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 that 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.

Location on the sequence:   VNGPKAGSRGLTSLADTFEH  V IEELLDEDQKVRPNEENNKD
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                         VNGPKAGSRGLTS-----LADTFEHVIEELLDEDQKVRPNEENNKD

Chimpanzee                    VNGPKAGSRGLTS-----LADTFEHVIEELLDEDQKVRPNE

Mouse                         VNGPRAGSRGLTTTS---LADTFEHVIEELLDEDQKVRPNE

Rat                           VNGPRAGSRGLTTTS---LADTFEHVIEELLDEDQKVRPNE

Pig                           VNGPKAGSRGLTSSSSSSLADTFEHVIEELLDEDQKVRPNE

Bovine                        MNGPKVGSRGLTSSSS--LADTFEHVIEELLDEDQKVRPSE

Cat                           VNGPKAGSRRLTS-----LADTFEHVIEELLDEDQKGRPNE

Dog                           VSGPKAGSRGLTS-----LADTFEHVIEELLDEDQKVRPNE

Horse                         VNGPKAGSRGLTS-----LADTFEHVIEDLLDEGQKVRPDE

Chicken                       LTGPNAGSRGLTS-----LADTFEHVIEELLDEDQDIQPSE

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


Literature citations

Submission
Perez-Pinera P.; Gonzalez-Martinez T.; Garcia-Suarez O.; Perez-Perez M.; Esteban I.; Monjil D.; Vega J.A.;
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT MET-66;

Characterization of single-nucleotide polymorphisms in coding regions of human genes.
Cargill M.; Altshuler D.; Ireland J.; Sklar P.; Ardlie K.; Patil N.; Shaw N.; Lane C.R.; Lim E.P.; Kalyanaraman N.; Nemesh J.; Ziaugra L.; Friedland L.; Rolfe A.; Warrington J.; Lipshutz R.; Daley G.Q.; Lander E.S.;
Nat. Genet. 22:231-238(1999)
Cited for: VARIANT MET-66;

Sequence variants of the brain-derived neurotrophic factor (BDNF) gene are strongly associated with obsessive-compulsive disorder.
Hall D.; Dhilla A.; Charalambous A.; Gogos J.A.; Karayiorgou M.;
Am. J. Hum. Genet. 73:370-376(2003)
Cited for: VARIANT MET-66; ROLE OF VARIANT MET-66 IN OBSESSIVE-COMPULSIVE DISORDER;

The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function.
Egan M.F.; Kojima M.; Callicott J.H.; Goldberg T.E.; Kolachana B.S.; Bertolino A.; Zaitsev E.; Gold B.; Goldman D.; Dean M.; Lu B.; Weinberger D.R.;
Cell 112:257-269(2003)
Cited for: VARIANT MET-66; CHARACTERIZATION OF VARIANT MET-66; ROLE IN EPISODIC MEMORY;

Molecular analysis of congenital central hypoventilation syndrome.
Sasaki A.; Kanai M.; Kijima K.; Akaba K.; Hashimoto M.; Hasegawa H.; Otaki S.; Koizumi T.; Kusuda S.; Ogawa Y.; Tuchiya K.; Yamamoto W.; Nakamura T.; Hayasaka K.;
Hum. Genet. 114:22-26(2003)
Cited for: VARIANT MET-66;

Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type.
Ribases M.; Gratacos M.; Armengol L.; de Cid R.; Badia A.; Jimenez L.; Solano R.; Vallejo J.; Fernandez F.; Estivill X.;
Mol. Psychiatry 8:745-751(2003)
Cited for: VARIANT MET-66; ASSOCIATION OF VARIANT MET-66 WITH ANR;

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.