HCN3 hyperpolarization activated cyclic nucleotide gated potassium channel 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HCN3provided by HGNC
Official Full Name: hyperpolarization activated cyclic nucleotide gated potassium channel 3provided by HGNC
Primary source: HGNC:HGNC:19183
See related: Ensembl:ENSG00000143630 MIM:609973; AllianceGenome:HGNC:19183
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
Summary: This gene encodes a multi-pass membrane protein that functions as a voltage gated cation channel. The encoded protein is a member of a family of closely related cyclic adenosine monophosphate-binding channel proteins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
Expression: Ubiquitous expression in liver (RPKM 3.6), duodenum (RPKM 2.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q22

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (155277463..155289848)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (154416023..154428409)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (155247254..155259639)

Chromosome 1 - NC_000001.11 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?

Cryo-EM structure of human HCN3 channel and its regulation by cAMP.
Title: Cryo-EM structure of human HCN3 channel and its regulation by cAMP.
Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.
Title: Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.
Reduced HCN3 expression in aganglionic bowel suggests its potential role in Hirschsprung's disease pathophysiology.
Title: Decreased expression of hyperpolarisation-activated cyclic nucleotide-gated channel 3 in Hirschsprung's disease.
KCTD3 is an accessory subunit of native HCN3 complexes
Title: Up-regulation of hyperpolarization-activated cyclic nucleotide-gated channel 3 (HCN3) by specific interaction with K+ channel tetramerization domain-containing protein 3 (KCTD3).
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.
human HCN3 is not modulated by intracellular cAMP, in contrast to other HCN subtypes
Title: Functional expression of the human HCN3 channel.

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Phenotypes

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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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cAMP binding	IEA Inferred from Electronic Annotation more info
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
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	IDA Inferred from Direct Assay more info	PubMed
enables voltage-gated sodium channel activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
NOT involved_in cellular response to cAMP	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to dopamine	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	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
involved_in regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sodium ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in sodium ion transmembrane transport	IDA Inferred from Direct Assay 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
is_active_in axon	IBA Inferred from Biological aspect of Ancestor more info
located_in cone cell pedicle	IEA Inferred from Electronic Annotation more info
is_active_in dendrite	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 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_020897.3 → NP_065948.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3

See identical proteins and their annotated locations for NP_065948.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the protein.

Source sequence(s)

AB040968, AL713999, BC028024, DA127524

Consensus CDS

CCDS1108.1

UniProtKB/Swiss-Prot

D3DV90, Q4VX12, Q8N6W6, Q9BWQ2, Q9P1Z3

UniProtKB/TrEMBL

Q86WJ5

Related

ENSP00000357342.3, ENST00000368358.4

Conserved Domains (4) summary

COG0664
Location:422 → 560

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

cd00038
Location:428 → 536

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:111 → 358

Ion_trans; Ion transport protein

pfam08412
Location:49 → 91

Ion_trans_N; Ion transport protein N-terminal

RNA

NR_073074.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at the 3' end and uses an alternate internal splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AK299333, AL713999

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

155277463..155289848

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011509817.3 → XP_011508119.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X2

See identical proteins and their annotated locations for XP_011508119.1

UniProtKB/TrEMBL

Q86WJ5

Conserved Domains (4) summary

COG0664
Location:368 → 506

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

cd00038
Location:374 → 482

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:111 → 304

Ion_trans; Ion transport protein

pfam08412
Location:49 → 91

Ion_trans_N; Ion transport protein N-terminal
XM_011509816.4 → XP_011508118.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1

See identical proteins and their annotated locations for XP_011508118.1

UniProtKB/TrEMBL

Q86WJ5

Conserved Domains (3) summary

COG0664
Location:375 → 513

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

cd00038
Location:381 → 489

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:64 → 311

Ion_trans; Ion transport protein
XM_047426226.1 → XP_047282182.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3
XM_011509818.2 → XP_011508120.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

See identical proteins and their annotated locations for XP_011508120.1

UniProtKB/TrEMBL

B7Z5R8

Conserved Domains (3) summary

COG0664
Location:183 → 321

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

cd00038
Location:189 → 297

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:5 → 119

Ion_trans; Ion transport protein
XM_017001918.2 → XP_016857407.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

UniProtKB/TrEMBL

B7Z5R8

Conserved Domains (3) summary

COG0664
Location:183 → 321

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

cd00038
Location:189 → 297

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:5 → 119

Ion_trans; Ion transport protein

RNA

XR_921904.3 RNA Sequence
XR_921903.3 RNA Sequence
XR_007062431.1 RNA Sequence
XR_921905.3 RNA Sequence
XR_007062434.1 RNA Sequence
XR_007062432.1 RNA Sequence
XR_007062433.1 RNA Sequence
XR_007062435.1 RNA Sequence

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

NW_003315906.1 Reference GRCh38.p14 ALT_REF_LOCI_1

Range

82486..94871

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054329479.1 → XP_054185454.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X2
XM_054329478.1 → XP_054185453.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1
XM_054329480.1 → XP_054185455.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3
XM_054329481.1 → XP_054185456.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4
XM_054329482.1 → XP_054185457.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4

RNA

XR_008485643.1 RNA Sequence
XR_008485642.1 RNA Sequence
XR_008485645.1 RNA Sequence
XR_008485644.1 RNA Sequence
XR_008485648.1 RNA Sequence
XR_008485646.1 RNA Sequence
XR_008485647.1 RNA Sequence
XR_008485649.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

154416023..154428409

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054337899.1 → XP_054193874.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X1
XM_054337900.1 → XP_054193875.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X3
XM_054337901.1 → XP_054193876.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4
XM_054337902.1 → XP_054193877.1 potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 3 isoform X4