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UniProtKB/Swiss-Prot P60880: Variant p.Ile67Asn

Synaptosomal-associated protein 25
Gene: SNAP25
Variant information

Variant position:  67
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 implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Asparagine (N) at position 67 (I67N, p.Ile67Asn).
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 (I) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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, 18 (CMS18) [MIM:616330]: A form of congenital myasthenic syndrome, a group of disorders characterized by failure of neuromuscular transmission, including pre-synaptic, synaptic, and post-synaptic disorders that are not of autoimmune origin. Clinical features are easy fatigability and 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. CMS18 is an autosomal dominant presynaptic disorder clinically characterized by early-onset muscle weakness and easy fatigability associated with delayed psychomotor development and ataxia. {ECO:0000269|PubMed:25381298}. 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 CMS18; interfers with calcium-induced fusion; inhibits exocytosis of catecholamine-containing vesicles.
Any additional useful information about the variant.

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



Sequence information

Variant position:  67
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  206
The length of the canonical sequence.

Location on the sequence:   LVMLDEQGEQLERIEEGMDQ  I NKDMKEAEKNLTDLGKFCGL
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                         LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Rhesus macaque                LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Chimpanzee                    LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Mouse                         LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Rat                           LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Bovine                        LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Chicken                       LVMLDEQGEQLERIEEGMDQINKDMKEAEKNLTDLGKFCGL

Drosophila                    LVALDDQGEQLDRIEEGMDQINADMREAEKNLSGMEKCCGI

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 – 206 Synaptosomal-associated protein 25
Domain 19 – 81 t-SNARE coiled-coil homology 1
Region 1 – 75 Interaction with CENPF
Lipidation 85 – 85 S-palmitoyl cysteine
Alternative sequence 58 – 89 ERIEEGMDQINKDMKEAEKNLTDLGKFCGLCV -> DRVEEGMNHINQDMKEAEKNLKDLGKCCGLFI. In isoform 2.
Helix 8 – 80


Literature citations

Mutant SNAP25B causes myasthenia, cortical hyperexcitability, ataxia, and intellectual disability.
Shen X.M.; Selcen D.; Brengman J.; Engel A.G.;
Neurology 83:2247-2255(2014)
Cited for: INVOLVEMENT IN CMS18; VARIANT CMS18 ASN-67; CHARACTERIZATION OF VARIANT CMS18 ASN-67;

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.