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

Summary

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

Location:: 8p21.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_03	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (27459756..27479261, complement)
RS_2023_03	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_000008.11 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
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?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Autosomal dominant nocturnal frontal lobe epilepsy 4 MedGen: C1835905 OMIM: 610353 GeneReviews: Autosomal Dominant Sleep-Related Hypermotor (Hyperkinetic) Epilepsy	Compare labs

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

D8S131 (e-PCR), detects polymorphism
- UniSTS:148759

NoName (e-PCR)
- UniSTS:482092

D8S131 (e-PCR), detects polymorphism
- UniSTS:148615

CHRNA2_2606 (e-PCR)
- UniSTS:280497

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	PubMed
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 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 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	PubMed
involved_in monoatomic ion transport	NAS Non-traceable Author Statement more info	PubMed
involved_in nervous system process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of membrane potential	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in response to acetylcholine	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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	PubMed
involved_in synaptic transmission, cholinergic	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
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	PubMed
located_in neuron projection cytoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay 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	PubMed

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

NG_015827.1 RefSeqGene

Range

5036..24541

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

Q15822, Q9HAQ3

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
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/Swiss-Prot

Q15822

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
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
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
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
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_03

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

27459756..27479261 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q9HAQ3
XM_047421311.1 → XP_047277267.1 neuronal acetylcholine receptor subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

Q9HAQ3
XM_047421312.1 → XP_047277268.1 neuronal acetylcholine receptor subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

Q9HAQ3

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

27737110..27756814 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/Swiss-Prot

Q9HAQ3
XM_054359683.1 → XP_054215658.1 neuronal acetylcholine receptor subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

Q9HAQ3
XM_054359684.1 → XP_054215659.1 neuronal acetylcholine receptor subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

Q9HAQ3