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UniProtKB/Swiss-Prot O95278: Variant p.Thr187Ala

Gene: EPM2A
Chromosomal location: 6q24
Variant information

Variant position:  187
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 Threonine (T) to Alanine (A) at position 187 (T187A, p.Thr187Ala).
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 polar (T) to small size and hydrophobic (A)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Epilepsy, progressive myoclonic 2 (EPM2) [MIM:254780]: An autosomal recessive and severe form of adolescent-onset progressive epilepsy. Typically, as seizures increase in frequency, cognitive function declines towards dementia, and affected individuals die usually within 10 years after onset. EPM2 occurs worldwide, but it is particularly common in the mediterranean countries of southern Europe and northern Africa, in southern India and in the Middle East. At the cellular level, it is characterized by accumulation of starch-like polyglucosans called Lafora bodies (LBs) that are most abundant in organs with the highest glucose metabolism: brain, heart, liver and skeletal muscle. Among other conditions involving polyglucosans, EPM2 is unique in that the inclusions are in neuronal dendrites but not axons and the forming polyglucosan fibrils are associated with the endoplasmic reticulum. {ECO:0000269|PubMed:11001928, ECO:0000269|PubMed:11175283, ECO:0000269|PubMed:11739371, ECO:0000269|PubMed:12019207, ECO:0000269|PubMed:12560877, ECO:0000269|PubMed:14532330, ECO:0000269|PubMed:14706656, ECO:0000269|PubMed:14722920, ECO:0000269|PubMed:15009235, ECO:0000269|PubMed:18311786, ECO:0000269|PubMed:25544560, ECO:0000269|PubMed:26231210, ECO:0000269|PubMed:9771710, ECO:0000269|PubMed:9931343}. 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 EPM2; abolishes interaction with NHLRC1.
Any additional useful information about the variant.

Sequence information

Variant position:  187
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  331
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.

Chain 1 – 331 Laforin
Binding site 197 – 197 Substrate
Alternative sequence 1 – 243 Missing. In isoform 6.
Alternative sequence 160 – 293 Missing. In isoform 5.
Mutagenesis 168 – 168 S -> AD. Abolishes interaction with NHLRC1.
Mutagenesis 169 – 169 C -> S. No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.
Mutagenesis 169 – 169 C -> S. No effect on phosphatase activity.
Mutagenesis 171 – 171 R -> A. No effect on phosphatase activity.
Mutagenesis 187 – 187 T -> D. Abolishes interaction with NHLRC1.
Mutagenesis 194 – 194 T -> D. Does not affect interaction with NHLRC1, PPP1R3C or PRKAA2.
Mutagenesis 197 – 197 D -> A. Strongly decreased phosphatase activity. No effect on glycogen binding.
Mutagenesis 205 – 205 C -> S. No effect on homodimerization or carbohydrate binding. Decreased phosphatase activity.

Literature citations

Two novel mutations in the EPM2A gene in a Korean patient with Lafora's progressive myoclonus epilepsy.
Ki C.S.; Kong S.Y.; Seo D.W.; Hong S.B.; Kim H.J.; Kim J.W.;
J. Hum. Genet. 48:51-54(2003)
Cited for: VARIANT EPM2 ALA-187;

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.