Top ▲

nicotinic acetylcholine receptor ε subunit

Click here for help

Target id: 477

Nomenclature: nicotinic acetylcholine receptor ε subunit

Family: Nicotinic acetylcholine receptors (nACh)

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 493 17p13.2 CHRNE cholinergic receptor nicotinic epsilon subunit 1
Mouse 4 493 11 43.14 cM Chrne cholinergic receptor, nicotinic, epsilon polypeptide 2
Rat 4 494 10q24 Chrne cholinergic receptor nicotinic epsilon subunit 16
Previous and Unofficial Names Click here for help
ACHRE | Acre | cholinergic receptor, nicotinic, epsilon (muscle) | cholinergic receptor, nicotinic epsilon | cholinergic receptor
Database Links Click here for help
Alphafold Q04844 (Hs), P20782 (Mm), P09660 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL2484 (Hs), CHEMBL3091265 (Mm), CHEMBL4961 (Rn)
Ensembl Gene ENSG00000108556 (Hs), ENSMUSG00000014609 (Mm), ENSRNOG00000003777 (Rn)
Entrez Gene 1145 (Hs), 11448 (Mm), 29422 (Rn)
Human Protein Atlas ENSG00000108556 (Hs)
KEGG Gene hsa:1145 (Hs), mmu:11448 (Mm), rno:29422 (Rn)
OMIM 100725 (Hs)
Orphanet ORPHA119425 (Hs)
Pharos Q04844 (Hs)
RefSeq Nucleotide NM_000080 (Hs), NM_009603 (Mm), NM_017194 (Rn)
RefSeq Protein NP_000071 (Hs), NP_033733 (Mm), NP_058890 (Rn)
UniProtKB Q04844 (Hs), P20782 (Mm), P09660 (Rn)
Wikipedia CHRNE (Hs)
Natural/Endogenous Ligands Click here for help
acetylcholine
Tissue Distribution Comments
The ε-subunit mRNA is expressed in vertebrate skeletal muscle. Whereas expression of the γ-subunit predominates in embryonic muscle, expression of the ε-subunit occurs during early neonatal development and persists in adult muscle.
Physiological Consequences of Altering Gene Expression Click here for help
In knockout mice, loss of the ε-subunit is partially compensated by expression of the γ-subunit, but results in premature death 2 to 3 months after birth. Mice display impaired neuromuscular transmission, progressive muscle weakness and atrophy.
Species:  Mouse
Tissue:  in vivo
Technique:  Gene knockout
References:  10,15
Mice with an ε-subunit null mutation associated with the human AChR deficiency syndrome die between 10 and 14 weeks after birth. However, mice with the ε null mutation but which also consitutively express the human γ-subunit survive into adult life.
Species:  Mouse
Tissue:  in vivo
Technique:  Knock-in
References:  3
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Myasthenic syndrome, congenital, 4A, slow-channel; CMS4A
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 605809
Orphanet: ORPHA590, ORPHA98913
References:  7-9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human L78P 4
Missense Human R217L 4
Missense Human L221F 4
Missense Human T264P 11
Missense Human L269F 6
Disease:  Myasthenic syndrome, congenital, 4B, fast-channel; CMS4B
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616324
Orphanet: ORPHA590, ORPHA98913
Role:  A number of frameshift mutations in CHRNE associated with CMS4B are described in Engel et al., 2003.
References:  7-9
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human W55R 13
Missense Human P121L 12
Missense Human A411P 14
Disease:  Myasthenic syndrome, congenital, 4C, associated with acetylcholine receptor deficiency; CMS4C
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 608931
Orphanet: ORPHA98913, ORPHA590
References:  5
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Frameshift: Insertion Human 1101insT Insertion of thymine after nucleotide 1101 directly generates a nonsense codon leading to a truncated protein. 5
Frameshift: Insertion Human 1293insG Insertion of guanine at nucleotide position 1293 results in three missense codons followed by a nonsense codon and truncated protein 5

References

Show »

1. Beeson D, Brydson M, Betty M, Jeremiah S, Povey S, Vincent A, Newsom-Davis J. (1993) Primary structure of the human muscle acetylcholine receptor. cDNA cloning of the gamma and epsilon subunits. Eur J Biochem, 215 (2): 229-38. [PMID:7688301]

2. Buonanno A, Mudd J, Merlie JP. (1989) Isolation and characterization of the beta and epsilon subunit genes of mouse muscle acetylcholine receptor. J Biol Chem, 264 (13): 7611-6. [PMID:2708381]

3. Cossins J, Webster R, Maxwell S, Burke G, Vincent A, Beeson D. (2004) A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition. Hum Mol Genet, 13 (23): 2947-57. [PMID:15471888]

4. Croxen R, Hatton C, Shelley C, Brydson M, Chauplannaz G, Oosterhuis H, Vincent A, Newsom-Davis J, Colquhoun D, Beeson D. (2002) Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology, 59 (2): 162-8. [PMID:12141316]

5. Engel AG, Ohno K, Bouzat C, Sine SM, Griggs RC. (1996) End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit. Ann Neurol, 40 (5): 810-7. [PMID:8957026]

6. Engel AG, Ohno K, Milone M, Wang HL, Nakano S, Bouzat C, Pruitt 2nd JN, Hutchinson DO, Brengman JM, Bren N et al.. (1996) New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome. Hum Mol Genet, 5 (9): 1217-27. [PMID:8872460]

7. Engel AG, Ohno K, Sine SM. (2003) Congenital myasthenic syndromes: A diverse array of molecular targets. J Neurocytol, 32 (5-8): 1017-37. [PMID:15034283]

8. Engel AG, Ohno K, Sine SM. (2003) Sleuthing molecular targets for neurological diseases at the neuromuscular junction. Nat Rev Neurosci, 4 (5): 339-52. [PMID:12728262]

9. Engel AG, Shen XM, Selcen D, Sine SM. (2010) What have we learned from the congenital myasthenic syndromes. J Mol Neurosci, 40 (1-2): 143-53. [PMID:19688192]

10. Missias AC, Mudd J, Cunningham JM, Steinbach JH, Merlie JP, Sanes JR. (1997) Deficient development and maintenance of postsynaptic specializations in mutant mice lacking an 'adult' acetylcholine receptor subunit. Development, 124 (24): 5075-86. [PMID:9362465]

11. Ohno K, Hutchinson DO, Milone M, Brengman JM, Bouzat C, Sine SM, Engel AG. (1995) Congenital myasthenic syndrome caused by prolonged acetylcholine receptor channel openings due to a mutation in the M2 domain of the epsilon subunit. Proc Natl Acad Sci USA, 92 (3): 758-62. [PMID:7531341]

12. Ohno K, Wang HL, Milone M, Bren N, Brengman JM, Nakano S, Quiram P, Pruitt JN, Sine SM, Engel AG. (1996) Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron, 17 (1): 157-70. [PMID:8755487]

13. Shen XM, Brengman JM, Edvardson S, Sine SM, Engel AG. (2012) Highly fatal fast-channel syndrome caused by AChR ε subunit mutation at the agonist binding site. Neurology, 79 (5): 449-54. [PMID:22592360]

14. Wang HL, Ohno K, Milone M, Brengman JM, Evoli A, Batocchi AP, Middleton LT, Christodoulou K, Engel AG, Sine SM. (2000) Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome. J Gen Physiol, 116 (3): 449-62. [PMID:10962020]

15. Witzemann V, Schwarz H, Koenen M, Berberich C, Villarroel A, Wernig A, Brenner HR, Sakmann B. (1996) Acetylcholine receptor epsilon-subunit deletion causes muscle weakness and atrophy in juvenile and adult mice. Proc Natl Acad Sci USA, 93 (23): 13286-91. [PMID:8917583]

16. Witzemann V, Stein E, Barg B, Konno T, Koenen M, Kues W, Criado M, Hofmann M, Sakmann B. (1990) Primary structure and functional expression of the alpha-, beta-, gamma-, delta- and epsilon-subunits of the acetylcholine receptor from rat muscle. Eur J Biochem, 194 (2): 437-48. [PMID:1702709]

Contributors

Show »

How to cite this page