CHRNA4 cholinergic receptor nicotinic alpha 4 subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHRNA4provided by HGNC
Official Full Name: cholinergic receptor nicotinic alpha 4 subunitprovided by HGNC
Primary source: HGNC:HGNC:1958
See related: Ensembl:ENSG00000101204 MIM:118504; AllianceGenome:HGNC:1958
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: EBN; BFNC; EBN1; NACHR; NACRA4; NACHRA4
Summary: This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
Expression: Biased expression in liver (RPKM 3.9), brain (RPKM 3.0) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.33

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (63343223..63361349, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (65149372..65167972, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (61974575..61992701, complement)

Chromosome 20 - NC_000020.11 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Nicotine promotes renal interstitial fibrosis via upregulation of XIAP in an alpha7-nAChR-dependent manner.
Title: Nicotine promotes renal interstitial fibrosis via upregulation of XIAP in an alpha7-nAChR-dependent manner.
Autosomal dominant sleep-related hypermotor epilepsy caused by a previously unreported CHRNA4 variant.
Title: Autosomal dominant sleep-related hypermotor epilepsy caused by a previously unreported CHRNA4 variant.
Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of alpha4beta2- nicotinic acetylcholine receptor intracellular structures.
Title: Sleep-related hypermotor epilepsy associated mutations uncover important kinetic roles of α4β2- nicotinic acetylcholine receptor intracellular structures.
Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.
Title: Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.
Novel variant in CHRNA4 with benign childhood epilepsy with centrotemporal spikes and contribution to precise medicine.
Title: Novel variant in CHRNA4 with benign childhood epilepsy with centrotemporal spikes and contribution to precise medicine.
Association Between Nicotine-dependent Gene Polymorphism and Smoking Cessation in Patients With Lung Cancer.
Title: Association Between Nicotine-dependent Gene Polymorphism and Smoking Cessation in Patients With Lung Cancer.
Concatemers to re-investigate the role of alpha5 in alpha4beta2 nicotinic receptors.
Title: Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors.
Depletion of miR-380 mitigates human bronchial epithelial cells injury to improve chronic obstructive pulmonary disease through targeting CHRNA4.
Title: Depletion of miR-380 mitigates human bronchial epithelial cells injury to improve chronic obstructive pulmonary disease through targeting CHRNA4.
Identification of the initial steps in signal transduction in the alpha4beta2 nicotinic receptor has been reported.
Title: Identification of the Initial Steps in Signal Transduction in the α4β2 Nicotinic Receptor: Insights from Equilibrium and Nonequilibrium Simulations.
SNPs of the CHRNA4 gene may play an important role in the response to antidepressant drugs among ethnic Han Chinese with major depressive disorder.
Title: [Association of CHRNA4 gene polymorphisms with response to antidepressant among ethnic Han Chinese].

Submit: New GeneRIF Correction See all GeneRIFs (157)

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
Autosomal dominant nocturnal frontal lobe epilepsy 1 MedGen: C1838049 OMIM: 600513 GeneReviews: Autosomal Dominant Sleep-Related Hypermotor (Hyperkinetic) Epilepsy	not available
Tobacco addiction, susceptibility to MedGen: C1861063 OMIM: 188890 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major 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

RH78607 (e-PCR)
- UniSTS:87070

D20S127E (e-PCR)
- UniSTS:77874

RH12050 (e-PCR)
- UniSTS:90455

RH64135 (e-PCR)
- UniSTS:85131

RH70691 (e-PCR)
- UniSTS:91561

RH75305 (e-PCR)
- UniSTS:85424

CHRNA4_1625 (e-PCR)
- UniSTS:280498

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables acetylcholine binding	IC Inferred by Curator more info	PubMed
enables acetylcholine receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables acetylcholine-gated monoatomic cation-selective channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables acetylcholine-gated monoatomic cation-selective channel activity	IDA Inferred from Direct Assay more info	PubMed
enables acetylcholine-gated monoatomic cation-selective channel activity	TAS Traceable Author Statement more info	PubMed
enables ligand-gated monoatomic ion channel activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in acetylcholine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in action potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in behavioral response to nicotine	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in calcium ion transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in chemical synaptic transmission	NAS Non-traceable Author Statement more info	PubMed
involved_in cognition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in inhibitory postsynaptic potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in membrane depolarization	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane depolarization	ISS Inferred from Sequence or Structural Similarity more info
involved_in monoatomic ion transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info
involved_in monoatomic ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in monoatomic ion transport	NAS Non-traceable Author Statement more info	PubMed
involved_in nervous system process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromuscular synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of dopamine secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of membrane potential	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
involved_in response to nicotine	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to nicotine	IDA Inferred from Direct Assay more info	PubMed
involved_in response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sensory perception of pain	ISS Inferred from Sequence or Structural Similarity more info
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in synaptic transmission, cholinergic	IBA Inferred from Biological aspect of Ancestor more info
involved_in synaptic transmission, cholinergic	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
part_of acetylcholine-gated channel complex	IBA Inferred from Biological aspect of Ancestor more info
part_of acetylcholine-gated channel complex	IDA Inferred from Direct Assay more info	PubMed
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in external side of plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
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
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: neuronal acetylcholine receptor subunit alpha-4

Names: cholinergic receptor, nicotinic alpha 4; cholinergic receptor, nicotinic, alpha 4 (neuronal); cholinergic receptor, nicotinic, alpha polypeptide 4; neuronal nicotinic acetylcholine receptor alpha-4 subunit

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_011931.1 RefSeqGene

Range

4995..23121

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000744.7 → NP_000735.1 neuronal acetylcholine receptor subunit alpha-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_000735.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AB209359, AK296430, AL121827, BC096291, L35901, U62433

Consensus CDS

CCDS13517.1

UniProtKB/Swiss-Prot

P43681, Q4JGR7, Q4VAQ5, Q4VAQ6

UniProtKB/TrEMBL

Q59FV0

Related

ENSP00000359285.4, ENST00000370263.9

Conserved Domains (3) summary

pfam02931
Location:37 → 243

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:250 → 618

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

pfam06484
Location:423 → 572

Ten_N; Teneurin Intracellular Region
NM_001256573.2 → NP_001243502.1 neuronal acetylcholine receptor subunit alpha-4 isoform 2

See identical proteins and their annotated locations for NP_001243502.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and has multiple coding region differences, compared to variant 1. These differences cause translation initiation at a downstream AUG and result in an isoform (2) with a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AB209359, AK296430, AL121827, BC096291, BC096292, L35901, U62433

UniProtKB/TrEMBL

Q4VAQ3, Q59FV0

Conserved Domains (3) summary

pfam02932
Location:74 → 442

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

cl26247
Location:216 → 320

DNA_pol3_delta2; DNA polymerase III, delta subunit

cl27321
Location:1 → 67

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

RNA

NR_046317.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' 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)

AB209359, AK296430, AL121827, BC096291, BC096293, L35901, U62433