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nicotinic acetylcholine receptor δ subunit

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Target id: 476

Nomenclature: nicotinic acetylcholine receptor δ 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 4 517 2q37.1 CHRND cholinergic receptor nicotinic delta subunit 7
Mouse 4 520 1 44.07 cM Chrnd cholinergic receptor, nicotinic, delta polypeptide 6
Rat 4 517 9q35 Chrnd cholinergic receptor nicotinic delta subunit 13
Previous and Unofficial Names Click here for help
ACHRD | Achr-4 | Acrd | cholinergic receptor, nicotinic, delta (muscle) | cholinergic receptor, nicotinic delta | cholinergic receptor
Database Links Click here for help
Alphafold Q07001 (Hs), P02716 (Mm), P25110 (Rn)
CATH/Gene3D 2.70.170.10
ChEMBL Target CHEMBL3011 (Hs), CHEMBL3137264 (Mm), CHEMBL3038460 (Mm), CHEMBL3885509 (Rn), CHEMBL4523658 (Rn)
Ensembl Gene ENSG00000135902 (Hs), ENSMUSG00000026251 (Mm), ENSRNOG00000019527 (Rn)
Entrez Gene 1144 (Hs), 11447 (Mm), 54240 (Rn)
Human Protein Atlas ENSG00000135902 (Hs)
KEGG Gene hsa:1144 (Hs), mmu:11447 (Mm), rno:54240 (Rn)
OMIM 100720 (Hs)
Orphanet ORPHA119422 (Hs)
Pharos Q07001 (Hs)
RefSeq Nucleotide NM_000751 (Hs), NM_021600 (Mm), NM_019298 (Rn)
RefSeq Protein NP_000742 (Hs), NP_067611 (Mm), NP_062171 (Rn)
UniProtKB Q07001 (Hs), P02716 (Mm), P25110 (Rn)
Wikipedia CHRND (Hs)
Natural/Endogenous Ligands Click here for help
acetylcholine

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Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PhTX-11 Small molecule or natural product Hs Antagonist 6.2 – 6.3 pIC50 12
⤷ pIC50 6.2 – 6.3 (IC50 5.8x10-7 – 4.6x10-7 M) [12]
Tissue Distribution Comments
The δ subunit mRNA us expressed in vertebrate skeletal muscle.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Multiple pterygium syndrome, lethal type; LMPS
Description: A fetal akinesia deformation sequence (FADS) disorder
Synonyms: Lethal multiple pterygium syndrome [Orphanet: ORPHA33108]
OMIM: 253290
Orphanet: ORPHA33108
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human F74L This mutation was seen in compound heterozygosity with R464X 8
Nonsense Human W57X 8
Nonsense Human R464X 1390C-T This mutation was seen in compound heterozygosity with F74L 8
Disease:  Myasthenic syndrome, congenital, 3A, slow-channel; CMS3A
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616321
Orphanet: ORPHA590, ORPHA98913
References:  2-3
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human S268F C>T Exon 8. Transmembrane region. 5
Disease:  Myasthenic syndrome, congenital, 3B, fast-channel; CMS3B
Synonyms: Congenital myasthenic syndrome [Orphanet: ORPHA590] [Disease Ontology: DOID:3635]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616322
Orphanet: ORPHA590, ORPHA98913
References:  2-3
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human 756delAG Exon 7/intron 7 boundary; null allele. 1
Missense Human L42P 10
Missense Human I58K 10
Missense Human E59K 175G-A 1
Missense Human P250Q c.749C>A Exon 7. Extracellular 11
Disease:  Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency; CMS3C
Synonyms: Congenital myasthenic syndrome [Disease Ontology: DOID:3635] [Orphanet: ORPHA590]
Postsynaptic congenital myasthenic syndromes [Orphanet: ORPHA98913]
Disease Ontology: DOID:3635
OMIM: 616323
Orphanet: ORPHA590, ORPHA98913
Comments:  Compound heterozygosity was found for the missense and deletion mutations listed below.
References:  2-4
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Deletion Human - - 2.2-kb deletion- resulting in the loss of half on exon 8 and all of exon 9. 9
Missense Human E381K c.1141G>A Exon 10. Intracellular 9

References

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1. Brownlow S, Webster R, Croxen R, Brydson M, Neville B, Lin JP, Vincent A, Newsom-Davis J, Beeson D. (2001) Acetylcholine receptor delta subunit mutations underlie a fast-channel myasthenic syndrome and arthrogryposis multiplex congenita. J Clin Invest, 108 (1): 125-30. [PMID:11435464]

2. 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]

3. 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]

4. Engel AG, Sine SM. (2005) Current understanding of congenital myasthenic syndromes. Curr Opin Pharmacol, 5 (3): 308-21. [PMID:15907919]

5. Gomez CM, Maselli RA, Vohra BP, Navedo M, Stiles JR, Charnet P, Schott K, Rojas L, Keesey J, Verity A et al.. (2002) Novel delta subunit mutation in slow-channel syndrome causes severe weakness by novel mechanisms. Ann Neurol, 51 (1): 102-12. [PMID:11782989]

6. LaPolla RJ, Mayne KM, Davidson N. (1984) Isolation and characterization of a cDNA clone for the complete protein coding region of the delta subunit of the mouse acetylcholine receptor. Proc Natl Acad Sci USA, 81 (24): 7970-4. [PMID:6096870]

7. Luther MA, Schoepfer R, Whiting P, Casey B, Blatt Y, Montal MS, Montal M, Linstrom J. (1989) A muscle acetylcholine receptor is expressed in the human cerebellar medulloblastoma cell line TE671. J Neurosci, 9 (3): 1082-96. [PMID:2564429]

8. Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N et al.. (2008) Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. Am J Hum Genet, 82 (2): 464-76. [PMID:18252226]

9. Müller JS, Baumeister SK, Schara U, Cossins J, Krause S, von der Hagen M, Huebner A, Webster R, Beeson D, Lochmüller H et al.. (2006) CHRND mutation causes a congenital myasthenic syndrome by impairing co-clustering of the acetylcholine receptor with rapsyn. Brain, 129 (Pt 10): 2784-93. [PMID:16916845]

10. Shen XM, Fukuda T, Ohno K, Sine SM, Engel AG. (2008) Congenital myasthenia-related AChR delta subunit mutation interferes with intersubunit communication essential for channel gating. J Clin Invest, 118 (5): 1867-76. [PMID:18398509]

11. Shen XM, Ohno K, Fukudome T, Tsujino A, Brengman JM, De Vivo DC, Packer RJ, Engel AG. (2002) Congenital myasthenic syndrome caused by low-expressor fast-channel AChR delta subunit mutation. Neurology, 59 (12): 1881-8. [PMID:12499478]

12. Strømgaard K, Mellor IR, Andersen K, Neagoe I, Pluteanu F, Usherwood PN, Krogsgaard-Larsen P, Jaroszewski JW. (2002) Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist. Bioorg Med Chem Lett, 12 (8): 1159-62. [PMID:11934578]

13. 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]

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