CHRNB3 cholinergic receptor nicotinic beta 3 subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHRNB3provided by HGNC
Official Full Name: cholinergic receptor nicotinic beta 3 subunitprovided by HGNC
Primary source: HGNC:HGNC:1963
See related: Ensembl:ENSG00000147432 MIM:118508; AllianceGenome:HGNC:1963
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are (hetero)pentamers composed of homologous subunits. The subunits that make up the muscle and neuronal forms of nAChRs are encoded by separate genes and have different primary structure. There are several subtypes of neuronal nAChRs that vary based on which homologous subunits are arranged around the central channel. They are classified as alpha-subunits if, like muscle alpha-1 (MIM 100690), they have a pair of adjacent cysteines as part of the presumed acetylcholine binding site. Subunits lacking these cysteine residues are classified as beta-subunits (Groot Kormelink and Luyten, 1997 [PubMed 9009220]). Elliott et al. (1996) [PubMed 8906617] stated that the proposed structure for each subunit is a conserved N-terminal extracellular domain followed by 3 conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region.[supplied by OMIM, Apr 2010]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 8p11.21

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (42697366..42737407)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (42965410..43005503)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (42552509..42592550)

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?

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.
This study shows that unorthodox acetylcholine binding sites can form at the alpha5/alpha4 and beta3/alpha4 interfaces in (alpha4beta2)2alpha5 and (alpha4beta2)2beta3 nicotinic acetylcholine receptors (nAChRs) and at the alpha4/alpha5 in (beta2alpha4)2alpha5 nAChRs.
Title: Unorthodox Acetylcholine Binding Sites Formed by α5 and β3 Accessory Subunits in α4β2* Nicotinic Acetylcholine Receptors.
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.
Data provide evidence that the protective genetic variant at rs6474413 identified in human genetic studies reduces gene expression and that decreased beta3 gene expression in mice reduces nicotine intake
Title: The β3 subunit of the nicotinic acetylcholine receptor: Modulation of gene expression and nicotine consumption.
This patient's chromosomal abnormality affected only one gene that is highly expressed in the brainstem and brain, involved in neurotransmission, and could be related to her Duane retraction syndrome.
Title: Nicotinic Receptor Mutation in a Mildly Dysmorphic Girl with Duane Retraction Syndrome.
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 CHRNB3 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.

Submit: New GeneRIF Correction See all GeneRIFs (34)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
CHRNB3 is more strongly associated with Fagerstr&#x000c3;&#x000b6;m test for cigarette dependence-based nicotine dependence than cigarettes per day: phenotype definition changes genome-wide association studies results. EBI GWAS Catalog EBI GWAS CatalogPubMed
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

D8S1981 (e-PCR)
- UniSTS:20498

Chrnb3 (e-PCR), detects polymorphism
- UniSTS:256427

CHRNB3_2327 (e-PCR)
- UniSTS:280501

NoName (e-PCR)
- UniSTS:485597

D8S1209 (e-PCR)
- UniSTS:150266

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables acetylcholine binding	IEA Inferred from Electronic Annotation more info
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 channel activity	TAS Traceable Author Statement more info	PubMed
enables heterocyclic compound 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 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 neuromuscular synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in presynaptic modulation of chemical synaptic transmission	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
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
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 presynapse	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 beta-3

Names: acetylcholine receptor, neuronal nicotinic, beta-3 subunit; acetylcholine receptor, nicotinic, beta 3 (neuronal); cholinergic receptor, nicotinic beta 3; cholinergic receptor, nicotinic, beta 3 (neuronal); cholinergic receptor, nicotinic, beta polypeptide 3

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_000749.5 → NP_000740.1 neuronal acetylcholine receptor subunit beta-3 isoform 1 precursor

See identical proteins and their annotated locations for NP_000740.1

Status: VALIDATED

Description

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

Source sequence(s)

AC087533, AC090739, AC103843

Consensus CDS

CCDS6134.1

UniProtKB/Swiss-Prot

Q05901, Q15827

Related

ENSP00000289957.2, ENST00000289957.3

Conserved Domains (1) summary

cl27321
Location:23 → 449

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001347717.2 → NP_001334646.1 neuronal acetylcholine receptor subunit beta-3 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AC087533, AC090739, AC103843

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

42697366..42737407

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011544390.3 → XP_011542692.1 neuronal acetylcholine receptor subunit beta-3 isoform X1

Conserved Domains (2) summary

pfam02931
Location:1 → 104

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:111 → 317

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region