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UniProtKB/Swiss-Prot P23763: Variant p.Arg49Pro

Vesicle-associated membrane protein 1
Gene: VAMP1
Variant information

Variant position:  49
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  US
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Arginine (R) to Proline (P) at position 49 (R49P, p.Arg49Pro).
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 (P)
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

Variant description:  In CMS25; unknown pathological significance.
Any additional useful information about the variant.

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



Sequence information

Variant position:  49
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  118
The length of the canonical sequence.

Location on the sequence:   TSNRRLQQTQAQVEEVVDII  R VNVDKVLERDQKLSELDDRA
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                         TSNRRLQQTQAQVEEVVDIIRVNVDKVLERDQKLSELDDRA

Mouse                         TSNRRLQQTQAQVEEVVDIMRVNVDKVLERDQKLSELDDRA

Rat                           TSNRRLQQTQAQVEEVVDIMRVNVDKVLERDQKLSELDDRA

Bovine                        TSNRRLQQTQAQVEEVVDIMRVNVDKVLERDQKLSELDDRA

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 1 – 118 Vesicle-associated membrane protein 1
Topological domain 1 – 96 Cytoplasmic
Domain 33 – 93 v-SNARE coiled-coil homology
Modified residue 63 – 63 Phosphoserine
Mutagenesis 42 – 42 E -> D. No change in susceptibility to C.botulinum BoNT/B, BoNT/D or BoNT/F.
Mutagenesis 48 – 48 I -> M. 1000-fold increase in susceptibility to C.botulinum BoNT/D, no change in susceptibility to BoNT/B or BoNT/F.


Literature citations

Homozygous mutations in VAMP1 cause a presynaptic congenital myasthenic syndrome.
Salpietro V.; Lin W.; Delle Vedove A.; Storbeck M.; Liu Y.; Efthymiou S.; Manole A.; Wiethoff S.; Ye Q.; Saggar A.; McElreavey K.; Krishnakumar S.S.; Pitt M.; Bello O.D.; Rothman J.E.; Basel-Vanagaite L.; Hubshman M.W.; Aharoni S.; Manzur A.Y.; Wirth B.; Houlden H.;
Ann. Neurol. 81:597-603(2017)
Cited for: INVOLVEMENT IN CMS25; VARIANT CMS25 PRO-49;

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.