Hcn4 hyperpolarization-activated, cyclic nucleotide-gated K+ 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Hcn4provided by MGI
Official Full Name: hyperpolarization-activated, cyclic nucleotide-gated K+ 4provided by MGI
Primary source: MGI:MGI:1298209
See related: Ensembl:ENSMUSG00000032338 AllianceGenome:MGI:1298209
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Hcn3; Bcng3
Summary: Enables intracellular cAMP-activated cation channel activity. Acts upstream of or within cation transport; in utero embryonic development; and regulation of heart contraction. Located in axon. Is expressed in eye; future brain; heart; septum transversum; and venous system. Human ortholog(s) of this gene implicated in Brugada syndrome 8; Gilles de la Tourette syndrome; idiopathic generalized epilepsy; and sick sinus syndrome. Orthologous to human HCN4 (hyperpolarization activated cyclic nucleotide gated potassium channel 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in whole brain E14.5 (RPKM 4.8), CNS E14 (RPKM 3.6) and 17 other tissues See more
Orthologs: human all
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Genomic context

Location:: 9 B; 9 31.8 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	9	NC_000075.7 (58730232..58770458)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	9	NC_000075.6 (58822949..58863175)

Chromosome 9 - NC_000075.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deficiency of CXXC finger protein 1 leads to small changes in heart rate but moderate epigenetic alterations and significant protein downregulation of hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) ion channels in mice.
Title: Deficiency of CXXC finger protein 1 leads to small changes in heart rate but moderate epigenetic alterations and significant protein downregulation of hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) ion channels in mice.
A circadian clock in the sinus node mediates day-night rhythms in Hcn4 and heart rate.
Title: A circadian clock in the sinus node mediates day-night rhythms in Hcn4 and heart rate.
HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.
Title: HCN channels in the mammalian cochlea: Expression pattern, subcellular location, and age-dependent changes.
Downregulated lncRNA RCPCD promotes differentiation of embryonic stem cells into cardiac pacemaker-like cells by suppressing HCN4 promoter methylation.
Title: Downregulated lncRNA RCPCD promotes differentiation of embryonic stem cells into cardiac pacemaker-like cells by suppressing HCN4 promoter methylation.
Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice.
Title: Ectopic HCN4 expression drives mTOR-dependent epilepsy in mice.
Expression of the pacemaker channel HCN4 in excitatory interneurons in the dorsal horn of the murine spinal cord.
Title: Expression of the pacemaker channel HCN4 in excitatory interneurons in the dorsal horn of the murine spinal cord.
Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome.
Title: Mitochondrial thioredoxin-2 maintains HCN4 expression and prevents oxidative stress-mediated sick sinus syndrome.
cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.
Title: cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.
Pdpk1 (PDK1) and AKT are involved in the regulation of HCN2 and HCN4 mRNA transcription, protein expression, HCN current density, and cell membrane location
Title: PDK1-AKT signaling pathway regulates the expression and function of cardiac hyperpolarization-activated cyclic nucleotide-modulated channels.
knockdown of HCN4 gave rise to sinus arrhythmia, and enhanced the parasympathetic response.
Title: HCN4 pacemaker channels attenuate the parasympathetic response and stabilize the spontaneous firing of the sinoatrial node.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2) 1 citation
Targeted (12) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cAMP binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables intracellularly cAMP-activated cation channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables intracellularly cAMP-activated cation channel activity	ISO Inferred from Sequence Orthology more info
enables monoatomic ion channel activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables potassium channel activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sodium channel activity	IEA Inferred from Electronic Annotation more info
enables voltage-gated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated potassium channel activity	ISO Inferred from Sequence Orthology more info
enables voltage-gated potassium channel activity involved in SA node cell action potential depolarization	ISO Inferred from Sequence Orthology more info
enables voltage-gated sodium channel activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in SA node cell action potential	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cAMP	ISO Inferred from Sequence Orthology more info
involved_in cellular response to cGMP	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane depolarization during SA node cell action potential	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic cation transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monoatomic cation transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of cardiac muscle cell action potential involved in regulation of contraction	ISO Inferred from Sequence Orthology more info
involved_in regulation of cardiac muscle contraction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of heart contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of heart rate	ISO Inferred from Sequence Orthology more info
involved_in regulation of heart rate by cardiac conduction	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane depolarization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of membrane depolarization	ISO Inferred from Sequence Orthology more info
involved_in regulation of membrane potential	ISO Inferred from Sequence Orthology more info
involved_in sodium ion import across plasma membrane	ISO Inferred from Sequence Orthology more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within sodium ion transport	IEA Inferred from Electronic Annotation more info
involved_in transmembrane transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of HCN channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of HCN channel complex	ISO Inferred from Sequence Orthology more info
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in basolateral plasma membrane	ISO Inferred from Sequence Orthology more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
part_of monoatomic ion channel complex	IEA Inferred from Electronic Annotation more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in terminal bouton	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Names: brain cyclic nucleotide-gated channel 3; hyperpolarization-activated, cyclic nucleotide-gated K+ 3

NCBI Reference Sequences (RefSeq)

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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)

NM_001081192.3 → NP_001074661.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

See identical proteins and their annotated locations for NP_001074661.1

Status: VALIDATED

Source sequence(s)

AC110530

Consensus CDS

CCDS52815.1

UniProtKB/Swiss-Prot

O70507

UniProtKB/TrEMBL

B2RY58

Related

ENSMUSP00000034889.9, ENSMUST00000034889.10

Conserved Domains (4) summary

COG0664
Location:589 → 724

Crp; cAMP-binding domain of CRP or a regulatory subunit of cAMP-dependent protein kinases [Signal transduction mechanisms]

cd00038
Location:595 → 703

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:280 → 525

Ion_trans; Ion transport protein

pfam08412
Location:218 → 260

Ion_trans_N; Ion transport protein N-terminal