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ยฉ 2026 GeneE
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GeneE
10 sources retrieved ยท Most recent: April 2026 ยท Index updated 15 days ago
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CHRNA1
cholinergic receptor nicotinic alpha 1 subunit
Chromosome 2 ยท 2q31.1
NCBI Gene: 1134Ensembl: ENSG00000138435.16HGNC: HGNC:1955UniProt: P02708
76PubMed Papers
23Diseases
22Drugs
48Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelReceptorTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
โœ“ Experimental GO Evidenceโœ“ Swiss-Prot Reviewed
neuromuscular synaptic transmissionneuromuscular junction developmentregulation of membrane potentialacetylcholine-gated monoatomic cation-selective channel activityCongenital myasthenic syndromesPostsynaptic congenital myasthenic syndromeslethal multiple pterygium syndromemuscle cramp
โœฆAI Summary

CHR2 encodes the alpha-1 subunit of the nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel essential for neuromuscular junction function. The protein forms part of acetylcholine-gated cation-selective channels that mediate signal transmission across the neuromuscular junction, enabling skeletal muscle contraction and neuromuscular synaptic transmission 1. CHR2 variants cause congenital myasthenic syndromes (CMS), including slow-channel and fast-channel subtypes, through impaired neuromuscular signal transmission 1. Additionally, CHR2 genetic polymorphisms represent risk factors for autoimmune myasthenia gravis (MG), where the rs35274388 variant in the promoter region associates with MG susceptibility, particularly late-onset disease 23. Genome-wide association studies confirmed CHR2 as a disease-associated locus in anti-acetylcholine receptor antibody-positive MG patients 3. Beyond neuromuscular disease, CHR2 upregulation characterizes primary focal hyperhidrosis pathogenesis. Silencing or antagonizing CHR2 reduces sweat secretion and attenuates sympathetic nervous system activation through decreased acetylcholine signaling 45. Clinically, CMS diagnosis requires electrophysiological confirmation and genetic testing, with treatment varying by pathomechanism; CHR2-related cases may respond differently to cholinesterase inhibitors compared to other CMS subtypes 1.

Sources cited
1
CHRNA1 variants cause congenital myasthenic syndromes affecting neuromuscular junction signal transmission; diagnostic approaches and therapeutic responses
PMID: 36835142
2
CHRNA1 contains a genome-wide association signal linked to autoimmune myasthenia gravis susceptibility in acetylcholine receptor antibody-positive patients
PMID: 35074870
3
CHRNA1 rs35274388 variant in the promoter region is a causal variant associated with myasthenia gravis, particularly late-onset disease
PMID: 40279038
4
CHRNA1 upregulation characterizes primary focal hyperhidrosis; CHRNA1 silencing reduces sweat secretion and sympathetic activation markers
PMID: 33476802
5
CHRNA1 antagonism via cisatracurium blocks the ion channel function and alleviates hyperhidrosis symptoms in mice models
PMID: 35393764
Disease Associationsโ“˜23
Congenital myasthenic syndromesOpen Targets
0.80Strong
Postsynaptic congenital myasthenic syndromesOpen Targets
0.80Strong
lethal multiple pterygium syndromeOpen Targets
0.77Strong
muscle crampOpen Targets
0.53Moderate
Muscle spasmOpen Targets
0.53Moderate
congenital myasthenic syndrome, dominant/recessiveOpen Targets
0.41Moderate
postsynaptic congenital myasthenic syndromeOpen Targets
0.37Weak
SeizureOpen Targets
0.36Weak
congenital myasthenic syndromeOpen Targets
0.34Weak
genetic disorderOpen Targets
0.34Weak
centronuclear myopathyOpen Targets
0.34Weak
congenital myopathyOpen Targets
0.34Weak
autismOpen Targets
0.33Weak
MyalgiaOpen Targets
0.32Weak
atrial fibrillationOpen Targets
0.29Weak
Non-immune hydrops fetalisOpen Targets
0.27Weak
acute respiratory distress syndromeOpen Targets
0.26Weak
strokeOpen Targets
0.26Weak
pyelonephritisOpen Targets
0.24Weak
body weight gainOpen Targets
0.20Weak
Multiple pterygium syndrome, lethal typeUniProt
Myasthenic syndrome, congenital, 1A, slow-channelUniProt
Myasthenic syndrome, congenital, 1B, fast-channelUniProt
Pathogenic Variants48
NM_000079.4(CHRNA1):c.517G>A (p.Gly173Ser)Pathogenic
Congenital myasthenic syndrome 1A|Lethal multiple pterygium syndrome|not provided|Congenital myasthenic syndrome 1A;Lethal multiple pterygium syndrome;Myasthenic syndrome, congenital, 1B, fast-channel|Congenital myasthenic syndrome 1A;Myasthenic syndrome, congenital, 1B, fast-channel|Congenital myopathy
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 173
NM_000079.4(CHRNA1):c.391C>T (p.Gln131Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 131
NM_000079.4(CHRNA1):c.1321G>A (p.Gly441Arg)Pathogenic
not provided|Lethal multiple pterygium syndrome|Autism;Seizure|Centronuclear myopathy
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 441
NM_000079.4(CHRNA1):c.175C>T (p.Gln59Ter)Pathogenic
not provided|Lethal multiple pterygium syndrome
โ˜…โ˜…โ˜†โ˜†2025โ†’ Residue 59
NM_000079.4(CHRNA1):c.997C>T (p.Arg333Trp)Pathogenic
Myasthenic syndrome, congenital, 1B, fast-channel|Lethal multiple pterygium syndrome|not provided
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 333
NM_000079.4(CHRNA1):c.518dup (p.Ser174fs)Pathogenic
not provided|Lethal multiple pterygium syndrome|Myasthenic syndrome, congenital, 1B, fast-channel;Lethal multiple pterygium syndrome;Congenital myasthenic syndrome 1A
โ˜…โ˜…โ˜†โ˜†2024โ†’ Residue 174
NM_000079.4(CHRNA1):c.380_381del (p.Lys127fs)Pathogenic
Congenital myasthenic syndrome|Lethal multiple pterygium syndrome
โ˜…โ˜…โ˜†โ˜†2023โ†’ Residue 127
NM_000079.4(CHRNA1):c.622G>A (p.Val208Met)Likely pathogenic
not provided
โ˜…โ˜…โ˜†โ˜†2021โ†’ Residue 208
NM_000079.4(CHRNA1):c.1171G>T (p.Glu391Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2026โ†’ Residue 391
NM_000079.4(CHRNA1):c.117_133dup (p.His45fs)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 45
NM_000079.4(CHRNA1):c.440_441insAGAATGG (p.Tyr147Ter)Likely pathogenic
Myasthenic syndrome, congenital, 1B, fast-channel
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 147
NM_000079.4(CHRNA1):c.613A>T (p.Lys205Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 205
NM_000079.4(CHRNA1):c.587G>A (p.Trp196Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 196
NM_000079.4(CHRNA1):c.757T>G (p.Phe253Val)Likely pathogenic
Myasthenic syndrome, congenital, 1B, fast-channel|Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 253
NM_000079.4(CHRNA1):c.639C>A (p.Cys213Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 213
NM_000079.4(CHRNA1):c.249C>A (p.Tyr83Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025โ†’ Residue 83
NM_000079.4(CHRNA1):c.44-1G>ALikely pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2025
NM_000079.4(CHRNA1):c.844G>T (p.Glu282Ter)Pathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2024โ†’ Residue 282
NM_000079.4(CHRNA1):c.254T>C (p.Leu85Pro)Likely pathogenic
Lethal multiple pterygium syndrome|Congenital myasthenic syndrome 1A
โ˜…โ˜†โ˜†โ˜†2024โ†’ Residue 85
NM_000079.4(CHRNA1):c.345-63_403delPathogenic
Lethal multiple pterygium syndrome
โ˜…โ˜†โ˜†โ˜†2024
View on ClinVar โ†—
Drug Targets22
ATRACURIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
ATRACURIUM BESYLATEEARLY_PHASE_1
Muscle-type nicotinic acetylcholine receptor antagonist
CISATRACURIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
Muscle spasm
CISATRACURIUM BESYLATEPhase III
Muscle-type nicotinic acetylcholine receptor antagonist
acute respiratory distress syndrome
DECAMETHONIUMApproved
Muscle-type nicotinic acetylcholine receptor partial agonist
Muscle spasm
DOXACURIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
muscle cramp
GALLAMINE TRIETHIODIDEApproved
Muscle-type nicotinic acetylcholine receptor antagonist
METOCURINE IODIDEApproved
Muscle-type nicotinic acetylcholine receptor antagonist
MIVACURIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
MIVACURIUM CHLORIDEPhase II
Muscle-type nicotinic acetylcholine receptor antagonist
Decreased liver function
PANCURONIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
PIPECURONIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
muscle cramp
PIPECURONIUM BROMIDEUNKNOWN
Muscle-type nicotinic acetylcholine receptor antagonist
RAPACURONIUM BROMIDEApproved
Muscle-type nicotinic acetylcholine receptor antagonist
Muscle spasm
ROCURONIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
Muscle spasm
ROCURONIUM BROMIDEPhase III
Muscle-type nicotinic acetylcholine receptor antagonist
SUCCINYLCHOLINE CHLORIDEApproved
Muscle-type nicotinic acetylcholine receptor agonist
SUXAMETHONIUMApproved
Muscle-type nicotinic acetylcholine receptor agonist
muscle cramp
TUBOCURARINEApproved
Muscle-type nicotinic acetylcholine receptor antagonist
TUBOCURARINE CHLORIDEUNKNOWN
Muscle-type nicotinic acetylcholine receptor antagonist
VECURONIUMApproved
Muscle-type nicotinic acetylcholine receptor antagonist
muscle cramp
VECURONIUM BROMIDEApproved
Muscle-type nicotinic acetylcholine receptor antagonist
Related Genes
RAPSNProtein interaction93%CHRNB4Protein interaction77%MUSKProtein interaction77%AIREProtein interaction76%CHRNB2Protein interaction76%CHRNA9Protein interaction73%
Tissue Expression6 tissues
Brain
100%
Heart
28%
Lung
7%
Liver
2%
Ovary
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
CHRNA1RAPSNCHRNB4MUSKAIRECHRNB2CHRNA9
PROTEIN STRUCTURE
Preparing viewerโ€ฆ
PDB9DMS ยท 1.92 ร… ยท EM
View on RCSB โ†—
Constraintโ“˜
LOEUFโ“˜
0.94LoF Tolerant
pLIโ“˜
0.00Tolerant
Observed/Expected LoF0.71 [0.54โ€“0.94]
RankingsWhere CHRNA1 stands among ~20K protein-coding genes
  • #6,237of 20,598
    Most Researched76
  • #94of 1,025
    FDA-Approved Drug Targets16 ยท top 10%
  • #1,371of 5,498
    Most Pathogenic Variants48 ยท top quartile
  • #8,783of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedCHRNA1
Sources retrieved10 papers
Response timeโ€”
๐Ÿ“„ Sources
10โ–ผ
1
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
PMID: 36835142
Int J Mol Sci ยท 2023
1.00
2
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis ยท 2022
0.90
3
Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: a genome-wide association study.
PMID: 35074870
Proc Natl Acad Sci U S A ยท 2022
0.80
4
Role of SLCO1B1, ABCB1, and CHRNA1 gene polymorphisms on the efficacy of rocuronium in Chinese patients.
PMID: 25279974
J Clin Pharmacol ยท 2015
0.70
5
Human muscle acetylcholine receptor alpha-subunit gene (CHRNA1) association with autoimmune myasthenia gravis in black, mixed-ancestry and Caucasian subjects.
PMID: 8738961
J Autoimmun ยท 1996
0.60