UniProtKB/Swiss-Prot Q04844: Variant p.Leu289Phe

Acetylcholine receptor subunit epsilon
Gene: CHRNE
Chromosomal location: 17p13.1
Variant information

Variant position:  289
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Leucine (L) to Phenylalanine (F) at position 289 (L289F, p.Leu289Phe).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and hydrophobic (L) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Myasthenic syndrome, congenital, slow-channel (SCCMS) [MIM:601462]: A common congenital myasthenic syndrome. Congenital myasthenic syndromes are characterized by muscle weakness affecting the axial and limb muscles (with hypotonia in early-onset forms), the ocular muscles (leading to ptosis and ophthalmoplegia), and the facial and bulbar musculature (affecting sucking and swallowing, and leading to dysphonia). The symptoms fluctuate and worsen with physical effort. Congenital myasthenic syndrome slow-channel type is caused by kinetic abnormalities of the AChR, resulting in prolonged endplate currents and prolonged AChR channel opening episodes. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In SCCMS; slows rate of AChR channel closure and increases apparent affinity for ACh; causes pathologic channel openings even in the absence of ACh resulting in a leaky channel.
Any additional useful information about the variant.



Sequence information

Variant position:  289
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  493
The length of the canonical sequence.

Location on the sequence:   GGQKCTVSINVLLAQTVFLF  L IAQKIPETSLSVPLLGRFLI
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         GGQKCTVSINVLLAQTVFLFLIAQKIPETSLSVPLLGRFLI

Mouse                         GGQKCTVSINVLLAQTVFLFLIAQKIPETSLSVPLLGRYLI

Rat                           GGQKCTVSINVLLAQTVFLFLIAQKIPETSLSVPLLGRYLI

Bovine                        GGQKCTVSINVLLAQTVFLFLIAQKTPETSLSVPLLGRYLI

Xenopus laevis                GGQKCTVSISVLLAQTVFLFLIAQMVPETSLSVPLIGKYLM

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 21 – 493 Acetylcholine receptor subunit epsilon
Transmembrane 273 – 291 Helical;


Literature citations

A leucine-to-phenylalanine substitution in the acetylcholine receptor ion channel in a family with the slow-channel syndrome.
Gomez C.M.; Gammack J.T.;
Neurology 45:982-985(1995)
Cited for: VARIANT SCCMS PHE-289;

New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome.
Engel A.G.; Ohno K.; Milone M.; Wang H.-L.; Nakano S.; Bouzat C.; Pruitt J.N. II; Hutchinson D.O.; Brengman J.M.; Bren N.; Sieb J.P.; Sine S.M.;
Hum. Mol. Genet. 5:1217-1227(1996)
Cited for: VARIANT SCCMS PHE-289; CHARACTERIZATION OF VARIANT SCCMS PHE-289;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.