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CHRNA2 cholinergic receptor nicotinic alpha 2 subunit [ Homo sapiens (human) ]

Gene ID: 1135, updated on 11-Apr-2024

Summary

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Official Symbol
CHRNA2provided by HGNC
Official Full Name
cholinergic receptor nicotinic alpha 2 subunitprovided by HGNC
Primary source
HGNC:HGNC:1956
See related
Ensembl:ENSG00000120903 MIM:118502; AllianceGenome:HGNC:1956
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
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central nervous system where they are involved in fast synaptic transmission. This gene encodes an alpha subunit that is widely expressed in the brain. The proposed structure for nAChR subunits is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. Mutations in this gene cause autosomal dominant nocturnal frontal lobe epilepsy type 4. Single nucleotide polymorphisms (SNPs) in this gene have been associated with nicotine dependence. [provided by RefSeq, Nov 2009]
Expression
Restricted expression toward prostate (RPKM 15.4) See more
Orthologs
mouse all
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Genomic context

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Location:
8p21.2
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (27459756..27479261, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (27737110..27756814, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (27317273..27336778, complement)

Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27132 Neighboring gene tripartite motif containing 35 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27133 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27134 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19046 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27135 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27136 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:27183969-27184798 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:27184956-27185152 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27138 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19047 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27139 Neighboring gene protein tyrosine kinase 2 beta Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19048 Neighboring gene Sharpr-MPRA regulatory region 9089 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27140 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27141 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:27219644-27220174 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27143 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27144 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27145 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27146 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27147 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27148 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27149 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27150 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27151 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27152 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27153 Neighboring gene Sharpr-MPRA regulatory region 13363 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:27287852-27288568 Neighboring gene microRNA 6842 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:27316840-27317083 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:27319910-27320838 Neighboring gene CRISPRi-validated cis-regulatory element chr8.973 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19049 Neighboring gene epoxide hydrolase 2 Neighboring gene MPRA-validated peak6969 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr8:27412252-27412752 Neighboring gene Sharpr-MPRA regulatory region 1589 Neighboring gene gulonolactone (L-) oxidase, pseudogene

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. Genome-wide association study implicates CHRNA2 in cannabis use disorder. Demontis D, et al. Nat Neurosci, 2019 Jul. PMID 31209380, Free PMC Article
  2. Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer. Kouvatsos N, et al. Proc Natl Acad Sci U S A, 2016 Aug 23. PMID 27493220, Free PMC Article
  3. Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy. Trivisano M, et al. Epilepsia, 2015 May. PMID 25847220
  4. Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function. Conti V, et al. Neurology, 2015 Apr 14. PMID 25770198, Free PMC Article
  5. Two rare variations, D478N and D478E, that occur at the same amino acid residue in nicotinic acetylcholine receptor (nAChR) α2 subunit influence nAChR function. Dash B, et al. Neuropharmacology, 2014 Oct. PMID 24950454, Free PMC Article

See all (49) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. The index variant (rs56372821) is a strong expression quantitative trait locus for CHRNA2; analyses of the genetically regulated gene expression identified a significant association of CHRNA2 expression with cannabis use disorder (CUD) in brain tissue. At the polygenic level, analyses revealed a significant decrease in the risk of CUD with increased load of variants associated with cognitive performance.
    Title: Genome-wide association study implicates CHRNA2 in cannabis use disorder.
  2. These results reveal a beige-selective immune-adipose interaction mediated through CHRNA2 and identify a novel function of nicotinic acetylcholine receptors in energy metabolism.
    Title: An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling.
  3. In our analysis, we found one pair of SNPs in CHRNA1 and CHRNA7, plus one pair of SNPs in CHRNA2 and CHRNA3 reached corrected significance in tests for GxG interaction. Our study suggested evidence of interactions between CHRNs in controlling the risk of NSCL/P.
    Title: Evaluating the effect of nicotinic cholinergic receptor genes on the risk of nonsyndromic cleft lip with or without cleft palate.
  4. A crystal structure of a human neuronal CHRNA2 extracellular domain in pentameric assembly has been reported.
    Title: Crystal structure of a human neuronal nAChR extracellular domain in pentameric assembly: Ligand-bound α2 homopentamer.
  5. The rare variants in CHRNA2 were significantly associated with smoking status.
    Title: The contribution of rare and common variants in 30 genes to risk nicotine dependence.
  6. a heterozygous single-nucleotide substitution in CHRNA2 gene (c.1126 C>T; p. Arg376Trp) in subjects with benign familial infantile seizures
    Title: Mutation of CHRNA2 in a family with benign familial infantile seizures: Potential role of nicotinic acetylcholine receptor in various phenotypes of epilepsy.
  7. CHRNA2 mutations play a causative role in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
    Title: Nocturnal frontal lobe epilepsy with paroxysmal arousals due to CHRNA2 loss of function.
  8. Results show that D478E variation in nAChR alpha2 subunit increases the peak current responses of both alpha2beta2- and alpha2beta4-nAChRs; but the D478N variation in nAChR alpha2 subunit only increases the peak current responses of alpha2beta2-nAChRs
    Title: Two rare variations, D478N and D478E, that occur at the same amino acid residue in nicotinic acetylcholine receptor (nAChR) α2 subunit influence nAChR function.
  9. Level of cigarettes per day during adolescence and young adulthood is associated with CHRNB3A6, CHRNA5A3B4, and CHRNA2
    Title: Effect of neuronal nicotinic acetylcholine receptor genes (CHRN) on longitudinal cigarettes per day in adolescents and young adults.
  10. Results indicate that the CHRNA2 signal peptide mutation T22I modulates the function of both alpha2beta2- and alpha2beta4-nAChR and decreases sensitivities to nicotine and acetylcholine, and quite possibly increasing susceptibility to nicotine dependence
    Title: A signal peptide missense mutation associated with nicotine dependence alters α2*-nicotinic acetylcholine receptor function.
Submit: New GeneRIF Correction See all GeneRIFs (25)

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

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
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 heterocyclic compound binding IEA
Inferred from Electronic Annotation
more info
  
enables quaternary ammonium group binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in acetylcholine receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to nicotine IEA
Inferred from Electronic Annotation
more info
  
involved_in excitatory postsynaptic potential IEA
Inferred from Electronic Annotation
more info
  
involved_in membrane depolarization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in modulation of inhibitory postsynaptic potential IEA
Inferred from Electronic Annotation
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 response to nicotine IBA
Inferred from Biological aspect of Ancestor
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
  
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 intercellular bridge IDA
Inferred from Direct Assay
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 neuron projection cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
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-2
Names
acetylcholine receptor, nicotinic, alpha 2 (neuronal)
cholinergic receptor, nicotinic alpha 2
cholinergic receptor, nicotinic, alpha 2 (neuronal)
cholinergic receptor, nicotinic, alpha polypeptide 2 (neuronal)

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_015827.1 RefSeqGene

    Range
    5036..24541
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000742.4 → NP_000733.2  neuronal acetylcholine receptor subunit alpha-2 isoform 1 precursor

    See identical proteins and their annotated locations for NP_000733.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AF311103, AW292180, CD013901, DA096824, DA407151, U62431
    Consensus CDS
    CCDS6059.1
    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3
    UniProtKB/TrEMBL
    A0A0X1KG79
    Related
    ENSP00000385026.1, ENST00000407991.3
    Conserved Domains (3) summary
    TIGR00860
    Location:57 → 522
    LIC; Cation transporter family protein
    pfam02931
    Location:59 → 265
    Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
    pfam02932
    Location:272 → 520
    Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

  2. NM_001282455.2 → NP_001269384.1  neuronal acetylcholine receptor subunit alpha-2 isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AF311103, AK296348, AW292180
    Consensus CDS
    CCDS64856.1
    UniProtKB/TrEMBL
    A0A0X1KG79
    Related
    ENSP00000240132.2, ENST00000240132.7
    Conserved Domains (3) summary
    TIGR00860
    Location:57 → 507
    LIC; Cation transporter family protein
    pfam02931
    Location:59 → 250
    Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
    pfam02932
    Location:257 → 505
    Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region

  3. NM_001347705.2 → NP_001334634.1  neuronal acetylcholine receptor subunit alpha-2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variant 4, encodes isoform 3.
    Source sequence(s)
    AF311103

  4. NM_001347706.2 → NP_001334635.1  neuronal acetylcholine receptor subunit alpha-2 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variant 3, encodes isoform 3.
    Source sequence(s)
    AF311103

  5. NM_001347707.2 → NP_001334636.1  neuronal acetylcholine receptor subunit alpha-2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variant 6, encodes isoform 4.
    Source sequence(s)
    AF311103

  6. NM_001347708.2 → NP_001334637.1  neuronal acetylcholine receptor subunit alpha-2 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variant 5, encodes isoform 4.
    Source sequence(s)
    AF311103, AK314787, DA407151

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_000008.11 Reference GRCh38.p14 Primary Assembly

    Range
    27459756..27479261 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047421313.1 → XP_047277269.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3

  2. XM_047421311.1 → XP_047277267.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3

  3. XM_047421312.1 → XP_047277268.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060932.1 Alternate T2T-CHM13v2.0

    Range
    27737110..27756814 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054359685.1 → XP_054215660.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3

  2. XM_054359683.1 → XP_054215658.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3

  3. XM_054359684.1 → XP_054215659.1  neuronal acetylcholine receptor subunit alpha-2 isoform X1

    UniProtKB/Swiss-Prot
    A8KAX3, B4DK19, J3KMY9, Q15822, Q9HAQ3
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q15822.2 GenPept UniProtKB/Swiss-Prot:Q15822

Gene LinkOut

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