CHRNB1

cholinergic receptor nicotinic beta 1 subunit, the group of Cholinergic receptors nicotinic subunits

Basic information

Region (hg38): 17:7445060-7457710

Previous symbols: [ "CHRNB" ]

Links

ENSG00000170175 ∙ NCBI:1140 ∙ OMIM:100710 ∙ HGNC:1961 ∙ Uniprot:P11230 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital myasthenic syndrome 2A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 2C (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 1A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 2C (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 2C (Moderate), mode of inheritance: AD
• postsynaptic congenital myasthenic syndrome (Supportive), mode of inheritance: AR
• congenital myasthenic syndrome 2A (Strong), mode of inheritance: AD
• congenital myasthenic syndrome 2C (Strong), mode of inheritance: AR
• congenital myasthenic syndrome 2C (Definitive), mode of inheritance: AR
• congenital myasthenic syndrome 2A (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myasthenic syndrome, congenital, 2A, slow-channel; Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency	AD/AR	Musculoskeletal; Neurologic; Pharmacogenomic	Most individuals with CMS benefit from AChE inhibitors and/or potassium channel blocker 3,4-diaminopyridine (3,4-DAP), though caution must be used in giving 3,4-DAP to young children and individuals with fast-channel syndromes; For Slow-channel congenital myasthenic syndrome, effective treatment has been reported with therapies such as quinidine, fluoxetine, and ephedrine, while cholinesterase inhibitors and amifampridine should be avoided	Musculoskeletal; Neurologic	8872460; 8651643; 10562302; 20301347; 25792100

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHRNB1 gene.

• Congenital myasthenic syndrome 2A (304 variants)
• not provided (127 variants)
• Congenital myasthenic syndrome 4C (62 variants)
• Inborn genetic diseases (28 variants)
• not specified (22 variants)
• Congenital myasthenic syndrome 2C (4 variants)
• CHRNB1-related condition (2 variants)
• See cases (2 variants)
• Congenital Myasthenic Syndrome, Dominant/Recessive (1 variants)
• Congenital myasthenic syndrome 2A;Congenital myasthenic syndrome 2C (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHRNB1 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			4	63		67
missense	2	2	164		2	170
nonsense	1		2			3
start loss						0
frameshift	6	4	4			14
inframe indel	1		5			6
splice donor/acceptor (+/-2bp)		5	1			6
splice region		1	12	9	1	23
non coding			19	40	47	106
Total	10	11	199	103	49

Highest pathogenic variant AF is 0.00000657

Variants in CHRNB1

This is a list of pathogenic ClinVar variants found in the CHRNB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-7445109-C-T		Congenital myasthenic syndrome 4C	Uncertain significance (Jan 13, 2018)
17-7445115-G-C		Congenital myasthenic syndrome 4C • not specified • CHRNB1-related disorder	Benign/Likely benign (Mar 03, 2020)
17-7445128-A-G		Congenital myasthenic syndrome 2A	Conflicting classifications of pathogenicity (Sep 03, 2022)
17-7445132-C-T		Congenital myasthenic syndrome 2A • Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
17-7445133-C-T		Congenital myasthenic syndrome 2A	Likely benign (Oct 03, 2023)
17-7445136-A-G		Congenital myasthenic syndrome 2A	Likely benign (Aug 06, 2021)
17-7445140-G-A		Congenital myasthenic syndrome 2A • Inborn genetic diseases	Uncertain significance (Sep 18, 2023)
17-7445148-G-C		Congenital myasthenic syndrome 2A	Likely benign (Jul 21, 2023)
17-7445150-T-G		Congenital myasthenic syndrome 2A	Uncertain significance (Aug 06, 2023)
17-7445153-T-C		Congenital myasthenic syndrome 2A	Uncertain significance (Aug 23, 2022)
17-7445153-TGCTGGGGGC-T		Congenital myasthenic syndrome 2A	Uncertain significance (Sep 01, 2022)
17-7445158-G-A		Congenital myasthenic syndrome 2A	Uncertain significance (Jan 27, 2020)
17-7445163-GC-AA		Congenital myasthenic syndrome 2A	Uncertain significance (Dec 19, 2017)
17-7445165-T-C		Congenital myasthenic syndrome 2A	Uncertain significance (Aug 19, 2022)
17-7445165-TGGGGGCGCC-T		Congenital myasthenic syndrome 2A	Uncertain significance (Nov 18, 2021)
17-7445166-G-C		Congenital myasthenic syndrome 2A • Congenital myasthenic syndrome 4C	Conflicting classifications of pathogenicity (Dec 19, 2023)
17-7445169-GGC-AA			Likely pathogenic (Feb 22, 2022)
17-7445171-C-G		Congenital myasthenic syndrome 2A	Uncertain significance (Nov 01, 2022)
17-7445171-C-T		Congenital myasthenic syndrome 2A	Uncertain significance (Oct 17, 2022)
17-7445178-C-T		Congenital myasthenic syndrome 2A	Likely benign (Mar 22, 2023)
17-7445180-C-G		Congenital myasthenic syndrome 2A • Congenital myasthenic syndrome 4C	Uncertain significance (Sep 22, 2023)
17-7445183-C-A		Congenital myasthenic syndrome 2A	Uncertain significance (Jul 27, 2022)
17-7445186-G-A		CHRNB1-related disorder • Congenital myasthenic syndrome 2A	Conflicting classifications of pathogenicity (Feb 21, 2023)
17-7445186-G-C			Uncertain significance (Jul 23, 2019)
17-7445189-A-G		Congenital myasthenic syndrome 2A	Uncertain significance (May 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHRNB1	protein_coding	protein_coding	ENST00000306071	11	12647

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.05e-8	0.850	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.438	266	287	0.927	0.0000177	3248
Missense in Polyphen		82	99.946	0.82045		1267
Synonymous	-0.191	123	120	1.02	0.00000795	1044
Loss of Function	1.58	15	23.2	0.647	0.00000104	257

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000392	0.000329
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.000274	0.000273
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.000489	0.000489

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. {ECO:0000269|PubMed:27375219}.
• Disease: DISEASE: Myasthenic syndrome, congenital, 2A, slow-channel (CMS2A) [MIM:616313]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2A is a slow-channel myasthenic syndrome. It is caused by kinetic abnormalities of the AChR, resulting in prolonged AChR channel opening episodes, prolonged endplate currents, and depolarization block. This is associated with calcium overload, which may contribute to subsequent degeneration of the endplate and postsynaptic membrane. {ECO:0000269|PubMed:27375219, ECO:0000269|PubMed:8651643, ECO:0000269|PubMed:8872460}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency (CMS2C) [MIM:616314]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. CMS2C is an autosomal recessive disorder of postsynaptic neuromuscular transmission, due to deficiency of AChR at the endplate that results in low amplitude of the miniature endplate potential and current. CMS2C is clinically characterized by early-onset muscle weakness with variable severity. {ECO:0000269|PubMed:10562302}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Neuroactive ligand-receptor interaction - Homo sapiens (human);role of nicotinic acetylcholine receptors in the regulation of apoptosis (Consensus)

Recessive Scores

• pRec: 0.146

Intolerance Scores

• loftool: 0.392
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.336
• hipred: N
• hipred_score: 0.323
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0599

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chrnb1
• 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)

Gene ontology

• Biological process: postsynaptic membrane organization;skeletal muscle contraction;cation transport;muscle contraction;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;muscle fiber development;nervous system process;excitatory postsynaptic potential
• Cellular component: integral component of plasma membrane;acetylcholine-gated channel complex;cell junction;neuromuscular junction;neuron projection;synapse;integral component of postsynaptic specialization membrane
• Molecular function: extracellular ligand-gated ion channel activity;channel activity;ligand-gated ion channel activity;acetylcholine receptor activity;acetylcholine-gated cation-selective channel activity;acetylcholine binding;transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential