CHRNE

CHRNE
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCHRNE, ACHRE, CMS1D, CMS1E, CMS2A, FCCMS, SCCMS, CMS4A, CMS4B, CMS4C, cholinergic receptor nicotinic epsilon subunit
External IDsOMIM: 100725; MGI: 87894; HomoloGene: 60; GeneCards: CHRNE; OMA:CHRNE - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000080

NM_009603

RefSeq (protein)

NP_000071

NP_033733

Location (UCSC)Chr 17: 4.9 – 4.93 MbChr 11: 70.51 – 70.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Acetylcholine receptor subunit epsilon is a protein that in humans is encoded by the CHRNE gene.[5][6]

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.[6]

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.[7]

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.[8] 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.[9]

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000108556Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000014609Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b "Entrez Gene: CHRNE cholinergic receptor, nicotinic, epsilon".
  7. ^ 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" (PDF). Brain. 129 (10): 2773–2783. doi:10.1093/brain/awl219. PMID 16945936. Archived from the original (PDF) on 2018-11-04. Retrieved 2019-04-11.
  8. ^ 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 JS, 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. S2CID 30868022.
  9. ^ Shen XM, Brengman JM, Edvardson S, Sine SM, Engel AG (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.

Further reading

[edit]
[edit]

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