CHRNE

CHRNE
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DF9
Identifiers
Aliases	CHRNE, ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS, CMS4A, CMS4B, CMS4C, cholinergic receptor nicotinic epsilon subunit
External IDs	OMIM: 100725; MGI: 87894; HomoloGene: 60; GeneCards: CHRNE; OMA:CHRNE - orthologs
Gene location (Human) Chr. Chromosome 17 (human) Band 17p13.2 Start 4,897,771 bp End 4,934,438 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B3|11 43.14 cM Start 70,505,709 bp End 70,510,042 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right auricle anterior pituitary cardiac muscle tissue of right atrium granulocyte testicle right lobe of liver skin of leg body of pancreas stromal cell of endometrium blood Top expressed in spermatid spermatocyte extraocular muscle seminiferous tubule muscle of thigh ankle embryo quadriceps femoris muscle lip muscle of leg More reference expression data BioGPS More reference expression data
Gene ontology Molecular function acetylcholine binding cation transmembrane transporter activity acetylcholine receptor activity ion channel activity extracellular ligand-gated ion channel activity ligand-gated ion channel activity acetylcholine-gated cation-selective channel activity transmembrane signaling receptor activity transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential Cellular component integral component of membrane postsynaptic membrane membrane plasma membrane synapse integral component of plasma membrane cell junction acetylcholine-gated channel complex neuromuscular junction integral component of postsynaptic specialization membrane neuron projection Biological process muscle contraction regulation of membrane potential response to nicotine synaptic transmission, cholinergic ion transport cation transmembrane transport neuromuscular synaptic transmission signal transduction ion transmembrane transport regulation of postsynaptic membrane potential excitatory postsynaptic potential chemical synaptic transmission nervous system process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1145 11448 Ensembl ENSG00000108556 ENSMUSG00000014609 UniProt Q04844 P20782 RefSeq (mRNA) NM_000080 NM_009603 RefSeq (protein) NP_000071 NP_033733 Location (UCSC) Chr 17: 4.9 – 4.93 Mb Chr 11: 70.51 – 70.51 Mb PubMed search
Wikidata
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Acetylcholine receptor subunit epsilon is a protein that in humans is encoded by the CHRNE gene.

Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome.

Role in health and disease

Congenital myasthenic syndrome (CMS) is associated with genetic defects that affect proteins of the neuromuscular junction. Postsynaptic defects are the most frequent cause of CMS and often result in abnormalities in the acetylcholine receptor (AChR). The majority of mutations causing CMS are found in the AChR subunits genes.

Out of all mutations associated with CMS, more than half are mutations in one of the four genes encoding the adult AChR subunits. Mutations of the AChR often result in endplate deficiency. The most common AChR gene mutation that underlies CMS is the mutation of the CHRNE gene. The CHRNE gene codes for the epsilon subunit of the AChR. Most mutations are autosomal recessive loss-of-function mutations and as a result there is endplate AChR deficiency. CHRNE is associated with changing the kinetic properties of the AChR. One type of mutation of the epsilon subunit of the AChR introduces an arginine (Arg) into the binding site at the α/ε subunit interface of the receptor. The addition of a cationic Arg into the anionic environment of the AChR binding site greatly reduces the kinetic properties of the receptor. The result of the newly introduced ARG is a 30-fold reduction of agonist affinity, 75-fold reduction of gating efficiency, and an extremely weakened channel opening probability. This type of mutation results in an extremely fatal form of CMS.

See also

• Nicotinic acetylcholine receptor

Further reading

• Hantaï D, Richard P, Koenig J, Eymard B (2005). "Congenital myasthenic syndromes". Curr. Opin. Neurol. 17 (5): 539–51. doi:10.1097/00019052-200410000-00004. PMID 15367858. S2CID 45357882.
• Yu XM, Hall ZW (1991). "Extracellular domains mediating epsilon subunit interactions of muscle acetylcholine receptor". Nature. 352 (6330): 64–7. Bibcode:1991Natur.352...64Y. doi:10.1038/352064a0. PMID 1712080. S2CID 4245374.
• Ohno K, Hutchinson DO, Milone M, et al. (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. U.S.A. 92 (3): 758–62. doi:10.1073/pnas.92.3.758. PMC 42699. PMID 7531341.
• Gomez CM, Gammack JT (1995). "A leucine-to-phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow-channel syndrome". Neurology. 45 (5): 982–5. doi:10.1212/wnl.45.5.982. PMID 7538206. S2CID 35877992.
• Lobos EA (1993). "Five subunit genes of the human muscle nicotinic acetylcholine receptor are mapped to two linkage groups on chromosomes 2 and 17". Genomics. 17 (3): 642–50. doi:10.1006/geno.1993.1384. PMID 7902325.
• Brenner HR, Rotzler S, Kues WA, et al. (1994). "Nerve-dependent induction of AChR epsilon-subunit gene expression in muscle is independent of state of differentiation". Dev. Biol. 165 (2): 527–36. doi:10.1006/dbio.1994.1272. PMID 7958418.
• Uchitel O, Engel AG, Walls TJ, et al. (1993). "Congenital myasthenic syndromes: II. Syndrome attributed to abnormal interaction of acetylcholine with its receptor". Muscle Nerve. 16 (12): 1293–301. doi:10.1002/mus.880161205. PMID 8232384. S2CID 26474245.
• Ohno K, Wang HL, Milone M, et al. (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. doi:10.1016/S0896-6273(00)80289-5. PMID 8755487. S2CID 17773515.
• Engel AG, Ohno K, Milone M, et al. (1997). "New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome". Hum. Mol. Genet. 5 (9): 1217–27. doi:10.1093/hmg/5.9.1217. PMID 8872460.{{cite journal}}: CS1 maint: numeric names: authors list (link)
• Engel AG, Ohno K, Bouzat C, et al. (1997). "End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit". Ann. Neurol. 40 (5): 810–7. doi:10.1002/ana.410400521. PMID 8957026. S2CID 83884178.
• Ohno K, Quiram PA, Milone M, et al. (1997). "Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations". Hum. Mol. Genet. 6 (5): 753–66. doi:10.1093/hmg/6.5.753. PMID 9158150.{{cite journal}}: CS1 maint: numeric names: authors list (link)
• Nichols P, Croxen R, Vincent A, et al. (1999). "Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome". Ann. Neurol. 45 (4): 439–43. doi:10.1002/1531-8249(199904)45:4<439::AID-ANA4>3.0.CO;2-W. PMID 10211467. S2CID 83632162.
• Croxen R, Newland C, Betty M, et al. (1999). "Novel functional epsilon-subunit polypeptide generated by a single nucleotide deletion in acetylcholine receptor deficiency congenital myasthenic syndrome". Ann. Neurol. 46 (4): 639–47. doi:10.1002/1531-8249(199910)46:4<639::AID-ANA13>3.0.CO;2-1. PMID 10514102. S2CID 85150509.
• Abicht A, Stucka R, Karcagi V, et al. (1999). "A common mutation (epsilon1267delG) in congenital myasthenic patients of Gypsy ethnic origin". Neurology. 53 (7): 1564–9. doi:10.1212/wnl.53.7.1564. PMID 10534268.
• Kindler CH, Verotta D, Gray AT, et al. (2000). "Additive inhibition of nicotinic acetylcholine receptors by corticosteroids and the neuromuscular blocking drug vecuronium". Anesthesiology. 92 (3): 821–32. doi:10.1097/00000542-200003000-00026. PMID 10719961. S2CID 27038179.
• Wang HL, Ohno K, Milone M, et al. (2000). "Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome". J. Gen. Physiol. 116 (3): 449–62. doi:10.1085/jgp.116.3.449. PMC 2233692. PMID 10962020.
• Sieb JP, Kraner S, Rauch M, Steinlein OK (2000). "Immature end-plates and utrophin deficiency in congenital myasthenic syndrome caused by epsilon-AChR subunit truncating mutations". Hum. Genet. 107 (2): 160–4. doi:10.1007/s004395000359. PMID 11030414. S2CID 22171041.
• Dan I, Watanabe NM, Kajikawa E, et al. (2002). "Overlapping of MINK and CHRNE gene loci in the course of mammalian evolution". Nucleic Acids Res. 30 (13): 2906–10. doi:10.1093/nar/gkf407. PMC 117062. PMID 12087176.

External links

• CHRNE protein, human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Human CHRNE genome location and CHRNE gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.