CHRNA5

protein-coding

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

Gene summary

The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

MANE transcript

NM_000745.4

Inheritance

—

ClinVar variants

U:49B:16

Top phenotype

CHRNA5-related condition

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr15:78,565,520-78,595,269

External References & Databases

Ensembl (ENSG00000169684)

Transcript & Mutation Effects

hg38 • Region Span ~29.7 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 CHRNA5 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 15

CHRNA5-related conditionTotal: 1

Lung adenocarcinomaTotal: 1

SMOKING AS A QUANTITATIVE TRAIT LOCUS 3Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000745.4. 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				3 clinvar	6 clinvar	9
missense			46 clinvar	5 clinvar	2 clinvar	53
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	49	8	8	65

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000745.4	RefSeq	NP_000736.2	6	MANE Select
ENST00000299565.9	Ensembl	ENSP00000299565.5	6	MANE Select
NM_001307945.2	RefSeq	NP_001294874.1	6	Standard
NM_001395171.1	RefSeq	NP_001382100.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

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

Molecular Function

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

Cellular Component

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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299565
Coding exons: 6
Length: 29750
Individuals with no LoFs: 125572
Homozygous LoFs: 0
Heterozygous LoFs: 175
Defined: 125747
p: 0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	197	244	0.807	0.0000131	3056
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00093	0.00092	rare
Latino/Admixed American	0.00070	0.00069	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00039	0.00038	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00077	0.00075	rare
South Asian	0.0013	0.0012	notable
Other	0.00098	0.00098	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: 0.0922

Intolerance Scores

LoFtool: 0.324
RVIS EVS: -0.22
RVIS percentile EVS: 37.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.271

Gene Damage Prediction

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