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

Gene ID: 1137, updated on 11-Apr-2024

Summary

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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
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Genomic context

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See CHRNA4 in Genome Data Viewer
Location:
20q13.33
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (63343223..63361349, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (65149372..65167972, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (61974575..61992701, complement)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:61924431-61924932 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:61924933-61925432 Neighboring gene collagen type XX alpha 1 chain Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:61952290-61952790 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr20:61971654-61972853 Neighboring gene RNA, U6 small nuclear 994, pseudogene Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_60863 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr20:61986832-61988031 Neighboring gene uncharacterized LOC100130587 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:61992809-61993442 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:62006107-62006606 Neighboring gene uncharacterized LOC124904953 Neighboring gene Sharpr-MPRA regulatory region 8221 Neighboring gene Sharpr-MPRA regulatory region 785 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:62013199-62013883 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62025225-62025986 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:62036487-62037438 Neighboring gene Sharpr-MPRA regulatory region 327 Neighboring gene uncharacterized LOC105372724 Neighboring gene potassium voltage-gated channel subfamily Q member 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Autosomal dominant sleep-related hypermotor epilepsy caused by a previously unreported CHRNA4 variant. Nielsen TØ, et al. Eur J Med Genet, 2022 Mar. PMID 35093606
  2. Concatemers to re-investigate the role of α5 in α4β2 nicotinic receptors. Prevost MS, et al. Cell Mol Life Sci, 2021 Feb. PMID 32472188
  3. Novel variant in CHRNA4 with benign childhood epilepsy with centrotemporal spikes and contribution to precise medicine. Neng X, et al. Mol Genet Genomic Med, 2020 Jul. PMID 32342646, Free PMC Article
  4. [Association of CHRNA4 gene polymorphisms with response to antidepressant among ethnic Han Chinese]. Yu J, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2019 Dec 10. PMID 31813155
  5. The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults. Jeong JE, et al. PLoS One, 2017. PMID 29240768, Free PMC Article

See all (209) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.
    Title: Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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

EBI GWAS Catalog

Description
A genome-wide association study in chronic obstructive pulmonary disease (COPD): identification of two major susceptibility loci.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ95812

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 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

  1. NG_011931.1 RefSeqGene

    Range
    4995..23121
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  2. 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

  1. 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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    63343223..63361349 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    65149372..65167972 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P43681.2 GenPept UniProtKB/Swiss-Prot:P43681

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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