HCN1 Gene

HGNC Family	Ion channels
Name	hyperpolarization activated cyclic nucleotide gated potassium channel 1
Description	The membrane protein encoded by this gene is a hyperpolarization-activated cation channel that contributes to the native pacemaker currents in heart and neurons. The encoded protein can homodimerize or heterodimerize with other pore-forming subunits to form a potassium channel. This channel may act as a receptor for sour tastes. [provided by RefSeq, Oct 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hyperpolarization‐activated cyclic nucleotide–gated (HCN) channels play a central role in establishing rhythmicity and regulating excitability in diverse tissues, and studies focused on the HCN1 isoform reveal its particularly versatile functions. In cardiac and neuronal cells, HCN1 contributes to the depolarizing “funny” current (I<sub>f</sub>/I<sub>h</sub>) that underlies pacemaker activity and burst firing, thus influencing spontaneous rhythmic firing and signal integration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In the retina, HCN1 is predominantly expressed in the inner segments of photoreceptors, where it accelerates the termination of rod responses under bright light conditions, thereby preserving the dynamic range of cone-driven signaling and preventing network saturation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " In addition, in neuronal systems HCN1 channels help set the pace for oscillatory activity and their dysfunction or genetic variants have been linked to disorders such as epilepsy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the molecular level, HCN1 channels are directly modulated by intracellular cyclic nucleotides, which shift their voltage dependence, and are subject to regulation by auxiliary proteins such as TRIP8b that control both channel gating and membrane trafficking. For instance, a specific di‐arginine endoplasmic reticulum retention signal within the HCN1 C terminus modulates surface expression, while computational studies support the view that electrostatic interactions – including with phosphoinositides – further contribute to HCN1 modulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_fs", "start_ref": "11", "end_ref": "13"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Thus, across multiple systems—from the heart and brain to the retina—HCN1 channels integrate intrinsic voltage signals with modulatory cues (e.g., cAMP levels and protein interactions) to finely tune electrical activity and ensure proper timing in both physiological and pathophysiological contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " \n Collectively, this evidence highlights HCN1 as a critical determinant of excitability whose multifaceted regulation underpins its role in pacemaking, signal termination, and rhythmic network activity.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laura Sartiani, Pascal Bochet, Elisabetta Cerbai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression of the hyperpolarization-activated, non-selective cation current I(f) in immortalized HL-1 cardiomyocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2002.021535"}], "href": "https://doi.org/10.1113/jphysiol.2002.021535"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12433951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12433951"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Martha A Bosch, Karen J Tonsfeldt, Oline K Rønnekleiv "}, {"type": "b", "children": [{"type": "t", "text": "mRNA expression of ion channels in GnRH neurons: subtype-specific regulation by 17β-estradiol."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Endocrinol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mce.2012.12.021"}], "href": "https://doi.org/10.1016/j.mce.2012.12.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23305677"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23305677"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ye Han, Yoav Noam, Alan S Lewis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Trafficking and gating of hyperpolarization-activated cyclic nucleotide-gated channels are regulated by interaction with tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) and cyclic AMP at distinct sites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.236125"}], "href": "https://doi.org/10.1074/jbc.M111.236125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21504900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21504900"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bin Tang, Thomas Sander, Kimberley B Craven, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2007.08.006"}], "href": "https://doi.org/10.1016/j.nbd.2007.08.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17931874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17931874"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mathias W Seeliger, Arne Brombas, Reto Weiler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of rod photoreceptor output by HCN1 channels is essential for regular mesopic cone vision."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms1540"}], "href": "https://doi.org/10.1038/ncomms1540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22068599"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22068599"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Luca Della Santina, Ilaria Piano, Lorenzo Cangiano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Processing of retinal signals in normal and HCN deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0029812"}], "href": "https://doi.org/10.1371/journal.pone.0029812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22279546"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22279546"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Vithiyanjali Sothilingam, Stylianos Michalakis, Marina Garcia Garrido, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HCN1 Channels Enhance Rod System Responsivity in the Retina under Conditions of Light Exposure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0147728"}], "href": "https://doi.org/10.1371/journal.pone.0147728"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26807953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26807953"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gian Carlo Demontis, Anna Moroni, Biagio Gravante, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional characterisation and subcellular localisation of HCN1 channels in rabbit retinal rod photoreceptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1113/jphysiol.2002.017640"}], "href": "https://doi.org/10.1113/jphysiol.2002.017640"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12096053"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12096053"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shu-Zhi Wu, Hua Ye, Xiao-Guo Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Pharmacol Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1440-1681.12877"}], "href": "https://doi.org/10.1111/1440-1681.12877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29047147"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29047147"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Amy Brewster, Roland A Bender, Yuncai Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Developmental febrile seizures modulate hippocampal gene expression of hyperpolarization-activated channels in an isoform- and cell-specific manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "20026437"}], "href": "https://doi.org/20026437"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12040066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12040066"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yuan Pan, Joseph G Laird, David M Yamaguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A di-arginine ER retention signal regulates trafficking of HCN1 channels from the early secretory pathway to the plasma membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-014-1705-1"}], "href": "https://doi.org/10.1007/s00018-014-1705-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25142030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25142030"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ainara Claveras Cabezudo, Asma Feriel Khoualdi, Nazzareno D'Avanzo "}, {"type": "b", "children": [{"type": "t", "text": "Computational Prediction of Phosphoinositide Binding to Hyperpolarization-Activated Cyclic-Nucleotide Gated Channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Physiol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fphys.2022.859087"}], "href": "https://doi.org/10.3389/fphys.2022.859087"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35399260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35399260"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Catherine Proenza, Neil Tran, Damiano Angoli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Different roles for the cyclic nucleotide binding domain and amino terminus in assembly and expression of hyperpolarization-activated, cyclic nucleotide-gated channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M200504200"}], "href": "https://doi.org/10.1074/jbc.M200504200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12034718"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12034718"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jun Chen, David R Piper, Michael C Sanguinetti "}, {"type": "b", "children": [{"type": "t", "text": "Voltage sensing and activation gating of HCN pacemaker channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Trends Cardiovasc Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1050-1738(01)00141-4"}], "href": "https://doi.org/10.1016/s1050-1738(01"}, {"type": "t", "text": "00141-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11796244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11796244"}]}]}]}
Synonyms	BCNG-1, HAC-2, BCNG1, EIEE24
Proteins	HCN1_HUMAN
NCBI Gene ID	348980
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HCN1 has 4,752 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 118 datasets.

Click the + buttons to view associations for HCN1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HCN1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HCN1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HCN1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HCN1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of HCN1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of HCN1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of HCN1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HCN1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HCN1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of HCN1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HCN1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of HCN1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HCN1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HCN1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HCN1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of HCN1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with HCN1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HCN1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of HCN1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HCN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HCN1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HCN1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with HCN1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HCN1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HCN1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HCN1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HCN1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HCN1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by HCN1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for HCN1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HCN1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HCN1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HCN1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HCN1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with HCN1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with HCN1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HCN1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HCN1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HCN1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HCN1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing HCN1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.