This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012] See more...

Aliases for HCN3 Gene

Aliases for HCN3 Gene

  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 3 2 3 5
  • Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 3 3 4
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 3 2
  • KIAA1535 4

External Ids for HCN3 Gene

Previous GeneCards Identifiers for HCN3 Gene

  • GC01P153105
  • GC01P150988
  • GC01P152025
  • GC01P152464
  • GC01P152060
  • GC01P153513
  • GC01P155247
  • GC01P126609

Summaries for HCN3 Gene

Entrez Gene Summary for HCN3 Gene

  • This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

GeneCards Summary for HCN3 Gene

HCN3 (Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 3) is a Protein Coding gene. Diseases associated with HCN3 include Pyruvate Kinase Deficiency Of Red Cells and Nemaline Myopathy 5. Among its related pathways are Sweet Taste Signaling and Potassium Channels. Gene Ontology (GO) annotations related to this gene include ion channel activity and cAMP binding. An important paralog of this gene is HCN4.

UniProtKB/Swiss-Prot Summary for HCN3 Gene

  • Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.

Gene Wiki entry for HCN3 Gene

Additional gene information for HCN3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HCN3 Gene

Genomics for HCN3 Gene

GeneHancer (GH) Regulatory Elements for HCN3 Gene

Promoters and enhancers for HCN3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J155276 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 532.1 +0.6 642 2.7 HNRNPK EP300 CTCF SIN3A NRF1 USF1 SP1 ZNF639 ZIC2 REST HCN3 CLK2 lnc-CLK2-1 GBA MUC1
GH01J155307 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas 25.3 +31.8 31768 4 ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 MYC POLR2G USF1 SP1 FDPS PKLR lnc-PKLR-1 GBA GON4L HCN3 CLK2 FAM189B THBS3 KHDC4
GH01J155222 Promoter/Enhancer 2.1 Ensembl ENCODE CraniofacialAtlas dbSUPER 19.9 -51.7 -51696 5.9 ZBTB40 EP300 CTCF SIN3A TCF12 NRF1 USF1 POLR2G SP1 BCLAF1 GBAP1 KHDC4 GON4L MSTO1 ENSG00000271267 MSTO2P CLK2 THBS3 LMNA RUSC1-AS1
GH01J155608 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 19.4 +332.8 332789 2.8 ZBTB40 EP300 NRF1 USF1 POLR2G SP1 PHF8 ZNF10 POLR2A CLOCK ENSG00000232519 MSTO1 piR-42651-001 HCN3 ASH1L MIR555 GBA LOC105371452 ASH1L-AS1
GH01J155304 Promoter/Enhancer 1.1 EPDnew ENCODE 33.1 +28.4 28381 2.1 POLR2G TGIF2 SKI POLR2A NFIC SAP130 MBD1 DRAP1 SMAD4 BCL6 FDPS lnc-FDPS-1 piR-52079-018 HCN3 GBA PKLR
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HCN3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for HCN3

Top Transcription factor binding sites by QIAGEN in the HCN3 gene promoter:
  • Arnt
  • ITF-2
  • MAZR
  • p53
  • POU2F1
  • POU2F1a
  • Tal-1beta

Genomic Locations for HCN3 Gene

Genomic Locations for HCN3 Gene
chr1:155,277,427-155,289,848
(GRCh38/hg38)
Size:
12,422 bases
Orientation:
Plus strand
chr1:155,247,374-155,259,639
(GRCh37/hg19)
Size:
12,266 bases
Orientation:
Plus strand

Genomic View for HCN3 Gene

Genes around HCN3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCN3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCN3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCN3 Gene

Proteins for HCN3 Gene

  • Protein details for HCN3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9P1Z3-HCN3_HUMAN
    Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3
    Protein Accession:
    Q9P1Z3
    Secondary Accessions:
    • D3DV90
    • Q4VX12
    • Q8N6W6
    • Q9BWQ2

    Protein attributes for HCN3 Gene

    Size:
    774 amino acids
    Molecular mass:
    86032 Da
    Quaternary structure:
    • Homotetramer. The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming subunits. Interacts with KCTD3 and PEX5L.
    SequenceCaution:
    • Sequence=AAH28024.2; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for HCN3 Gene

Post-translational modifications for HCN3 Gene

  • Glycosylation at Asn291
  • Modification sites at PhosphoSitePlus

Other Protein References for HCN3 Gene

No data available for DME Specific Peptides for HCN3 Gene

Domains & Families for HCN3 Gene

Gene Families for HCN3 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Plasma proteins
  • Predicted membrane proteins
  • Voltage-gated ion channels

Protein Domains for HCN3 Gene

Blocks:
  • Cyclic nucleotide-binding domain
  • Ion transport N-terminal
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for HCN3 Gene

GenScript: Design optimal peptide antigens:
  • Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3_HUMAN)
  • HCN3 protein (Q2T9L6_HUMAN)
  • Hyperpolarization activated cyclic nucleotide-gated potassium channel (Q86WJ5_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9P1Z3

UniProtKB/Swiss-Prot:

HCN3_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.
Family:
  • Belongs to the potassium channel HCN family.
genes like me logo Genes that share domains with HCN3: view

Function for HCN3 Gene

Molecular function for HCN3 Gene

UniProtKB/Swiss-Prot Function:
Hyperpolarization-activated potassium channel. May also facilitate the permeation of sodium ions.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by Cs(1+) and ZD7288. Is apparently not activated by cAMP.

Phenotypes From GWAS Catalog for HCN3 Gene

Gene Ontology (GO) - Molecular Function for HCN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005248 voltage-gated sodium channel activity IMP 22748890
GO:0005249 voltage-gated potassium channel activity IMP 22748890
GO:0005267 potassium channel activity IEA --
genes like me logo Genes that share ontologies with HCN3: view
genes like me logo Genes that share phenotypes with HCN3: view

Animal Models for HCN3 Gene

MGI Knock Outs for HCN3:
  • Hcn3 Hcn3<tm1.1Biel>

Animal Model Products

  • Taconic Biosciences Mouse Models for HCN3

CRISPR Products

miRNA for HCN3 Gene

miRTarBase miRNAs that target HCN3

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HCN3 Gene

Localization for HCN3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCN3 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCN3 gene
Compartment Confidence
plasma membrane 5
extracellular 1
cytoskeleton 1
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
cytosol 1
peroxisome 0

Gene Ontology (GO) - Cellular Components for HCN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0030424 axon IEA --
genes like me logo Genes that share ontologies with HCN3: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HCN3 Gene

Pathways & Interactions for HCN3 Gene

PathCards logo

SuperPathways for HCN3 Gene

genes like me logo Genes that share pathways with HCN3: view

Pathways by source for HCN3 Gene

3 Reactome pathways for HCN3 Gene
1 KEGG pathway for HCN3 Gene
1 Qiagen pathway for HCN3 Gene
  • Sperm Motility

Gene Ontology (GO) - Biological Process for HCN3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0034765 regulation of ion transmembrane transport IEA --
GO:0035725 sodium ion transmembrane transport IMP 22748890
genes like me logo Genes that share ontologies with HCN3: view

No data available for SIGNOR curated interactions for HCN3 Gene

Drugs & Compounds for HCN3 Gene

(6) Drugs for HCN3 Gene - From: DGIdb, IUPHAR, and HMDB

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

(1) Additional Compounds for HCN3 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Na(+)
  • Na+
  • SODIUM ion
7440-23-5
genes like me logo Genes that share compounds with HCN3: view

Transcripts for HCN3 Gene

mRNA/cDNA for HCN3 Gene

1 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HCN3 Gene

ExUns: 1 ^ 2a · 2b ^ 3a · 3b · 3c · 3d ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b ^ 9 ^ 10 ^ 11
SP1: -
SP2: - -
SP3: -
SP4: -
SP5:

Relevant External Links for HCN3 Gene

GeneLoc Exon Structure for
HCN3

Expression for HCN3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for HCN3 Gene

mRNA differential expression in normal tissues according to GTEx for HCN3 Gene

This gene is overexpressed in Brain - Cerebellum (x5.4) and Brain - Cerebellar Hemisphere (x4.8).

Protein differential expression in normal tissues from HIPED for HCN3 Gene

This gene is overexpressed in Plasma (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HCN3 Gene



Protein tissue co-expression partners for HCN3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for HCN3

SOURCE GeneReport for Unigene cluster for HCN3 Gene:

Hs.706960

mRNA Expression by UniProt/SwissProt for HCN3 Gene:

Q9P1Z3-HCN3_HUMAN
Tissue specificity: Detected in brain.

Evidence on tissue expression from TISSUES for HCN3 Gene

  • Nervous system(4.7)
genes like me logo Genes that share expression patterns with HCN3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and Phenotype-based relationships between genes and organs from Gene ORGANizer for HCN3 Gene

Orthologs for HCN3 Gene

This gene was present in the common ancestor of animals.

Orthologs for HCN3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia HCN3 31 30
  • 94.89 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HCN3 31
  • 91 (a)
OneToOne
cow
(Bos Taurus)
Mammalia HCN3 31 30
  • 90.96 (n)
OneToOne
dog
(Canis familiaris)
Mammalia HCN3 31 30
  • 90.65 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hcn3 30
  • 89.09 (n)
mouse
(Mus musculus)
Mammalia Hcn3 17 31 30
  • 88.87 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 79 (a)
ManyToMany
chicken
(Gallus gallus)
Aves HCN3 31
  • 82 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii HCN3 (2 of 2) 31
  • 84 (a)
OneToMany
hcn3 31
  • 62 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002150 30
  • 60.71 (n)
fruit fly
(Drosophila melanogaster)
Insecta Ih 31
  • 25 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 52 (a)
ManyToMany
Species where no ortholog for HCN3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)
  • lizard (Anolis carolinensis)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for HCN3 Gene

ENSEMBL:
Gene Tree for HCN3 (if available)
TreeFam:
Gene Tree for HCN3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HCN3: view image

Paralogs for HCN3 Gene

(4) SIMAP similar genes for HCN3 Gene using alignment to 3 proteins:

  • HCN3_HUMAN
  • Q2T9L6_HUMAN
  • Q86WJ5_HUMAN
genes like me logo Genes that share paralogs with HCN3: view

Variants for HCN3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for HCN3 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs137971983 Uncertain Significance: not provided 155,285,928(+) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
rs41264939 Uncertain Significance: Pyruvate kinase deficiency of red cells 155,289,679(+) A/C THREE_PRIME_UTR_VARIANT
rs528740550 Uncertain Significance: Pyruvate kinase deficiency of red cells 155,289,531(+) G/A THREE_PRIME_UTR_VARIANT
rs559809916 Uncertain Significance: Pyruvate kinase deficiency of red cells 155,289,505(+) A/G THREE_PRIME_UTR_VARIANT
rs8847 Benign: Pyruvate kinase deficiency of red cells 155,289,532(+) C/T THREE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for HCN3 Gene

Structural Variations from Database of Genomic Variants (DGV) for HCN3 Gene

Variant ID Type Subtype PubMed ID
dgv3n68 CNV loss 17160897
esv23319 CNV gain 19812545
esv2758971 CNV gain 17122850
esv33869 CNV loss 17666407
nsv101 CNV insertion 15895083
nsv3021 CNV insertion 18451855
nsv3032 CNV insertion 18451855
nsv436027 CNV insertion 17901297
nsv831636 CNV loss 17160897
nsv952214 CNV deletion 24416366

Variation tolerance for HCN3 Gene

Residual Variation Intolerance Score: 61.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.04; 60.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HCN3 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCN3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCN3 Gene

Disorders for HCN3 Gene

MalaCards: The human disease database

(3) MalaCards diseases for HCN3 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
pyruvate kinase deficiency of red cells
  • pkd
nemaline myopathy 5
  • nem5
bladder neck obstruction
  • obstruction of bladder neck or vesicourethral orifice
- elite association - COSMIC cancer census association via MalaCards
Search HCN3 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HCN3

genes like me logo Genes that share disorders with HCN3: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HCN3 Gene

Publications for HCN3 Gene

  1. The DNA sequence and biological annotation of human chromosome 1. (PMID: 16710414) Gregory SG … Prigmore E (Nature 2006) 3 4 54
  2. Endogenous channels in HEK cells and potential roles in HCN ionic current measurements. (PMID: 15979128) Varghese A … Sigg DC (Progress in biophysics and molecular biology 2006) 3 23 54
  3. International Union of Pharmacology. LI. Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels. (PMID: 16382102) Hofmann F … Kaupp UB (Pharmacological reviews 2005) 2 3 54
  4. Functional expression of the human HCN3 channel. (PMID: 16043489) Stieber J … Hofmann F (The Journal of biological chemistry 2005) 3 4 54
  5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PMID: 15489334) Gerhard DS … MGC Project Team (Genome research 2004) 3 4 54

Products for HCN3 Gene

Sources for HCN3 Gene