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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

HCN4 Gene

protein-coding   GIFtS: 66
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)
About This Section

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, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

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 sick sinus syndrome 2, and among its related super-pathways are Transmission across Chemical Synapses and Voltage gated Potassium channels. GO annotations related to this gene include cAMP binding and voltage-gated potassium 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. May contribute to the native pacemaker currents in heart (If) and in
neurons (Ih). Activated by cAMP. 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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000015.9  NC_018926.2  NT_010194.17  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for HCN4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
About This Section

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: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming
subunits
Subcellular location: Membrane; Multi-pass membrane protein
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:

  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_Q9Y3Q4

  • HCN4 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    HCN4 Protein Expression
    REFSEQ proteins: NP_005468.1  
    ENSEMBL proteins: 
     ENSP00000261917  
    Reactome Protein details: Q9Y3Q4
    Human Recombinant Protein Products for HCN4: 
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    Novus Biologicals HCN4 Protein
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    Browse Sino Biological Cell Lysates 
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for HCN4 

    Gene Ontology (GO): 5 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005886plasma membrane TAS--
    GO:0005887integral to plasma membrane IBA--
    GO:0016020membrane ----
    GO:0016021integral to membrane ----
    GO:0043195terminal bouton IEA--

    HCN4 for ontologies           About GeneDecksing



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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)
    About This Section
    HGNC Gene Families: 
    CNG: Voltage-gated ion channels / Cyclic nucleotide-regulated channels

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

    5/7 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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    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. May contribute to the native pacemaker currents in heart (If) and in
    neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli

         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): 5/7 molecular function terms (GO ID links to tree view) (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005216ion channel activity ----
    GO:0005222intracellular cAMP activated cation channel activity IEA--
    GO:0005249voltage-gated potassium channel activity IBA--
    GO:0005261cation channel activity TAS10228147
    GO:0005272sodium channel activity IEA--
         
    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 7 alleles(MGI details for Hcn4):
     cardiovascular system  growth/size  homeostasis/metabolism  mortality/aging  muscle 
     normal 

    HCN4 for phenotypes           About GeneDecksing

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

       inGenious Targeting Laboratory - Custom generated mouse model solutions for HCN4 
       inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for HCN4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for HCN4 
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    miRNA
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    8/61 QIAGEN miScript miRNA 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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    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    SuperPaths for HCN4 About   (see all 8)                                                                                              See pathways by source

    SuperPathContained pathways About
    1Transmission across Chemical Synapses
    Neuronal System0.67
    2Potassium Channels
    Potassium Channels0.43
    3Sweet Taste Signaling
    Sperm Motility0.37
    4Synaptic transmission: ion currents
    Synaptic transmission: ion currents
    5Potassium transporters: inward current
    Potassium transporters: inward current

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    3 EMD Millipore Pathways for HCN4
        Potassium transporters- inward current
    Synaptic transmission- ion currents
    Sodium channels and transporters- inward current

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

    3        Reactome Pathways for HCN4
        Potassium Channels
    HCN channels
    Neuronal System

    1 PharmGKB Pathway for HCN4
        Antiarrhythmic Pathway, Pharmacodynamics


    HCN4 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for HCN4

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

    5 Interacting proteins for HCN4 (Q9Y3Q43 ENSP000002619174) via UniProtKB, MINT, STRING, and/or I2D
    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): 5/10 biological process terms (GO ID links to tree view) (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001701in utero embryonic development IEA--
    GO:0006811ion transport ----
    GO:0006812cation transport TAS10228147
    GO:0006936muscle contraction TAS10228147
    GO:0007268synaptic transmission TAS--

    HCN4 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    HCN4 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    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)

    Search CenterWatch for drugs/clinical trials and news about HCN4

    (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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    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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    Additional mRNA sequence: 

    AJ132429.1 AJ238850.1 DQ854814.1 

    2 DOTS entries:

    DT.108315  DT.108314 

    24/42 AceView cDNA sequences (see all 42):

    AI989696 AV726930 NM_005477 AI638000 BE552405 BE327046 BE045688 BX090501 
    AJ132429 BM979827 AA902394 AI990915 AI990839 AW770740 AA969962 BE327512 
    AI273647 BE552011 AJ238850 AI702698 AW770658 AW136545 BE218041 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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    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 
     5/6 selected tissues (see all 6) fully expand
     
     Brain (Nervous System)    fully expand to see all 15 entries
             Thalamus
             Septum   
     
     Heart (Cardiovascular System)    fully expand to see all 2 entries
             Sinoatrial Node Cells Sinoatrial Node
     
     Spinal Cord (Nervous System)    fully expand to see all 2 entries
             Dorsal Horn   
     
     Endothelium (Cardiovascular System)
             cardinal vein/common   
     
     Eye (Sensory Organs)
             Type3a Off Cone Bipolar Cells Inner Nuclear Layer

    See HCN4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for HCN4

    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)
    About This Section

    This gene was present in the common ancestor of eukaryotes.

    Orthologs for HCN4 gene from 7/14 species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Hcn41 , 5 hyperpolarization-activated, cyclic nucleotide-gated more1, 5 89.54(n)1
    95.66(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 more 74.87(n)
    79.6(a)
      427478  XM_425050.3  XP_425050.3 
    lizard
    (Anolis carolinensis)
    Reptilia HCN46
    hyperpolarization activated cyclic nucleotide-gate...
    70(a)
    1 ↔ 1
    GL343517.1(227271-308602)
    zebrafish
    (Danio rerio)
    Actinopterygii hcn46
    hcn4l6
    (see all 3)
    hyperpolarization activated cyclic nucleotide-gate...
    hyperpolarization activated cyclic nucleotide-gate...
    (see all 3)
    57(a)
    52(a)
    (see all 3)
    1 ↔ many
    1 ↔ many
    (see all 3)
    18(804501-943685)
    25(30195791-30296040)
    fruit fly
    (Drosophila melanogaster)
    Insecta Ih3 intracellular cyclic nucleotide
    activated cation more
    54(a)     --
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons KAT11 Potassium channel KAT1 37.28(n)
    23.21(a)
      834666  NM_123993.2  NP_199436.1 
    rice
    (Oryza sativa)
    Liliopsida Os02g02458001 hypothetical protein 38.3(n)
    24.41(a)
      4328864  NM_001052957.1  NP_001046422.2 


    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)
    About This Section
    Paralogs for HCN4 gene
    KCNH62  KCNH32  KCNH52  HCN32  KCNH42  HCN22  CNGA22  CNGA12  
    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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/1037 SNPs in HCN4 are shown (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--------
    VAR_0265344
    ----see VAR_0265342 D N mis40--------
    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--------

    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
    SABiosciences Cancer Mutation 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.)
    About This Section
    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

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

    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)
    About This Section

    PubMed articles for HCN4 gene, integrated from 9 sources (see all 63):
    (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. (1999)
    2. Two pacemaker channels from human heart with profoundly different activation kinetics. (PubMed id 10228147)1, 2, 3 Ludwig A.... Biel M. (1999)
    3. Role of HCN4 channel in preventing ventricular arrhythmia. (PubMed id 19165230)1, 2, 9 Ueda K....Kimura A. (2009)
    4. A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews. (PubMed id 20662977)1, 2 Laish-Farkash A.... Luria D. (2010)
    5. Variation at the NFATC2 locus increases the risk of t hiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipr il and rosiglitazone Medication (DREAM) study. (PubMed id 20628086)1, 4 Bailey S.D....Anand S. (2010)
    6. Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. (PubMed id 16407510)1, 2 Milanesi R.... DiFrancesco D. (2006)
    7. 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. (2005)
    8. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. (PubMed id 15123648)1, 2 Ueda K....Kimura A. (2004)
    9. Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4. (PubMed id 12813043)1, 9 Stieber J....Hofmann F. (2003)
    10. Novel pharmacological activity of loperamide and CP-339,818 on human HCN channels characterized with an automated electrophysiology assay. (PubMed id 18162181)1, 9 Lee Y.T....Bowlby M.R. (2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 10021 HGNC: 16882 AceView: HCN4 Ensembl:ENSG00000138622 euGenes: HUgn10021
    ECgene: HCN4 H-InvDB: HCN4

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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.)
    About This Section
    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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