UniProtKB/Swiss-Prot O95278: Variant p.Glu210Lys

Laforin
Gene: EPM2A
Chromosomal location: 6q24
Variant information

Variant position:  210
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 Glutamate (E) to Lysine (K) at position 210 (E210K, p.Glu210Lys).
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 acidic (E) to large size and basic (K)
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

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.
Any additional useful information about the variant.



Sequence information

Variant position:  210
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  331
The length of the canonical sequence.

Location on the sequence:   MNFQTEWDIVQNSSGCNRYP  E PMTPDTMIKLYREEGLAYIW
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                         MNFQTEWDIVQNSSGCNRYPEPMTPDTMIKLYREEGLAYIW

                              MNFQTEWDIVQNSSGCNRYPEPMTPDTMIKLYKEEGLVYIW

Mouse                         MNFQTEWDIIQNSSGCNRYPEPMTPDTMMKLYKEEGLSYIW

Rat                           MNFQTEWDIIQNSSGCNRYPEPMTPDTMMKLYKEEGLAYIW

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 – 331 Laforin
Binding site 197 – 197 Substrate
Alternative sequence 1 – 243 Missing. In isoform 6.
Alternative sequence 160 – 293 Missing. In isoform 5.
Alternative sequence 200 – 331 Missing. In isoform 4.
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.
Beta strand 208 – 210


Literature citations

Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin.
Singh S.; Satishchandra P.; Shankar S.K.; Ganesh S.;
Hum. Mutat. 29:E1-12(2008)
Cited for: VARIANTS EPM2 ASN-140; TYR-148; LYS-210 AND TRP-310; CHARACTERIZATION OF VARIANT EPM2 TRP-310; SUBCELLULAR LOCATION;

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.