CHRNA2

cholinergic receptor nicotinic alpha 2 subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 8:27459756-27479883

Links

ENSG00000120903 ∙ NCBI:1135 ∙ OMIM:118502 ∙ HGNC:1956 ∙ Uniprot:Q15822 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nocturnal frontal lobe epilepsy 4 (Strong), mode of inheritance: AD
• autosomal dominant nocturnal frontal lobe epilepsy 4 (Limited), mode of inheritance: AD
• autosomal dominant nocturnal frontal lobe epilepsy (Supportive), mode of inheritance: AD
• familial sleep-related hypermotor epilepsy (Limited), mode of inheritance: AD
• benign familial infantile epilepsy (Disputed Evidence), mode of inheritance: AD
• autosomal dominant nocturnal frontal lobe epilepsy 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, nocturnal frontal lobe, type 4	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	16826524; 20301348
As the attacks had been interpreted in some instances as being nightmares/sleep walking, genetic diagnosis may be helpful

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNA2 gene.

• Autosomal_dominant_nocturnal_frontal_lobe_epilepsy (587 variants)
• not_provided (207 variants)
• Inborn_genetic_diseases (140 variants)
• Autosomal_dominant_nocturnal_frontal_lobe_epilepsy_4 (75 variants)
• not_specified (59 variants)
• CHRNA2-related_disorder (22 variants)
• Benign_familial_infantile_epilepsy (2 variants)
• Intellectual_disability (2 variants)
• Seizure (2 variants)
• Seizures,_benign_familial_infantile,_6 (1 variants)
• Epilepsy (1 variants)
• Myoclonic_epilepsy (1 variants)
• Familial_sleep-related_hypermotor_epilepsy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNA2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000742.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	168	3	174
missense	2	2	306	103	1	414
nonsense			16			16
start loss						0
frameshift		1	27	1		29
splice donor/acceptor (+/-2bp)			7	1		8
Total	2	3	359	273	4

Highest pathogenic variant AF is 0.0000013790232

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNA2	protein_coding	protein_coding	ENST00000407991	6	20122

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.45e-10	0.243	125690	0	58	125748	0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.301	334	319	1.05	0.0000218	3444
Missense in Polyphen		174	174.65	0.99626		1940
Synonymous	-0.540	150	142	1.06	0.0000111	1102
Loss of Function	0.696	16	19.3	0.829	8.51e-7	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000417	0.000417
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000329	0.000308
Middle Eastern	0.000326	0.000326
South Asian	0.000101	0.0000980
Other	0.000330	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.
• Disease: DISEASE: Epilepsy, nocturnal frontal lobe, 4 (ENFL4) [MIM:610353]: An autosomal dominant focal epilepsy characterized by nocturnal seizures associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. {ECO:0000269|PubMed:16826524}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Seizures, benign familial infantile, 6 (BFIS6) [MIM:610353]: A form of benign familial infantile epilepsy, a neurologic disorder characterized by afebrile seizures occurring in clusters during the first year of life, without neurologic sequelae. BFIS6 inheritance is autosomal dominant. {ECO:0000269|PubMed:25847220}. Note=The disease may be caused by mutations affecting the gene represented in this entry.
• Pathway: 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;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: 0.178

Intolerance Scores

• loftool: 0.352
• rvis_EVS: -0.75
• rvis_percentile_EVS: 13.67

Haploinsufficiency Scores

• pHI: 0.0459
• hipred: N
• hipred_score: 0.197
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.166

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrna2
• Phenotype: homeostasis/metabolism 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); normal phenotype

Gene ontology

• Biological process: ion transport;signal transduction;chemical synaptic transmission;ion transmembrane transport;regulation of membrane potential;nervous system process;protein heterooligomerization;excitatory postsynaptic potential
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;integral component of membrane;cell junction;neuron projection;synapse;postsynaptic membrane
• Molecular function: extracellular ligand-gated ion channel activity;acetylcholine receptor activity;acetylcholine-gated cation-selective channel activity;acetylcholine binding