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Aliases for HCN4 Gene

Aliases for HCN4 Gene

  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4 2 3 5
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 4 2 3
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Cation Channel 4 3
  • SSS2 3

External Ids for HCN4 Gene

Previous GeneCards Identifiers for HCN4 Gene

  • GC15M069662
  • GC15M066718
  • GC15M071189
  • GC15M071329
  • GC15M071400
  • GC15M073612
  • GC15M050443

Summaries for HCN4 Gene

Entrez Gene Summary for HCN4 Gene

  • This gene encodes a member of the hyperpolarization-activated cyclic nucleotide-gated potassium channels. The encoded protein shows slow kinetics of activation and inactivation, and is necessary for the cardiac pacemaking process. This channel may also mediate responses to sour stimuli. Mutations in this gene have been linked to sick sinus syndrome 2, also known as atrial fibrillation with bradyarrhythmia or familial sinus bradycardia. Two pseudogenes have been identified on chromosome 15. [provided by RefSeq, Oct 2008]

GeneCards Summary for HCN4 Gene

HCN4 (Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4) is a Protein Coding gene. Diseases associated with HCN4 include sick sinus syndrome 2 and brugada syndrome 8. Among its related pathways are Transmission across Chemical Synapses and cAMP signaling pathway. GO annotations related to this gene include identical protein binding and voltage-gated potassium channel activity. An important paralog of this gene is KCNH1.

UniProtKB/Swiss-Prot for HCN4 Gene

  • Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.

Gene Wiki entry for HCN4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HCN4 Gene

Genomics for HCN4 Gene

Regulatory Elements for HCN4 Gene

Genomic Location for HCN4 Gene

Chromosome:
15
Start:
73,319,859 bp from pter
End:
73,369,264 bp from pter
Size:
49,406 bases
Orientation:
Minus strand

Genomic View for HCN4 Gene

Genes around HCN4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCN4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCN4 Gene

Proteins for HCN4 Gene

  • Protein details for HCN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y3Q4-HCN4_HUMAN
    Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
    Protein Accession:
    Q9Y3Q4
    Secondary Accessions:
    • Q9UMQ7

    Protein attributes for HCN4 Gene

    Size:
    1203 amino acids
    Molecular mass:
    129042 Da
    Quaternary structure:
    • Homotetramer. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits.
    Miscellaneous:
    • Inhibited by extracellular cesium ions.

    Three dimensional structures from OCA and Proteopedia for HCN4 Gene

neXtProt entry for HCN4 Gene

Proteomics data for HCN4 Gene at MOPED

Post-translational modifications for HCN4 Gene

  • Glycosylation at Asn 458
  • Modification sites at PhosphoSitePlus

Other Protein References for HCN4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HCN4 Gene

Domains & Families for HCN4 Gene

Gene Families for HCN4 Gene

Suggested Antigen Peptide Sequences for HCN4 Gene

Graphical View of Domain Structure for InterPro Entry

Q9Y3Q4

UniProtKB/Swiss-Prot:

HCN4_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 HCN4: view

Function for HCN4 Gene

Molecular function for HCN4 Gene

GENATLAS Biochemistry:
hyperpolarization-activated and cyclic nucleotide gated potassium channel 4,expressed in the brain,predominantly in thalamus,heart and testis,playing a critical role in shaping the autonomous activity of single neurons and the periodocity of network oscillations
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening.
UniProtKB/Swiss-Prot Function:
Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.

Gene Ontology (GO) - Molecular Function for HCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005248 voltage-gated sodium channel activity IMP 22748890
GO:0042802 identical protein binding IPI 22006928
genes like me logo Genes that share ontologies with HCN4: view
genes like me logo Genes that share phenotypes with HCN4: view

Human Phenotype Ontology for HCN4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for HCN4 Gene

MGI Knock Outs for HCN4:

Animal Model Products

  • Taconic Biosciences Mouse Models for HCN4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for HCN4 Gene

Localization for HCN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCN4 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HCN4 Gene COMPARTMENTS Subcellular localization image for HCN4 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 1
cytosol 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for HCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0016020 membrane IEA --
genes like me logo Genes that share ontologies with HCN4: view

Pathways & Interactions for HCN4 Gene

genes like me logo Genes that share pathways with HCN4: view

Pathways by source for HCN4 Gene

3 Reactome pathways for HCN4 Gene
1 PharmGKB pathway for HCN4 Gene
2 KEGG pathways for HCN4 Gene
1 Qiagen pathway for HCN4 Gene

SIGNOR curated interactions for HCN4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for HCN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002027 regulation of heart rate IMP 16407510
GO:0006811 ion transport IEA --
GO:0006812 cation transport IDA 12750403
GO:0006936 muscle contraction TAS 10228147
GO:0035725 sodium ion transmembrane transport IMP 22748890
genes like me logo Genes that share ontologies with HCN4: view

Drugs & Compounds for HCN4 Gene

(9) Drugs for HCN4 Gene - From: IUPHAR, DGIdb, Novoseek, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
cilobradine Pharma Antagonist, Pore Blocker 0
Cs<sup>+</sup> Pharma Antagonist, Pore Blocker 0
EC18 Pharma Pore Blocker 0
ivabradine Pharma Antagonist, Pore Blocker 0

(5) Additional Compounds for HCN4 Gene - From: Tocris and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Sodium
  • Sodium ion
7440-23-5
Cesium chloride
7647-17-8
YS-035 hydrochloride
89805-39-0
Zatebradine hydrochloride
91940-87-3
ZD 7288
133059-99-1

(4) Tocris Compounds for HCN4 Gene

Compound Action Cas Number
Cesium chloride Potassium channel blocker; neuroprotective 7647-17-8
YS-035 hydrochloride Inhibits K+ outward/pacemaker current 89805-39-0
Zatebradine hydrochloride Blocks hyperpolarization-activated current (If) 91940-87-3
ZD 7288 Inhibits pacemaker (If) current 133059-99-1
genes like me logo Genes that share compounds with HCN4: view

Transcripts for HCN4 Gene

mRNA/cDNA for HCN4 Gene

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

Unigene Clusters for HCN4 Gene

Hyperpolarization activated cyclic nucleotide-gated potassium channel 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for HCN4 Gene

No ASD Table

Relevant External Links for HCN4 Gene

GeneLoc Exon Structure for
HCN4
ECgene alternative splicing isoforms for
HCN4

Expression for HCN4 Gene

mRNA expression in normal human tissues for HCN4 Gene

mRNA differential expression in normal tissues according to GTEx for HCN4 Gene

This gene is overexpressed in Heart - Atrial Appendage (x16.3), Testis (x12.2), and Heart - Left Ventricle (x9.1).

Protein differential expression in normal tissues from HIPED for HCN4 Gene

This gene is overexpressed in Lung (30.2), Plasma (13.2), Peripheral blood mononuclear cells (12.5), and Frontal cortex (8.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for HCN4 Gene



SOURCE GeneReport for Unigene cluster for HCN4 Gene Hs.86941

mRNA Expression by UniProt/SwissProt for HCN4 Gene

Q9Y3Q4-HCN4_HUMAN
Tissue specificity: Highly expressed in thalamus, testis and in heart, both in ventricle and atrium. Detected at much lower levels in amygdala, substantia nigra, cerebellum and hippocampus.
genes like me logo Genes that share expression patterns with HCN4: view

Protein tissue co-expression partners for HCN4 Gene

Primer Products

In Situ Assay Products

Orthologs for HCN4 Gene

This gene was present in the common ancestor of animals.

Orthologs for HCN4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia HCN4 35
  • 90.69 (n)
  • 94.41 (a)
HCN4 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Hcn4 35
  • 89.18 (n)
  • 94.91 (a)
Hcn4 16
Hcn4 36
  • 95 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia HCN4 35
  • 98.98 (n)
  • 99.07 (a)
HCN4 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hcn4 35
  • 89.28 (n)
  • 95.32 (a)
dog
(Canis familiaris)
Mammalia HCN4 36
  • 93 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HCN4 36
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 97 (a)
OneToMany
-- 36
  • 97 (a)
OneToMany
-- 36
  • 94 (a)
OneToMany
chicken
(Gallus gallus)
Aves HCN4 35
  • 73.88 (n)
  • 78.11 (a)
HCN4 36
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HCN4 36
  • 72 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hcn4 35
  • 70.95 (n)
  • 77.63 (a)
zebrafish
(Danio rerio)
Actinopterygii hcn4l 35
  • 73.63 (n)
  • 79.77 (a)
hcn4 36
  • 64 (a)
OneToMany
hcn4l 36
  • 59 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Ih 37
  • 54 (a)
Ih 36
  • 30 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 50 (a)
ManyToMany
Species with no ortholog for HCN4:
  • 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)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HCN4 Gene

ENSEMBL:
Gene Tree for HCN4 (if available)
TreeFam:
Gene Tree for HCN4 (if available)

Paralogs for HCN4 Gene

(3) SIMAP similar genes for HCN4 Gene using alignment to 1 proteins:

genes like me logo Genes that share paralogs with HCN4: view

Variants for HCN4 Gene

Sequence variations from dbSNP and Humsavar for HCN4 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type
rs104894485 Sick sinus syndrome 2 (SSS2) 73,325,378(-) TCCAC(A/G)ACTAC reference, missense
VAR_026535 Sick sinus syndrome 2 (SSS2)
VAR_066614 Sick sinus syndrome 2 (SSS2)
rs547338 -- 73,344,810(+) TGTGG(A/C)AACAA intron-variant
rs549377 -- 73,320,492(+) CATTA(C/T)TTGGG utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for HCN4 Gene

Variant ID Type Subtype PubMed ID
nsv904343 CNV Gain 21882294
nsv524049 CNV Loss 19592680
esv998986 CNV Insertion 20482838
esv28407 CNV Loss 19812545

Variation tolerance for HCN4 Gene

Residual Variation Intolerance Score: 7.35% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.57; 56.01% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HCN4 Gene

HapMap Linkage Disequilibrium report
HCN4
Human Gene Mutation Database (HGMD)
HCN4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCN4 Gene

Disorders for HCN4 Gene

MalaCards: The human disease database

(13) MalaCards diseases for HCN4 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
sick sinus syndrome 2
  • sick sinus syndrome 2, autosomal dominant
brugada syndrome 8
  • brgda8
familial sick sinus syndrome
  • familial sinus node dysfunction
brugada syndrome
  • sudden unexpected nocturnal death syndrome
sick sinus syndrome
  • sinus node infection
- elite association - COSMIC cancer census association via MalaCards
Search HCN4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

HCN4_HUMAN
  • Brugada syndrome 8 (BRGDA8) [MIM:613123]: A tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269 PubMed:19165230}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Sick sinus syndrome 2 (SSS2) [MIM:163800]: The term sick sinus syndrome encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia (tachycardia-bradycardia syndrome) are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth. {ECO:0000269 PubMed:15123648, ECO:0000269 PubMed:16407510, ECO:0000269 PubMed:20662977}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for HCN4

Genetic Association Database (GAD)
HCN4
Human Genome Epidemiology (HuGE) Navigator
HCN4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HCN4
genes like me logo Genes that share disorders with HCN4: view

No data available for Genatlas for HCN4 Gene

Publications for HCN4 Gene

  1. Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. (PMID: 10430953) Seifert R. … Kaupp U.B. (Proc. Natl. Acad. Sci. U.S.A. 1999) 2 3 4 67
  2. Role of HCN4 channel in preventing ventricular arrhythmia. (PMID: 19165230) Ueda K. … Kimura A. (J. Hum. Genet. 2009) 3 23
  3. Novel pharmacological activity of loperamide and CP-339,818 on human HCN channels characterized with an automated electrophysiology assay. (PMID: 18162181) Lee Y.T. … Bowlby M.R. (Eur. J. Pharmacol. 2008) 3 23
  4. Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. (PMID: 17646576) Nof E. … Glikson M. (Circulation 2007) 3 23
  5. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. (PMID: 16382102) Hofmann F. … Kaupp U.B. (Pharmacol. Rev. 2005) 2 3

Products for HCN4 Gene

Sources for HCN4 Gene

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