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HCN4 Gene

protein-coding   GIFtS: 67
GCID: GC15M073612

Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium...

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel
41 2
SSS22 5
Hyperpolarization Activated Cyclic Nucleotide-Gated Cation Channel 42
Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated
Channel 42

External Ids:    HGNC: 168821   Entrez Gene: 100212   Ensembl: ENSG000001386227   OMIM: 6052065   UniProtKB: Q9Y3Q43   

Export aliases for HCN4 gene to outside databases

Previous GC identifers: GC15M069662 GC15M066718 GC15M071189 GC15M071329 GC15M071400 GC15M050443


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 sinusitis, and brugada syndrome 8. GO annotations related to this gene include voltage-gated potassium channel activity and cation channel activity. An important paralog of this gene is KCNH6.

UniProtKB/Swiss-Prot: HCN4_HUMAN, Q9Y3Q4
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 rythm 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


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000015.10  NC_018926.2  NT_010194.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the HCN4 gene promoter:
         HOXA9B   HOXA9   Pax-5   Lmo2   Meis-1b   RORalpha1   PPAR-gamma1   PPAR-gamma2   c-Myc   Meis-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidHCN4 promoter sequence
   Search Chromatin IP Primers for HCN4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat HCN4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 15q24.1   Ensembl cytogenetic band:  15q24.1   HGNC cytogenetic band: 15q24.1

HCN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HCN4 gene location

GeneLoc information about chromosome 15         GeneLoc Exon Structure

GeneLoc location for GC15M073612:  view genomic region     (about GC identifiers)

Start:
73,612,200 bp from pter      End:
73,661,605 bp from pter
Size:
49,406 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: HCN4_HUMAN, Q9Y3Q4 (See protein sequence)
Recommended Name: Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4  
Size: 1203 amino acids; 129042 Da
Subunit: Homotetramer. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming
subunits
Miscellaneous: Inhibited by extracellular cesium ions
3 PDB 3D structures from and Proteopedia for HCN4:
3OTF (3D)        3U11 (3D)        4HBN (3D)    
Secondary accessions: Q9UMQ7

Explore the universe of human proteins at neXtProt for HCN4: NX_Q9Y3Q4

Explore proteomics data for HCN4 at MOPED

Post-translational modifications: 

  • Glycosylation2 at Asn458
  • Modification sites at PhosphoSitePlus

  • See HCN4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005468.1  
    ENSEMBL proteins: 
     ENSP00000261917  
    Reactome Protein details: Q9Y3Q4

    HCN4 Human Recombinant Protein Products:

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    Cloud-Clone Corp. CLIAs for HCN4


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CNG: Voltage-gated ion channels / Cyclic nucleotide-regulated channels

    IUPHAR Guide to PHARMACOLOGY protein family classification: HCN4
    Cyclic nucleotide-regulated channels

    Selected InterPro protein domains (see all 7):
     IPR018488 cNMP-bd_CS
     IPR018490 cNMP-bd-like
     IPR005821 Ion_trans_dom
     IPR000595 cNMP-bd_dom
     IPR003938 K_chnl_volt-dep_EAG/ELK/ERG

    Graphical View of Domain Structure for InterPro Entry Q9Y3Q4

    ProtoNet protein and cluster: Q9Y3Q4

    2 Blocks protein domains:
    IPB000595 Cyclic nucleotide-binding domain
    IPB013621 Ion transport N-terminal


    UniProtKB/Swiss-Prot: HCN4_HUMAN, Q9Y3Q4
    Domain: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino
    acids at every third position
    Similarity: Belongs to the potassium channel HCN family
    Similarity: Contains 1 cyclic nucleotide-binding domain


    HCN4 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: HCN4_HUMAN, Q9Y3Q4
    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 rythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate
    responses to sour stimuli
    Enzyme regulation: Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an
    active tetramer and channel opening

         Genatlas biochemistry entry for HCN4:
    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

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005222intracellular cAMP activated cation channel activity IDA16407510
    GO:0005248voltage-gated sodium channel activity IMP--
    GO:0005249voltage-gated potassium channel activity IMP--
    GO:0005261cation channel activity TAS10228147
         
    HCN4 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for HCN4:
     Decreased Salmonella enterica   Decreased viability with pacli 

         6 MGI mutant phenotypes (inferred from 9 alleles(MGI details for Hcn4):
     cardiovascular system  growth/size/body  homeostasis/metabolism  mortality/aging  muscle 
     normal 

    HCN4 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Hcn4tm1.1Jsr for HCN4

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for HCN4
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       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for HCN4

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    miRTarBase miRNAs that target HCN4:
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    Block miRNA regulation of human, mouse, rat HCN4 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate HCN4 (see all 61):
    hsa-miR-642a hsa-miR-520f hsa-miR-300 hsa-miR-631 hsa-miR-106a hsa-miR-128 hsa-miR-218 hsa-miR-149
    SwitchGear 3'UTR luciferase reporter plasmidHCN4 3' UTR sequence
    Inhib. RNA
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    HCN4_HUMAN, Q9Y3Q4: Cell membrane; Multi-pass membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane4
    cytoskeleton1
    cytosol1
    extracellular1
    peroxisome1

    Gene Ontology (GO): 5 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane IBA--
    GO:0016020membrane ----
    GO:0031226intrinsic component of plasma membrane IDA16407510
    GO:0043195terminal bouton IEA--

    HCN4 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for HCN4 About   (see all 7)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Sodium channels and transporters inward current
    Sodium channels and transporters inward current
    HCN channels0.00
    2Transmission across Chemical Synapses
    Neuronal System0.68
    3Potassium Channels
    Potassium Channels0.43
    4Sweet Taste Signaling
    Sperm Motility0.37
    5Synaptic transmission ion currents
    Synaptic transmission ion currents

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 Downloadable PowerPoint Slide of GeneGlobe Pathway Central Maps for HCN4
        Sperm Motility

    1 Reactome Pathway for HCN4
        HCN channels

    1 PharmGKB Pathway for HCN4
        Antiarrhythmic Pathway, Pharmacodynamics


    HCN4 for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for HCN4
    Interactions:

        Search GeneGlobe Interaction Network for HCN4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 13)

    Selected Interacting proteins for HCN4 (Q9Y3Q41, 3 ENSP000002619174) via UniProtKB, MINT, STRING, and/or I2D (see all 14)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ABL1P005193, ENSP000003614234I2D: score=1 STRING: ENSP00000361423
    FYNP062413, ENSP000003576564I2D: score=1 STRING: ENSP00000357656
    HCN1O607413, ENSP000003073424I2D: score=1 STRING: ENSP00000307342
    HCN2Q9UL513, ENSP000002512874I2D: score=2 STRING: ENSP00000251287
    HCN3Q9P1Z33, ENSP000003573424I2D: score=1 STRING: ENSP00000357342
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001701in utero embryonic development IEA--
    GO:0002027regulation of heart rate IMP16407510
    GO:0006811ion transport ----
    GO:0006812cation transport TAS10228147
    GO:0006936muscle contraction TAS10228147

    HCN4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for HCN4

    2 HMDB Compounds for HCN4    About this table
    CompoundSynonyms CAS #PubMed Ids
    Cyclic AMPCyclic AMP (see all 19)60-92-4--
    SodiumSodium (see all 2)7440-23-5--

    6 IUPHAR Ligands for HCN4 (HCN4)    About this table
    LigandTypeActionAffinityPubmed IDs
    cilobradine
    Pore BlockerAntagonist616387796
    ivabradine
    Pore BlockerAntagonist5.716387796
    zatebradine
    Pore BlockerAntagonist5.716387796
    EC18
    Pore BlockerNone5.422091830
    ZD7288
    Pore BlockerAntagonist4.716043489
    Cs+
    Pore BlockerAntagonist3.816043489

    2 Novoseek inferred chemical compound relationships for HCN4 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    potassium 29 2 19324302 (1)
    phenylalanine 28.6 3 16079136 (1), 12813043 (1)



    HCN4 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for HCN4 gene: 
    NM_005477.2  

    Unigene Cluster for HCN4:

    Hyperpolarization activated cyclic nucleotide-gated potassium channel 4
    Hs.86941  [show with all ESTs]
    Unigene Representative Sequence: NM_005477
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000261917(uc002avp.3)
    miRNA
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    hsa-miR-642a hsa-miR-520f hsa-miR-300 hsa-miR-631 hsa-miR-106a hsa-miR-128 hsa-miR-218 hsa-miR-149
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    Additional mRNA sequence: 

    AJ132429.1 AJ238850.1 DQ854814.1 

    2 DOTS entries:

    DT.108315  DT.108314 

    Selected AceView cDNA sequences (see all 42):

    AI638000 BE045688 AI989696 AA902394 AJ132429 NM_005477 BX090501 BE327046 
    BE552405 AI990915 AV726930 BM979827 AI990839 BE218041 AW770658 AW136545 
    BE552011 AA995375 BE220369 AJ238850 AW770740 BE463817 BE327512 BE221167 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    HCN4 expression in normal human tissues (normalized intensities)      HCN4 embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: CATTTTATAA
    HCN4 Expression
    About this image


    HCN4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Heart (Cardiovascular System)    fully expand to see all 4 entries
             Sinoatrial Node Cells Sinoatrial Node
             Early cardiomyocytes
     
     Brain (Nervous System)    fully expand to see all 9 entries
             Thalamus
     
     NULL (Cardiovascular System)    fully expand to see all 2 entries
             Floating colonies of cardiomyocytes
     
     Neurons
             Type3a Off Cone Bipolar Cells Inner Nuclear Layer
     
     Eye (Sensory Organs)
             Type3a Off Cone Bipolar Cells Inner Nuclear Layer
    HCN4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    HCN4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.86941

    UniProtKB/Swiss-Prot: HCN4_HUMAN, Q9Y3Q4
    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

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    In Situ
    Assay Products:
     

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HCN4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for HCN4 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hcn41 , 5 hyperpolarization-activated, cyclic nucleotide-gated K+ 4 less1, 5 89.18(n)1
    94.91(a)1
      9 (31.80 cM)5
    3309531  NM_001081192.11  NP_001074661.11 
     588235125 
    chicken
    (Gallus gallus)
    Aves HCN41 hyperpolarization activated cyclic nucleotide-gated potassium channel 4 less 73.88(n)
    78.11(a)
      427478  XM_425050.4  XP_425050.3 
    lizard
    (Anolis carolinensis)
    Reptilia HCN46
    hyperpolarization activated cyclic nucleotide-gate...
    72(a)
    1 ↔ 1
    GL343517.1(227271-308602)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia hcn41 hyperpolarization activated cyclic nucleotide-gated potassium channel 4 less 70.95(n)
    77.63(a)
      100495521  XM_004915967.1  XP_004916024.1 
    zebrafish
    (Danio rerio)
    Actinopterygii hcn4l1 hyperpolarization activated cyclic nucleotide-gated potassium channel 4l less 73.63(n)
    79.77(a)
      556759  XM_679638.5  XP_684730.5 
    fruit fly
    (Drosophila melanogaster)
    Insecta Ih3 intracellular cyclic nucleotide
    activated cation channel less
    54(a)     --


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for HCN4 gene
    KCNH62  KCNH32  KCNH52  HCN32  KCNH42  HCN22  CNGA12  CNGA22  
    HCN12  KCNH22  KCNH72  CNGB12  CNGA42  CNGA32  CNGB32  KCNH82  
    KCNH12  
    3 SIMAP similar genes for HCN4 using alignment to 1 protein entry:     HCN4_HUMAN:
    HCN3    HCN1    HCN2

    HCN4 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for HCN4 (see all 1037)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 15 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0265354
    Sick sinus syndrome 2 (SSS2)4--see VAR_0265352 S R mis40--------
    VAR_0666144
    Sick sinus syndrome 2 (SSS2)4--see VAR_0666142 A V mis40--------
    rs1048944881,2
    Cpathogenic153666122(-) GCCAGA/CGTGAG 2 R S mis10--------
    rs1048944851,2
    Cpathogenic153667284(-) TCCACA/GACTAC 2 N D mis10--------
    rs1453708151,2
    C--53661281(+) CCACCA/CTCTGA 1 -- ds50010--------
    rs1886586351,2
    --53661381(+) TGGATA/GGAGCC 1 -- ds50010--------
    rs2010487781,2
    --53661385(+) TGGAG-/CCCA  
            
    GGTGC
    1 -- ds50010--------
    rs125941321,2
    C,A,H--53661433(+) AGTAGT/GGGGTG 1 -- ds50011Minor allele frequency- G:0.00NA 2
    rs1413376821,2
    C--53661500(+) ACATGC/TCCACT 1 -- ds50010--------
    rs1450781771,2
    --53661663(+) CTCTGA/GGCCAT 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for HCN4 (73612200 - 73661605 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 4 variations for HCN4:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv998986CNV Insertion20482838
    nsv524049CNV Loss19592680
    esv28407CNV Loss19812545
    nsv904343CNV Gain21882294

    Human Gene Mutation Database (HGMD): HCN4
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing HCN4
    DNA2.0 Custom Variant and Variant Library Synthesis for HCN4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 605206   
    OMIM disorders: 163800  613123  
    UniProtKB/Swiss-Prot: HCN4_HUMAN, Q9Y3Q4
  • 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. Note=The disease is caused by mutations affecting the
    gene represented in this entry
  • 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. Note=The disease is caused by mutations affecting
    the gene represented in this entry

  • 17 diseases for HCN4:    About MalaCards
    sinusitis    brugada syndrome 8    sick sinus syndrome 2, autosomal dominant    sick sinus syndrome 2
    sick sinus syndrome    brugada syndrome 1    brugada syndrome    syncope
    long qt syndrome    obsessive-compulsive disorder    fainting    mood disorder
    hypertrophic cardiomyopathy    multiple myeloma    myeloma    neuronitis
    cerebritis

    2 diseases from the University of Copenhagen DISEASES database for HCN4:
    Sick sinus syndrome     Brugada syndrome

    HCN4 for disorders           About GeneDecksing

    Genetic Association Database (GAD): HCN4
    Human Genome Epidemiology (HuGE) Navigator: HCN4 (3 documents)

    Export disorders for HCN4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for HCN4 gene, integrated from 10 sources (see all 68):
    (articles sorted by number of sources associating them with HCN4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis. (PubMed id 10430953)1, 2, 3 Seifert R....Kaupp U.B. (Proc. Natl. Acad. Sci. U.S.A. 1999)
    2. Two pacemaker channels from human heart with profoundly different activation kinetics. (PubMed id 10228147)1, 2, 3 Ludwig A.... Biel M. (EMBO J. 1999)
    3. Role of HCN4 channel in preventing ventricular arrhythmia. (PubMed id 19165230)1, 2, 9 Ueda K....Kimura A. (J. Hum. Genet. 2009)
    4. Local and global interpretations of a disease-causing mutation near the ligand entry path in hyperpolarization-activated cAMP-gated channel. (PubMed id 23103389)1, 2 Xu X....Zhou L. (Structure 2012)
    5. A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews. (PubMed id 20662977)1, 2 Laish-Farkash A.... Luria D. (J. Cardiovasc. Electrophysiol. 2010)
    6. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (Diabetes Care 2010)
    7. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. (PubMed id 16407510)1, 2 Milanesi R.... DiFrancesco D. (N. Engl. J. Med. 2006)
    8. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. (PubMed id 16382102)1, 3 Hofmann F....Kaupp U.B. (Pharmacol. Rev. 2005)
    9. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. (PubMed id 15123648)1, 2 Ueda K....Kimura A. (J. Biol. Chem. 2004)
    10. Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4. (PubMed id 12813043)1, 9 Stieber J....Hofmann F. (J. Biol. Chem. 2003)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
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    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 10021 HGNC: 16882 AceView: HCN4 Ensembl:ENSG00000138622 euGenes: HUgn10021
    ECgene: HCN4 H-InvDB: HCN4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for HCN4 Pharmacogenomics, SNPs, Pathways

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for HCN4 gene:
    Search GeneIP for patents involving HCN4

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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