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; AllianceGenome:HGNC:4846
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: FEB2; BCNG2; EIG17; HAC-1; BCNG-2; GEFSP11
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
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Genomic context

Location:: 19p13.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (589881..617159)
RS_2023_03	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (543772..571465)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (589881..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?

HCN2 channel-induced rescue of brain, eye, heart and gut teratogenesis caused by nicotine, ethanol and aberrant notch signalling.
Title: HCN2 channel-induced rescue of brain, eye, heart and gut teratogenesis caused by nicotine, ethanol and aberrant notch signalling.
Downregulation of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the hippocampus of patients with medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS).
Title: Downregulation of hyperpolarization-activated cyclic nucleotide-gated channels (HCN) in the hippocampus of patients with medial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS).
Effects of HCN2 Mutations on Dendritic Excitability and Synaptic Plasticity: A Computational Study.
Title: Effects of HCN2 Mutations on Dendritic Excitability and Synaptic Plasticity: A Computational Study.
overexpression of TBX3 and HCN2 could reprogram human-induced pluripotent stem cells-derived cardiomyocytes into pacemaker-like cells
Title: HCN2 and TBX3 Reprogram Human-Induced Pluripotent Stem Cells-Derived Cardiomyocytes into Pacemaker-Like Cells.
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(s)-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.

Submit: New GeneRIF Correction See all GeneRIFs (32)

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

Associated conditions

Description	Tests
Febrile seizures, familial, 2 MedGen: C1865342 OMIM: 602477 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cAMP binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables intracellular cAMP-activated cation channel activity	IDA Inferred from Direct Assay more info	PubMed
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	PubMed
enables voltage-gated potassium channel activity	IDA Inferred from Direct Assay more info	PubMed
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
involved_in cell-cell signaling	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to cGMP	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane depolarization during cardiac muscle cell action potential	IC Inferred by Curator more info	PubMed
involved_in potassium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in potassium ion transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
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	PubMed
involved_in regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in sodium ion import across plasma membrane	IDA Inferred from Direct Assay more info	PubMed
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	PubMed
part_of HCN channel complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info	PubMed
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of 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

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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

O60742, O60743, O75267, Q9UBS2, 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