CHRNB2

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

Basic information

Region (hg38): 1:154567777-154580013

Links

ENSG00000160716 ∙ NCBI:1141 ∙ OMIM:118507 ∙ HGNC:1962 ∙ Uniprot:P17787 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nocturnal frontal lobe epilepsy 3 (Strong), mode of inheritance: AD
• autosomal dominant nocturnal frontal lobe epilepsy 3 (Strong), mode of inheritance: AD
• autosomal dominant nocturnal frontal lobe epilepsy (Supportive), mode of inheritance: AD
• sleep-related hypermotor epilepsy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epilepsy, nocturnal frontal lobe, type 3	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	11062464; 20301348
As the attacks had been interpreted in some instances as being nightmares/sleep walking, a genetic diagnosis may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNB2 gene.

• Autosomal dominant nocturnal frontal lobe epilepsy (416 variants)
• not provided (143 variants)
• Inborn genetic diseases (65 variants)
• not specified (46 variants)
• Autosomal dominant nocturnal frontal lobe epilepsy 3 (30 variants)
• CHRNB2-related condition (2 variants)
• Microcephaly;Seizure;Deeply set eye (1 variants)
• Generalized-onset seizure (1 variants)
• Autosomal dominant nocturnal frontal lobe epilepsy 1 (1 variants)
• See cases (1 variants)
• Intellectual disability (1 variants)
• Seizure (1 variants)
• Focal clonic seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNB2 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			5	151	2	158
missense	1	3	220	16	1	241
nonsense			8			8
start loss			2			2
frameshift			17			17
inframe indel			8			8
splice donor/acceptor (+/-2bp)			3			3
splice region			9	5	1	15
non coding			1	30	15	46
Total	1	3	264	197	18

Variants in CHRNB2

This is a list of pathogenic ClinVar variants found in the CHRNB2 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-154567831-A-G			Benign (Jun 19, 2018)
1-154567990-C-T			Benign (Jun 14, 2018)
1-154567992-C-T			Benign (Jun 26, 2018)
1-154567994-C-A			Likely benign (Jun 19, 2018)
1-154567996-G-C		not specified	Benign (Apr 17, 2014)
1-154568006-C-G			Benign (Jun 22, 2015)
1-154568008-A-C		not specified	Likely benign (Feb 11, 2016)
1-154568042-G-A			Uncertain significance (Jul 08, 2022)
1-154568045-A-G		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Nov 06, 2023)
1-154568045-A-T		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Feb 08, 2022)
1-154568046-T-A		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Nov 08, 2022)
1-154568048-G-T		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Apr 05, 2023)
1-154568051-C-T			Uncertain significance (Jul 01, 2014)
1-154568051-C-CGGCGCTGCGGCCCCGT		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Jan 27, 2024)
1-154568054-C-A		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Aug 07, 2023)
1-154568056-C-G		Autosomal dominant nocturnal frontal lobe epilepsy	Likely benign (Apr 07, 2022)
1-154568057-T-C		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Aug 30, 2022)
1-154568057-T-G		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Dec 03, 2020)
1-154568058-G-C		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Aug 31, 2022)
1-154568061-G-A		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Sep 20, 2018)
1-154568061-GC-G		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Jun 13, 2022)
1-154568062-C-G		Inborn genetic diseases	Likely benign (Jun 01, 2018)
1-154568065-C-G		Autosomal dominant nocturnal frontal lobe epilepsy	Likely benign (May 15, 2023)
1-154568066-G-C		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Feb 18, 2020)
1-154568066-G-T		Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance (Jan 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNB2	protein_coding	protein_coding	ENST00000368476	6	12246

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000730	0.983	125730	0	18	125748	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.10	221	328	0.673	0.0000242	3226
Missense in Polyphen		91	150.31	0.60541		1596
Synonymous	-0.196	148	145	1.02	0.0000118	1024
Loss of Function	2.11	8	17.6	0.456	8.68e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000145	0.000145
Ashkenazi Jewish	0.00	0.00
East Asian	0.000165	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000880	0.0000879
Middle Eastern	0.000165	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

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 permeable to sodiun ions. {ECO:0000269|PubMed:22361591}.
• Disease: DISEASE: Epilepsy, nocturnal frontal lobe, 3 (ENFL3) [MIM:605375]: An autosomal dominant focal epilepsy characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements. {ECO:0000269|PubMed:11062464, ECO:0000269|PubMed:11104662}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Nicotine addiction - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Nicotine Pathway (Dopaminergic Neuron), Pharmacodynamics;Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Nicotine Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Nicotine Activity on Dopaminergic Neurons;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;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: 0.278

Intolerance Scores

• loftool: 0.0740
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.646
• ghis: 0.694

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.447

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrnb2
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); craniofacial phenotype; homeostasis/metabolism phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; normal 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); vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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

Gene ontology

• Biological process: action potential;conditioned taste aversion;response to hypoxia;ion transport;calcium ion transport;smooth muscle contraction;signal transduction;chemical synaptic transmission;synaptic transmission, cholinergic;neuromuscular synaptic transmission;visual perception;sensory perception of sound;learning;memory;locomotory behavior;associative learning;visual learning;regulation of dopamine secretion;sensory perception of pain;vestibulocochlear nerve development;optic nerve morphogenesis;lateral geniculate nucleus development;central nervous system projection neuron axonogenesis;positive regulation of B cell proliferation;regulation of synaptic transmission, dopaminergic;positive regulation of synaptic transmission, dopaminergic;positive regulation of dopamine secretion;ion transmembrane transport;response to nicotine;behavioral response to nicotine;social behavior;regulation of dopamine metabolic process;B cell activation;response to cocaine;regulation of circadian sleep/wake cycle, REM sleep;regulation of membrane potential;regulation of circadian sleep/wake cycle, non-REM sleep;response to ethanol;negative regulation of action potential;regulation of dendrite morphogenesis;nervous system process;cognition;protein heterooligomerization;membrane depolarization;regulation of synapse assembly;excitatory postsynaptic potential;synaptic transmission involved in micturition;acetylcholine receptor signaling pathway;response to acetylcholine;regulation of synaptic vesicle exocytosis
• Cellular component: plasma membrane;integral component of plasma membrane;acetylcholine-gated channel complex;external side of plasma membrane;integral component of membrane;cell junction;neuron projection;plasma membrane raft;synapse;dopaminergic synapse;cholinergic synapse;integral component of presynaptic membrane;integral component of postsynaptic specialization 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;protein heterodimerization activity