CHRNB4 cholinergic receptor nicotinic beta 4 subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHRNB4provided by HGNC
Official Full Name: cholinergic receptor nicotinic beta 4 subunitprovided by HGNC
Primary source: HGNC:HGNC:1964
See related: Ensembl:ENSG00000117971 MIM:118509; AllianceGenome:HGNC:1964
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: This gene is found within a conserved gene cluster and encodes one of the beta subunits of the nicotinic acetylcholine receptor (nAChRs) superfamily which form ligand-gated ion channels with a central pore that forms a cation channel. Neuronal nAChRs are pentameric structures that can be either homomeric or heteromeric, with heteromeric structures containing both alpha and beta subunits. Each subunit contains an extracellular amino terminus and four transmembrane domains. Nicotine is one of the agonists that binds to the receptor. Variants in this gene have been associated with nicotine dependence and lung cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2017]
Expression: Biased expression in testis (RPKM 1.1), adrenal (RPKM 0.6) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q25.1

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (78624111..78661641, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (76487585..76519049, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (78916453..78933552, complement)

Chromosome 15 - NC_000015.10 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 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 relationship between CHRNA5/A3/B4 gene cluster polymorphisms and lung cancer risk: An updated meta-analysis and systematic review.
Title: The relationship between CHRNA5/A3/B4 gene cluster polymorphisms and lung cancer risk: An updated meta-analysis and systematic review.
Results indicate rs4887074 is associated with nicotinic receptor CHRNB4 expression, and along with two regulatory variants of nicotinic receptors CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk.
Title: Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence.
We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4. The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners.
Title: Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.
our results show that a genomic region with functionally related genes, such as the CHRNA5/CHRNA3/CHRNB4 cluster, is under coordinated regulatory control.
Title: The CHRNA5/CHRNA3/CHRNB4 Nicotinic Receptor Regulome: Genomic Architecture, Regulatory Variants, and Clinical Associations.
The results of this study suggests a pleiotropic role of Chr15q25 CHRNA5-CHRNA3-CHRNB4 gene cluster with complex influences in ADHD, tobacco smoking and cognitive performance.
Title: Pleiotropic effects of Chr15q25 nicotinic gene cluster and the relationship between smoking, cognition and ADHD.
focus on the CHRNA5/A3/B4 gene cluster and its role in nicotine dependence (review)
Title: Contribution of Variants in CHRNA5/A3/B4 Gene Cluster on Chromosome 15 to Tobacco Smoking: From Genetic Association to Mechanism.
MAFA controls autonomic nervous system-mediated insulin secretion by activating the transcription of nicotinic (ChrnB2 and ChrnB4) receptor genes, which is impaired in patients with type 2 diabetes.
Title: MafA-Controlled Nicotinic Receptor Expression Is Essential for Insulin Secretion and Is Impaired in Patients with Type 2 Diabetes.
Our data suggest that gene variance in the CHRNA5-CHRNA3-CHRNB4 cluster is associated with an increased risk of death, incidence of COPD and tobacco-related cancer in smokers.
Title: Gene variance in the nicotinic receptor cluster (CHRNA5-CHRNA3-CHRNB4) predicts death from cardiopulmonary disease and cancer in smokers.
two SNPs (rs6495308 and rs11072768) in CHRNA5-A3-B4 have a indirect effect on lung cancer through smoking behaviors
Title: Chromosome 15q25 (CHRNA3-CHRNB4) Variation Indirectly Impacts Lung Cancer Risk in Chinese Males.
Data suggest that CHRNA5-A3-B4 gene variants do not exhibit a robust association with smoking cessation and are unlikely to be useful for clinically optimizing smoking cessation pharmacotherapy for Caucasian smokers.
Title: Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

Submit: New GeneRIF Correction See all GeneRIFs (77)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. EBI GWAS Catalog EBI GWAS CatalogPubMed
A variant associated with nicotine dependence, lung cancer and peripheral arterial disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Beyond cigarettes-per-day: A genome-wide association study of the biomarker carbon monoxide. EBI GWAS Catalog EBI GWAS CatalogPubMed
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Familial aggregation of common sequence variants on 15q24-25.1 in lung cancer. EBI GWAS Catalog EBI GWAS CatalogPubMed
GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease. 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

STS-U48861 (e-PCR)
- UniSTS:54681

Chrnb4 (e-PCR), detects polymorphism
- UniSTS:256428

RH47011 (e-PCR)
- UniSTS:82367

NoName (e-PCR)
- UniSTS:483804

RH70650 (e-PCR)
- UniSTS:37877

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables acetylcholine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
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 acetylcholine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in behavioral response to nicotine	IEA Inferred from Electronic Annotation more info
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
involved_in excitatory postsynaptic potential	IEA Inferred from Electronic Annotation more info
involved_in locomotory behavior	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 monoatomic ion transport	TAS Traceable Author Statement more info	PubMed
involved_in neuronal action potential	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transmission of nerve impulse	IEA Inferred from Electronic Annotation more info
involved_in regulation of neurotransmitter secretion	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of smooth muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in smooth muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in synaptic transmission involved in micturition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synaptic transmission, cholinergic	TAS Traceable Author Statement more info	PubMed

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
part_of acetylcholine-gated channel complex	TAS Traceable Author Statement more info	PubMed
located_in cholinergic 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	IC Inferred by Curator more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic specialization membrane	IEA Inferred from Electronic Annotation more info
located_in specific granule membrane	TAS Traceable Author Statement more info
is_active_in synapse	IBA Inferred from Biological aspect of Ancestor more info
located_in tertiary granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: neuronal acetylcholine receptor subunit beta-4

Names: acetylcholine receptor, nicotinic, beta 4 (neuronal); cholinergic receptor, nicotinic, beta 4 (neuronal); cholinergic receptor, nicotinic, beta polypeptide 4; neuronal nicotinic receptor beta 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.

mRNA and Protein(s)

NM_000750.5 → NP_000741.1 neuronal acetylcholine receptor subunit beta-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_000741.1

Status: REVIEWED

Description

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

Source sequence(s)

AC067863, AI625439, BC096081, BF311784, BX348201, BY795907, CN366252, HY213565, U48861, U62439

Consensus CDS

CCDS10306.1

UniProtKB/Swiss-Prot

A4FTX5, E9PHE8, P30926, Q16607, Q4VBA5, Q8WXC8, Q9BQR4

Related

ENSP00000261751.3, ENST00000261751.8

Conserved Domains (1) summary

cl27321
Location:5 → 480

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain
NM_001256567.3 → NP_001243496.1 neuronal acetylcholine receptor subunit beta-4 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 2) with a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC067863, AI625439, BC096081, U48861, U62439

Consensus CDS

CCDS58392.1

UniProtKB/Swiss-Prot

P30926

Related

ENSP00000416386.2, ENST00000412074.6

Conserved Domains (1) summary

pfam02931
Location:27 → 120

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

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_000015.10 Reference GRCh38.p14 Primary Assembly

Range

78624111..78661641 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011521187.3 → XP_011519489.1 neuronal acetylcholine receptor subunit beta-4 isoform X1

See identical proteins and their annotated locations for XP_011519489.1

Conserved Domains (3) summary

TIGR00860
Location:21 → 477

LIC; Cation transporter family protein

pfam02931
Location:24 → 229

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:236 → 475

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_011521186.3 → XP_011519488.1 neuronal acetylcholine receptor subunit beta-4 isoform X1

See identical proteins and their annotated locations for XP_011519488.1

Conserved Domains (3) summary

TIGR00860
Location:21 → 477

LIC; Cation transporter family protein

pfam02931
Location:24 → 229

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:236 → 475

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_011521191.3 → XP_011519493.1 neuronal acetylcholine receptor subunit beta-4 isoform X6

See identical proteins and their annotated locations for XP_011519493.1

Conserved Domains (2) summary

pfam02931
Location:1 → 158

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:165 → 404

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_017021886.2 → XP_016877375.1 neuronal acetylcholine receptor subunit beta-4 isoform X2

Conserved Domains (3) summary

TIGR00860
Location:2 → 450

LIC; Cation transporter family protein

pfam02931
Location:1 → 202

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:209 → 448

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_017021885.2 → XP_016877374.1 neuronal acetylcholine receptor subunit beta-4 isoform X2

Conserved Domains (3) summary

TIGR00860
Location:2 → 450

LIC; Cation transporter family protein

pfam02931
Location:1 → 202

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:209 → 448

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_011521190.3 → XP_011519492.1 neuronal acetylcholine receptor subunit beta-4 isoform X6

See identical proteins and their annotated locations for XP_011519492.1

Conserved Domains (2) summary

pfam02931
Location:1 → 158

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:165 → 404

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_011521192.3 → XP_011519494.1 neuronal acetylcholine receptor subunit beta-4 isoform X7

Conserved Domains (2) summary

pfam02931
Location:9 → 50

Neur_chan_LBD; Neurotransmitter-gated ion-channel ligand binding domain

pfam02932
Location:57 → 296

Neur_chan_memb; Neurotransmitter-gated ion-channel transmembrane region
XM_017021889.3 → XP_016877378.1 neuronal acetylcholine receptor subunit beta-4 isoform X5
XM_017021888.2 → XP_016877377.1 neuronal acetylcholine receptor subunit beta-4 isoform X4
XM_017021887.2 → XP_016877376.1 neuronal acetylcholine receptor subunit beta-4 isoform X3

Alternate T2T-CHM13v2.0

Genomic

NC_060939.1 Alternate T2T-CHM13v2.0

Range

76487585..76519049 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054377235.1 → XP_054233210.1 neuronal acetylcholine receptor subunit beta-4 isoform X1
XM_054377236.1 → XP_054233211.1 neuronal acetylcholine receptor subunit beta-4 isoform X1
XM_054377242.1 → XP_054233217.1 neuronal acetylcholine receptor subunit beta-4 isoform X6
XM_054377238.1 → XP_054233213.1 neuronal acetylcholine receptor subunit beta-4 isoform X2
XM_054377237.1 → XP_054233212.1 neuronal acetylcholine receptor subunit beta-4 isoform X2
XM_054377243.1 → XP_054233218.1 neuronal acetylcholine receptor subunit beta-4 isoform X6
XM_054377244.1 → XP_054233219.1 neuronal acetylcholine receptor subunit beta-4 isoform X7
XM_054377241.1 → XP_054233216.1 neuronal acetylcholine receptor subunit beta-4 isoform X5
XM_054377240.1 → XP_054233215.1 neuronal acetylcholine receptor subunit beta-4 isoform X4
XM_054377239.1 → XP_054233214.1 neuronal acetylcholine receptor subunit beta-4 isoform X3