CHRNB3

protein-coding

cholinergic receptor nicotinic beta 3 subunit, the group of Cholinergic receptors nicotinic subunits

Gene 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]

MANE transcript

NM_000749.5

Inheritance

—

ClinVar variants

U:72B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr8:42,697,366-42,737,407

External References & Databases

Ensembl (ENSG00000147432)

Transcript & Mutation Effects

hg38 • Region Span ~40.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHRNB3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 68

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000749.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		1 clinvar	2
missense			69 clinvar	2 clinvar	1 clinvar	72
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	72	2	2	76

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000749.5	RefSeq	NP_000740.1	6	MANE Select
ENST00000289957.3	Ensembl	ENSP00000289957.2	6	MANE Select
NM_001347717.2	RefSeq	NP_001334646.1	4	Standard
ENST00000534391.1	Ensembl	ENSP00000433913.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuroactive ligand-receptor interaction - Homo sapiens (human)
Neuronal System
Neurotransmitter receptors and postsynaptic signal transmission
Transmission across Chemical Synapses
Highly calcium permeable nicotinic acetylcholine receptors

Biological Process

signal transduction
chemical synaptic transmission
synaptic transmission, cholinergic
neuromuscular synaptic transmission
ion transmembrane transport

Molecular Function

extracellular ligand-gated ion channel activity
channel activity
acetylcholine receptor activity
acetylcholine-gated cation-selective channel activity
acetylcholine binding

Cellular Component

plasma membrane
integral component of plasma membrane
acetylcholine-gated channel complex
integral component of membrane
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000289957
Coding exons: 6
Length: 40032
Individuals with no LoFs: 125572
Homozygous LoFs: 1
Heterozygous LoFs: 174
Defined: 125747
p: 0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.841	220	258	0.853	0.0000142	2994
Missense (PolyPhen)		110	132.63	0.82939		1536
Synonymous	0.839	96	107	0.897	0.00000683	900
Loss of Function	1.71	11	19.1	0.577	9.76e-7	228

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00054	0.00049	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0058	0.0058	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00034	0.00033	rare
South Asian	0.00024	0.00023	rare
Other	0.00049	0.00033	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.490
RVIS EVS: -0.34
RVIS percentile EVS: 30.56

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.210

Gene Damage Prediction

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