CHRNA5

cholinergic receptor nicotinic alpha 5 subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 15:78565519-78595269

Links

ENSG00000169684 ∙ NCBI:1138 ∙ OMIM:118505 ∙ HGNC:1959 ∙ Uniprot:P30532 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNA5 gene.

• not provided (14 variants)
• Inborn genetic diseases (11 variants)
• Lung adenocarcinoma (2 variants)
• Smoking as a quantitative trait locus 3 (2 variants)
• Squamous cell carcinoma (1 variants)
• Susceptibility to severe coronavirus disease (COVID-19) due to high levels of fibrinogen and C-reactive protein (1 variants)
• Lung cancer susceptibility 2 (1 variants)
• nicotine response - Toxicity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNA5 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				3	6	9
missense			11	3	2	16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3			3
Total	0	0	14	6	8

Variants in CHRNA5

This is a list of pathogenic ClinVar variants found in the CHRNA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-78565736-C-T		not specified	Uncertain significance (Oct 27, 2022)
15-78565773-G-A			Benign (Dec 31, 2019)
15-78565799-C-T		not specified	Uncertain significance (Dec 19, 2023)
15-78565806-G-A			Likely benign (Apr 10, 2018)
15-78565812-C-T			Benign (Oct 24, 2018)
15-78580871-A-T		not specified	Uncertain significance (Dec 14, 2023)
15-78580878-C-T			Benign (Dec 31, 2019)
15-78580950-A-G			Likely benign (Aug 16, 2018)
15-78580960-G-T		not specified	Uncertain significance (Oct 20, 2023)
15-78588218-C-A		Lung adenocarcinoma	Uncertain significance (Jun 06, 2022)
15-78589842-G-A		not specified	Uncertain significance (Jul 19, 2023)
15-78589891-A-G			Benign (Dec 31, 2019)
15-78589915-C-T		not specified	Uncertain significance (Feb 26, 2024)
15-78589978-C-T		not specified	Uncertain significance (Jan 26, 2023)
15-78590092-G-A		not specified	Uncertain significance (Jan 27, 2022)
15-78590104-C-T		Smoking as a quantitative trait locus 3	Likely benign (Dec 07, 2019)
15-78590180-G-T			Likely benign (Mar 06, 2018)
15-78590248-C-A		not specified	Uncertain significance (Nov 29, 2023)
15-78590254-T-A		not specified	Uncertain significance (Oct 03, 2022)
15-78590343-G-C		not specified	Uncertain significance (Jul 05, 2023)
15-78590383-C-T		not specified	Uncertain significance (Mar 29, 2022)
15-78590384-C-T			Benign (Dec 31, 2019)
15-78590449-G-A		not specified	Uncertain significance (Apr 05, 2023)
15-78590467-C-T			Likely benign (Jul 03, 2023)
15-78590479-T-A			Benign (Dec 31, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNA5	protein_coding	protein_coding	ENST00000299565	6	29750

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000215	0.723	125572	0	175	125747	0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	197	244	0.807	0.0000131	3056
Missense in Polyphen		108	140.4	0.76921		1636
Synonymous	0.932	73	83.9	0.871	0.00000466	931
Loss of Function	1.16	11	16.0	0.686	6.73e-7	234

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00163	0.00162
Ashkenazi Jewish	0.00	0.00
East Asian	0.000389	0.000381
Finnish	0.00	0.00
European (Non-Finnish)	0.000771	0.000747
Middle Eastern	0.000389	0.000381
South Asian	0.00127	0.00124
Other	0.000979	0.000978

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);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Nicotine Activity on Dopaminergic Neurons;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: 0.0922

Intolerance Scores

• loftool: 0.324
• rvis_EVS: -0.22
• rvis_percentile_EVS: 37.54

Haploinsufficiency Scores

• pHI: 0.0747
• hipred: N
• hipred_score: 0.397
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.271

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrna5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: signal transduction;chemical synaptic transmission;synaptic transmission, cholinergic;neuromuscular synaptic transmission;ion transmembrane transport;response to nicotine;behavioral response to nicotine;regulation of membrane potential;nervous system process;excitatory postsynaptic potential;regulation of synaptic vesicle exocytosis
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;cell junction;neuron projection;synapse;postsynaptic membrane;dopaminergic 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