Details for: CHRNA1

Gene ID: 1134

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: CHRNA1

Ensembl ID: ENSG00000138435

Description: cholinergic receptor nicotinic alpha 1 subunit

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • muscle cell CL0000187
    CSI 5.33
    rCSI 10.95%
    PRS 99.43
  • epithelial cell CL0000066
    CSI 4.37
    rCSI 6.72%
    PRS 99.18
  • basal cell of epidermis CL0002187
    CSI 1.9
    rCSI 3.37%
    PRS 94.9

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [CHRNA1](/details-gene/1134) (Cholinergic Receptor Nicotinic Alpha 1 Subunit) is a protein-coding gene located on chromosome 2q31.1. It encodes the alpha subunit of the adult muscle-type nicotinic acetylcholine receptor (nAChR), a ligand-gated ion channel essential for neuromuscular transmission. This receptor is located on the postsynaptic membrane of the neuromuscular junction and is activated by acetylcholine, leading to muscle contraction. Expression data highlights its paramount significance in [muscle cell](/details-cell/CL0000187)s, consistent with its canonical function. Notably, significant expression is also observed in [epithelial cell](/details-cell/CL0000066)s and [basal cell of epidermis](/details-cell/CL0002187), suggesting important non-neuronal roles. Clinically, mutations in [CHRNA1](/details-gene/1134) are associated with several congenital myasthenic syndromes ([100690](https://omim.org/entry/100690), [601462](https://omim.org/entry/601462)), and the protein is a primary autoantigen in the autoimmune disease myasthenia gravis. ## Cellular Roles and Expression Landscape The expression profile of [CHRNA1](/details-gene/1134) firmly establishes its identity as a key component of the neuromuscular system. **Overall**, the gene shows its highest significance in [muscle cell](/details-cell/CL0000187) (CSI: 5.33), which is expected given its role as the primary ligand-binding subunit of the nAChR at the motor endplate. This specialized function is critical for translating neuronal signals into muscle contraction. Beyond its classical role in muscle, [CHRNA1](/details-gene/1134) demonstrates a significant presence in non-excitable tissues. It is highly significant in [epithelial cell](/details-cell/CL0000066) (CSI: 4.37) and [basal cell of epidermis](/details-cell/CL0002187) (CSI: 1.90). This expression pattern suggests that cholinergic signaling, mediated by [CHRNA1](/details-gene/1134)-containing receptors, may be involved in processes such as epithelial cell adhesion, differentiation, and tissue homeostasis. The presence in basal cells of the epidermis, the proliferative layer of the skin, may point towards a role in regulating skin development and repair. This dual expression landscape indicates that [CHRNA1](/details-gene/1134) functions not only in rapid synaptic transmission but also in potentially slower, modulatory roles in non-neuronal tissues. ## Pathways and Molecular Function Functional annotations for [CHRNA1](/details-gene/1134) are highly consistent with its role as a subunit of a ligand-gated ion channel at the synapse. The gene product is a core component of the [Acetylcholine-gated channel complex](/details-go/GO:0005892) located at the [Postsynaptic membrane](/details-go/GO:0045211) and specifically at the [Neuromuscular junction](/details-go/GO:0031594). **Biological Processes:** Its involvement is central to [Neuromuscular synaptic transmission](/details-go/GO:0007274), [Skeletal muscle contraction](/details-go/GO:0003009), and the broader [Acetylcholine receptor signaling pathway](/details-go/GO:0095500). These functions are mediated through its role in [Monoatomic cation transport](/details-go/GO:0006812), leading to [Membrane depolarization](/details-go/GO:0051899) of the muscle fiber upon acetylcholine binding. **Molecular Function:** At the molecular level, [CHRNA1](/details-gene/1134) is defined by its [Acetylcholine binding](/details-go/GO:0042166) and [Acetylcholine receptor activity](/details-go/GO:0015464). It functions as an [Acetylcholine-gated monoatomic cation-selective channel activity](/details-go/GO:0022848), a process fundamental to its physiological output. **Reactome Pathways:** The gene is a key player in the [Neuronal system](/details-reactome/R-HSA-112316), specifically in [Transmission across chemical synapses](/details-reactome/R-HSA-112315) and [Neurotransmitter receptors and postsynaptic signal transmission](/details-reactome/R-HSA-112314). Its specific context is detailed in pathways like [Postsynaptic nicotinic acetylcholine receptors](/details-reactome/R-HSA-622327), underscoring its essential role in converting a chemical signal (acetylcholine) into an electrical one at the muscle endplate. ## Research Directions The well-established role of [CHRNA1](/details-gene/1134) in neuromuscular disease provides a strong foundation for further research, while its expression in non-excitable tissues opens new avenues of investigation. **Testable Hypotheses:** 1. The high significance of [CHRNA1](/details-gene/1134) in [epithelial cell](/details-cell/CL0000066)s and [basal cell of epidermis](/details-cell/CL0002187) suggests a non-canonical role in regulating keratinocyte proliferation and differentiation. We hypothesize that autocrine or paracrine acetylcholine signaling through [CHRNA1](/details-gene/1134)-containing nAChRs is a key regulator of epidermal homeostasis and wound healing. 2. Given that T lymphocytes can recognize epitopes on the [CHRNA1](/details-gene/1134) protein in myasthenia gravis ([Link](https://doi.org/10.1172/jci113369)), we hypothesize that specific HLA haplotypes are associated with the presentation of pathogenic [CHRNA1](/details-gene/1134)-derived peptides, and that identifying these genetic links could predict disease severity and response to immunotherapy. **Proposed Experiment:** To test the first hypothesis regarding the role of [CHRNA1](/details-gene/1134) in skin biology, a 3D human skin organoid model derived from primary keratinocytes could be employed. [CHRNA1](/details-gene/1134) expression would be silenced using lentiviral-delivered shRNA. Control and knockdown organoids would be cultured and subjected to mechanical wounding. The impact of [CHRNA1](/details-gene/1134) deficiency on wound closure rates would be monitored. Furthermore, tissue sections would be analyzed via immunofluorescence for markers of proliferation (Ki67) and differentiation (Keratin 10, Loricrin) to determine if cholinergic signaling through this receptor is required for proper epidermal stratification and repair. **Therapeutic Potential:** [CHRNA1](/details-gene/1134) is a clinically significant therapeutic focus. For congenital myasthenic syndromes caused by gain-of-function (slow-channel) mutations, small molecule open-channel blockers could be a targeted therapeutic strategy to normalize neuromuscular transmission. Conversely, for loss-of-function mutations, therapies aimed at increasing receptor expression or function (e.g., 3,4-diaminopyridine) are relevant. In the context of the autoimmune disease myasthenia gravis, the [CHRNA1](/details-gene/1134) protein itself is not the target of intervention, but rather the autoimmune response against it. Therefore, it serves as a critical biomarker and the antigenic basis for developing highly specific immunotherapies, such as antigen-specific tolerization protocols, aimed at silencing the pathogenic T and B cell response.

Genular Protein ID: 3939718576

Symbol: ACHA_HUMAN

Name: N/A

UniProtKB Accession Codes:

P02708 B4DRV6 D3DPE8

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 2 CTD 1 ChEBI 2 ChEMBL 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 3 DrugCentral 1 EMBL 14 Ensembl 2 ExpressionAtlas 1 GO 26 Gene3D 2 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 8 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 NCBIfam 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PIR 2 PRINTS 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 RNAct 1 Reactome 2 RefSeq 2 Rhea 2 SIGNOR 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 6688857

Title: Cloning and sequence analysis of calf cDNA and human genomic DNA encoding alpha-subunit precursor of muscle acetylcholine receptor.

PubMed ID: 6688857

DOI: 10.1038/305818a0

PubMed ID: 3338555

Title: The human medulloblastoma cell line TE671 expresses a muscle-like acetylcholine receptor. Cloning of the alpha-subunit cDNA.

PubMed ID: 3338555

DOI: 10.1016/0014-5793(88)81430-3

PubMed ID: 1694127

Title: The human muscle nicotinic acetylcholine receptor alpha-subunit exist as two isoforms: a novel exon.

PubMed ID: 1694127

DOI: 10.1002/j.1460-2075.1990.tb07378.x

PubMed ID: 7725386

Title: Cloning of a cDNA coding for the acetylcholine receptor alpha-subunit from a thymoma associated with myasthenia gravis.

PubMed ID: 7725386

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 2449458

Title: Amphipathic segment of the nicotinic receptor alpha subunit contains epitopes recognized by T lymphocytes in myasthenia gravis.

PubMed ID: 2449458

DOI: 10.1172/jci113369

PubMed ID: 8441631

Title: Differential expression of human nicotinic acetylcholine receptor alpha subunit variants in muscle and non-muscle tissues.

PubMed ID: 8441631

DOI: 10.1093/nar/21.2.233

PubMed ID: 8788941

Title: Functional and non-functional isoforms of the human muscle acetylcholine receptor.

PubMed ID: 8788941

DOI: 10.1113/jphysiol.1995.sp021090

PubMed ID: 15609996

Title: Alpha-conotoxins ImI and ImII target distinct regions of the human alpha7 nicotinic acetylcholine receptor and distinguish human nicotinic receptor subtypes.

PubMed ID: 15609996

DOI: 10.1021/bi048918g

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 27375219

Title: Mutations causing slow-channel myasthenia reveal that a valine ring in the channel pore of muscle AChR is optimized for stabilizing channel gating.

PubMed ID: 27375219

DOI: 10.1002/humu.23043

PubMed ID: 28440223

Title: Structural insights into the molecular mechanisms of myasthenia gravis and their therapeutic implications.

PubMed ID: 28440223

DOI: 10.7554/elife.23043

PubMed ID: 7619526

Title: Mutation of the acetylcholine receptor alpha subunit causes a slow-channel myasthenic syndrome by enhancing agonist binding affinity.

PubMed ID: 7619526

DOI: 10.1016/0896-6273(95)90080-2

PubMed ID: 8872460

Title: New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.

PubMed ID: 8872460

DOI: 10.1093/hmg/5.9.1217

PubMed ID: 9158151

Title: Mutations in different functional domains of the human muscle acetylcholine receptor alpha subunit in patients with the slow-channel congenital myasthenic syndrome.

PubMed ID: 9158151

DOI: 10.1093/hmg/6.5.767

PubMed ID: 9221765

Title: Slow-channel myasthenic syndrome caused by enhanced activation, desensitization, and agonist binding affinity attributable to mutation in the M2 domain of the acetylcholine receptor alpha subunit.

PubMed ID: 9221765

DOI: 10.1523/jneurosci.17-15-05651.1997

PubMed ID: 10195214

Title: Acetylcholine receptor M3 domain: stereochemical and volume contributions to channel gating.

PubMed ID: 10195214

DOI: 10.1038/6326

PubMed ID: 12588888

Title: Mutation causing severe myasthenia reveals functional asymmetry of AChR signature cystine loops in agonist binding and gating.

PubMed ID: 12588888

DOI: 10.1172/jci16997

PubMed ID: 15079006

Title: Mutation in the AChR ion channel gate underlies a fast channel congenital myasthenic syndrome.

PubMed ID: 15079006

DOI: 10.1212/01.wnl.0000118205.99701.41

PubMed ID: 16685696

Title: Slow-channel mutation in acetylcholine receptor alphaM4 domain and its efficient knockdown.

PubMed ID: 16685696

DOI: 10.1002/ana.20861

PubMed ID: 18252226

Title: Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders.

PubMed ID: 18252226

DOI: 10.1016/j.ajhg.2007.11.006

Sequence Information:

  • Length: 457
  • Mass: 51839
  • Checksum: 89480567D85C15B8
  • Sequence:
    • MEPWPLLLLF SLCSAGLVLG SEHETRLVAK LFKDYSSVVR PVEDHRQVVE VTVGLQLIQL 
INVDEVNQIV TTNVRLKQQW VDYNLKWNPD DYGGVKKIHI PSEKIWRPDL VLYNNADGDF 
AIVKFTKVLL QYTGHITWTP PAIFKSYCEI IVTHFPFDEQ NCSMKLGTWT YDGSVVAINP 
ESDQPDLSNF MESGEWVIKE SRGWKHSVTY SCCPDTPYLD ITYHFVMQRL PLYFIVNVII 
PCLLFSFLTG LVFYLPTDSG EKMTLSISVL LSLTVFLLVI VELIPSTSSA VPLIGKYMLF 
TMVFVIASII ITVIVINTHH RSPSTHVMPN WVRKVFIDTI PNIMFFSTMK RPSREKQDKK 
IFTEDIDISD ISGKPGPPPM GFHSPLIKHP EVKSAIEGIK YIAETMKSDQ ESNNAAAEWK 
YVAMVMDHIL LGVFMLVCII GTLAVFAGRL IELNQQG