CHRNA6 cholinergic receptor nicotinic alpha 6 subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHRNA6provided by HGNC
Official Full Name: cholinergic receptor nicotinic alpha 6 subunitprovided by HGNC
Primary source: HGNC:HGNC:15963
See related: Ensembl:ENSG00000147434 MIM:606888; AllianceGenome:HGNC:15963
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: CHNRA6
Summary: This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 2010]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 8p11.21

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (42752620..42768786, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (43020720..43036889, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (42607763..42623929, 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?

Involvement of CHRNA6 in the Immune Response in Lung Squamous Cell Carcinoma and its Potential as a Drug Target for the Disease.
Title: Involvement of CHRNA6 in the Immune Response in Lung Squamous Cell Carcinoma and its Potential as a Drug Target for the Disease.
This study is the first showing that CHRNB3/A6 are highly associated with nicotine dependence in a large Chinese Han sample.
Title: Significant association of the CHRNB3-CHRNA6 gene cluster with nicotine dependence in the Chinese Han population.
To gain a better understanding of the pathological processes underlying ND and ND-related behaviors and to promote the development of effective smoking cessation therapies, we here present the most recent studies concerning the genetic effects of the CHRNB3-CHRNA6 gene cluster in ND.
Title: Crucial roles of the CHRNB3-CHRNA6 gene cluster on chromosome 8 in nicotine dependence: update and subjects for future research.
More low frequency variants in the CHRNA6/CHRNB3 gene region were observed in cases compared to controls.
Title: Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence.
Chrna6 has a cellular expression signature for retinal ganglion cells with high correlation to Thy1, a known marker. Immunofluorescence confirms this gene is preferentially expressed by RGCs in the young and adult mouse retina and expression is reduced in glaucoma.
Title: Effects of glaucoma on Chrna6 expression in the retina.
Data show efficient expression of (alpha6beta2)2beta3 nicotinic acetylcholine receptors (AChRs) in Xenopus oocytes using free subunits with only small changes in alpha6 subunits, while not altering AChR pharmacology or channel structure.
Title: Efficient expression of functional (α6β2)2β3 AChRs in Xenopus oocytes from free subunits using slightly modified α6 subunits.
the CHRNB3-A6 locus contains multiple variants affecting risk for vulnerability to cocaine and nicotine dependence as well as bipolar disorder, suggesting that they have pleiotropic effects.
Title: Variants near CHRNB3-CHRNA6 are associated with DSM-5 cocaine use disorder: evidence for pleiotropy.
Polymorphism in CHRNA6 gene is associated with esophageal adenocarcinoma.
Title: A genetic variant in CHRNB3-CHRNA6 increases risk of esophageal squamous cell carcinoma in Chinese populations.
The common variant rs13273442 in the CHRNB3-CHNRA6 region is associated significantly with nicotine dependence in European Americans and African Americans.
Title: Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans.
N-terminal alpha-helix (Asp57); complementary face/inner beta-fold (Arg87 or Asp92) and principal face/outer beta-fold (Ser156 or Asn171) residues in the halpha6 subunit are crucial for functional expression.
Title: Analysis of rare variations reveals roles of amino acid residues in the N-terminal extracellular domain of nicotinic acetylcholine receptor (nAChR) alpha6 subunit in the functional expression of human alpha6*-nAChRs.

Submit: New GeneRIF Correction See all GeneRIFs (34)

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
Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior. 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

SHGC-5780 (e-PCR)
- UniSTS:80411

RH71244 (e-PCR)
- UniSTS:84811

CHRNA6_1902 (e-PCR)
- UniSTS:280500

RH135820 (e-PCR)
- UniSTS:209638

G17210 (e-PCR)
- UniSTS:39660

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
contributes_to acetylcholine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables acetylcholine-gated monoatomic cation-selective channel activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in acetylcholine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemical synaptic transmission	TAS Traceable Author Statement more info	PubMed
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 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 presynaptic modulation of chemical synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in regulation of dopamine secretion	IEA Inferred from Electronic Annotation more info
involved_in response to nicotine	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	TAS Traceable Author Statement 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
located_in dopaminergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic membrane	IEA Inferred from Electronic Annotation more info
located_in presynaptic 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-6

Names: acetylcholine receptor, nicotinic, alpha 6 (neuronal); alpha(alpha)6 nicotinic acetylcholine receptor (nAChR) subunit; cholinergic receptor, nicotinic alpha 6; cholinergic receptor, nicotinic, alpha 6 (neuronal); cholinergic receptor, nicotinic, alpha polypeptide 6

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_001199279.1 → NP_001186208.1 neuronal acetylcholine receptor subunit alpha-6 isoform 2 precursor

See identical proteins and their annotated locations for NP_001186208.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an exon in the coding region but maintains the reading frame, compared to variant 1. This variant encodes isoform 2, which is shorter than isoform 1.

Source sequence(s)

AK298798, BC014456, DC307404

Consensus CDS

CCDS56536.1

UniProtKB/Swiss-Prot

Q15825

Related

ENSP00000433871.1, ENST00000534622.5

Conserved Domains (3) summary

TIGR00860
Location:34 → 469

LIC; Cation transporter family protein

pfam02931
Location:34 → 225

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:232 → 468

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
NM_004198.3 → NP_004189.1 neuronal acetylcholine receptor subunit alpha-6 isoform 1 precursor

See identical proteins and their annotated locations for NP_004189.1

Status: REVIEWED

Description

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

Source sequence(s)

BC014456, DC307404

Consensus CDS

CCDS6135.1

UniProtKB/Swiss-Prot

B2R8V4, B4DQH1, Q15825

Related

ENSP00000276410.3, ENST00000276410.7

Conserved Domains (1) summary

cl27321
Location:34 → 484

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain