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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P23415: Variant p.Arg299Leu

Glycine receptor subunit alpha-1
Gene: GLRA1
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Variant information Variant position: help 299 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Arginine (R) to Leucine (L) at position 299 (R299L, p.Arg299Leu). 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: help Change from large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In HKPX1; requires much higher glycine levels for channel activation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 299 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 457 The length of the canonical sequence.
Location on the sequence: help ARVGLGITTVLTMTTQSSGS R ASLPKVSYVKAIDIWMAVCL 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         ARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCL

Mouse                         ARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCL

Rat                           ARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCL

Bovine                        ARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCL

Zebrafish                     ARVGLGITTVLTMTTQSSGSRASLPKVSYVKAIDIWMAVCL
Sequence annotation in neighborhood: help 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 29 – 457 Glycine receptor subunit alpha-1
Topological domain 299 – 309 Extracellular
Site 289 – 289 Important for obstruction of the ion pore in the closed conformation
Mutagenesis 282 – 282 G -> A. Increased single-channel conductance. No effect on glycine sensitivity, but decreased rate of activation.
Mutagenesis 304 – 304 K -> C. Decreases channel conductance; the mutant channel requires much higher glycine concentrations for activation.
Helix 299 – 301



Literature citations
Mutations in the alpha 1 subunit of the inhibitory glycine receptor cause the dominant neurologic disorder, hyperekplexia.
Shiang R.; Ryan S.G.; Zhu Y.-Z.; Hahn A.F.; O'Connell P.; Wasmuth J.J.;
Nat. Genet. 5:351-357(1993)
Cited for: VARIANTS HKPX1 LEU-299 AND GLN-299; Decreased agonist affinity and chloride conductance of mutant glycine receptors associated with human hereditary hyperekplexia.
Langosch D.; Laube B.; Runstroem N.; Schmieden V.; Bormann J.; Betz H.;
EMBO J. 13:4223-4228(1994)
Cited for: CHARACTERIZATION OF VARIANTS HKPX1 LEU-299 AND GLN-299; FUNCTION; SUBCELLULAR LOCATION; An additional family with Startle disease and a G1192A mutation at the alpha 1 subunit of the inhibitory glycine receptor gene.
Schorderet D.F.; Pescia G.; Bernasconi A.; Regli F.;
Hum. Mol. Genet. 3:1201-1201(1994)
Cited for: VARIANT HKPX1 LEU-299; Identification of intracellular and extracellular domains mediating signal transduction in the inhibitory glycine receptor chloride channel.
Lynch J.W.; Rajendra S.; Pierce K.D.; Handford C.A.; Barry P.H.; Schofield P.R.;
EMBO J. 16:110-120(1997)
Cited for: CHARACTERIZATION OF VARIANTS HKPX1 ASN-272; LEU-299; GLN-299; GLU-304 AND CYS-307; FUNCTION; SUBCELLULAR LOCATION; BIOPHYSICOCHEMICAL PROPERTIES;
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.