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UniProtKB/Swiss-Prot P28472: Variant p.Gly32Arg

Gamma-aminobutyric acid receptor subunit beta-3
Gene: GABRB3
Variant information

Variant position:  32
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 Glycine (G) to Arginine (R) at position 32 (G32R, p.Gly32Arg).
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 glycine (G) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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, childhood absence 5 (ECA5) [MIM:612269]: A subtype of idiopathic generalized epilepsy characterized by an onset at age 6-7 years, frequent absence seizures (several per day) and bilateral, synchronous, symmetric 3-Hz spike waves on EEG. Tonic-clonic seizures often develop in adolescence. Absence seizures may either remit or persist into adulthood. {ECO:0000269|PubMed:18514161, ECO:0000269|PubMed:22303015}. 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 ECA5; the mutant protein is hyperglycosylated and has reduced mean current densities compared to wild-type.
Any additional useful information about the variant.

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



Sequence information

Variant position:  32
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  473
The length of the canonical sequence.

Location on the sequence:   IFSAPVLVAVVCCAQSVNDP  G NMSFVKETVDKLLKGYDIRL
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                         IFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRL

Mouse                         IFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRL

Rat                           IFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRL

Chicken                       IFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRL

Drosophila                    LLGAQL--QLIRCIRKDVLAGRLENVTQTISNILQGYDIRL

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 26 – 473 Gamma-aminobutyric acid receptor subunit beta-3
Topological domain 26 – 245 Extracellular
Glycosylation 33 – 33 N-linked (GlcNAc...) asparagine
Alternative sequence 1 – 85 Missing. In isoform 4.
Alternative sequence 3 – 80 GLAGGRLFGIFSAPVLVAVVCCAQSVNDPGNMSFVKETVDKLLKGYDIRLRPDFGGPPVCVGMNIDIASIDMVSEVNM -> ATYQTEE. In isoform 3.


Literature citations

Hyperglycosylation and reduced GABA currents of mutated GABRB3 polypeptide in remitting childhood absence epilepsy.
Tanaka M.; Olsen R.W.; Medina M.T.; Schwartz E.; Alonso M.E.; Duron R.M.; Castro-Ortega R.; Martinez-Juarez I.E.; Pascual-Castroviejo I.; Machado-Salas J.; Silva R.; Bailey J.N.; Bai D.; Ochoa A.; Jara-Prado A.; Pineda G.; Macdonald R.L.; Delgado-Escueta A.V.;
Am. J. Hum. Genet. 82:1249-1261(2008)
Cited for: VARIANT ECA5 ARG-32; CHARACTERIZATION OF VARIANT ECA5 ARG-32; VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2); CHARACTERIZATION OF VARIANTS ECA5 SER-11 AND PHE-15 (ISOFORM 2); FUNCTION; SUBCELLULAR LOCATION; SUBUNIT;

GABRB3 mutation, G32R, associated with childhood absence epilepsy alters alpha1beta3gamma2L gamma-aminobutyric acid type A (GABAA) receptor expression and channel gating.
Gurba K.N.; Hernandez C.C.; Hu N.; Macdonald R.L.;
J. Biol. Chem. 287:12083-12097(2012)
Cited for: CHARACTERIZATION OF VARIANT ECA5 ARG-32; FUNCTION; SUBCELLULAR LOCATION; SUBUNIT;

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.