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

    Gene ID: 10021, updated on 27-Nov-2024

    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; AllianceGenome:HGNC:16882
    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; EIG18; BRGDA8
    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
    NEW
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    Try the new Transcript table

    Genomic context

    See HCN4 in Genome Data Viewer
    Location:
    15q24.1
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 15 NC_000015.10 (73319859..73368958, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 15 NC_060939.1 (71136994..71186091, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 15 NC_000015.9 (73612200..73661299, complement)

    Chromosome 15 - NC_000015.10Genomic Context describing neighboring genes Neighboring gene neogenin 1 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:73457693-73458892 Neighboring gene nucleophosmin 1 pseudogene 43 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr15:73517560-73518759 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6632 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:73617084-73617584 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:73617585-73618085 Neighboring gene microRNA 12135 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr15:73622233-73623136 Neighboring gene uncharacterized LOC105370890 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr15:73635762-73636961 Neighboring gene MPRA-validated peak2386 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:73644210-73644710 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr15:73644711-73645211 Neighboring gene Sharpr-MPRA regulatory region 342 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 Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Brugada syndrome 8
    MedGen: C2751083 OMIM: 613123 GeneReviews: Brugada Syndrome
    not available
    Epilepsy, idiopathic generalized, susceptibility to, 18
    MedGen: C5561983 OMIM: 619521 GeneReviews: Not available
    not available
    Sick sinus syndrome 2, autosomal dominant
    MedGen: C1834144 OMIM: 163800 GeneReviews: Not available
    not available

    EBI GWAS Catalog

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

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in SA node cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in blood circulation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cellular response to cAMP IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in cellular response to cGMP IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in membrane depolarization during SA node cell action potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in membrane depolarization during cardiac muscle cell action potential IC
    Inferred by Curator
    more info
    PubMed 
    involved_in monoatomic cation transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in muscle contraction TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in potassium ion import across plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in potassium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in potassium ion transmembrane transport IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in potassium ion transmembrane transport IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cardiac muscle cell action potential involved in regulation of contraction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cardiac muscle contraction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of heart rate IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of heart rate by cardiac conduction IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of membrane depolarization IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of membrane depolarization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of membrane potential IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in sinoatrial node development NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in sodium ion import across plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in sodium ion transmembrane transport IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in sodium ion transmembrane transport IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of HCN channel complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of HCN channel complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in axon IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    is_active_in dendrite IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in 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)

    NEW Try the new Transcript table

    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
      5307..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
      Q9UMQ7, Q9Y3Q4
      Related
      ENSP00000261917.3, ENST00000261917.4
      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: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000015.10 Reference GRCh38.p14 Primary Assembly

      Range
      73319859..73368958 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011521148.3XP_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

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060939.1 Alternate T2T-CHM13v2.0

      Range
      71136994..71186091 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054377165.1XP_054233140.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 isoform X1