UniProtKB/Swiss-Prot O95278: Variant p.Phe88Leu

Laforin
Gene: EPM2A
Chromosomal location: 6q24
Variant information

Variant position:  88
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 Phenylalanine (F) to Leucine (L) at position 88 (F88L, p.Phe88Leu).
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 aromatic (F) to medium size and hydrophobic (L)
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; does not affect glycogen binding.
Any additional useful information about the variant.



Sequence information

Variant position:  88
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:   AEEAAQDGAEPGRVDTFWYK  F LKREPGGELSWEGNGPHHDR
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                         AEEAAQDGAEPGRVDTFWYKFLKREPGGELSWEGNGPHHDR

                              PGEAARDGAEPARVDTFWYKFLKREPGGALSWEGNGPHHDR

Mouse                         AYEEA-GGAEPGRVDTFWYKFLQREPGGELHWEGNGPHHDR

Rat                           PEEEAADGAEPGRIDTFWYKFLQREPGGELHWEGNGPHHDR

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
Domain 1 – 124 CBM20
Binding site 87 – 87 Substrate
Alternative sequence 1 – 243 Missing. In isoform 6.
Alternative sequence 1 – 159 MRFRFGVVVPPAVAGARPELLVVGSRPELGRWEPRGAVRLRPAGTAAGDGALALQEPGLWLGEVELAAEEAAQDGAEPGRVDTFWYKFLKREPGGELSWEGNGPHHDRCCTYNENNLVDGVYCLPIGHWIEATGHTNEMKHTTDFYFNIAGHQAMHYSR -> MIFNK. In isoform 7.
Alternative sequence 1 – 138 Missing. In isoform 8.
Mutagenesis 87 – 87 K -> A. Loss of phosphatase activity. Abolishes glycogen binding.
Mutagenesis 99 – 99 W -> A. Strongly reduces phosphatase activity. Strongly reduces glycogen binding.
Beta strand 84 – 91


Literature citations

The carbohydrate-binding domain of Lafora disease protein targets Lafora polyglucosan bodies.
Ganesh S.; Tsurutani N.; Suzuki T.; Hoshii Y.; Ishihara T.; Delgado-Escueta A.V.; Yamakawa K.;
Biochem. Biophys. Res. Commun. 313:1101-1109(2004)
Cited for: BINDING TO GLYCOGEN AND LAFORA BODIES; DOMAIN; CHARACTERIZATION OF VARIANTS EPM2 PRO-25; LYS-28; GLY-32 AND LEU-88; CHARACTERIZATION OF VARIANT PRO-46;

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.