HCN1 hyperpolarization activated cyclic nucleotide gated potassium channel 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HCN1provided by HGNC
Official Full Name: hyperpolarization activated cyclic nucleotide gated potassium channel 1provided by HGNC
Primary source: HGNC:HGNC:4845
See related: Ensembl:ENSG00000164588 MIM:602780; AllianceGenome:HGNC:4845
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: BCNG1; DEE24; HAC-2; BCNG-1; EIEE24; GEFSP10
Summary: 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]
Expression: Biased expression in brain (RPKM 4.9), heart (RPKM 0.8) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 5p12

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (45254948..45696380, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (45508691..45949554, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (45255050..45696482, complement)

Chromosome 5 - NC_000005.10 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 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?

Structural basis for hyperpolarization-dependent opening of human HCN1 channel.
Title: Structural basis for hyperpolarization-dependent opening of human HCN1 channel.
HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients.
Title: HCN1 pathogenic variants associated with childhood epilepsy in a cohort of Chinese patients.
The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis.
Title: The Impact of Altered HCN1 Expression on Brain Function and Its Relationship with Epileptogenesis.
Do the functional properties of HCN1 mutants correlate with the clinical features in epileptic patients?
Title: Do the functional properties of HCN1 mutants correlate with the clinical features in epileptic patients?
Biophysical analysis of an HCN1 epilepsy variant suggests a critical role for S5 helix Met-305 in voltage sensor to pore domain coupling.
Title: Biophysical analysis of an HCN1 epilepsy variant suggests a critical role for S5 helix Met-305 in voltage sensor to pore domain coupling.
HCN1 channels: A versatile tool for signal processing by primary sensory neurons.
Title: HCN1 channels: A versatile tool for signal processing by primary sensory neurons.
Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice.
Title: Developmental HCN channelopathy results in decreased neural progenitor proliferation and microcephaly in mice.
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).
Mutating two residues of HCN1 located at the interface between the voltage sensor and the pore domain resulted in the open state upon depolarization instead of hyperpolarization.
Title: Gating mechanism of hyperpolarization-activated HCN pacemaker channels.
All-atom molecular dynamics simulations (~20 mus) of HCN1 channel under hyperpolarization reveals an initial downward movement of the S4 voltage-sensor but following the transfer of last gating charge, the S4 breaks into two sub-helices with the lower sub-helix becoming parallel to the membrane.
Title: Helix breaking transition in the S4 of HCN channel is critical for hyperpolarization-dependent gating.

Submit: New GeneRIF Correction See all GeneRIFs (33)

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
Developmental and epileptic encephalopathy, 24 MedGen: C4014531 OMIM: 615871 GeneReviews: Not available	Compare labs
Generalized epilepsy with febrile seizures plus, type 10 MedGen: C5193120 OMIM: 618482 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies novel breast cancer susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

SHGC-14547 (e-PCR)
- UniSTS:37122

RH74834 (e-PCR)
- UniSTS:91674

RH120500 (e-PCR)
- UniSTS:133665

SHGC-53846 (e-PCR)
- UniSTS:8226

G66855 (e-PCR)
- UniSTS:166716

D5S2086 (e-PCR), detects polymorphism
- UniSTS:80190

SHGC-78170 (e-PCR)
- UniSTS:101199

D5S2024 (e-PCR)
- UniSTS:50786

RH46224 (e-PCR)
- UniSTS:86883

D5S1728 (e-PCR)
- UniSTS:63882

HCN1 (e-PCR)
- UniSTS:505766

G65478 (e-PCR)
- UniSTS:166570

D5S1753 (e-PCR)
- UniSTS:80871

HCN1__6701 (e-PCR)
- UniSTS:463606

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cAMP binding	IDA Inferred from Direct Assay more info	PubMed
enables cAMP binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables intracellular cAMP-activated cation channel activity involved in regulation of presynaptic membrane potential	IEA Inferred from Electronic Annotation more info
enables intracellularly cAMP-activated cation channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables potassium channel activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables voltage-gated monoatomic cation channel activity	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated potassium channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables voltage-gated potassium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables voltage-gated potassium channel activity	ISS Inferred from Sequence or Structural Similarity more info
enables voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in apical protein localization	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to cAMP	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to cAMP	ISS Inferred from Sequence or Structural Similarity more info
involved_in general adaptation syndrome, behavioral process	IEA Inferred from Electronic Annotation more info
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in potassium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in potassium ion transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in potassium ion transmembrane transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein homotetramerization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of membrane depolarization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynaptic membrane potential	IEA Inferred from Electronic Annotation more info
involved_in retinal cone cell development	IEA Inferred from Electronic Annotation more info
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
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
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
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic active zone membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

Names: brain cyclic nucleotide-gated channel 1

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_042183.1 RefSeqGene

Range

4739..446171

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_021072.4 → NP_066550.2 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 1

See identical proteins and their annotated locations for NP_066550.2

Status: REVIEWED

Source sequence(s)

AC099514, AC114975, AF064876, AF488549, CK299850, DR003732

Consensus CDS

CCDS3952.1

UniProtKB/Swiss-Prot

O60741

UniProtKB/TrEMBL

Q86WJ6

Related

ENSP00000307342.4, ENST00000303230.6

Conserved Domains (4) summary

COG0664
Location:469 → 604

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

cd00038
Location:475 → 583

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:160 → 405

Ion_trans; Ion transport protein

pfam08412
Location:98 → 140

Ion_trans_N; Ion transport protein N-terminal