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UniProtKB/Swiss-Prot P18505: Variant p.Phe246Ser

Gamma-aminobutyric acid receptor subunit beta-1
Gene: GABRB1
Variant information

Variant position:  246
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Phenylalanine (F) to Serine (S) at position 246 (F246S, p.Phe246Ser).
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 small size and polar (S)
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

Variant description:  In DEE45; no effect on localization to the plasma membrane; increased GABA-gated chloride ion channel activity; increased single channel burst duration.
Any additional useful information about the variant.

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



Sequence information

Variant position:  246
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  474
The length of the canonical sequence.

Location on the sequence:   TTGAYPRLSLSFRLKRNIGY  F ILQTYMPSTLITILSWVSFW
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                         TTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFW

Mouse                         TTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFW

Rat                           TTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFW

Bovine                        TTGAYPRLSLSFRLKRNIGYFILQTYMPSTLITILSWVSFW

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 – 474 Gamma-aminobutyric acid receptor subunit beta-1
Transmembrane 246 – 267 Helical
Alternative sequence 88 – 474 Missing. In isoform 2.


Literature citations

De novo mutations in epileptic encephalopathies.
Allen A.S.; Berkovic S.F.; Cossette P.; Delanty N.; Dlugos D.; Eichler E.E.; Epstein M.P.; Glauser T.; Goldstein D.B.; Han Y.; Heinzen E.L.; Hitomi Y.; Howell K.B.; Johnson M.R.; Kuzniecky R.; Lowenstein D.H.; Lu Y.F.; Madou M.R.; Marson A.G.; Mefford H.C.; Esmaeeli Nieh S.; O'Brien T.J.; Ottman R.; Petrovski S.; Poduri A.; Ruzzo E.K.; Scheffer I.E.; Sherr E.H.; Yuskaitis C.J.; Abou-Khalil B.; Alldredge B.K.; Bautista J.F.; Berkovic S.F.; Boro A.; Cascino G.D.; Consalvo D.; Crumrine P.; Devinsky O.; Dlugos D.; Epstein M.P.; Fiol M.; Fountain N.B.; French J.; Friedman D.; Geller E.B.; Glauser T.; Glynn S.; Haut S.R.; Hayward J.; Helmers S.L.; Joshi S.; Kanner A.; Kirsch H.E.; Knowlton R.C.; Kossoff E.H.; Kuperman R.; Kuzniecky R.; Lowenstein D.H.; McGuire S.M.; Motika P.V.; Novotny E.J.; Ottman R.; Paolicchi J.M.; Parent J.M.; Park K.; Poduri A.; Scheffer I.E.; Shellhaas R.A.; Sherr E.H.; Shih J.J.; Singh R.; Sirven J.; Smith M.C.; Sullivan J.; Lin Thio L.; Venkat A.; Vining E.P.; Von Allmen G.K.; Weisenberg J.L.; Widdess-Walsh P.; Winawer M.R.;
Nature 501:217-221(2013)
Cited for: INVOLVEMENT IN DEE45; VARIANT DEE45 SER-246;

Epileptic encephalopathy de novo GABRB mutations impair GABAA receptor function.
Janve V.S.; Hernandez C.C.; Verdier K.M.; Hu N.; Macdonald R.L.;
Ann. Neurol. 79:806-825(2016)
Cited for: CHARACTERIZATION OF VARIANT DEE45 SER-246; FUNCTION; 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.