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UniProtKB/Swiss-Prot O95970: Variant p.Glu383Ala

Leucine-rich glioma-inactivated protein 1
Gene: LGI1
Chromosomal location: 10q24
Variant information

Variant position:  383
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 Alanine (A) at position 383 (E383A, p.Glu383Ala).
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 small size and hydrophobic (A)
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, familial temporal lobe, 1 (ETL1) [MIM:600512]: A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. {ECO:0000269|PubMed:11810107, ECO:0000269|PubMed:12205652, ECO:0000269|PubMed:12601709, ECO:0000269|PubMed:12771268, ECO:0000269|PubMed:15079010, ECO:0000269|PubMed:17067999, ECO:0000269|PubMed:17296837, ECO:0000269|PubMed:17562837, ECO:0000269|PubMed:18625862, ECO:0000269|PubMed:19552651}. 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 ETL1; loss of protein secretion; protein is retained in the endoplasmic reticulum; does not affect glycosylation status of the protein.
Any additional useful information about the variant.

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



Sequence information

Variant position:  383
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  557
The length of the canonical sequence.

Location on the sequence:   NGNGFYSHQSLHAWYRDTDV  E YLEIVRTPQTLRTPHLILSS
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                         NGNGFYSHQSLHAWYRDTDVEYLEIVRTPQTLRTPHLILSS

Chimpanzee                    NGNGFYSHQSLHAWYRDTDVEYLEIVRTPQTLRTPHLILSS

Mouse                         NGNGFYSHQSLHAWYRDTDVEYLEIARPPLALRTPHLILSS

Rat                           NGNGFYSHQSLHAWYRDTDVEYLEIARPPLTLRTPHLILSS

Bovine                        NGNGFYSHQSLHAWYRDTDVEYLEIARTPQTLRTPHLILSS

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 35 – 557 Leucine-rich glioma-inactivated protein 1
Repeat 366 – 415 EAR 4
Alternative sequence 292 – 557 Missing. In isoform 2.
Beta strand 379 – 387


Literature citations

The epilepsy gene LGI1 encodes a secreted glycoprotein that binds to the cell surface.
Sirerol-Piquer M.S.; Ayerdi-Izquierdo A.; Morante-Redolat J.M.; Herranz-Perez V.; Favell K.; Barker P.A.; Perez-Tur J.;
Hum. Mol. Genet. 15:3436-3445(2006)
Cited for: SUBCELLULAR LOCATION; GLYCOSYLATION; MUTAGENESIS OF ASN-192; ASN-277 AND ASN-422; CHARACTERIZATION OF VARIANTS ETL1 ARG-46; ARG-145; ARG-200; CYS-318 AND ALA-383;

Two novel epilepsy-linked mutations leading to a loss of function of LGI1.
Chabrol E.; Popescu C.; Gourfinkel-An I.; Trouillard O.; Depienne C.; Senechal K.; Baulac M.; LeGuern E.; Baulac S.;
Arch. Neurol. 64:217-222(2007)
Cited for: SUBCELLULAR LOCATION; VARIANT ETL1 PRO-232; CHARACTERIZATION OF VARIANTS ETL1 PRO-232 AND ALA-383;

Mutations in LGI1 cause autosomal-dominant partial epilepsy with auditory features.
Kalachikov S.; Evgrafov O.; Ross B.; Winawer M.; Barker-Cummings C.; Boneschi F.M.; Choi C.; Morozov P.; Das K.; Teplitskaya E.; Yu A.; Cayanis E.; Penchaszadeh G.; Kottmann A.H.; Pedley T.A.; Hauser W.A.; Ottman R.; Gilliam T.C.;
Nat. Genet. 30:335-341(2002)
Cited for: VARIANT ETL1 ALA-383;

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.