CHRNB4

cholinergic receptor nicotinic beta 4 subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 15:78624111-78727754

Links

ENSG00000117971 ∙ NCBI:1143 ∙ OMIM:118509 ∙ HGNC:1964 ∙ Uniprot:P30926 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lung cancer (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNB4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNB4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					4	4
missense			22	3	4	29
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1			1
Total	0	0	23	3	8

Variants in CHRNB4

This is a list of pathogenic ClinVar variants found in the CHRNB4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-78624813-CG-AT		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
15-78625057-A-G			Benign (Apr 27, 2020)
15-78625140-C-T		not specified	Likely benign (Mar 01, 2023)
15-78625156-G-A		not specified	Uncertain significance (Jan 06, 2023)
15-78625173-T-C		not specified	Uncertain significance (Feb 28, 2023)
15-78625187-G-T			Likely benign (Aug 03, 2018)
15-78625219-C-G		Chronic obstructive pulmonary disease	Pathogenic (-)
15-78625219-C-T		not specified	Uncertain significance (Mar 20, 2023)
15-78628996-G-A		not specified	Uncertain significance (Sep 28, 2022)
15-78629001-G-A		Amyotrophic lateral sclerosis	Benign (Mar 31, 2020)
15-78629056-A-G		not specified	Uncertain significance (Jul 13, 2022)
15-78629122-C-T		not specified	Uncertain significance (Jan 17, 2023)
15-78629128-C-T		not specified	Uncertain significance (Oct 05, 2021)
15-78629181-G-A			Benign (Feb 25, 2018)
15-78629237-C-T			Benign (Jan 30, 2018)
15-78629260-G-A			Likely benign (Dec 01, 2022)
15-78629283-A-T		not specified	Uncertain significance (Jun 27, 2022)
15-78629336-C-T			Benign (Jan 30, 2018)
15-78629352-T-C		not specified	Uncertain significance (Apr 01, 2024)
15-78629377-T-C		not specified	Uncertain significance (Aug 08, 2022)
15-78629395-C-A		not specified	Uncertain significance (Sep 14, 2022)
15-78629407-T-C		not specified	Uncertain significance (Jul 14, 2023)
15-78629523-C-T		not specified	Uncertain significance (Dec 22, 2023)
15-78629585-G-A			Benign (Jul 16, 2018)
15-78629647-C-T		Frontotemporal dementia	Likely pathogenic (Feb 02, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNB4	protein_coding	protein_coding	ENST00000261751	6	103636

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.143	0.857	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	257	317	0.811	0.0000200	3246
Missense in Polyphen		107	150.54	0.71078		1653
Synonymous	-1.01	152	137	1.11	0.00000957	1029
Loss of Function	2.95	5	18.8	0.266	9.76e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000968	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000654	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Nicotine Pathway (Chromaffin Cell), Pharmacodynamics;Nicotine Activity on Chromaffin Cells;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Neutrophil degranulation;Highly sodium permeable acetylcholine nicotinic receptors;Innate Immune System;Immune System;Neuronal System;Neurotransmitter receptors and postsynaptic signal transmission;Transmission across Chemical Synapses;Highly calcium permeable nicotinic acetylcholine receptors;Presynaptic nicotinic acetylcholine receptors;Highly calcium permeable postsynaptic nicotinic acetylcholine receptors;Postsynaptic nicotinic acetylcholine receptors;Activation of Nicotinic Acetylcholine Receptors;Acetylcholine binding and downstream events (Consensus)

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.144
• rvis_EVS: 0.73
• rvis_percentile_EVS: 86.3

Haploinsufficiency Scores

• pHI: 0.143
• hipred: N
• hipred_score: 0.282

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.154

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Chrnb4
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: action potential;ion transport;smooth muscle contraction;regulation of smooth muscle contraction;signal transduction;chemical synaptic transmission;synaptic transmission, cholinergic;neuromuscular synaptic transmission;locomotory behavior;ion transmembrane transport;response to nicotine;behavioral response to nicotine;regulation of membrane potential;neutrophil degranulation;regulation of neurotransmitter secretion;nervous system process;protein heterooligomerization;positive regulation of transmission of nerve impulse;excitatory postsynaptic potential;synaptic transmission involved in micturition
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;integral component of membrane;cell junction;specific granule membrane;neuron projection;synapse;postsynaptic membrane;tertiary granule membrane;cholinergic synapse
• Molecular function: extracellular ligand-gated ion channel activity;protein binding;ligand-gated ion channel activity;acetylcholine receptor activity;acetylcholine-gated cation-selective channel activity;acetylcholine binding;protein heterodimerization activity