CHRNA3

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

Basic information

Region (hg38): 15:78593052-78621295

Links

ENSG00000080644 ∙ NCBI:1136 ∙ OMIM:118503 ∙ HGNC:1957 ∙ Uniprot:P32297 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bladder dysfunction, autonomic, with impaired pupillary reflex and secondary congenital anomalies of the kidney and urinary tract	AR	Renal	The condition can involve chronic kidney disease andrecurrent urinary tract infections, and awareness may allow prompt diagnosis and management (of note, surgical management of VUR has not been reported as effective)	Neurologic; Renal	31708116

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNA3 gene.

• Urinary bladder, atony of (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNA3 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			1	20	7	28
missense			25	4	3	32
nonsense		1				1
start loss		1				1
frameshift	1	3	1			5
inframe indel			2		2	4
splice donor/acceptor (+/-2bp)						0
splice region				1	3	4
non coding			4	3	4	11
Total	1	5	33	27	16

Variants in CHRNA3

This is a list of pathogenic ClinVar variants found in the CHRNA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-78593158-G-C		not specified	Uncertain significance (Aug 14, 2023)
15-78593235-T-G		not specified	Uncertain significance (Mar 18, 2024)
15-78593805-T-C		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
15-78594000-T-C		Squamous cell carcinoma	Uncertain significance (Jun 06, 2022)
15-78596626-AG-A			Uncertain significance (Apr 12, 2022)
15-78596629-G-A		Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
15-78596634-C-T			Likely benign (Jul 21, 2022)
15-78596644-C-G		Inborn genetic diseases	Uncertain significance (Jul 27, 2021)
15-78596650-G-A			Uncertain significance (Jun 12, 2024)
15-78596663-A-T			Uncertain significance (May 03, 2022)
15-78596692-C-T		Inborn genetic diseases	Uncertain significance (Aug 05, 2023)
15-78596693-G-T		Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
15-78596749-TAAAA-T			Benign (Oct 23, 2023)
15-78596749-TAAAAG-T			Likely benign (Sep 26, 2022)
15-78601259-G-A			Benign (Jan 25, 2024)
15-78601288-CAAT-C			Uncertain significance (Nov 08, 2022)
15-78601290-A-G		CHRNA3-related disorder	Likely benign (Oct 13, 2022)
15-78601295-C-T			Likely benign (Nov 08, 2022)
15-78601310-G-A			Likely benign (Apr 09, 2023)
15-78601383-G-A			Likely benign (Sep 29, 2023)
15-78601399-A-C			Benign (Dec 13, 2023)
15-78601445-G-A		Urinary bladder, atony of;Smoking as a quantitative trait locus 3	Benign/Likely benign (Jan 27, 2024)
15-78601473-C-G		Inborn genetic diseases	Uncertain significance (Oct 26, 2022)
15-78601479-G-A			Likely benign (Aug 19, 2023)
15-78601492-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNA3	protein_coding	protein_coding	ENST00000326828	6	28244

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.42e-7	0.618	125642	0	106	125748	0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.735	247	282	0.877	0.0000166	3288
Missense in Polyphen		119	155.9	0.76331		1816
Synonymous	-2.55	158	122	1.29	0.00000842	1016
Loss of Function	1.09	13	18.0	0.722	7.67e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000666	0.000666
Ashkenazi Jewish	0.00	0.00
East Asian	0.000436	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000511	0.000510
Middle Eastern	0.000436	0.000435
South Asian	0.000655	0.000653
Other	0.000815	0.000815

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 (Dopaminergic Neuron), Pharmacodynamics;Nicotine Pathway (Chromaffin Cell), Pharmacodynamics;Nicotine Metabolism Pathway;Nicotine Action Pathway;Nicotine Activity on Dopaminergic Neurons;Nicotine Activity on Chromaffin Cells;Highly sodium permeable acetylcholine nicotinic receptors;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: 0.252

Intolerance Scores

• loftool: 0.0990
• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.78

Haploinsufficiency Scores

• pHI: 0.287
• hipred: N
• hipred_score: 0.390
• ghis: 0.459

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.159

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrna3
• Phenotype: vision/eye phenotype; digestive/alimentary 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); renal/urinary system phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: ion transport;regulation of smooth muscle contraction;signal transduction;activation of transmembrane receptor protein tyrosine kinase activity;chemical synaptic transmission;synaptic transmission, cholinergic;neuromuscular synaptic transmission;nervous system development;locomotory behavior;regulation of acetylcholine secretion, neurotransmission;ion transmembrane transport;response to nicotine;behavioral response to nicotine;regulation of membrane potential;regulation of dendrite morphogenesis;nervous system process;excitatory postsynaptic potential;synaptic transmission involved in micturition;acetylcholine receptor signaling pathway;response to acetylcholine
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;postsynaptic density;integral component of membrane;cell junction;dendrite;neuron projection;neuronal cell body;plasma membrane raft;synapse;postsynaptic membrane
• 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