UniProtKB/SwissProt variant VAR

Variant information

Variant position:

219

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 Aspartate (D) to Asparagine (N) at position 219 (D219N, p.Asp219Asn).

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 (D) to medium size and polar (N)

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, idiopathic generalized 13 (EIG13) [MIM:611136]: A disorder characterized by recurring generalized seizures in the absence of detectable brain lesions and/or metabolic abnormalities. Generalized seizures arise diffusely and simultaneously from both hemispheres of the brain. Seizure types include juvenile myoclonic seizures, absence seizures, and generalized tonic-clonic seizures. {ECO:0000269|PubMed:21714819}. Note=Disease susceptibility is associated with variations 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 EIG13; the mutant protein is partially retained in the endoplasmic reticulum and has decreased expression at the plasma membrane; causes decreased current amplitude in response to GABA compared to wild-type and alters receptor gating kinetics including faster desensitization.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs587777364 [ dbSNP | Ensembl ]

Sequence information

Variant position:

219

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

Protein sequence length:

456

The length of the canonical sequence.

Location on the sequence:

TREPARSVVVAEDGSRLNQY D LLGQTVDSGIVQSSTGEYVV

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                         TREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVV

Mouse                         TREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVV

Rat                           TREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVV

Bovine                        TREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVV

Chicken                       TREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVV

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.

Type	Positions	Description
Chain	28 – 456	Gamma-aminobutyric acid receptor subunit alpha-1
Topological domain	28 – 251	Extracellular

Literature citations

Novel alpha1 and gamma2 GABAA receptor subunit mutations in families with idiopathic generalized epilepsy.
Lachance-Touchette P.; Brown P.; Meloche C.; Kinirons P.; Lapointe L.; Lacasse H.; Lortie A.; Carmant L.; Bedford F.; Bowie D.; Cossette P.;
Eur. J. Neurosci. 34:237-249(2011)
Cited for: INVOLVEMENT IN EIG13; VARIANT EIG13 ASN-219; CHARACTERIZATION OF VARIANT EIG13 ASN-219;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P14867: Variant p.Asp219Asn