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HCN4 hyperpolarization activated cyclic nucleotide gated potassium channel 4 [ Homo sapiens (human) ]

Gene ID: 10021, updated on 7-Dec-2018

Summary

Official Symbol
HCN4provided by HGNC
Official Full Name
hyperpolarization activated cyclic nucleotide gated potassium channel 4provided by HGNC
Primary source
HGNC:HGNC:16882
See related
Ensembl:ENSG00000138622 MIM:605206
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
SSS2
Summary
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]
Expression
Biased expression in testis (RPKM 3.3), heart (RPKM 1.0) and 3 other tissues See more
Orthologs

Genomic context

See HCN4 in Genome Data Viewer
Location:
15q24.1
Exon count:
9
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 15 NC_000015.10 (73319859..73369264, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (73612200..73661605, complement)

Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene neogenin 1 Neighboring gene FKBP prolyl isomerase 1A pseudogene 2 Neighboring gene nucleophosmin 1 pseudogene 43 Neighboring gene uncharacterized LOC105370890 Neighboring gene VISTA enhancer hs2161 Neighboring gene serine-aspartate repeat-containing protein I-like Neighboring gene REC114 meiotic recombination protein Neighboring gene mitochondrial ribosomal protein S15 pseudogene 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Brugada syndrome 8
MedGen: C2751083 OMIM: 613123 GeneReviews: Brugada Syndrome
Compare labs
Sick sinus syndrome 2, autosomal dominant
MedGen: C1834144 OMIM: 163800 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
NHGRI GWA Catalog
Meta-analysis identifies six new susceptibility loci for atrial fibrillation.
NHGRI GWA Catalog

Pathways from BioSystems

  • HCN channels, organism-specific biosystem (from REACTOME)
    HCN channels, organism-specific biosystemHyperpolarization-activated cyclic nucleotide-gated (HCN) channels are nonselective ligand-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred ...
  • Neuronal System, organism-specific biosystem (from REACTOME)
    Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
  • Potassium Channels, organism-specific biosystem (from REACTOME)
    Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
  • TarBasePathway, organism-specific biosystem (from WikiPathways)
    TarBasePathway, organism-specific biosystemThis cataloge pathway was created using the database from "http://diana.cslab.ece.ntua.gr/tarbase/" with exclusions based on evidance type. This pathway only incldes miR targeted genes expressed in A...
  • Taste transduction, organism-specific biosystem (from KEGG)
    Taste transduction, organism-specific biosystemFive basic tastes are recognized by humans and most other animals - bitter, sweet, sour, salty and umami. In vertebrates, taste stimuli are detected by taste receptor cells (TRCs). At least three dis...
  • Taste transduction, conserved biosystem (from KEGG)
    Taste transduction, conserved biosystemFive basic tastes are recognized by humans and most other animals - bitter, sweet, sour, salty and umami. In vertebrates, taste stimuli are detected by taste receptor cells (TRCs). At least three dis...
  • cAMP signaling pathway, organism-specific biosystem (from KEGG)
    cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
  • cAMP signaling pathway, conserved biosystem (from KEGG)
    cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
SA node cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
blood circulation NAS
Non-traceable Author Statement
more info
PubMed 
cation transport IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to cAMP IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to cGMP IDA
Inferred from Direct Assay
more info
PubMed 
membrane depolarization during SA node cell action potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane depolarization during cardiac muscle cell action potential IC
Inferred by Curator
more info
PubMed 
muscle contraction TAS
Traceable Author Statement
more info
PubMed 
potassium ion import across plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion transmembrane transport IDA
Inferred from Direct Assay
more info
PubMed 
potassium ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cardiac muscle cell action potential involved in regulation of contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cardiac muscle contraction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate by cardiac conduction IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of ion transmembrane transport IEA
Inferred from Electronic Annotation
more info
 
regulation of membrane depolarization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of membrane potential IMP
Inferred from Mutant Phenotype
more info
PubMed 
sodium ion import across plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
sodium ion transmembrane transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
HCN channel complex IDA
Inferred from Direct Assay
more info
PubMed 
intrinsic component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
perinuclear region of cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4
Names
hyperpolarization activated cyclic nucleotide-gated cation channel 4

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_009063.1 RefSeqGene

    Range
    5001..54406
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_005477.3NP_005468.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

    See identical proteins and their annotated locations for NP_005468.1

    Status: REVIEWED

    Source sequence(s)
    AC068397, AJ132429, AJ238850, BM979827, BP291686
    Consensus CDS
    CCDS10248.1
    UniProtKB/Swiss-Prot
    Q9Y3Q4
    Related
    ENSP00000261917.3, ENST00000261917.3
    Conserved Domains (4) summary
    COG0664
    Location:589724
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:595703
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam00520
    Location:280525
    Ion_trans; Ion transport protein
    pfam08412
    Location:218260
    Ion_trans_N; Ion transport protein N-terminal

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000015.10 Reference GRCh38.p12 Primary Assembly

    Range
    73319859..73369264 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011521148.2XP_011519450.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 isoform X1

    Conserved Domains (3) summary
    COG0664
    Location:183318
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:189297
    CAP_ED; effector domain of the CAP family of transcription factors; members include CAP (or cAMP receptor protein (CRP)), which binds cAMP, FNR (fumarate and nitrate reduction), which uses an iron-sulfur cluster to sense oxygen) and CooA, a heme containing CO ...
    pfam00520
    Location:5119
    Ion_trans; Ion transport protein
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