HCN4 hyperpolarization activated cyclic nucleotide-gated potassium channel 4 [Homo sapiens] - Gene

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Summary

Official Symbol: HCN4provided by HGNC
Official Full Name: hyperpolarization activated cyclic nucleotide-gated potassium channel 4provided by HGNC
Primary source: HGNC:16882
See related: Ensembl:ENSG00000138622; HPRD:09240; MIM:605206; Vega:OTTHUMG00000137563
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
Also known as: SSS2
Summary: 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]

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Genomic context

Location :: 15q24.1

Sequence :: Chromosome: 15; NC_000015.9 (73612200..73661605, complement)

See HCN4 in Epigenomics, MapViewer

Chromosome 15 - NC_000015.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

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.
A novel mutation is found in HCN4 gene causing symptoms of sinus bradycardia in unrelated male Moroccan Jews.
Title: A novel mutation in the HCN4 gene causes symptomatic sinus bradycardia in Moroccan Jews.
These findings suggest HCN4 as a genetic susceptibility factor for mood and anxiety disorders
Title: Association of polymorphisms in HCN4 with mood disorders and obsessive compulsive disorder.
HCN4 channels are expressed in different patterns in brain and heart; the N terminus is important for HCN4 channel activation
Title: Tissue-specific N terminus of the HCN4 channel affects channel activation.
Higher HCN4 mRNA levels in the hypertrophic cardiomyopathy hearts suggest that up-regulation of HCN4 gene expression might be responsible for ventricular arrhythmia that leads to sudden death.
Title: Expression of hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN4) is increased in hypertrophic cardiomyopathy.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
In this review, we focus on genotype-phenotype correlation of HCN4 mutations and discuss the relative contribution of various ion channels to sinus node function.
Title: The Contribution of HCN4 to normal sinus node function in humans and animal models.
The HCN4 channel played a preventive role in triggering bradycardia-induced ventricular arrhythmias.
Title: Role of HCN4 channel in preventing ventricular arrhythmia.
novel mechanism using three endogenous Src kinases to rescue a trafficking defective HCN4 mutant channel (D553N) by enhancing the tyrosine phosphorylation of the mutant channel protein.
Title: Rescue of a trafficking defective human pacemaker channel via a novel mechanism: roles of Src, Fyn, and Yes tyrosine kinases.

Submit: New GeneRIF Correction See all (24)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Products	Interactant	Other Gene	Source	Pubs	Description
Q9Y3Q4	Q9UL51	HCN2	HPRD	PubMed
BioGRID:115338	BioGRID:131543	HCN1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:115338	BioGRID:107081	HCN2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:115338	BioGRID:121691	HCN3	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
cAMP binding	IEA Inferred from Electronic Annotation more info
cation channel activity	TAS Traceable Author Statement more info	PubMed
intracellular cAMP activated cation channel activity	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
sodium channel activity	IEA Inferred from Electronic Annotation more info
voltage-gated ion channel activity	IEA Inferred from Electronic Annotation more info
voltage-gated potassium channel activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
blood circulation	NAS Non-traceable Author Statement more info	PubMed
cation transport	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
muscle contraction	TAS Traceable Author Statement more info	PubMed
potassium ion transport	IEA Inferred from Electronic Annotation more info
regulation of heart contraction	IEA Inferred from Electronic Annotation more info
synaptic transmission	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
integral to membrane	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info
terminal button	IEA Inferred from Electronic Annotation more info

General protein information

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

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

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_009063.1 RefSeqGene

Range

5001..54406

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005477.2 → NP_005468.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4

Status: REVIEWED

Source sequence(s)

AC068397, AJ132429, AJ238850, BM979827, BP291686

Consensus CDS

CCDS10248.1

UniProtKB/Swiss-Prot

Q9Y3Q4

Related

ENSP00000261917, OTTHUMP00000174871, ENST00000261917, OTTHUMT00000268900

Conserved Domains (3) summary

cd00038
Location:595 – 703
Blast Score: 233

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 ...

pfam08412
Location:217 – 293
Blast Score: 410

Ion_trans_N; Ion transport protein N-terminal

PLN03192
Location:253 – 740
Blast Score: 285

PLN03192; Voltage-dependent potassium channel; Provisional

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000015.9 Reference GRCh37.p5 Primary Assembly

Range

73612200..73661605, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000147.1 Alternate HuRef

Range

50443643..50492812, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC009660.15 (115666..123051)	None
genomic	AC068397.6 (128934..169891)	None
genomic	CH471082.1	EAW77925.1
genomic	JA696662.1	CCF23300.1
mRNA	AJ132429.1	CAB42604.1
mRNA	AJ238850.1	CAB52754.1
mRNA	BM979827.1	None
mRNA	BP291686.1	None
mRNA	DQ854814.1	None
other-genetic	BC156298.1	AAI56299.1
other-genetic	BC172471.1	AAI72471.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q9Y3Q4.1	GenPept	UniProtKB/Swiss-Prot:Q9Y3Q4

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Additional Links

Epigenomics
MIM 605206
PharmGKB PA394
GeneTests for MIM: 605206
Gene Connection for the Heart - Sick Sinus Syndrome database Sinus_diseases_mut.htm
UCSC UCSC
UniGene Hs.86941