U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

HCN3 hyperpolarization activated cyclic nucleotide gated potassium channel 3 [ Homo sapiens (human) ]

Gene ID: 57657, updated on 3-Apr-2024

Summary

Go to the top of the page Help
Official Symbol
HCN3provided by HGNC
Official Full Name
hyperpolarization activated cyclic nucleotide gated potassium channel 3provided by HGNC
Primary source
HGNC:HGNC:19183
See related
Ensembl:ENSG00000143630 MIM:609973; AllianceGenome:HGNC:19183
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
Summary
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]
Expression
Ubiquitous expression in liver (RPKM 3.6), duodenum (RPKM 2.6) and 25 other tissues See more
Orthologs
mouse all
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
See HCN3 in Genome Data Viewer
Location:
1q22
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (155277463..155289848)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (154416023..154428409)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (155247254..155259639)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene secretory carrier membrane protein 3 Neighboring gene CDC like kinase 2 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155243888-155244388 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155254443-155254943 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:155263898-155264430 Neighboring gene pyruvate kinase L/R Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:155275791-155276290 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1813 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1814 Neighboring gene farnesyl diphosphate synthase Neighboring gene RUSC1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1400 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155291392-155292375 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1401 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1402 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1403 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1404 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1405 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1815 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:155295943-155296500 Neighboring gene RUN and SH3 domain containing 1

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

Related articles in PubMed

  1. Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung's disease. O'Donnell AM, et al. World J Gastroenterol, 2015 May 14. PMID 25987789, Free PMC Article
  2. Endogenous channels in HEK cells and potential roles in HCN ionic current measurements. Varghese A, et al. Prog Biophys Mol Biol, 2006 Jan-Apr. PMID 15979128
  3. An interactive tool for extracting exons and SNP from genomic sequence: isolation of HCN1 and HCN3 ion channel genes. Liu Y, et al. J Bioinform Comput Biol, 2003 Oct. PMID 15290763
  4. Genetic analysis of hyperpolarization-activated cyclic nucleotide-gated cation channels in sudden unexpected death in epilepsy cases. Tu E, et al. Brain Pathol, 2011 Nov. PMID 21615589, Free PMC Article
  5. Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons. Yi F, et al. Science, 2016 May 6. PMID 26966193, Free PMC Article

See all (20) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.
    Title: Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.
  2. Reduced HCN3 expression in aganglionic bowel suggests its potential role in Hirschsprung's disease pathophysiology.
    Title: Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung's disease.
  3. KCTD3 is an accessory subunit of native HCN3 complexes
    Title: Up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) by specific interaction with K+ channel tetramerization domain-containing protein 3 (KCTD3).
  4. Genetic analysis in 48 Sudden unexpected death in epilepsy cases identified six novel and three previously reported nonsynonymous (amino acid changing) variants in HCN1 , HCN2, HCN3 and HCN4.
    Title: Genetic analysis of hyperpolarization-activated cyclic nucleotide-gated cation channels in sudden unexpected death in epilepsy cases.
  5. human HCN3 is not modulated by intracellular cAMP, in contrast to other HCN subtypes
    Title: Functional expression of the human HCN3 channel.
Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

Go to the top of the page

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

Markers

Homology

Clone Names

  • KIAA1535, MGC131493

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables cAMP binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables voltage-gated potassium channel activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables voltage-gated potassium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables voltage-gated sodium channel activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Process Evidence Code Pubs
NOT involved_in cellular response to cAMP IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to dopamine IEA
Inferred from Electronic Annotation
more info
  
involved_in potassium ion transmembrane transport IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in potassium ion transmembrane transport 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 potential IMP
Inferred from Mutant Phenotype
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
  
is_active_in axon IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cone cell pedicle IEA
Inferred from Electronic Annotation
more info
  
is_active_in dendrite IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in neuronal cell body IEA
Inferred from Electronic Annotation
more info
  
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

Go to the top of the page Help
Preferred Names
potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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.

mRNA and Protein(s)

  1. NM_020897.3 → NP_065948.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

    See identical proteins and their annotated locations for NP_065948.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.
    Source sequence(s)
    AB040968, AL713999, BC028024, DA127524
    Consensus CDS
    CCDS1108.1
    UniProtKB/Swiss-Prot
    D3DV90, Q4VX12, Q8N6W6, Q9BWQ2, Q9P1Z3
    UniProtKB/TrEMBL
    Q86WJ5
    Related
    ENSP00000357342.3, ENST00000368358.4
    Conserved Domains (4) summary
    COG0664
    Location:422 → 560
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:428 → 536
    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:111 → 358
    Ion_trans; Ion transport protein
    pfam08412
    Location:49 → 91
    Ion_trans_N; Ion transport protein N-terminal

RNA

  1. NR_073074.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs at the 3' end and uses an alternate internal splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AK299333, AL713999

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    155277463..155289848
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011509817.3 → XP_011508119.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X2

    See identical proteins and their annotated locations for XP_011508119.1

    UniProtKB/TrEMBL
    Q86WJ5
    Conserved Domains (4) summary
    COG0664
    Location:368 → 506
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:374 → 482
    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:111 → 304
    Ion_trans; Ion transport protein
    pfam08412
    Location:49 → 91
    Ion_trans_N; Ion transport protein N-terminal

  2. XM_011509816.4 → XP_011508118.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1

    See identical proteins and their annotated locations for XP_011508118.1

    UniProtKB/TrEMBL
    Q86WJ5
    Conserved Domains (3) summary
    COG0664
    Location:375 → 513
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:381 → 489
    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:64 → 311
    Ion_trans; Ion transport protein

  3. XM_047426226.1 → XP_047282182.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3

  4. XM_011509818.2 → XP_011508120.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

    See identical proteins and their annotated locations for XP_011508120.1

    UniProtKB/TrEMBL
    B7Z5R8
    Conserved Domains (3) summary
    COG0664
    Location:183 → 321
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:189 → 297
    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:5 → 119
    Ion_trans; Ion transport protein

  5. XM_017001918.2 → XP_016857407.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

    UniProtKB/TrEMBL
    B7Z5R8
    Conserved Domains (3) summary
    COG0664
    Location:183 → 321
    Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]
    cd00038
    Location:189 → 297
    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:5 → 119
    Ion_trans; Ion transport protein

RNA

  1. XR_921904.3 RNA Sequence

  2. XR_921903.3 RNA Sequence

  3. XR_007062431.1 RNA Sequence

  4. XR_921905.3 RNA Sequence

  5. XR_007062434.1 RNA Sequence

  6. XR_007062432.1 RNA Sequence

  7. XR_007062433.1 RNA Sequence

  8. XR_007062435.1 RNA Sequence

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NW_003315906.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    82486..94871
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054329479.1 → XP_054185454.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X2

  2. XM_054329478.1 → XP_054185453.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1

  3. XM_054329480.1 → XP_054185455.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3

  4. XM_054329481.1 → XP_054185456.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

  5. XM_054329482.1 → XP_054185457.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

RNA

  1. XR_008485643.1 RNA Sequence

  2. XR_008485642.1 RNA Sequence

  3. XR_008485645.1 RNA Sequence

  4. XR_008485644.1 RNA Sequence

  5. XR_008485648.1 RNA Sequence

  6. XR_008485646.1 RNA Sequence

  7. XR_008485647.1 RNA Sequence

  8. XR_008485649.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    154416023..154428409
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054337899.1 → XP_054193874.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1

  2. XM_054337900.1 → XP_054193875.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3

  3. XM_054337901.1 → XP_054193876.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

  4. XM_054337902.1 → XP_054193877.1  potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

RNA

  1. XR_008486122.1 RNA Sequence

  2. XR_008486121.1 RNA Sequence

  3. XR_008486124.1 RNA Sequence

  4. XR_008486123.1 RNA Sequence

  5. XR_008486127.1 RNA Sequence

  6. XR_008486125.1 RNA Sequence

  7. XR_008486126.1 RNA Sequence

  8. XR_008486128.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9P1Z3.2 GenPept UniProtKB/Swiss-Prot:Q9P1Z3

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous