UniProtKB/Swiss-Prot P23560: Variant p.Val66Met

Brain-derived neurotrophic factor
Gene: BDNF
Chromosomal location: 11p13
Variant information

Variant position:  66
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 Valine (V) to Methionine (M) at position 66 (V66M, p.Val66Met).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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

Polymorphism:  Variations in BDNF are associated with susceptibility to bulimia nervosa 2 (BULN2) [MIM:610269]. Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. BDNF has been implicated in the regulation of food intake and body weight in rodents. A strong association has been reported of the Met-66 allele of the Val-66-Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Met-66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN) in European patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene showed an effect on BN and late age at onset of weight loss. These are two variants associated with the pathophysiology of ED in different populations. These variants support a role for BDNF in the susceptibility to aberrant eating behaviors.
Additional information on the polymorphism described.

Variant description:  Polymorphism; impairs localization to secretory granules or synapses; associated with poorer episodic memory; may have a protective effect in obsessive-compulsive disorder.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.

Sequence information

Variant position:  66
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  247
The length of the canonical sequence.

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.











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.

Propeptide 19 – 128
Mutagenesis 54 – 54 R -> A. Abolishes processing by S1P.

Literature citations

No reference for the current variant in UniProtKB/Swiss-Prot.

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.