CHRNE

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Cholinergic receptor, nicotinic, epsilon (muscle)
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CHRNE ; ACHRE; CMS1D; CMS1E; CMS2A; FCCMS; SCCMS
External IDs OMIM100725 MGI87894 HomoloGene60 IUPHAR: ε ChEMBL: 2484 GeneCards: CHRNE Gene
RNA expression pattern
PBB GE CHRNE 207274 at tn.png
More reference expression data
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:
4.8 – 4.81 Mb
Chr 11:
70.61 – 70.62 Mb
PubMed search [1] [2]

Acetylcholine receptor subunit epsilon is a protein that in humans is encoded by the CHRNE gene.[1][2]

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 achetylcholine 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.[2]


Role in health and disease[edit]

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.[3]

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. [4] 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. [5]

See also[edit]

References[edit]

  1. ^ Beeson D, Brydson M, Betty M, Jeremiah S, Povey S, Vincent A, Newsom-Davis J (Sep 1993). "Primary structure of the human muscle acetylcholine receptor. cDNA cloning of the gamma and epsilon subunits". Eur J Biochem 215 (2): 229–38. doi:10.1111/j.1432-1033.1993.tb18027.x. PMID 7688301. 
  2. ^ a b "Entrez Gene: CHRNE cholinergic receptor, nicotinic, epsilon". 
  3. ^ Cossins, J.; Burke, G.; Maxwell, S.; Spearman, H.; Man, S.; Kuks, J.; Vincent, A.; Palace, J.; Fuhrer, C.; Beeson, D. (2006). "Diverse molecular mechanisms involved in AChR deficiency due to rapsyn mutations". Brain 129 (10): 2773–2783. doi:10.1093/brain/awl219. PMID 16945936.  edit
  4. ^ Abicht, A.; Dusl, M.; Gallenmüller, C.; Guergueltcheva, V.; Schara, U.; Della Marina, A.; Wibbeler, E.; Almaras, S.; Mihaylova, V.; Von Der Hagen, M.; Huebner, A.; Chaouch, A.; Müller, J. S.; Lochmüller, H. (2012). "Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients". Human Mutation 33 (10): 1474–1484. doi:10.1002/humu.22130. PMID 22678886.  edit
  5. ^ Shen, X. -M.; Brengman, J. M.; Edvardson, S.; Sine, S. M.; Engel, A. G. (2012). "Highly fatal fast-channel syndrome caused by AChR   subunit mutation at the agonist binding site". Neurology 79 (5): 449–454. doi:10.1212/WNL.0b013e31825b5bda. PMC 3405251. PMID 22592360.  edit

Further reading[edit]

External links[edit]

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