HCN2 Gene

Domains & Families for HCN2 Gene

Gene Families for HCN2 Gene

Suggested Antigen Peptide Sequences for HCN2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9UL51

UniProtKB/Swiss-Prot:

HCN2_HUMAN :
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
  • Belongs to the potassium channel HCN family.
Domain:
  • 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.
Family:
  • 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 IEA --
GO:0005222 intracellular cAMP activated cation channel activity IDA 10228147
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005248 voltage-gated sodium channel activity IMP 22748890
GO:0005249 voltage-gated potassium channel activity IMP 22748890
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

  • Taconic Biosciences Mouse Models for HCN2

Inhibitory RNA Products

Clone Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets 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

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCN2 gene
Compartment Confidence
plasma membrane 5
cytosol 2

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 IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with HCN2: view

Pathways & Interactions for HCN2 Gene

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

Pathways by source for HCN2 Gene

1 Cell Signaling Technology pathway for HCN2 Gene
1 BioSystems pathway for HCN2 Gene
3 Reactome pathways for HCN2 Gene
1 PharmGKB pathway for HCN2 Gene
1 KEGG pathway for HCN2 Gene
1 Qiagen pathway for HCN2 Gene

Gene Ontology (GO) - Biological Process for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006810 transport IEA --
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0007267 cell-cell signaling TAS 9630217
genes like me logo Genes that share ontologies with HCN2: view

No data available for SIGNOR curated interactions for HCN2 Gene

Drugs & Compounds for HCN2 Gene

(11) Drugs for HCN2 Gene - From: DrugBank, ApexBio, DGIdb, IUPHAR, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ivabradine Approved Pharma Antagonist, Pore Blocker 0
cyclic amp Experimental Pharma Target 0
Cyclic GMP Experimental Pharma Target 0
Zatebradine hydrochloride Pharma Blocks hyperpolarization-activated current (If) 0
ZD 7288 Pharma HCN channel inhibitor, Inhibits pacemaker (If) current 0

(2) Additional Compounds for HCN2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Bertholite
  • Chloor
  • Chlor
  • Chlore
  • Chloride
16887-00-6
sodium
  • Sodium
  • Sodium ion
7440-23-5

(2) Tocris Compounds for HCN2 Gene

Compound Action Cas Number
Zatebradine hydrochloride Blocks hyperpolarization-activated current (If) 91940-87-3
ZD 7288 Inhibits pacemaker (If) current 133059-99-1

(2) ApexBio Compounds for HCN2 Gene

Compound Action Cas Number
Zatebradine hydrochloride 91940-87-3
ZD 7288 HCN channel inhibitor 133059-99-1
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:

Inhibitory RNA Products

Clone Products

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
HCN2
ECgene alternative splicing isoforms for
HCN2

Expression for HCN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HCN2 Gene

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

This gene is overexpressed in Brain - Putamen (basal ganglia) (x6.2), Brain - Spinal cord (cervical c-1) (x5.3), Brain - Caudate (basal ganglia) (x5.0), Brain - Substantia nigra (x4.8), Brain - Cortex (x4.7), and Brain - Nucleus accumbens (basal ganglia) (x4.6).

Protein differential expression in normal tissues from HIPED for HCN2 Gene

This gene is overexpressed in Frontal cortex (26.8), Retina (21.2), Platelet (10.6), and Spinal cord (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HCN2 Gene



Protein tissue co-expression partners for HCN2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HCN2 Gene:

HCN2

SOURCE GeneReport for Unigene cluster for HCN2 Gene:

Hs.124161

mRNA Expression by UniProt/SwissProt for HCN2 Gene:

Q9UL51-HCN2_HUMAN
Tissue specificity: Highly expressed throughout the brain. Detected at low levels in heart.
genes like me logo Genes that share expression patterns with HCN2: view

Primer 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
chimpanzee
(Pan troglodytes)
Mammalia LOC467640 34
  • 94.4 (n)
HCN2 35
  • 78 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HCN2 34 35
  • 93.03 (n)
cow
(Bos Taurus)
Mammalia HCN2 34 35
  • 91.4 (n)
oppossum
(Monodelphis domestica)
Mammalia HCN2 35
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hcn2 34
  • 87.93 (n)
mouse
(Mus musculus)
Mammalia Hcn2 34 16 35
  • 87.39 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HCN2 35
  • 67 (a)
OneToOne
chicken
(Gallus gallus)
Aves HCN2 34 35
  • 84.59 (n)
lizard
(Anolis carolinensis)
Reptilia HCN2 35
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hcn2 34
  • 76.49 (n)
zebrafish
(Danio rerio)
Actinopterygii hcn2b 34 35
  • 71.32 (n)
HCN2 (2 of 2) 35
  • 65 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Ih 36 35
  • 53 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.20011 34
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 53 (a)
ManyToMany
Species where no ortholog for HCN2 was found in the sources mined by GeneCards:
  • 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

ENSEMBL:
Gene Tree for HCN2 (if available)
TreeFam:
Gene Tree for HCN2 (if available)

Paralogs for HCN2 Gene

(3) SIMAP similar genes for HCN2 Gene using alignment to 1 proteins:

Pseudogenes.org 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
rs879255365 Benign 615,960(+) GCCGC(-/CGCCGCCGC)AGGTC cds-indel
rs10401400 -- 602,261(+) CCTCC(C/T)CTCTC intron-variant
rs10403485 -- 612,234(+) ACCAC(A/G)CAGAA intron-variant
rs10404628 -- 612,717(+) GCCTT(A/T)TTTTT intron-variant
rs10405282 -- 610,591(+) ACCCC(C/T)GCCAC intron-variant, nc-transcript-variant

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

Variant ID Type Subtype PubMed ID
nsv954667 CNV deletion 24416366
nsv953938 CNV deletion 24416366
nsv828350 CNV loss 20364138
nsv577978 CNV gain 21841781
nsv470101 CNV loss 18288195
nsv428360 CNV gain 18775914
nsv1142247 CNV tandem duplication 24896259
nsv1116526 OTHER inversion 24896259
nsv1071484 CNV deletion 25765185
esv3643356 CNV loss 21293372
esv3417596 CNV duplication 20981092
esv3361020 CNV duplication 20981092
esv3037 CNV loss 18987735
esv27631 CNV gain 19812545
esv2717749 CNV deletion 23290073
esv2717748 CNV deletion 23290073
esv2717746 CNV deletion 23290073
esv2658944 CNV deletion 23128226
esv1739089 CNV insertion 17803354
dgv6174n54 CNV loss 21841781
dgv484e201 CNV deletion 23290073
dgv483e201 CNV deletion 23290073
dgv482e201 CNV deletion 23290073
dgv1676n106 CNV deletion 24896259
dgv134n111 CNV deletion 26073780

Variation tolerance for HCN2 Gene

Residual Variation Intolerance Score: 2.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.56; 86.07% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HCN2 Gene

Human Gene Mutation Database (HGMD)
HCN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCN2

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

Disorders for HCN2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for HCN2 Gene - From: DISEASES

Disorder Aliases PubMed IDs
sinoatrial node disease
  • sa node
- elite association - COSMIC cancer census association via MalaCards
Search HCN2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for HCN2

Genetic Association Database (GAD)
HCN2
Human Genome Epidemiology (HuGE) Navigator
HCN2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HCN2
genes like me logo Genes that share disorders with HCN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas 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) 2 3 4 22 64
  2. Augmented currents of an HCN2 variant in patients with febrile seizure syndromes. (PMID: 20437590) Dibbens L.M. … Petrou S. (Ann. Neurol. 2010) 3 22 46 64
  3. 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 22 46 64
  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 64
  5. Tetramerization dynamics of C-terminal domain underlies isoform- specific cAMP gating in hyperpolarization-activated cyclic nucleotide- gated channels. (PMID: 22006928) Lolicato M. … Moroni A. (J. Biol. Chem. 2011) 3 4 64

Products for HCN2 Gene

Sources for HCN2 Gene

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