UniProtKB/Swiss-Prot P02708: Variant p.Arg254Leu

Acetylcholine receptor subunit alpha
Gene: CHRNA1
Chromosomal location: 2q24-q32
Variant information

Variant position:  254
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 Arginine (R) to Leucine (L) at position 254 (R254L, p.Arg254Leu).
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 large size and basic (R) to medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Multiple pterygium syndrome, lethal type (LMPS) [MIM:253290]: Multiple pterygia are found infrequently in children with arthrogryposis and in fetuses with fetal akinesia syndrome. In lethal multiple pterygium syndrome there is intrauterine growth retardation, multiple pterygia, and flexion contractures causing severe arthrogryposis and fetal akinesia. Subcutaneous edema can be severe, causing fetal hydrops with cystic hygroma and lung hypoplasia. Oligohydramnios and facial anomalies are frequent. {ECO:0000269|PubMed:18252226}. 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 LMPS.
Any additional useful information about the variant.



Sequence information

Variant position:  254
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  482
The length of the canonical sequence.

Location on the sequence:   TYSCCPDTPYLDITYHFVMQ  R LPLYFIVNVIIPCLLFSFLT
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.

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 – 482 Acetylcholine receptor subunit alpha
Topological domain 21 – 255 Extracellular


Literature citations

Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders.
Michalk A.; Stricker S.; Becker J.; Rupps R.; Pantzar T.; Miertus J.; Botta G.; Naretto V.G.; Janetzki C.; Yaqoob N.; Ott C.-E.; Seelow D.; Wieczorek D.; Fiebig B.; Wirth B.; Hoopmann M.; Walther M.; Koerber F.; Blankenburg M.; Mundlos S.; Heller R.; Hoffmann K.;
Am. J. Hum. Genet. 82:464-476(2008)
Cited for: VARIANT LMPS LEU-254;

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.