HCN2 hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HCN2provided by HGNC
Official Full Name: hyperpolarization activated cyclic nucleotide gated potassium and sodium channel 2provided by HGNC
Primary source: HGNC:HGNC:4846
See related: Ensembl:ENSG00000099822 MIM:602781
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: BCNG2; HAC-1; BCNG-2
Summary: The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017]
Expression: Biased expression in brain (RPKM 15.0), heart (RPKM 4.6) and 2 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19p13.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (589881..617159)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (589893..617159)

Chromosome 19 - NC_000019.10 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: 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

No significant association was found between HCN1/HCN2 alleles, genotypes or haplotypes, and drug resistance in patients, however, it was suggested that HCN2 rs3752158 is involved in the susceptibility to juvenile myoclonic epilepsy.
Title: Case-control pharmacogenetic study of HCN1/HCN2 variants and genetic generalized epilepsies.
Data suggest that HCN2 variants can confer susceptibility to Genetic generalized epilepsy via a gain-of-function mechanism.
Title: Gain-of-function HCN2 variants in genetic epilepsy.
beta2-adrenoceptors alone strongly enhanced the activity of HCN2 channels, and co-expression of odorant receptors further diversified the HCN2 channel activity.
Title: Dual expression of constitutively active Gα<sub>s</sub>-protein-coupled receptors differentially establishes the resting activity of the cAMP-gated HCN2 channel in a single compartment.
TRIP8b competes with a portion of the cAMP-binding site or distorts the binding site by making interactions with the binding pocket, thus acting predominantly as a competitive antagonist that inhibits the cyclic-nucleotide dependence of HCN channels.
Title: Mechanism for the inhibition of the cAMP dependence of HCN ion channels by the auxiliary subunit TRIP8b.
HCN2 has a role in maturation and processing of the amyloid precursor protein
Title: Maturation and processing of the amyloid precursor protein is regulated by the potassium/sodium hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2).
promoter methylation status does not appear to be a major determinant of HCN2 expression in normal and adenoid cystic carcinoma ( ACC )tissues. HCN2 hypomethylation is a biomarker of ACC and may play an important role in the carcinogenesis of ACC.
Title: Identification of methylated genes in salivary gland adenoid cystic carcinoma xenografts using global demethylation and methylation microarray screening.
Aged patients with sinus rhythm exhibited significantly higher expression levels of HCN2 and HCN4 channel mRNA and protein (P<0.05), but significantly lower expression levels of miR1 and 133, compared with those of adult patients with sinus rhythm.
Title: Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in patients with age-associated atrial fibrillation.
Data show that Rab8b-interacting protein TRIP8b does not compete with cyclic AMP for the same binding region of hyperpolarization activated cyclic nucleotide gated potassium channel 2 (HCN2).
Title: Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.
N-glycosylation is not required for HCN2 channels to function.
Title: Effects of N-glycosylation on hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.
Thermal hyperalgesia under chronic inflammatory conditions is mediated by HCN2 channels.
Title: HCN2 channels account for mechanical (but not heat) hyperalgesia during long-standing inflammation.

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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HCN channels, organism-specific biosystem (from REACTOME)
HCN channels, organism-specific biosystemHyperpolarization-activated cyclic nucleotide-gated (HCN) channels are nonselective ligand-gated cation channels in the plasma membranes of heart and brain cells. HCN channels are sometimes referred ...
Neuronal System, organism-specific biosystem (from REACTOME)
Neuronal System, organism-specific biosystemThe human brain contains at least 100 billion neurons, each with the ability to influence many other cells. Clearly, highly sophisticated and efficient mechanisms are needed to enable communication a...
Potassium Channels, organism-specific biosystem (from REACTOME)
Potassium Channels, organism-specific biosystemPotassium channels are tetrameric ion channels that are widely distributed and are found in all cell types. Potassium channels control resting membrane potential in neurons, contribute to regulation ...
TarBasePathway, organism-specific biosystem (from WikiPathways)
TarBasePathway, organism-specific biosystemThis cataloge pathway was created using the database from "http://diana.cslab.ece.ntua.gr/tarbase/" with exclusions based on evidance type. This pathway only incldes miR targeted genes expressed in A...
cAMP signaling pathway, organism-specific biosystem (from KEGG)
cAMP signaling pathway, organism-specific biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...
cAMP signaling pathway, conserved biosystem (from KEGG)
cAMP signaling pathway, conserved biosystemcAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands incl...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S814 (e-PCR)
- UniSTS:153879

PMC196911P5 (e-PCR)
- UniSTS:271827

Homology

Homologs of the HCN2 gene: The HCN2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 238 organisms have orthologs with human gene HCN2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cAMP binding	IEA Inferred from Electronic Annotation more info
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
intracellular cAMP-activated cation channel activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
voltage-gated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
voltage-gated potassium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
cell-cell signaling	TAS Traceable Author Statement more info	PubMed
cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
cellular response to cGMP	IDA Inferred from Direct Assay more info	PubMed
membrane depolarization during cardiac muscle cell action potential	IC Inferred by Curator more info	PubMed
potassium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of ion transmembrane transport	IEA Inferred from Electronic Annotation more info
regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
sodium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
sodium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
HCN channel complex	IDA Inferred from Direct Assay more info	PubMed
integral component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
voltage-gated potassium channel complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

Names: brain cyclic nucleotide-gated channel 2; hyperpolarization activated cyclic nucleotide gated potassium channel 2

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.

Genomic

NG_052810.1 RefSeqGene

Range

4989..32267

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001194.4 → NP_001185.3 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2

See identical proteins and their annotated locations for NP_001185.3

Status: REVIEWED

Source sequence(s)

AC005559, AF065164, AJ012582, BC039619

Consensus CDS

CCDS12035.1

UniProtKB/Swiss-Prot

Q9UL51

Related

ENSP00000251287.1, ENST00000251287.3

Conserved Domains (4) summary

COG0664
Location:538 → 673

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

cd00038
Location:544 → 652

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:229 → 474

Ion_trans; Ion transport protein

pfam08412
Location:167 → 209

Ion_trans_N; Ion transport protein N-terminal